Sensitive and Precise Quantification of Insulin-Like mRNA Expression in Caenorhabditis elegans

Insulin-like signaling regulates developmental arrest, stress resistance and lifespan in the nematode Caenorhabditis elegans. However, the genome encodes 40 insulin-like peptides, and the regulation and function of individual peptides is largely uncharacterized. We used the nCounter platform to measure mRNA expression of all 40 insulin-like peptides as well as the insulin-like receptor daf-2, its transcriptional effector daf-16, and the daf-16 target gene sod-3. We validated the platform using 53 RNA samples previously characterized by high density oligonucleotide microarray analysis. For this set of genes and the standard nCounter protocol, sensitivity and precision were comparable between the two platforms. We optimized conditions of the nCounter assay by varying the mass of total RNA used for hybridization, thereby increasing sensitivity up to 50-fold and reducing the median coefficient of variation as much as 4-fold. We used deletion mutants to demonstrate specificity of the assay, and we used optimized conditions to assay insulin-like gene expression throughout the C. elegans life cycle. We detected expression for nearly all insulin-like genes and find that they are expressed in a variety of distinct patterns suggesting complexity of regulation and specificity of function. We identified insulin-like genes that are specifically expressed during developmental arrest, larval development, adulthood and embryogenesis. These results demonstrate that the nCounter platform provides a powerful approach to analyzing insulin-like gene expression dynamics, and they suggest hypotheses about the function of individual insulin-like genes

The violent adolescent : profiles of youngsters apprehended with weapons on school property.

The present study was designed to examine the issues which surround young people who are apprehended on or around Boston Public School property carrying weapons or dangerous objects. The records of 40 students were randomly selected, according to specific criteria, from the files at the Barron Assessment and Counseling Center. The BACC was designed to be a disciplinary measure. The main goal of the program is to help the youngsters understand the ramifications of their actions. Specifically, the hypotheses which guided the study were designed to determine: (1) if the students apprehended were conduct-disordered; (2) if the students were responding to cultural and environmental norms; (3) their socio-economic status; (4) if the students were substance abusers; (5) their academic status; (6) the precipitating actions which caused apprehension; (7) if the students were involved in the criminal justice system; and (8) the recidivism rate of this population. A summary of the research findings indicated that this cross section of youngsters were more behavior-disordered than was hypothesized. In fact, 37% of the youngsters in the sample exhibited moderate to severe conduct disorders and one-third had been adjudicated or were waiting judgement in some aspect of the criminal justice system. A majority of the sample resided in neighborhoods with high-crime rates and were products of single-parent homes with multiple siblings. Most of their families were subsidized by Public Assistance. Eighty percent of the sample were black males and the median age was 15.4, while the median grade level was 8.8. It could not be concluded from self-report data what percent of the youngsters abused drugs. Only 8% of the sample were caught using a weapon in a fight. The intelligence classification of the sample cluster was in the average range (80%); however, the sample as a whole was underachieving by approximately two years below grade level. The students were judged to be deficient in critical thinking skills based on other findings which were not anticipated

The Adsorption of Amino Acids at the Mercury-Water Interphase. II: Glycyl-glycine

The adsorption of glycyl-glycine from 0.1 mol 1-1 aqueous KPF6 solutions has been studied by electrocapillary and capacity methods. In contrast to glycine, glycyl-glycine behaves as a typical organic adsorbate. Its adsorption isotherm is congruent when potential is used as the electrical variable and not when charge is used. The large repulsive effects between adsorbed \u27Species are ascribed to solvation rather than electrostatic effects

Synthetic lethal analysis of Caenorhabditis elegans posterior embryonic patterning genes identifies conserved genetic interactions

Phenotypic robustness is evidenced when single-gene mutations do not result in an obvious phenotype. It has been suggested that such phenotypic stability results from 'buffering' activities of homologous genes as well as non-homologous genes acting in parallel pathways. One approach to characterizing mechanisms of phenotypic robustness is to identify genetic interactions, specifically, double mutants where buffering is compromised. To identify interactions among genes implicated in posterior patterning of the Caenorhabditis elegans embryo, we measured synthetic lethality following RNA interference of 22 genes in 15 mutant strains. A pair of homologous T-box transcription factors (tbx-8 and tbx-9) is found to interact in both C. elegans and C. briggsae, indicating that their compensatory function is conserved. Furthermore, a muscle module is defined by transitive interactions between the MyoD homolog hlh-1, another basic helix-loop-helix transcription factor, hnd-1, and the MADS-box transcription factor unc-120. Genetic interactions within a homologous set of genes involved in vertebrate myogenesis indicate broad conservation of the muscle module and suggest that other genetic modules identified in C. elegans will be conserved

Near-universal hospitalization of US emergency department patients with cancer and febrile neutropenia

IMPORTANCE: Febrile neutropenia (FN) is the most common oncologic emergency and is among the most deadly. Guidelines recommend risk stratification and outpatient management of both pediatric and adult FN patients deemed to be at low risk of complications or mortality, but our prior single-center research demonstrated that the vast majority (95%) are hospitalized. OBJECTIVE: From a nationwide perspective, to determine the proportion of cancer patients of all ages hospitalized after an emergency department (ED) visit for FN, and to analyze variability in hospitalization rates. Our a priori hypothesis was that >90% of US cancer-associated ED FN visits would end in hospitalization. DESIGN: Analysis of data from the Nationwide Emergency Department Sample, 2006-2014. SETTING: Stratified probability sample of all US ED visits. PARTICIPANTS: Inclusion criteria were: (1) Clinical Classification Software code indicating cancer, (2) diagnostic code indicating fever, and (3) diagnostic code indicating neutropenia. We excluded visits ending in transfer. EXPOSURE: The hospital at which the visit took place. MAIN OUTCOMES AND MEASURES: Our main outcome is the proportion of ED FN visits ending in hospitalization, with an a priori hypothesis of >90%. Our secondary outcomes are: (a) hospitalization rates among subsets, and (b) proportion of variability in the hospitalization rate attributable to which hospital the patient visited, as measured by the intra-class correlation coefficient (ICC). RESULTS: Of 348,868 visits selected to be representative of all US ED visits, 94% ended in hospitalization (95% Confidence Interval [CI] 93-94%). Each additional decade of age conferred 1.23x increased odds of hospitalization. Those with private (92%), self-pay (92%), and other (93%) insurance were less likely to be hospitalized than those with public insurance (95%, odds ratios [OR] 0.74-0.76). Hospitalization was least likely at non-metropolitan hospitals (84%, OR 0.15 relative to metropolitan teaching hospitals), and was also less likely at metropolitan non-teaching hospitals (94%, OR 0.64 relative to metropolitan teaching hospitals). The ICC adjusted for hospital random effects and patient and hospital characteristics was 26% (95%CI 23-29%), indicating that 26% of the variability in hospitalization rate was attributable to which hospital the patient visited. CONCLUSIONS AND RELEVANCE: Nearly all cancer-associated ED FN visits in the US end in hospitalization. Inter-hospital variation in hospitalization practices explains 26% of the limited variability in hospitalization decisions. Simple, objective tools are needed to improve risk stratification for ED FN patients

A new approach to finding galaxy groups using Markov Clustering

We present a proof of concept of a new galaxy group finder method, Markov graph CLustering (MCL) that naturally handles probabilistic linking criteria. We introduce a new figure of merit, the variation of information (VI) statistic, used to optimize the free parameter(s) of the MCL algorithm. We explain that the common friends-of-friends (FoF) method is a subset of MCL. We test MCL in real space on a realistic mock galaxy catalogue constructed from an N-body simulation using the galform model. With a fixed linking length FoF produces the best group catalogues as quantified by the VI statistic. By making the linking length sensitive to the local galaxy density, the quality of the FoF and MCL group catalogues improve significantly, with MCL being preferred over FoF due to a smaller VI value. The MCL group catalogue recovers accurately the underlying halo multiplicity function at all multiplicities. MCL provides better and more consistent group purity and halo completeness values at all multiplicities than FoF. As MCL allows for probabilistic pairwise connections, it is a promising algorithm to find galaxy groups in photometric surveys