Pattern formation by lateral inhibition with feedback: a mathematical model of Delta-Notch intercellular signalling

In many developing tissues, adjacent cells diverge in character so as to create a fine-grained pattern of cells in contrasting states of differentiation. It has been proposed that such patterns can be generated through lateral inhibition—a type cells–cell interaction whereby a cell that adopts a particular fate inhibits its immediate neighbours from doing likewise. Lateral inhibition is well documented in flies, worms and vertebrates. In all of these organisms, the transmembrane proteins Notch and Delta (or their homologues) have been identified as mediators of the interaction—Notch as receptor, Delta as its ligand on adjacent cells. However, it is not clear under precisely what conditions the Delta-Notch mechanism of lateral inhibition can generate the observed types of pattern, or indeed whether this mechanism is capable of generating such patterns by itself. Here we construct and analyse a simple and general mathematical model of such contact-mediated lateral inhibition. In accordance with experimental data, the model postulates that receipt of inhibition (i.e. activation of Notch) diminishes the ability to deliver inhibition (i.e. to produce active Delta). This gives rise to a feedback loop that can amplify differences between adjacent cells. We investigate the pattern-forming potential and temporal behavior of this model both analytically and through numerical simulation. Inhomogeneities are self-amplifying and develop without need of any other machinery, provided the feedback is sufficiently strong. For a wide range of initial and boundary conditions, the model generates fine-grained patterns similar to those observed in living systems

HepData and JetWeb: HEP data archiving and model validation

The CEDAR collaboration is extending and combining the JetWeb and HepData systems to provide a single service for tuning and validating models of high-energy physics processes. The centrepiece of this activity is the fitting by JetWeb of observables computed from Monte Carlo event generator events against their experimentally determined distributions, as stored in HepData. Caching the results of the JetWeb simulation and comparison stages provides a single cumulative database of event generator tunings, fitted against a wide range of experimental quantities. An important feature of this integration is a family of XML data formats, called HepML.Comment: 4 pages, 0 figures. To be published in proceedings of CHEP0

iCN718, an Updated and Improved Genome-Scale Metabolic Network Reconstruction of Acinetobacter baumannii AYE.

Acinetobacter baumannii has become an urgent clinical threat due to the recent emergence of multi-drug resistant strains. There is thus a significant need to discover new therapeutic targets in this organism. One means for doing so is through the use of high-quality genome-scale reconstructions. Well-curated and accurate genome-scale models (GEMs) of A. baumannii would be useful for improving treatment options. We present an updated and improved genome-scale reconstruction of A. baumannii AYE, named iCN718, that improves and standardizes previous A. baumannii AYE reconstructions. iCN718 has 80% accuracy for predicting gene essentiality data and additionally can predict large-scale phenotypic data with as much as 89% accuracy, a new capability for an A. baumannii reconstruction. We further demonstrate that iCN718 can be used to analyze conserved metabolic functions in the A. baumannii core genome and to build strain-specific GEMs of 74 other A. baumannii strains from genome sequence alone. iCN718 will serve as a resource to integrate and synthesize new experimental data being generated for this urgent threat pathogen

The equilibrium model for the effect of temperature on enzymes: Insights and implications

A new, experimentally-validated “Equilibrium Model” describes the effect of temperature on enzymes, and provides a new mechanism for the reversible loss of enzyme activity with temperature. It incorporates two new, fundamental parameters that allow a complete description of the effect of temperature on enzyme activity: ΔHeq and Teq. ΔHeq emerges as an intrinsic and quantitative measure of enzyme eurythermal adaptation, while Teq, the equilibrium temperature, has fundamental and technological significance for our understanding of the effect of temperature on enzymatic reactions. For biotechnological purposes, these parameters need to be considered when enzymes are applied or engineered for activity at high temperatures

Factors affecting tuberculosis health message recall 2 years after active case finding in Blantyre, Malawi.

SETTING: Urban slums, Blantyre, Malawi. OBJECTIVE: To explore tuberculosis (TB) community-wide active case finding (cwACF) recall and accompanying messaging 2 years after the intervention. DESIGN: This mixed-methods study used population-weighted random cluster sampling to select three cwACF-receiving and three non-cwACF-receiving neighbourhoods in Blantyre. Qualitative data were collected using 12 focus group discussions (community peer-group members) and five in-depth interviews (TB officers) with script guides based on the concepts of the Health Belief Model (HBM). Thematic analysis was used to explore transcripts employing deductive coding. Questionnaires completed by focus group participants were used to collect quantitative data, providing a 'knowledge score' evaluated through univariate/multivariate analysis, analysis of variance and multiple linear regression. RESULTS: Community peer-group participants (n = 118) retained high awareness and positive opinions of cwACF and recognised the relationship between early diagnosis and reduced transmission, considering cwACF to have prompted subsequent health-seeking behaviour. TB-affected individuals (personal/family: 47.5%) had significantly higher knowledge scores than unaffected individuals (P = 0.039), but only if resident in cwACF-receiving neighbourhoods (P = 0.005 vs. P = 0.582), implying effect modification between exposures, albeit statistically under-powered (P = 0.229). CONCLUSION: Consistent with epidemiological evidence and HBM theory, cwACF may have a permanent impact on knowledge and behaviour, particularly in communities with a high prevalence of TB-affected individuals. Behaviour change strategies should be explicitly included in cwACF planning and evaluation

Computational Materials Techniques for Thermal Protection Solutions: Materials and Process Design

Integrated computational materials techniques that span the atomistic and continuum scales have the potential to aid the design and manufacturing of thermal protection materials. Two cases demonstrating the practical application of these methods are discussed. Case one examines the selection of a high temperature coating for carbon/carbon, with the target application being a solar thermal propulsion heat exchanger. The performance of various refractory metal and metal-carbide coatings is characterized considering extreme thermal (3500 degrees Kelvin) and chemical (hydrogen flows) conditions. The recession rate, hydrogen leakage, and likelihood of mechanical failure are characterized and provide directions for further experimental investigation. Case two examines the process optimization of a heat shield material composed of a woven silica fiber preform and cyanate ester resin. Frequently, internal voids were found to be present in this composite after the resin infusion and curing stages of manufacturing. Using the manufacturing conditions, computations indicate that both water adsorption and resin cure shrinkage are contributing factors to void formation. The results suggest an alternative process configuration for curing that would mitigate voids

Retention of Student Pharmacists\u27 Knowledge and Skills Regarding Overdose Management with Naloxone

BACKGROUND: Overdose education and naloxone training was recently implemented into the required curriculum of the College of Pharmacy at the University of Rhode Island. The objective of this study was to compare the retention of knowledge between student pharmacists who received a didactic lecture only versus student pharmacists who received the same lecture plus a skills-based objective structured clinical examination (OSCE) with a standardized patient actor. METHODS: Students in their first-professional year (P1) of the Doctor of Pharmacy program (n = 129) and students in their second-professional (P2) year (n = 123) attended a required lecture on opioid overdose, including detailed naloxone training. P2 students were additionally required to participate in an OSCE assessment following the didactic lecture component. An anonymous, voluntary survey was offered to all students approximately 6 months later. A Chi-Square or Fisher\u27s Exact Test was performed on the survey responses to assess any difference in the responses between the two groups. RESULTS: A total of 99 P1 students (76.7%) and 116 P2 students (94.3%) completed the survey. P1 students were found to be more knowledgeable regarding the duration of naloxone action and identification of risk factors for opioid overdose. P2 students were found to be more knowledgeable regarding non-medical ways patients may obtain opioids and the correct order of emergency response during a suspected opioid overdose... Conclusions: P2 students did not demonstrate superior retention of information regarding naloxone and opioid use disorder on survey questions compared with P1 students. There was a trend towards P2 students feeling more confident in their ability to counsel patients for overdose prevention and reporting disagreement with the statement that overdose prevention for people who use drugs is a waste of time and money compared with the P1 students, but these did not reach statistical significance. Since the opioid crisis continues unabated, naloxone training using OSCE and didactic methods remain an on-going required part of the pharmacy curriculum

Neon and Sulfur Abundances of Planetary Nebulae in the Magellanic Clouds

The chemical abundances of neon and sulfur for 25 planetary nebulae (PNe) in the Magellanic Clouds are presented. These abundances have been derived using mainly infrared data from the Spitzer Space Telescope. The implications for the chemical evolution of these elements are discussed. A comparison with similarly obtained abundances of Galactic PNe and HII regions and Magellanic Clouds HII regions is also given. The average neon abundances are 6.0x10(-5) and 2.7x10(-5) for the PNe in the Large and Small Magellanic Clouds respectively. These are ~1/3 and 1/6 of the average abundances of Galactic planetary nebulae to which we compare. The average sulfur abundances for the LMC and SMC are respectively 2.7x10(-6) and 1.0x10(-6). The Ne/S ratio (23.5) is on average higher than the ratio found in Galactic PNe (16) but the range of values in both data sets is similar for most of the objects. The neon abundances found in PNe and HII regions agree with each other. It is possible that a few (3-4) of the PNe in the sample have experienced some neon enrichment, but for two of these objects the high Ne/S ratio can be explained by their very low sulfur abundances. The neon and sulfur abundances derived in this paper are also compared to previously published abundances using optical data and photo-ionization models.Comment: 13 pages, 4 tables, 5 figures. Accepted for publication in Ap

Schubert calculus of Richardson varieties stable under spherical Levi subgroups

We observe that the expansion in the basis of Schubert cycles for $H^*(G/B)$ of the class of a Richardson variety stable under a spherical Levi subgroup is described by a theorem of Brion. Using this observation, along with a combinatorial model of the poset of certain symmetric subgroup orbit closures, we give positive combinatorial descriptions of certain Schubert structure constants on the full flag variety in type $A$. Namely, we describe $c_{u,v}^w$ when $u$ and $v$ are inverse to Grassmannian permutations with unique descents at $p$ and $q$, respectively. We offer some conjectures for similar rules in types $B$ and $D$, associated to Richardson varieties stable under spherical Levi subgroups of SO(2n+1,\C) and SO(2n,\C), respectively.Comment: Section 4 significantly shortened, and other minor changes made as suggested by referees. Final version, to appear in Journal of Algebraic Combinatoric