The oxDNA Coarse-Grained Model as a Tool to Simulate DNA Origami.

This chapter introduces how to run molecular dynamics simulations for DNA origami using the oxDNA coarse-grained model.

Detection of Shortwave-Infrared Cerenkov Luminescence from Medical Isotopes.

Medical radioisotopes produce Cerenkov luminescence (CL) from charged subatomic particles (ß+/-) traveling faster than light in dielectric media (e.g., tissue). CL is a blue-weighted and continuous emission, decreasing proportionally to increasing wavelength. CL imaging (CLI) provides an economic PET alternative with the advantage of also being able to image ß- and α emitters. Like any optical modality, CLI is limited by the optical properties of tissue (scattering, absorption, and ambient photon removal). Shortwave-infrared (SWIR, 900-1700 nm) CL has been detected from MeV linear accelerators but not yet from keV medical radioisotopes. Methods: Indium-gallium-arsenide sensors and SWIR lenses were mounted onto an ambient light-excluding preclinical enclosure. An exposure and processing pipeline was developed for SWIR CLI and then performed across 6 radioisotopes at in vitro and in vivo conditions. Results: SWIR CL was detected from the clinical radioisotopes 90Y, 68Ga, 18F, 89Zr, 131I, and 32P (biomedical research). SWIR CLI's advantage over visible-wavelength (VIS) CLI (400-900 nm) was shown via increased light penetration and decreased scattering at depth. The SWIR CLI radioisotope sensitivity limit (8.51 kBq/µL for 68Ga), emission spectrum, and ex vivo and in vivo examples are reported. Conclusion: This work shows that radioisotope SWIR CLI can be performed with unmodified commercially available components. SWIR CLI has significant advantages over VIS CLI, with preserved VIS CLI features such as radioisotope radiance levels and dose response linearity. Further improvements in SWIR optics and technology are required to enable widespread adoption.

Teacher approaches, attitudes, and challenges to sexuality education: A case study of three junior high schools in Ghana.

While school-based sexuality education programs are established to reduce risky sexual behaviour among young people, teachers who play a central role are challenged by social factors which affect program outcomes. This study aimed to investigate the training and support offered to teachers on the delivery of sex education in three contrasting Junior High Schools in Ghana, the attitudes and approaches to the delivery of sex education, and the response of students to teacher delivery of sex education. A qualitative study design was employed with 13 in-depth interviews with head teachers, teachers, and students. Although teachers received similar training, teachers adopted different attitudes and approaches which resulted in student accounts of disinterest in sex education programs. Applying the health-promoting schools framework, the study concluded that the individual values and attitudes, as well as the type of school support, affects teacher modes of delivery and influences student interest in sex education, and should be considered in the design of in-school sex education programs.

Randomized controlled evaluation of the effect of music therapy with cognitive-behavioral therapy on social anxiety symptoms.

OBJECTIVE: This study examined the effects of music therapy with cognitive behavioral therapy on social anxiety in a sample of schooling adolescents in south-east Nigeria. METHODS: We adopted a randomized controlled trial design involving a treatment group and a waiting-list control group. A total of 155 schooling adolescents served as the study sample. The sample size was ascertained using GPower software. A 12-week MTCBP manual for social anxiety was employed to deliver the intervention. Data analyses were completed using repeated measures analysis of variance. RESULTS: We found that social anxiety significantly decreased in the treatment group over time, whereas the waitlist control group showed no significant changes in social anxiety. Therefore, music therapy with cognitive-behavioral therapy was significantly beneficial in decreasing social anxiety symptoms of the treatment group. The follow-up assessment performed after 3 months revealed a significant reduction in social anxiety for the treatment group. CONCLUSION: The study, therefore, suggests that the use of music therapy with cognitive-behavioral therapy is significant in reducing social anxiety among schooling adolescents.

Efficacy of prison-based cognitive behavioral rehabilitation intervention on violent sexual behaviors among sex offenders in Nigerian prisons.

BACKGROUND/OBJECTIVE: Evidence showed that reoffending habits are increasing among offenders with violent sexual behaviors. Given the recidivism rates, a psychotherapeutic intervention becomes imperative. This study examined the efficacy of prison-based cognitive behavioral rehabilitation intervention (PCBRI) on violent sexual behaviors among sex offenders in Nigerian prisons. METHOD: A total of45 participants were the sample size. Compulsive Sexual Behavior Inventory and Hypersexual Behavior Inventory were employed in assessing the participants at 3 points. Using a simple random allocation sequence, 23 participants were exposed to PCBRI programme and 22 participants allocated to control condition. The data obtained were analyzed using repeated measures 2-way analysis of variance. RESULTS: Results indicated a significant effect of the treatment on violent sexual behaviors among sex offenders in Nigerian prisons exposed to the PCBRI programme when compared to the no-intervention group. Result also showed a significant interaction effect of time and group on sex offenders with violent sexual behaviors. Follow-up tests showed significant decrease in violent sexual behaviors after 6 months for the PCBRI group in comparison to the control group. CONCLUSION: This study concluded that PCBRI approach is a type of psychotherapy that reduces violent sexual behaviors among sex offenders in Southeast Nigeria.

Coarse-grained modelling of the structural properties of DNA origami.

We use the oxDNA coarse-grained model to provide a detailed characterization of the fundamental structural properties of DNA origami, focussing on archetypal 2D and 3D origami. The model reproduces well the characteristic pattern of helix bending in a 2D origami, showing that it stems from the intrinsic tendency of anti-parallel four-way junctions to splay apart, a tendency that is enhanced both by less screened electrostatic interactions and by increased thermal motion. We also compare to the structure of a 3D origami whose structure has been determined by cryo-electron microscopy. The oxDNA average structure has a root-mean-square deviation from the experimental structure of 8.4 Å, which is of the order of the experimental resolution. These results illustrate that the oxDNA model is capable of providing detailed and accurate insights into the structure of DNA origami, and has the potential to be used to routinely pre-screen putative origami designs and to investigate the molecular mechanisms that regulate the properties of DNA origami.

Direct Simulation of the Self-Assembly of a Small DNA Origami.

By using oxDNA, a coarse-grained nucleotide-level model of DNA, we are able to directly simulate the self-assembly of a small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, we see attachment of new staple strands occurring in parallel, but with cooperativity evident for the binding of the second domain of a staple if the adjacent junction is already partially formed. For a system with exactly one copy of each staple strand, we observe a complete assembly pathway in an intermediate temperature window; at low temperatures successful assembly is prevented by misbonding while at higher temperature the free-energy barriers to assembly become too large for assembly on our simulation time scales. For high-concentration systems involving a large staple strand excess, we never see complete assembly because there are invariably instances where two copies of the same staple both bind to the scaffold, creating a kinetic trap that prevents the complete binding of either staple. This mutual staple blocking could also lead to aggregates of partially formed origamis in real systems, and helps to rationalize certain successful origami design strategies.

Reasonable disagreement and the generally unacceptable: a philosophical analysis of Making Fair Choices.

In this article we consider the conclusions and recommendations of the World Health Organisation's report Making Fair Choices from a philosophical perspective. In particular we reflect on the report's return to substantive claims about justice in the allocation of health care resources and its argument that certain trade-offs are 'generally unacceptable'.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA.

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na(+)] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

Improving productive efficiency in hospitals: findings from a review of the international evidence.

At present, health systems across Europe face the same challenges: a changing demographic profile, a rise in multi-morbidity and long-term conditions, increasing health care costs, large public debts and other legacies of an economic downturn. In light of these concerns, this article provides an overview of the international evidence on how to improve productive efficiency in secondary care settings. Updating and expanding upon a recent review of the literature by Hurst and Williams (2012), we set out evidence on potential interventions in the policy environment, hospital management, and operational processes. We conclude with five key lessons for policy makers and practitioners on how to improve productive efficiency within hospital settings, and identify several gaps in the existing evidence base.

Coarse-graining DNA for simulations of DNA nanotechnology.

To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches to such coarse-graining, focussing on those at the nucleotide level that allow the self-assembly processes associated with DNA nanotechnology to be studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly suited to this task, and has opened up this field to systematic study by simulations. We illustrate some of the range of DNA nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of DNA.

Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells.

Expression of heat shock proteins (HSPs) is classically activated at temperatures above the physiologic range (>or=42 degrees C) via activation of the stress-activated transcription factor, heat shock factor-1 (HSF-1). Several studies suggest that less extreme hyperthermia, especially within the febrile range, as occurs during fever and exertional/environmental hyperthemia, can also activate HSF-1 and enhance HSP expression. We compared HSP72 protein and mRNA expression in human A549 lung epithelial cells continuously exposed to 38.5 degrees C, 39.5 degrees C, or 41 degrees C or exposed to a classic heat shock (42 degrees C for 2 h). We found that expression of HSP72 protein and mRNA increased linearly as incubation temperature was increased from 37 degrees C to 41 degrees C, but increased abruptly when the incubation temperature was raised to 42 degrees C. A similar response in luciferase activity was observed using A549 cells stably transfected with an HSF-1-responsive luciferase reporter plasmid. However, activation of intranuclear HSF-1 DNA-binding activity was comparable at 38.5 degrees C, 39.5 degrees C, and 41 degrees C and only modestly greater at 42 degrees C but the mobility of HSF1 protein on a denaturing gel was altered with increasing exposure temperature and was distinctly different at 42 degrees C. These findings indicate that the proportional changes in HSF-1-dependent HSP72 expression at febrile-range temperatures are dependent upon exposure time and temperature but not on the degree of HSF-1 DNA-binding activity. Instead, HSF-1-mediated HSP expression following hyperthermia and heat shock appears to be mediated, in addition to HSF-1 activation, by posttranslational modifications of HSF-1 protein.

Courtship pheromone production and body size as correlates of larval diet in males of the arctiid moth,Utetheisa ornatrix.

Hydroxydanaidal, the corematal courtship pheromone of maleUtetheisa ornatrix, shows pronounced quantitative variation in natural populations of the moth. Males that, as larvae, fed on seed-bearing rather than immature food plants (Crotalaria spectabilis orC. mucronata) produce higher levels of hydroxydanaidal. Such males also have higher systemic loads of pyrrolizidine alkaloid, the known metabolic precursor of hydroxydanaidal, whichUtetheisa sequester from their larval diet and which is concentrated in the seeds ofCrotalaria. Males raised on seed-bearing plants also achieve higher adult weight. In the context of sexual selection, therefore, femaleUtetheisa could, through assessment of male hydroxydanaidal levels, gauge both the alkaloid content and body weight of their suitors.