Showing papers by "British Columbia Institute of Technology published in 2011"

Global Influenza Seasonality: Reconciling Patterns across Temperate and Tropical Regions

Abstract: BACKGROUND: Despite the significant disease burden of the influenza virus in humans, our understanding of the basis for its pronounced seasonality remains incomplete. Past observations that influenza epidemics occur in the winter across temperate climates, combined with insufficient knowledge about the epidemiology of influenza in the tropics, led to the perception that cool and dry conditions were a necessary, and possibly sufficient, driver of influenza epidemics. Recent reports of substantial levels of influenza virus activity and well-defined seasonality in tropical regions, where warm and humid conditions often persist year-round, have rendered previous hypotheses insufficient for explaining global patterns of influenza. OBJECTIVE: In this review, we examined the scientific evidence for the seasonal mechanisms that potentially explain the complex seasonal patterns of influenza disease activity observed globally. METHODS: In this review we assessed the strength of a range of hypotheses that attempt to explain observations of influenza seasonality across different latitudes and how they relate to each other. We reviewed studies describing population-scale observations, mathematical models, and ecological, laboratory, and clinical experiments pertaining to influenza seasonality. The literature review includes studies that directly mention the topic of influenza seasonality, as well as other topics we believed to be relevant. We also developed an analytical framework that highlights the complex interactions among environmental stimuli, mediating mechanisms, and the seasonal timing of influenza epidemics and identify critical areas for further research. CONCLUSIONS: The central questions in influenza seasonality remain unresolved. Future research is particularly needed in tropical localities, where our understanding of seasonality remains poor, and will require a combination of experimental and observational studies. Further understanding of the environmental factors that drive influenza circulation also may be useful to predict how dynamics will be affected at regional levels by global climate change.

Digital Learners in Higher Education: Generation is Not the Issue

Abstract: Generation is often used to explain and rationalize the use of information and communication technologies (ICTs) in higher education. However, a comprehensive review of the research and popular literature on the topic and an empirical study at one postsecondary institution in Canada suggest there are no meaningful generational differences in how learners say they use ICTs or their perceived behavioural characteristics. The study also concluded that the post-secondary students at the institution in question use a limited set of ICTs and their use is driven by three key issues: familiarity, cost, and immediacy. The findings are based on focus group interviews with 69 students and survey responses from a random sample of 438 second year students in 14 different programs in five schools in the institution. The results of this investigation add to a growing body of research that questions the popular view that generation can be used to explain the use of ICTs in higher education.

Gene Expression Noise in Spatial Patterning: hunchback Promoter Structure Affects Noise Amplitude and Distribution in Drosophila Segmentation

Abstract: Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb14F, and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

Determination of major phenolic compounds in Echinacea spp. raw materials and finished products by high-performance liquid chromatography with ultraviolet detection: single-laboratory validation matrix extension

Abstract: A method previously validated to determine caftaric acid, chlorogenic acid, cynarin, echinacoside, and cichoric acid in echinacea raw materials has been successfully applied to dry extract and liquid tincture products in response to North American consumer needs. Single-laboratory validation was used to assess the repeatability, accuracy, selectivity, LOD, LOQ, analyte stability (ruggedness), and linearity of the method, with emphasis on finished products. Repeatability precision for each phenolic compound was between 1.04 and 5.65% RSD, with HorRat values between 0.30 and 1.39 for raw and dry extract finished products. HorRat values for tinctures were between 0.09 and 1.10. Accuracy of the method was determined through spike recovery studies. Recovery of each compound from raw material negative control (ginseng) was between 90 and 114%, while recovery from the finished product negative control (maltodextrin and magnesium stearate) was between 97 and 103%. A study was conducted to determine if cichoric acid, a major phenolic component of Echinacea purpurea (L.) Moench and E. angustifolia DC, degrades during sample preparation (extraction) and HPLC analysis. No significant degradation was observed over an extended testing period using the validated method.

Trap-depth determination from residual gas collisions

Abstract: We present a method for determining the depth of an atomic or molecular trap of any type. This method relies on a measurement of the trap loss rate induced by collisions with background gas particles. Given a fixed gas composition, the loss rate uniquely determines the trap depth. Because of the ``soft'' long-range nature of the van der Waals interaction, these collisions transfer kinetic energy to trapped particles across a broad range of energy scales, from room temperature to the microkelvin energy scale. The resulting loss rate therefore exhibits a significant variation over an enormous range of trap depths, making this technique a powerful diagnostic with a large dynamic range. We present trap depth measurements of a Rb magneto-optical trap using this method and a different technique that relies on measurements of loss rates during optical excitation of colliding atoms to a repulsive molecular state. The main advantage of the method presented here is its large dynamic range and applicability to traps of any type requiring only knowledge of the background gas density and the interaction potential between the trapped and background gas particles.

Determination of indoor humidity profile using a whole-building hygrothermal model

Abstract: During the design of a new building or retrofitting of an existing one, it is important to reliably assess the indoor humidity levels of the building as it can potentially affect the building envelope durability, occupants’ comfort and health risks associated with mould growth. Simplistic assumptions of indoor humidity profiles, which ignore the dynamic coupling of the indoor environment and building enclosure, may lead to inaccurate conclusions about the indoor environment and moisture performance of the building enclosure. In this paper, a whole-building hygrothermal model called HAMFitPlus, which takes into account the dynamic interactions between building envelope components, mechanical systems and indoor heat and moisture generation mechanisms, is used to assess the indoor humidity condition of an existing occupied house. HAMFitPlus is developed on SimuLink development platform and integrates COMSOL multiphysics with MatLab. The basic input parameters of the model are discussed in detail, and its simulation results are presented. In general, the HAMFitPlus simulation results are in good agreement with the measured data.

Tropically stable novel oral lipid formulation of amphotericin B (iCo-010): biodistribution and toxicity in a mouse model

Abstract: Background: The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010). Methods: BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone ® 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected. Results: The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone ® resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone ® treatment induced necrotic changes in hepatic and kidney tissues. Conclusions: Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.

Analysis of alkylamides in Echinacea plant materials and dietary supplements by ultrafast liquid chromatography with diode array and mass spectrometric detection.

Abstract: Alkylamides are a class of compounds present in plants of the genus Echinacea (Asteraceae), which have been shown to have high bioavailability and immunomodulatory effects. Fast analysis to identify these components in a variety of products is essential to profile products used in clinical trials and for quality control of these products. A method based on ultrafast liquid chromatography (UFLC) coupled with diode array detection and electrospray ionization mass spectrometry was developed for the analysis of alkylamides from the roots of Echinacea angustifolia (DC.) Hell., Echinacea purpurea (L.) Moench, and commercial dietary supplements. A total of 24 alkylamides were identified by LC-MS. The analysis time for these components is 15 min. Compared to the alkylamide profiles determined in the Echinacea root materials, the commercial products showed a more complex profile due to the blending of root and aerial parts of E. purpurea. This versatile method allows for the identification of alkylamides in a variety of Echinacea products and presents the most extensive characterization of alkylamides in E. angustifolia roots so far.

Iterated belief change due to actions and observations

Abstract: In action domains where agents may have erroneous beliefs, reasoning about the effects of actions involves reasoning about belief change. In this paper, we use a transition system approach to reason about the evolution of an agent's beliefs as actions are executed. Some actions cause an agent to perform belief revision while others cause an agent to perform belief update, but the interaction between revision and update can be nonelementary. We present a set of rationality properties describing the interaction between revision and update, and we introduce a new class of belief change operators for reasoning about alternating sequences of revisions and updates. Our belief change operators can be characterized in terms of a natural shifting operation on total pre-orderings over interpretations. We compare our approach with related work on iterated belief change due to action, and we conclude with some directions for future research.

Purification of alkylamides from Echinacea angustifolia (DC.) Hell. Roots by high-speed countercurrent chromatography.

Abstract: High-speed countercurrent chromatography (HSCCC) was used for the separation of alkylamides from the roots of Echinacea angustifolia (DC.) Hell. For this purpose, the alkylamides were extracted with hexane and subjected to semipreparative HSCCC using a two-phase solvent system consisting of n-hexane, ethyl acetate, methanol, and water (4:1:2:1). The lower aqueous phase was used as the mobile phase at a flow rate of 3 mL/min and a rotary speed of 1000 rpm. This procedure led to the isolation of four pure alkylamides, that is, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide (38.9 mg, 97% purity), dodeca-2E,4E,8Z-trienoic acid isobutylamide (4.4 mg, 92% purity), dodeca-2E,4E-dienoic acid isobutylamide (3.2 mg, 99% purity), and dodeca-2E,4E-dienoic acid 2-methylbutylamide (0.3 mg, 92% purity). The identity and purity of the isolated alkylamides were confirmed by LC-ESI-MS and (1)H NMR and (13)C NMR data. To the best of the authors' knowledge, this is the first report of dodeca-2E,4E-dienoic acid 2-methylbutylamide in E. angustifolia roots.

Digital Learners in Higher Education: A Research Project Update

Abstract: This article provides an update of the Digital Learners in Higher Education Research project. In Phase 1 of the project, concluded that there is no empirically-sound basis for most of the claims that have been made about the net generation. It also found there are no meaningful differences between net generation and non-net generation students at this institution in terms of their use of technology, nor in their behavioural characteristics and learning preferences at one Canadian postsecondary institution. Phase 2 of the study will explore the “whys” of these findings, with the intention of informing teaching and learning practices.

Method and device for accurately measuring the incident flux of ambient particles in a high or ultra-high vacuum environment

Abstract: An apparatus and method that can measure flux density in-situ under high vacuum conditions includes a means for confining a collection of identical, elemental sensor particles to a volume of space by initial cooling by laser or another method, then confinement in a sensor volume using externally applied magnetic and/or optical fields.

Education and Sustainability: Learning Across the Diaspora, Indigenous, and Minority Divide

Abstract: This book critically examines the impact of migration, education, development, and the spread of English on global bio-linguistic and cultural diversity. Derived from findings from a comparative eco-linguistic study of intergenerational language, culture, and education change in the Tibetan Diaspora, the book extends its analysis to consider the plight of other peoples who find themselves straddling the Indigenous-Minority-Diaspora divide. MacPherson explores the overlapping and distinctive sustainability challenges facing indigenous and minority communities when they are connected by and within diasporas, and seeks to adequately explain the discontinuities and disjunctures between their educational struggles and achievement levels.

In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009 and iCo-010) against Candida albicans, human monocytic and kidney cell lines.

Abstract: Background: Invasive fungal infections such as candidiasis constitute an increasingly important medical problem. Drugs currently used for the treatment of candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B (AmpB) presents several limitations such as its nephrotoxicity and limited solubility. We have developed two novel lipid-based AmpB formulations which in vivo show less nephrotoxicity and enhanced solubility compared to Fungizone™ a commercial AmpB formulation. The purpose of this study was to determine the cytotoxicity of Fungizone™, Ambisome™ and two novel AmpB formulations (iCo-009 and iCo-010) against Candida albicans, human kidney (293T) cells and monocytic (THP1) cells. Methods: Cell cytotoxicity to the AmpB formulations was evaluated by MTS and LDH assays. In vitro anti-Candida albicans activity was assessed after a 48 h drug incubation.

Low voltage distribution substation integration in smart Microgrid

Abstract: A strategy is proposed to introduce a limited set of monitoring and control functions into a legacy low voltage distribution substation, and as such integrate it into a larger command and control architecture of a smart Microgrid. The focus of the work shall be on the retrofit strategy of some of the key components for measurement, monitoring, protection and control systems of the substation. Also Volt/VAR optimization of the feeder shall be considered as a part of the design. The article discusses the structure of the substation under study, followed by the actual design of IEC 61850 subsystems for the substation. A simulation model of the pilot project and its results is also included in the paper.

Determination of ginsenoside content in Asian and North American ginseng raw materials and finished products by high-performance liquid chromatography: single-laboratory validation.

Abstract: A single-laboratory validation study was conducted for the quantification of Rg1, Re, Rb1, Rc, Rb2, and Rd in Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) raw materials and finished products by RP-HPLC. The extraction with aqueous methanol was optimized for whole root, powdered extract, and finished product (raw, tablet, and capsule matrixes) test articles. Root materials were treated with base to hydrolyze acidic malonyl ginsenosides to their neutral counterparts. Calibration curves for each ginsenoside were linear over the following ranges (microg/g): 5-394 for Rg1, 15-1188 for Re, 39-2981 for Rb1, 6-499 for Rc, 5-406 for Rb2, and 7-600 for Rd, all having a coefficient of determination (r2) of > or = 99.5%. The LOD for Rg1, Re, Rb1, Rc, Rb2, and Rd was determined to be 1.06, 1.25, 2.19, 1.24, 1.27, and 1.70 microg/mL, respectively. Quantitative determinations performed with eight test materials by two analysts over 3 days (n = 12) resulted in RSDr values that ranged from 1.11 to 7.61%.

A comparison between the effects of ozone and alkaline peroxide treatments on tmp properties and subsequent low consistency refining

Abstract: As part of a program to reduce electrical energy consumption in the refining process, the effects of the ozone and alkaline peroxide treatments on fibre and handsheet properties, prior and subsequent to low consistency (LC) refining, were assessed and compared by applying different levels of ozone and a range of peroxide and alkali charges to a primary stage hemlock thermomechanical pulp (TMP). Both highly alkaline peroxide treatments and ozone treatments decreased the specific energy required for strong mechanical pulp. The improvement in pulp strength through alkaline peroxide treatment mainly resulted from pulp surface changes caused by generation of acid groups. The highly alkaline peroxide treatments significantly increased pulp brightness but did not promote the further fibrillation during the subsequent LC refining. On the other hand, ozone treatments provided tensile strength increases, along with small brightness enhancements for the dark hemlock TMP, and increased the tensile gains obtained through LC refining. The effects of ozone treatments on tensile strength before and after LC refining were the result of pulp surface modifications, fibre swelling, and loss of fibre wall integrity due to non-selective chemical attack. High levels of ozone treatment caused tear strength to decrease during subsequent LC refining.

Integration of Problem-Based Learning and Web-Based Multimedia to Enhance a Soil Management Course

Abstract: In an attempt to address declining enrolment in soil science programs and the changing learning needs of 21st century students, several universities in North America and around the world have re-organized their soil science curriculum and adopted innovative educational approaches and web-based teaching resources. At the University of British Columbia, Canada, an interdisciplinary team set out to integrate teaching approaches to address this trend. The objective of this project was to develop an interactive web-based teaching resource, which combined a face-to-face problem-based learning (PBL) case study with multimedia to illustrate the impacts of three land-uses on soil transformation and quality. The Land Use Impacts (LUI) tool (http://soilweb.landfood.ubc.ca/luitool/) was a collaborative and concentrated effort to maximize the advantages of two educational approaches: (1) the web’s interactivity, flexibility, adaptability and accessibility, and (2) PBL’s ability to foster an authentic learning environment, encourage group work and promote the application of core concepts. The design of the LUI case study was guided by Herrington’s development principles for web-based authentic learning. The LUI tool presented students with rich multimedia (streaming videos, text, data, photographs, maps, and weblinks) and real world tasks (site assessment and soil analysis) to encourage students to utilize knowledge of soil science in collaborative problemsolving. Preliminary student feedback indicated that the LUI tool effectively conveyed case study objectives and was appealing to students. The resource is intended primarily for students enrolled in an upper level undergraduate/graduate university course titled Sustainable Soil Management but it is flexible enough to be adapted to other natural resource courses. Project planning and an interactive overview of the tool will be given during the presentation.

Differences between Saudi Arabian and Australian radiographers' knowledge and attitudes about paediatric CT doses

Abstract: Purpose: Computed tomography (CT) is used extensively in diagnostic radiology for examination of human soft tissues and is widely used in the paediatric population. Researchers and government regulators have expressed concerns about the cancer risk of CT radiation on children. Th e authors surveyed Saudi Arabian and Australian radiographers to enable comparison of their attitudes and knowledge towards paediatric CT radiation dose. Methods: Radiographers from all exclusively paediatric public hospitals in Australia and Saudi Arabia were sent a structured, purpose-designed questionnaire. Data were analysed using univariate statistics. Results: 56 of 71 eligible Saudi Arabian radiographers (79%) and 50 of 83 Australian radiographers (60%) participated. Australian participants were more highly educated and had longer work experience than their Saudi counterparts, and undertook most forms of ongoing training and education signifi cantly more frequently. Australians' mean ratings of radiation risk for head and chest CT scans were similar to those given by Saudi respondents, but Australians' mean ratings for abdomen/pelvis CT scans were signifi cantly lower. More Australians reported intervening to reduce paediatric dose (95.7% vs 72.7%, P < 0.005), and 88.0% believed that over 60% of CT scans are justifi ed compared with 8.9% of Saudi participants. Conclusion: Australian and Saudi Arabian radiographers working in paediatric hospitals diff er in their knowledge bases. Knowledge can be improved through enhancement of hospital protocols and continuing education and training, and will lead to reduced radiation exposure among paediatric patients.

Moisture response of sheathing board in conventional and rain-screen wall systems with shiplap cladding

Abstract: Building enclosures are subjected to a random climatic loading on the exterior surface and a relatively stable indoor condition on the interior. These loadings result in a transport of heat, air, and moisture across the building enclosure. In this paper, the drying and wetting of sheathing board in two exterior walls, more specifically 2×6 in.2 wood-frame conventional (no strapping between sheathing membrane and cladding) and a rain-screen wall system (with vertical strapping), are investigated through an experimental field study. The experiment is carried out at British Columbia Institute of Technology field exposure test facility, where the test walls are exposed to the coastal climate (Vancouver weather) on the exterior and controlled indoor temperature and relative humidity conditions in the interior. The field experimental results indicate significant moisture accumulation on the exterior sheathing boards (plywood) during the Winter period. During the 9-month monitoring period from March 13 to Dec. 6, 2009, the plywood underwent a process of drying and wetting. In both the conventional and rain-screen wall systems, the plywood dried to a comparable moisture level during the Summer before the wetting process started. For the wall systems considered in this study, the plywood in the rain-screen wall has a tendency of faster drying and wetting in the Spring and Fall seasons, respectively, in comparison to the plywood in the conventional wall, which is attributed to the presence of an air gap in the rain-screen wall between the sheathing membrane and the cladding. A similar trend is observed during the monitoring period from December 7 to June 15, 2010.

Retroviral Genetic Algorithms - Implementation with Tags and Validation Against Benchmark Functions.

Abstract: Classical understandings of biological evolution inspired creation of the entire order of Evolutionary Computation (EC) heuristic optimization techniques. In turn, the development of EC has shown how living organisms use biomolecular implementations of these techniques to solve particular problems in survival and adaptation. An example of such a natural Genetic Algorithm (GA) is the way in which a higher organism’s adaptive immune system selects antibodies and competes against its complement, the development of antigen variability by pathogenic organisms. In our approach, we use operators that implement the reproduction and diversification of genetic material in a manner inspired by retroviral reproduction and a genetic-engineering technique known as DNA shuffling. We call this approach Retroviral Genetic Algorithms, or retroGA (Spirov and Holloway, 2010). Here, we extend retroGA to include: (1) the utilization of tags in strings; (2) the capability of the Reproduction-Crossover operator to read these tags and interpret them as instructions; and (3), as a consequence, to use more than one reproductive strategy. We validated the efficacy of the extended retroGA technique with benchmark tests on concatenated trap functions and compared these with Royal Road and Royal Staircase functions.

Probing student problem solving skills in mathematical induction using a scenario based think aloud protocol

Abstract: Think aloud protocol has traditionally been used to probe thinking and problem solving skills. In a series of student interview sessions where think aloud protocol was used to study student problem solving skills in mathematical induction at the University of British Columbia, a significant percentage of the students had difficulty verbalizing their thoughts while solving a problem. At other times, students felt pressured in coming up with a solution, or they were afraid of making incorrect steps and wanted to be certain before they actually articulated their thought process. As a result, a number of interviews resulted in almost complete silence and little was gained. To this end, we developed an enhanced, scenario based think-aloud protocol, designed to engage subjects during the interviews without having them feeling pressured or having to perform in front of an interviewer. In the process, the subject becomes less and less conscious of being studied and becomes more immersed in the actual problem solving with her own thoughts and ideas. In this paper we will describe this augmented think aloud protocol, and discuss our experiences of using this tool to assess mathematical induction reasoning in computer science students. A number of essential skills are identified through these interviews that may help instructors identify improved pedagogical methods for teaching the subject.

Expert System for the Modelling of an Educational Profile for Life-Long Learners

Abstract: An artificial intelligence-based computer modelling software, Soft Counsel, is used to guide candidates who already have prior learning experience of the subject and to optimize their plan for further educational upgrading. Candidates' answers to a survey questionnaire are used by an expert system to generate specific questions relevant to the candidate and her/his educational profile, and to recommend suitable broad areas of upgrading. After the candidate selects an area, the software produces a refined questionnaire, which leads to a list of recommended courses. In a third and final step of refinement, the software queries the candidate about their knowledge of each course and produces a detailed study plan. Once the proposed study plan is accepted by the candidate, Soft Counsel searches educational and training providers in the designated geographical area and provides a list of those that match the study plan.

Erratum to: Determination of indoor humidity profile using a whole-building hygrothermal model

Abstract: This publication could be one of several versions: author’s original, accepted manuscript or the publisher’s version. / La version de cette publication peut être l’une des suivantes : la version prépublication de l’auteur, la version acceptée du manuscrit ou la version de l’éditeur. For the publisher’s version, please access the DOI link below./ Pour consulter la version de l’éditeur, utilisez le lien DOI ci-dessous.

Practical steps for discontinuation of life-sustaining treatment.

Abstract: Discontinuing life-sustaining interventions requires an artful skill perhaps even more challenging than providing life-sustaining treatments. Critical care nurses require advanced skills to provide comfort care and, ultimately, a "good death" that encompasses the family and patient. Educational focus has been placed on maintaining the living, but with increasing palliation in critical care, education must include comfort care. This article focuses on the art of discontinuing life-sustaining treatment and providing a seamless, comfortable transition for patient and family. Included in it are seven steps, derived from my own experiences, that are meant to assist new practitioners in their beginning journeys of providing a "good death". The seven steps are interconnected and, depending on the context, will flow back and forth, as needed. The seven steps are: talk with the family, ensure orders are written, prepare drugs, to extubate or not, what about the monitor, ensure readiness, and proceed.

Gene expression noise in embryonic spatial patterning: Reliable formation of the head-to-tail axis in the fruit fly

Abstract: Fruit flies serve as a model for understanding the genetic regulation involved in specifying the complex body plans of higher animals. The head-to-tail (anterior-posterior) axis of the fly (Drosophila) is established in the first hours of development. Maternally supplied factors form concentration gradients which direct embryonic (zygotic) genes where to be activated to express proteins. These protein patterns specify the positions and cell types of the body's tissues. Recent research has shown, comparing between embryos, that the zygotic gene products are much more precisely positioned than the maternal gradients, indicating an embryonic error reduction mechanism. Within embryos, there is the additional aspect that DNA and mRNA operate at very low copy number, and the associated high relative noise has the potential to strongly affect protein expression patterns. In recent work, we have focused on the noise aspects of positional specification within individual embryos. We simulate activation of hunchback (hb), a primary target of the maternal Bicoid (Bcd) protein gradient, which forms an expression pattern dividing the embryo into anterior and posterior halves. We use a master equation approach to simulate the stochastic dynamics of hb regulation, using the known details of the hb promoter, the region of DNA responsible for transcribing hb mRNA. This includes the binding/unbinding of Bcd molecules at the promoter, hb transcription, subsequent translation to Hb protein, binding/unbinding of Hb at the promoter (self-regulation), and diffusion of the Bcd and Hb proteins. Model parameters were set by deterministically matching large scale pattern features for a series of experimental expression patterns: wild-type (WT) embryos; hb mutants lacking self-regulation; and constructs in which portions of the hb promoter were used to express a reporter gene (lacZ). The model was then solved stochastically to predict the noise output in these different experiments. In subsequent noise measurements we experimentally corroborated a number of the predictions. These include that mRNA is noisier than protein, and that Hb self-regulation reduces noise. Results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, and is uncorrelated with Bcd fluctuations. This contradicts prior work, which had assumed a complete dependence of Hb fluctuations on Bcd fluctuations. In the constructs and mutant, which lack self-regulation, we find that increasing the number and strength of Bcd binding sites (there are 6 in the core hb promoter) provides a rudimentary level of noise reduction. The model is robust to the various Bcd binding site numbers seen across different fly species. New directions in the project include incorporating a known inhibitor of hb, Kruppel, into the model to study its effect on the noise dynamics. Our study has identified particular ways in which hb output noise is controlled. Since these involve common modes of gene regulation (e.g. multiple regulatory sites, self-regulation), these results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.