Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications

This chapter summarizes several approaches combining theory, simulation and experiment that aim for a better understanding of phenomena in lipid bilayers and membrane protein systems, covering topics such as lipid rafts, membrane mediated interactions, attraction between transmembrane proteins, and aggregation in biomembranes leading to large superstructures such as the light harvesting complex of green plants. After a general overview of theoretical considerations and continuum theory of lipid membranes we introduce different options for simulations of biomembrane systems, addressing questions such as: What can be learned from generic models? When is it expedient to go beyond them? And what are the merits and challenges for systematic coarse graining and quasi-atomistic coarse grained models that ensure a certain chemical specificity

Informal Pathways to Engineering: Interim Findings from a Longitudinal Study

Informal Pathways to Engineering: Interim Findings This study, based on social cognitive career theory, seeks to investigate the effect of informal, out­of­school activities, as well as other factors (self­efficacy, outcome expectations, and personal interests, and intrapersonal factors) on students’ interest in engineering and decisions to engage in engineering­related activities. The study uses a longitudinal design in which children, parents, and educators (classroom teachers, school principals, and informal educators) are interviewed and surveyed over a period of three years (corresponding with the middle school years). Thirty families from Massachusetts and 30 families from Indiana were enrolled in the study in Year 1. Due to attrition, 40 families are currently enrolled across both sites. Children were enrolled in the study if their parents indicated that their children were interested in engineering­related activities (instead of “engineering” we used the phrase “designing, creating, or building”). For example, 100% of the sample had played with engineering­related toys (such as Legos, K’NEX, robots); 85% of the sample had watched a TV show, webisode or DVD related to designing, creating, or building; and 75% had previously built something, not in school. At the start of the study, most children (80%) reported that they knew what engineering was or had heard of it and the same proportion agreed or strongly agreed that “engineering is cool.” Upon enrollment in the study, 21 children (35%) reported that they would like to be an engineer someday. This paper will explore the intrapersonal, psychosocial, and external factors that may have played a role in children’s interest in engineering activities. For example, we will explore parental influence on children’s engineering interests and will examine the question of whether children who are interested in engineering have had exposure to parents or relatives with an engineering background. (Nine of the 60 children (15%) in the sample had one or more parents who was an engineer, while slightly more than half of the sample (51%) reported that they did not have any regular interaction with engineers.) In addition, we will look at the relationship between parental engineering knowledge, engineering­related self­efficacy, and children’s interests, examining the question of whether children who are interested in engineering have parents who feel confident in their engineering­related knowledge. For example, all but one parent in the study agreed that engineering improves society, yet only slightly more than half of the parents (55%) reported that they actually knew what engineers do. One­third of parents reported that they didn’t know how to help their children learn about engineering; they didn’t know how engineering could be used to help society; and they didn’t know how engineering is different from science. The broader significance and importance of this project will be to support the engineering field’s ability to inspire more children to pursue engineering pathways, from initial interest in engineering clubs and other extracurricular activities to choices in college majors and an ultimate career as a professional engineer. In addition, the project will help us consider how we might provide resources and education to parents to help them support their children

Expression profile and transcription factor binding site exploration of imprinted genes in human and mouse

<p>Abstract</p> <p>Background</p> <p>In mammals, imprinted genes are regulated by an epigenetic mechanism that results in parental origin-specific expression. Though allele-specific regulation of imprinted genes has been studied for several individual genes in detail, little is known about their overall tissue-specific expression patterns and interspecies conservation of expression.</p> <p>Results</p> <p>We performed a computational analysis of microarray expression data of imprinted genes in human and mouse placentae and in a variety of adult tissues. For mouse, early embryonic stages were also included. The analysis reveals that imprinted genes are expressed in a broad spectrum of tissues for both species. Overall, the relative tissue-specific expression levels of orthologous imprinted genes in human and mouse are not highly correlated. However, in both species distinctive expression profiles are found in tissues of the endocrine pathways such as adrenal gland, pituitary, pancreas as well as placenta. In mouse, the placental and embryonic expression patterns of imprinted genes are highly similar. Transcription factor binding site (TFBS) prediction reveals correlation of tissue-specific expression patterns and the presence of distinct TFBS signatures in the upstream region of human imprinted genes.</p> <p>Conclusion</p> <p>Imprinted genes are broadly expressed pre- and postnatally and do not exhibit a distinct overall expression pattern when compared to non-imprinted genes. The relative expression of most orthologous gene pairs varies significantly between human and mouse suggesting rapid species-specific changes in gene regulation. Distinct expression profiles of imprinted genes are confined to certain human and mouse hormone producing tissues, and placentae. In contrast to the overall variability, distinct expression profiles and enriched TFBS signatures are found in human and mouse endocrine tissues and placentae. This points towards an important role played by imprinted gene regulation in these tissues.</p

Sykepleiers rolle ved tidlig identifisering og behandling av sepsis

Bakgrunn Årsaken til at vi skriver om sepsis er at det er tilstanden med høyest dødelighet sammenlignet med andre infeksjonsrelaterte tilstander. Sykepleiere står i en utmerket posisjon til å identifisere symptomer og tegn. Hensikt Hensikten med oppgaven er å belyse diagnosen sepsis og hvordan sykepleiere kan gjenkjenne og identifisere tegn på tilstanden. Metode I denne oppgaven har vi brukt en integrativ litteraturstudie hvor fire forskningsartikler er valgt ut og analysert. Supplert med øvrig litteratur og egne erfaringer danner dette basis for vår besvarelse. Resultater Våre resultater viser at sykepleiere har manglende kunnskaper om sepsis, men at de samtidig spiller en viktig rolle i identifiseringen. Sykepleierne viser til et behov for økte kunnskaper og ferdigheter. Nøkkelord Sepsis, septisk sjokk, identifisering, behandling, oppdagelse, verktøy, tverrfaglig samarbeid, ferdigheter, undervisning, kunnska

Near-Infrared Characterization of Breast Tumors In Vivo using Spectrally-Constrained Reconstruction

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34–86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors

Characterization of Hemoglobin, Water, and NIR Scattering in Breast Tissue: Analysis of Intersubject Variability and Menstrual Cycle Changes

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 μM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p\u3c0.0001), but no other average near-infrared parameter changes were significant. While repeatable and systematic changes were observed in all parameters for individual subjects, large intersubject variations were present in all parameters. In a survey of thirty-nine normal subjects, the total hemoglobin varied from 9 to 45 μM, with a systematic correlation observed between total hemoglobin concentration and breast radiographic density. Scattering power and scattering amplitude were also correlated with radiographic density, but oxygen saturation and water fraction were not. Images of breast lesions indicate that total hemoglobin-based contrast can be up to 200% relative to the background in the same breast. Yet, since the background hemoglobin values vary considerably among breasts, the maximum hemoglobin concentrations observed in cancer tumors may vary considerably as well. In light of these observations, it may be important to use hemoglobin contrast values relative to the background for a given breast, rather than absolute hemoglobin contrast when trying to compare the features of breast lesions among subjects

Impact of preoperative patient education on the prevention of postoperative complications after major visceral surgery: the cluster randomized controlled PEDUCAT trial

Background: The prevention of postoperative complications is of prime importance after complex elective abdominal operations. Preoperative patient education may prevent postoperative complications and improve patients’ wellbeing, but evidence for its efficacy is poor. The aims of the PEDUCAT trial were (a) to assess the impact of preoperative patient education on postoperative complications and patient-reported outcomes in patients scheduled for elective complex visceral surgery and (b) to evaluate the feasibility of cluster randomization in this setting. Methods: Adult patients (age ≥ 18 years) scheduled for elective major visceral surgery were randomly assigned in clusters to attend a preoperative education seminar or to the control group receiving the department’s standard care. Outcome measures were the postoperative complications pneumonia, deep vein thrombosis (DVT), pulmonary embolism, burst abdomen, and in-hospital fall, together with patient-reported outcomes (postoperative pain, anxiety and depression, patient satisfaction, quality of life), length of hospital stay (LOS), and postoperative mortality within 30 days after the index operation. Statistical analysis was primarily by intention to treat. Results: In total 244 patients (60 clusters) were finally included (intervention group 138 patients; control group 106 patients). Allocation of hospital wards instead of individual patients facilitated study conduct and reduced confusion about group assignment. In the intervention and control groups respectively, pneumonia occurred in 7.4% versus 8.3% (p = 0.807), pulmonary embolism in 1.6% versus 1.0% (p = 0.707), burst abdomen in 4.2% versus 1.0% (p = 0.165), and in-hospital falls in 0.0% versus 4.2% of patients (p = 0.024). DVT did not occur in any of the patients. Mortality rates (1.4% versus 1.9%, p = 0.790) and LOS (14.2 (+/− 12.0) days versus 16.1 (+/− 15.0) days, p = 0.285) were also similar in the intervention and control groups. Conclusions: Cluster randomization was feasible in the setting of preoperative patient education and reduced the risk of contamination effects. The results of this trial indicate good postoperative outcomes in patients undergoing major visceral surgery without superiority of preoperative patient education compared to standard patient care at a high-volume center. However, preoperative patient education is a helpful instrument not only for teaching patients but also for training the nursing staff. Trial registration: German Clinical Trials Registry, DRKS00004226 . Registered on 23 October 2012. Registered 8 days after the first enrollment

The in-motion-app for remote general movement assessment : a multi-site observational study

Objectives To determine whether videos taken by parents of their infants' spontaneous movements were in accordance with required standards in the In-Motion-App, and whether the videos could be remotely scored by a trained General Movement Assessment (GMA) observer. Additionally, to assess the feasibility of using home-based video recordings for automated tracking of spontaneous movements, and to examine parents' perceptions and experiences of taking videos in their homes. Design The study was a multi-centre prospective observational study. Setting Parents/families of high-risk infants in tertiary care follow-up programmes in Norway, Denmark and Belgium. Methods Parents/families were asked to video record their baby in accordance with the In-Motion standards which were based on published GMA criteria and criteria covering lighting and stability of smartphone. Videos were evaluated as GMA 'scorable' or 'non-scorable' based on predefined criteria. The accuracy of a 7-point body tracker software was compared with manually annotated body key points. Parents were surveyed about the In-Motion-App information and clarity. Participants The sample comprised 86 parents/families of high-risk infants. Results The 86 parent/families returned 130 videos, and 121 (96%) of them were in accordance with the requirements for GMA assessment. The 7-point body tracker software detected more than 80% of body key point positions correctly. Most families found the instructions for filming their baby easy to follow, and more than 90% reported that they did not become more worried about their child's development through using the instructions. Conclusions This study reveals that a short instructional video enabled parents to video record their infant's spontaneous movements in compliance with the standards required for remote GMA. Further, an accurate automated body point software detecting infant body landmarks in smartphone videos will facilitate clinical and research use soon. Home-based video recordings could be performed without worrying parents about their child's development

Fluorescence-Based Flow Sorting in Parallel with Transposon Insertion Site Sequencing Identifies Multidrug Efflux Systems in Acinetobacter baumannii

Multidrug efflux pumps provide clinically significant levels of drug resistance in a number of Gram-negative hospital-acquired pathogens. These pathogens frequently carry dozens of genes encoding putative multidrug efflux pumps. However, it can be difficult to determine how many of these pumps actually mediate antimicrobial efflux, and it can be even more challenging to identify the regulatory proteins that control expression of these pumps. In this study, we developed an innovative high-throughput screening method, combining transposon insertion sequencing and cell sorting methods (TraDISort), to identify the genes encoding major multidrug efflux pumps, regulators, and other factors that may affect the permeation of antimicrobials, using the nosocomial pathogen Acinetobacter baumannii. A dense library of more than 100,000 unique transposon insertion mutants was treated with ethidium bromide, a common substrate of multidrug efflux pumps that is differentially fluorescent inside and outside the bacterial cytoplasm. Populations of cells displaying aberrant accumulations of ethidium were physically enriched using fluorescence-activated cell sorting, and the genomic locations of transposon insertions within these strains were determined using transposon-directed insertion sequencing. The relative abundance of mutants in the input pool compared to the selected mutant pools indicated that the AdeABC, AdeIJK, and AmvA efflux pumps are the major ethidium efflux systems in A. baumannii. Furthermore, the method identified a new transcriptional regulator that controls expression of amvA. In addition to the identification of efflux pumps and their regulators, TraDISort identified genes that are likely to control cell division, cell morphology, or aggregation in A. baumannii. IMPORTANCE Transposon-directed insertion sequencing (TraDIS) and related technologies have emerged as powerful methods to identify genes required for bacterial survival or competitive fitness under various selective conditions. We applied fluorescence-activated cell sorting (FACS) to physically enrich for phenotypes of interest within a mutant population prior to TraDIS. To our knowledge, this is the first time that a physical selection method has been applied in parallel with TraDIS rather than a fitness-induced selection. The results demonstrate the feasibility of this combined approach to generate significant results and highlight the major multidrug efflux pumps encoded in an important pathogen. This FACS-based approach, TraDISort, could have a range of future applications, including the characterization of efflux pump inhibitors, the identification of regulatory factors controlling gene or protein expression using fluorescent reporters, and the identification of genes involved in cell replication, morphology, and aggregation

Integration und berufliche Ausbildung: Expertise

Die Expertise entwickelt Handlungsempfehlungen zur Verbesserung der Ausbildungslage junger Menschen mit Migrationshintergrund. Diese Handlungsempfehlungen orientieren sich an zentralen Forschungsergebnissen zu den Partizipationsmöglichkeiten junger Migranten und Migrantinnen an beruflicher Ausbildung. Im Vordergrund stehen hierbei die interkulturellen Potenziale junger Fachkräfte sowie die Ausbildungschancen junger Menschen mit Migrationshintergrund. Die qualitativ angelegte Untersuchung des Bundesinstituts für Berufsbildung zum Einsatz interkultureller Kompetenzen zeigt auf, wie junge Fachkräfte mit Migrationshintergrund diese in ihrem Berufsalltag einsetzen. Dies betrifft sowohl Berufe, deren Tätigkeiten sich auf das Inland konzentrieren, wie Arzthelferinnen und Einzelhandelskaufleute, als auch solche mit Auslandskontakten, wie Speditions- und Außenhandelskaufleute. Der Einsatz interkultureller Kompetenzen weist berufsübergreifende Ähnlichkeiten, aber auch berufsspezifische Unterschiede auf. Die Ausbildungschancen und damit auch die Aussichten auf eine tragfähige berufliche Integration haben sich im vergangenen Jahrzehnt für junge Menschen mit Migrationshintergrund in Deutschland überproportional verschlechtert. Angesichts der erklärten bildungspolitischen Zielsetzung der Bundesregierung wie der Sozialparteien, allen jungen Menschen in Deutschland eine voll qualifizierende Berufsausbildung zu ermöglichen, ist eine breit angelegte und abgestimmte Qualifizierungsoffensive für junge Menschen mit Migrationshintergrund wünschenswert. Die Handlungsempfehlungen plädieren für ein integriertes und abgestimmtes Förder-Programm dessen Maßnahmen sich an folgenden Zielsetzungen orientieren sollen: a) eine qualifizierte Ausbildung für alle; b) Potenziale ausschöpfen und c) berufliche Qualifizierungsnetzwerke lokal und regional fördern. (IAB