Oblique Packing and Tunable Excitonic Coupling in DNA-Templated Squaraine Rotaxane Dimer Aggregates

When molecules are aggregated such that their excited states form delocalized excitons, their spatial arrangement, or packing, can be coarsely controlled by templating and finely controlled by chemical substitution; however, challenges remain in controlling their packing on intermediate length scales. Here, we use an approach based on mechanically interlocked molecules to promote an elusive oblique packing arrangement in a series of three squaraine rotaxane dimers. We template the squaraine rotaxane dimers using DNA and observe two excitonically split bands of near-equal intensity in their absorption spectra – a distinct signature of oblique packing, validated by theoretical modeling of the experimental results. Additional fine control of packing is demonstrated by fluorinating the macrocycle of the rotaxane, which promotes denser packing and stronger excitonic interactions

Tunable Electronic Structure via DNA-Templated Heteroaggregates of Two Distinct Cyanine Dyes

Molecular excitons are useful for applications in light harvesting, organic optoelectronics, and nanoscale computing. Electronic energy transfer (EET) is a process central to the function of devices based on molecular excitons. Achieving EET with a high quantum efficiency is a common obstacle to excitonic devices, often owing to the lack of donor and acceptor molecules that exhibit favorable spectral overlap. EET quantum efficiencies may be substantially improved through the use of heteroaggregates─aggregates of chemically distinct dyes─rather than individual dyes as energy relay units. However, controlling the assembly of heteroaggregates remains a significant challenge. Here, we use DNA Holliday junctions to assemble homo- and heterotetramer aggregates of the prototypical cyanine dyes Cy5 and Cy5.5. In addition to permitting control over the number of dyes within an aggregate, DNA-templated assembly confers control over aggregate composition, i.e., the ratio of constituent Cy5 and Cy5.5 dyes. By varying the ratio of Cy5 and Cy5.5, we show that the most intense absorption feature of the resulting tetramer can be shifted in energy over a range of almost 200 meV (1600 cm–1). All tetramers pack in the form of H-aggregates and exhibit quenched emission and drastically reduced excited-state lifetimes compared to the monomeric dyes. We apply a purely electronic exciton theory model to describe the observed progression of the absorption spectra. This model agrees with both the measured data and a more sophisticated vibronic model of the absorption and circular dichroism spectra, indicating that Cy5 and Cy5.5 heteroaggregates are largely described by molecular exciton theory. Finally, we extend the purely electronic exciton model to describe an idealized J-aggregate based on Förster resonance energy transfer (FRET) and discuss the potential advantages of such a device over traditional FRET relays

Tuning Between Quenching and Energy Transfer in DNA-Templated Heterodimer Aggregates

Molecular excitons, which propagate spatially via electronic energy transfer, are central to numerous applications including light harvesting, organic optoelectronics, and nanoscale computing; they may also benefit applications such as photothermal therapy and photoacoustic imaging through the local generation of heat via rapid excited-state quenching. Here we show how to tune between energy transfer and quenching for heterodimers of the same pair of cyanine dyes by altering their spatial configuration on a DNA template. We assemble “transverse” and “adjacent” heterodimers of Cy5 and Cy5.5 using DNA Holliday junctions. We find that the transverse heterodimers exhibit optical properties consistent with excitonically interacting dyes and fluorescence quenching, while the adjacent heterodimers exhibit optical properties consistent with nonexcitonically interacting dyes and disproportionately large Cy5.5 emission, suggestive of energy transfer between dyes. We use transient absorption spectroscopy to show that quenching in the transverse heterodimer occurs via rapid nonradiative decay to the ground state (∼31 ps) and that in the adjacent heterodimer rapid energy transfer from Cy5 to Cy5.5 (∼420 fs) is followed by Cy5.5 excited-state relaxation (∼700 ps). Accessing such drastically different photophysics, which may be tuned on demand for different target applications, highlights the utility of DNA as a template for dye aggregation

Assessment of Heat-Related Health Impacts in Brisbane, Australia: Comparison of Different Heatwave Definitions

Background: There is no global definition of a heatwave because local acclimatisation and adaptation influence the impact of extreme heat. Even at a local level there can be multiple heatwave definitions, based on varying temperature levels or time periods. We investigated the relationship between heatwaves and health outcomes using ten different heatwave definitions in Brisbane, Australia. ---------- Methodology/Principal Findings: We used daily data on climate, air pollution, and emergency hospital admissions in Brisbane between January 1996 and December 2005; and mortality between January 1996 and November 2004. Case-crossover analyses were used to assess the relationship between each of the ten heatwave definitions and health outcomes. During heatwaves there was a statistically significant increase in emergency hospital admissions for all ten definitions, with odds ratios ranging from 1.03 to 1.18. A statistically significant increase in the odds ratios of mortality was also found for eight definitions. The size of the heat-related impact varied between definitions.---------- Conclusions/Significance Even a small change in the heatwave definition had an appreciable effect on the estimated health impact. It is important to identify an appropriate definition of heatwave locally and to understand its health effects in order to develop appropriate public health intervention strategies to prevent and mitigate the impact of heatwaves

Assessment of management to mitigate anthropogenic effects on large whales

Author Posting. © Society for Conservation Biology, 2012. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Conservation Biology 27 (2013): 121-133, doi:10.1111/j.1523-1739.2012.01934.x.United States and Canadian governments have responded to legal requirements to reduce human-induced whale mortality via vessel strikes and entanglement in fishing gear by implementing a suite of regulatory actions. We analyzed the spatial and temporal patterns of mortality of large whales in the Northwest Atlantic (23.5°N to 48.0°N), 1970 through 2009, in the context of management changes. We used a multinomial logistic model fitted by maximum likelihood to detect trends in cause-specific mortalities with time. We compared the number of human-caused mortalities with U.S. federally established levels of potential biological removal (i.e., species-specific sustainable human-caused mortality). From 1970 through 2009, 1762 mortalities (all known) and serious injuries (likely fatal) involved 8 species of large whales. We determined cause of death for 43% of all mortalities; of those, 67% (502) resulted from human interactions. Entanglement in fishing gear was the primary cause of death across all species (n= 323), followed by natural causes (n= 248) and vessel strikes (n= 171). Established sustainable levels of mortality were consistently exceeded in 2 species by up to 650%. Probabilities of entanglement and vessel-strike mortality increased significantly from 1990 through 2009. There was no significant change in the local intensity of all or vessel-strike mortalities before and after 2003, the year after which numerous mitigation efforts were enacted. So far, regulatory efforts have not reduced the lethal effects of human activities to large whales on a population-range basis, although we do not exclude the possibility of success of targeted measures for specific local habitats that were not within the resolution of our analyses. It is unclear how shortfalls in management design or compliance relate to our findings. Analyses such as the one we conducted are crucial in critically evaluating wildlife-management decisions. The results of these analyses can provide managers with direction for modifying regulated measures and can be applied globally to mortality-driven conservation issues.We thank S. and H. Simmons for funding for this project

AGL StimSelect: Software for automated selection of stimuli for artificial grammar learning

Artificial Grammar Learning (AGL) is an experimental paradigm that has been used extensively in cognitive research for many years to study implicit learning, associative learning, and generalization based either on similarity or rules. Without computer assistance it is virtually impossible to generate appropriate grammatical training stimuli along with grammatical or non-grammatical test stimuli that control relevant psychological variables. We present the first flexible, fully automated software for selecting AGL stimuli. The software allows users to specify a grammar of interest, and to manipulate characteristics of training and test sequences, and their relationship to each other. The user thus has direct control over stimulus features that may influence learning and generalization in AGL tasks. The software enables researchers to develop AGL designs that would not be feasible without automatic stimulus selection. It is implemented in Matlab

The role of the proteasome in the generation of MHC class I ligands and immune responses

The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses

Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects

The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol

Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM