329 research outputs found
A quantum dynamical comparison of the electronic couplings derived from quantum electrodynamics and Förster theory:Application to 2D molecular aggregates
The objective of this study is to investigate under what circumstances Förster theory of electronic (resonance) energy transfer breaks down in molecular aggregates. This is achieved by simulating the dynamics of exciton diffusion, on the femtosecond timescale, in molecular aggregates using the Liouville–von Neumann equation of motion. Specifically the focus of this work is the investigation of both spatial and temporal deviations between exciton dynamics driven by electronic couplings calculated from Förster theory and those calculated from quantum electrodynamics. The quantum electrodynamics (QED) derived couplings contain medium- and far-zone terms that do not exist in Förster theory. The results of the simulations indicate that Förster coupling is valid when the dipole centres are within a few nanometres of one another. However, as the distance between the dipole centres increases from 2 nm to 10 nm, the intermediate- and far-zone coupling terms play non-negligible roles and Förster theory begins to break down. Interestingly, the simulations illustrate how contributions to the exciton dynamics from the intermediate- and far-zone coupling terms of QED are quickly washed-out by the near-zone mechanism of Förster theory for lattices comprising closely packed molecules. On the other hand, in the case of sparsely packed arrays, the exciton dynamics resulting from the different theories diverge within the 100 fs lifetime of the trajectories. These results could have implications for the application of spectroscopic ruler techniques as well as design principles relating to energy harvesting materials
Understanding the identity work and aspirations of Indigenous males navigating elite Australian higher education
In Australia, there has been increased attention to attracting Indigenous peoples into higher education but, despite a recent growth in enrolment numbers, they remain severely underrepresented. This underrepresentation is particularly notable among Indigenous males, who are the least likely to attend. In this paper, we investigate the experiences of four Indigenous young men who attended an elite higher education institution. Aligned with other research on the experiences of Black and Minority Ethnic males in higher education, the article captures how their experience in privileged institutions compels them to reflect on their own positionality and the cultural interface between Indigenous and non-Indigenous knowledges. All data were thematically analysed and this paper reports on two key themes: influencers to pursue higher education and motivational factors at university. In considering the journey of these young men into elite higher education spaces, we are interested in the discursive constitution of their Indigenous identities and how their aspirations are realised in reference to a strong sense of cultural pride and social justice
The Effect of Simulation based Training on Medical Students’ Perceptions, Knowledge, and Skill at Baseline and 6 month Follow up
The principal goal of most simulation-based learning is enhanced clinical skill, with the desired outcome being skill retention and improved performance over time. While evide nce supports simulation based training at the clerkship, graduate, and post graduate level, the evidence supporting its long term benefit at the pre clerkship level is less well established. Using quantitative methods, this research assessed the effect of skill based clinical simulation training on all second year medical students’ enrolled in two simulation courses at the University of Michigan during the 2013 2014 academic year (n=39). Pre course, post course, and 6 month follow up questionnaires were adm inistered, and analysis of variance was used to assess change in students\u27 knowledge, self reported confidence, and competency. Students in Course 1 (n=12) completed a post course and 6 month follow up skills test, and results were compared to faculty cont rols. Differences between groups were assessed using t tests. Odds ratios were calculated.Knowledge improved from pre course to post course; the gain was retained at follow up only for students in Course 1. Students perceived the courses as improving know ledge, confidence, and skill, though scores were significantly lower at follow up. For the subset of students participating in the skills test, the time to complete central line and thoracentesis at follow up did not significantly differ from post course; however, an increase was observed for lumbar puncture. Compared to faculty, students took significantly more time to complete the central line procedure. Outcomes for needle redirects and correct sequencing were mixed, with most procedures showing no signi ficant difference between measurement periods. Assessing students’ skill and the maintenance of that skill over time using objective and empirically derived measures can be challenging. The evaluation strategy described herein could be adapted to many proc edures commonly practiced within primary care and other medical specialties. Brief exposure to clinical simulation early in medical training and prior to clerkships can have a positive and lasting effecton medical students’ knowledge, confidence, and skil l for selected procedures
Staphylococcus aureus Biofilm and Planktonic cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes
<p>Abstract</p> <p>Background</p> <p>Many chronic diseases, such as non-healing wounds are characterized by prolonged inflammation and respond poorly to conventional treatment. Bacterial biofilms are a major impediment to wound healing. Persistent infection of the skin allows the formation of complex bacterial communities termed biofilm. Bacteria living in biofilms are phenotypically distinct from their planktonic counterparts and are orders of magnitude more resistant to antibiotics, host immune response, and environmental stress. <it>Staphylococcus aureus </it>is prevalent in cutaneous infections such as chronic wounds and is an important human pathogen.</p> <p>Results</p> <p>The impact of <it>S. aureus </it>soluble products in biofilm-conditioned medium (BCM) or in planktonic-conditioned medium (PCM) on human keratinocytes was investigated. Proteomic analysis of BCM and PCM revealed differential protein compositions with PCM containing several enzymes involved in glycolysis. Global gene expression of keratinocytes exposed to biofilm and planktonic <it>S. aureus </it>was analyzed after four hours of exposure. Gene ontology terms associated with responses to bacteria, inflammation, apoptosis, chemotaxis, and signal transduction were enriched in BCM treated keratinocytes. Several transcripts encoding cytokines were also upregulated by BCM after four hours. ELISA analysis of cytokines confirmed microarray results at four hours and revealed that after 24 hours of exposure, <it>S. aureus </it>biofilm induced sustained low level cytokine production compared to near exponential increases of cytokines in planktonic treated keratinocytes. The reduction in cytokines produced by keratinocytes exposed to biofilm was accompanied by suppressed phosphorylation of MAPKs. Chemical inhibition of MAPKs did not drastically reduce cytokine production in BCM-treated keratinocytes suggesting that the majority of cytokine production is mediated through MAPK-independent mechanisms.</p> <p>Conclusions</p> <p>Collectively the results indicate that <it>S. aureus </it>biofilms induce a distinct inflammatory response compared to their planktonic counterparts. The differential gene expression and production of inflammatory cytokines by biofilm and planktonic cultures in keratinocytes could have implications for the formation and persistence of chronic wounds. The formation of a biofilm should be considered in any study investigating host response to bacteria.</p
Ultrafast dynamics in light-driven molecular rotary motors probed by femtosecond stimulated raman spectroscopy
Photochemical isomerization in sterically crowded chiral alkenes is the driving force for molecular rotary motors in nanoscale machines. Here the excited state dynamics and structural evolution of the prototypical light driven rotary motor are followed on the ultrafast timescale by femtosecond stimulated Raman spectroscopy (FSRS) and transient absorption (TA). TA reveals a sub 100 fs blue shift and decay of the Franck-Condon bright state arising from relaxation along the reactive potential energy surface. The decay is accompanied by coherently excited vibrational dynamics which survive the excited state structural evolution. The ultrafast Franck-Condon bright state relaxation is to a dark excited state, which FSRS reveals to have a rich spectrum compared to the electronic ground state, with the most intense Raman active modes shifted to significantly lower wavenumber. This is discussed in terms of a reduced bond order of the central bridging bond and overall weakening of bonds in the dark state, which is supported by electronic structure calculations. The observed evolution in the FSRS spectrum is assigned to vibrational cooling accompanied by partitioning of the dark state between the product isomer and the original ground state. Formation of the product isomer is observed in real time by FSRS. It is formed vibrationally hot and cools over several picoseconds, completing the characterization of the light driven half of the photocycle
Application of machine learning to microseismic event detection in distributed acoustic sensing data
Survey of bacterial diversity in chronic wounds using Pyrosequencing, DGGE, and full ribosome shotgun sequencing
<p>Abstract</p> <p>Background</p> <p>Chronic wound pathogenic biofilms are host-pathogen environments that colonize and exist as a cohabitation of many bacterial species. These bacterial populations cooperate to promote their own survival and the chronic nature of the infection. Few studies have performed extensive surveys of the bacterial populations that occur within different types of chronic wound biofilms. The use of 3 separate16S-based molecular amplifications followed by pyrosequencing, shotgun Sanger sequencing, and denaturing gradient gel electrophoresis were utilized to survey the major populations of bacteria that occur in the pathogenic biofilms of three types of chronic wound types: diabetic foot ulcers (D), venous leg ulcers (V), and pressure ulcers (P).</p> <p>Results</p> <p>There are specific major populations of bacteria that were evident in the biofilms of all chronic wound types, including <it>Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia</it>, and <it>Serratia </it>spp. Each of the wound types reveals marked differences in bacterial populations, such as pressure ulcers in which 62% of the populations were identified as obligate anaerobes. There were also populations of bacteria that were identified but not recognized as wound pathogens, such as <it>Abiotrophia para-adiacens </it>and <it>Rhodopseudomonas </it>spp. Results of molecular analyses were also compared to those obtained using traditional culture-based diagnostics. Only in one wound type did culture methods correctly identify the primary bacterial population indicating the need for improved diagnostic methods.</p> <p>Conclusion</p> <p>If clinicians can gain a better understanding of the wound's microbiota, it will give them a greater understanding of the wound's ecology and will allow them to better manage healing of the wound improving the prognosis of patients. This research highlights the necessity to begin evaluating, studying, and treating chronic wound pathogenic biofilms as multi-species entities in order to improve the outcomes of patients. This survey will also foster the pioneering and development of new molecular diagnostic tools, which can be used to identify the community compositions of chronic wound pathogenic biofilms and other medical biofilm infections.</p
Infrared spectroscopy reveals multi-step multi-timescale photoactivation in the photoconvertible protein archetype dronpa
Photochromic fluorescent proteins play key roles in super-resolution microscopy and optogenetics. The light-driven structural changes that modulate the fluorescence involve both trans-to-cis isomerization and proton transfer. The mechanism, timescale and relative contribution of chromophore and protein dynamics are currently not well understood. Here, the mechanism of off-to-on-state switching in dronpa is studied using femtosecond-to-millisecond time-resolved infrared spectroscopy and isotope labelling. Chromophore and protein dynamics are shown to occur on multiple timescales, from picoseconds to hundreds of microseconds. Following excitation of the trans chromophore, a ground-state primary product is formed within picoseconds. Surprisingly, the characteristic vibrational spectrum of the neutral cis isomer appears only after several tens of nanoseconds. Further fluctuations in protein structure around the neutral cis chromophore are required to form a new intermediate, which promotes the final proton-transfer reaction. These data illustrate the interplay between chromophore dynamics and the protein environment underlying fluorescent protein photochromism
Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds
Background: Despite a growing consensus that biofilms contribute to a delay in the healing of chronic wounds, conflicting evidence pertaining to their identification and management can lead to uncertainty regarding treatment. This, in part, has been driven by reliance on in vitro data or animal models, which may not directly correlate to clinical evidence on the importance of biofilms. Limited data presented in human studies have further contributed to the uncertainty. Guidelines for care of chronic wounds with a focus on biofilms are needed to help aid the identification and management of biofilms, providing a clinical focus to support clinicians in improving patient care through evidence-based medicine. Methods: A Global Wound Biofilm Expert Panel, comprising 10 clinicians and researchers with expertise in laboratory and clinical aspects of biofilms, was identified and convened. A modified Delphi process, based on published scientific data and expert opinion, was used to develop consensus statements that could help identify and treat biofilms as part of the management of chronic nonhealing wounds. Using an electronic survey, panel members rated their agreement with statements about biofilm identification and treatment, and the management of chronic nonhealing wounds. Final consensus statements were agreed on in a face-to-face meeting. Results: Participants reached consensus on 61 statements in the following topic areas: understanding biofilms and the problems they cause clinicians; current diagnostic options; clinical indicators of biofilms; future options for diagnostic tests; treatment strategies; mechanical debridement; topical antiseptics; screening antibiofilm agents; and levels of evidence when choosing antibiofilm treatments. Conclusion: This consensus document attempts to clarify misunderstandings about the role of biofilms in clinical practice, and provides a basis for clinicians to recognize biofilms in chronic nonhealing wounds and manage patients optimally. A new paradigm for wound care, based on a stepped-down treatment approach, was derived from the consensus statements
A Multi-Parameter, High-Content, High-Throughput Screening Platform to Identify Natural Compounds that Modulate Insulin and Pdx1 Expression
Diabetes is a devastating disease that is ultimately caused by the malfunction or loss of insulin-producing pancreatic beta-cells. Drugs capable of inducing the development of new beta-cells or improving the function or survival of existing beta-cells could conceivably cure this disease. We report a novel high-throughput screening platform that exploits multi-parameter high-content analysis to determine the effect of compounds on beta-cell survival, as well as the promoter activity of two key beta-cell genes, insulin and pdx1. Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. B-score statistical transformation was used to correct systemic row and column biases. Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts. The ability of compounds purified from these extracts to significantly modulate insulin mRNA levels was confirmed with real-time PCR. Insulin secretion was analyzed by RIA. Follow-up studies focused on two lead compounds, one that stimulates insulin gene expression and one that inhibits insulin gene expression. Thus, we demonstrate that multi-parameter, high-content screening can identify novel regulators of beta-cell gene expression, such as bivittoside D. This work represents an important step towards the development of drugs to increase insulin expression in diabetes and during in vitro differentiation of beta-cell replacements
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