Electronic Structure and Excited-State Dynamics of DNA-Templated Monomers and Aggregates of Asymmetric Polymethine Dyes.

Aggregates of conjugated organic molecules (i.e., dyes) may exhibit relatively large one- and two-exciton interaction energies, which has motivated theoretical studies on their potential use in quantum information science (QIS). In practice, one way of realizing large one- and two-exciton interaction energies is by maximizing the transition dipole moment (µ) and difference static dipole moment (Δd) of the constituent dyes. In this work, we characterized the electronic structure and excited-state dynamics of monomers and aggregates of four asymmetric polymethine dyes templated via DNA. Using steady-state and time-resolved absorption and fluorescence spectroscopy along with quantum-chemical calculations, we found the asymmetric polymethine dye monomers exhibited a large µ, an appreciable Δd, and a long excited-state lifetime (τp). We formed dimers of all four dyes and observed that one dye, Dy 754, displayed the strongest propensity for aggregation and exciton delocalization. Motivated by these results, we undertook a more comprehensive survey of Dy 754 dimer and tetramer aggregates using steady-state absorption and circular dichroism spectroscopy. Modeling these spectra revealed an appreciable excitonic hopping parameter (J). Lastly, we used femtosecond transient absorption spectroscopy to characterize τp of the dimer and tetramer, which we observed to be exceedingly short. This work revealed that asymmetric polymethine dyes exhibited µ, Δd, monomer τp, and J values promising for QIS; however, further work is needed to overcome excited-state quenching and achieve long aggregate τp.

Strategies for Controlling the Spatial Orientation of Single Molecules Tethered on DNA Origami Templates Physisorbed on Glass Substrates: Intercalation and Stretching.

Nanoarchitectural control of matter is crucial for next-generation technologies. DNA origami templates are harnessed to accurately position single molecules; however, direct single molecule evidence is lacking regarding how well DNA origami can control the orientation of such molecules in three-dimensional space, as well as the factors affecting control. Here, we present two strategies for controlling the polar (θ) and in-plane azimuthal (ϕ) angular orientations of cyanine Cy5 single molecules tethered on rationally-designed DNA origami templates that are physically adsorbed (physisorbed) on glass substrates. By using dipolar imaging to evaluate Cy5's orientation and super-resolution microscopy, the absolute spatial orientation of Cy5 is calculated relative to the DNA template. The sequence-dependent partial intercalation of Cy5 is discovered and supported theoretically using density functional theory and molecular dynamics simulations, and it is harnessed as our first strategy to achieve θ control for a full revolution with dispersion as small as ±4.5°. In our second strategy, ϕ control is achieved by mechanically stretching the Cy5 from its two tethers, being the dispersion ±10.3° for full stretching. These results can in principle be applied to any single molecule, expanding in this way the capabilities of DNA as a functional templating material for single-molecule orientation control. The experimental and modeling insights provided herein will help engineer similar self-assembling molecular systems based on polymers, such as RNA and proteins.

Exciton Delocalization and Scaffold Stability in Bridged Nucleotide-Substituted, DNA Duplex-Templated Cyanine Aggregates.

Molecular excitons play a foundational role in chromophore aggregates found in light-harvesting systems and offer potential applications in engineered excitonic systems. Controlled aggregation of chromophores to promote exciton delocalization has been achieved by covalently tethering chromophores to deoxyribonucleic acid (DNA) scaffolds. Although many studies have documented changes in the optical properties of chromophores upon aggregation using DNA scaffolds, more limited work has investigated how structural modifications of DNA via bridged nucleotides and chromophore covalent attachment impact scaffold stability as well as the configuration and optical behavior of attached aggregates. Here we investigated the impact of two types of bridged nucleotides, LNA and BNA, as a structural modification of duplex DNA-templated cyanine (Cy5) aggregates. The bridged nucleotides were incorporated in the domain of one to four Cy5 chromophores attached between adjacent bases of a DNA duplex. We found that bridged nucleotides increase the stability of DNA scaffolds carrying Cy5 aggregates in comparison with natural nucleotides in analogous constructs. Exciton coupling strength and delocalization in Cy5 aggregates were evaluated via steady-state absorption, circular dichroism, and theoretical modeling. Replacing natural nucleotides with bridged nucleotides resulted in a noticeable increase in the coupling strength (≥10 meV) between chromophores and increased H-like stacking behavior (i.e., more face-to-face stacking). Our results suggest that bridged nucleotides may be useful for increasing scaffold stability and coupling between DNA templated chromophores.

Respiratory Impacts of Wildland Fire Smoke: Future Challenges and Policy Opportunities. An Official American Thoracic Society Workshop Report.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1) the science of wildland fire incidence and fire management, 2) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3) communication strategies to address these health risks, and 4) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Rising Sea Levels: Helping Decision-Makers Confront the Inevitable.

Sea-level rise (SLR) is not just a future trend; it is occurring now in most coastal regions across the globe. It thus impacts not only long-range planning in coastal environments, but also emergency preparedness. Its inevitability and irreversibility on long time scales, in addition to its spatial non-uniformity, uncertain magnitude and timing, and capacity to drive non-stationarity in coastal flooding on planning and engineering timescales, create unique challenges for coastal risk-management decision processes. This review assesses past United States federal efforts to synthesize evolving SLR science in support of coastal risk management. In particular, it outlines the: (1) evolution in global SLR scenarios to those using a risk-based perspective that also considers low-probability but high-consequence outcomes, (2) regionalization of the global scenarios, and (3) use of probabilistic approaches. It also describes efforts to further contextualize regional scenarios by combining local mean sea-level changes with extreme water level projections. Finally, it offers perspectives on key issues relevant to the future uptake, interpretation, and application of sea-level change scenarios in decision-making. These perspectives have utility for efforts to craft standards and guidance for preparedness and resilience measures to reduce the risk of coastal flooding and other impacts related to SLR.

Seed dispersal of the Australian cycad Macrozamia miquelii (Zamiaceae): are cycads megafauna-dispersed "grove forming" plants?

PREMISE OF THE STUDY: Plants that invest in large, heavy seeds and colorful, fleshy fruits or analogous structures seem adapted for dispersal by large vertebrates. Some such plants, like Australian cycads in the genus Macrozamia, do not disperse well, which could be explained by seed-dispersal relationships with megafauna that are rare or extinct in contemporary ecosystems. Such plants provide an opportunity to investigate the ecological consequences of low seed-dispersal distances. • METHODS: We investigated seed dispersal of Macrozamia miquelii in Central Queensland by tracking the fate of marked seeds, identifying the dispersal fauna and quantifying population demography and spatial structure. • KEY RESULTS: We found that 70-100% of marked seeds remained within 1 m of maternal females (cycads are dioecious). Of the 812 seeds recovered (from 840 originally marked) only 24 dispersed >1 m from maternal females, the greatest observed dispersal being 5 m. We found an average of 2.2 seedlings and 0.7 juveniles within 1.5 m of mature females, which suggests that most seeds that remain in the vicinity of maternal females perish. Within-stand densities ranged between 1000 and 5000 plants/ha. The brushtail possum Trichosurus vulpecula was the only animal observed to move the seeds. • CONCLUSIONS: Macrozamia are adapted for dispersal by megafauna that are rare or absent in contemporary ecosystems. We argue that Macrozamia are "grove forming" plants that derive ecological benefit from existing as high-density, spatially discrete populations, the function of megafaunal dispersal adaptations being the infrequent dispersal of seeds en masse to establish new such groves in the landscape.

Review essay: empires, ancient and modern.

This essay drews attention to two books on empires by historians which deserve the attention of sociologists. Bang's model of the workings of the Roman economy powerfully demonstrates the tributary nature of per-industrial tributary empires. Darwin's analysis concentrates on modern overseas empires, wholly different in character as they involved the transportation of consumption items for the many rather than luxury goods for the few. Darwin is especially good at describing the conditions of existence of late nineteenth century empires, noting that their demise was caused most of all by the failure of balance of power politics in Europe. Concluding thoughts are offered about the USA.

Demonstration as a means to translate conservation science into practice.

To be relevant to societal interests and needs, conservation science must explicitly lend itself to solving real-world problems. Failure to evaluate under field conditions how a new technology or method performs or the cost of its implementation can prevent its acceptance by end users. Demonstration, defined here as the translation of scientific understanding into metrics of performance and cost of implementation under real-world conditions, is a logical step in the challenging progression from fundamental research to application. Demonstration reduces scientific uncertainty and validates the hypothesis that a management approach is both effective and financially sustainable. Much like adaptive management, demonstration enables researchers and resource managers to avoid trial-and-error approaches and instead conduct unbiased assessment of management interventions. The participation of end users and regulators in the development and execution of demonstration projects ensures that performance measures are credible and increases the probability that successful innovations will be adopted. Four actions might better connect science to the needs of resource managers via demonstration. First, we recommend that demonstration be conducted as a formal process that documents successes and failures. Second, demonstration should be budgeted as an integral component of government agencies' science programs and executed as a partnership between researchers and managers. Third, public and private funders should increase the opportunities and incentives for academics to engage in demonstration. Fourth, social influences on adoption of new technologies and methods should be further explored. When end users can evaluate explicitly whether a new approach is likely to achieve management objectives, save money, and reduce risk under uncertainty, the professional community successfully has bridged a chasm between research and application.

Increased low density lipoprotein and increased likelihood of positive prostate biopsy in black americans.

PURPOSE: Differences in prostate cancer incidence, grade and stage at diagnosis, and survival in black vs nonblack men are well documented. Recent studies indicate that lipids may have a role in oncogenesis, including that of prostate cancer. We investigated the relationship between circulating lipids in black and nonblack patients, and newly diagnosed prostate cancer. MATERIALS AND METHODS: The study population included consecutive patients who underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination at Atlanta Veterans Affairs Medical Center. Age, race, prostate specific antigen, prostate volume, body mass index, family history, high and low density lipoprotein, triglyceride and cholesterol lowering medications were included in data analysis. RESULTS: A total of 1,775 men with complete information were included in data analysis. A total of 521 black and 451 white men had positive biopsies. Using 100 mg/dl or less as the referent the adjusted OR reflecting the association of low density lipoprotein and prostate cancer diagnosis in black men was 1.49 (95% CI 1.04-2.13, p = 0.031), 1.51 (95% CI 0.96-2.39, p = 0.076) and 3.24 (95% CI 1.59-6.92, p = 0.002) for low density lipoprotein greater than 100 to 130, greater than 130 to 160 and greater than 160 mg/dl, respectively. Corresponding results in nonblack men showed no significant association. CONCLUSIONS: Increased serum low density lipoprotein is associated with an increased likelihood of prostate cancer diagnosis in black men but not in nonblack men. This association is strongest in the highest low density lipoprotein risk category. The reasons for the racial differences are unknown but may include genetic, dietary or other environmental factors.

The value of digital rectal examination as a predictor of prostate cancer diagnosis among United States Veterans referred for prostate biopsy.

BACKGROUND: As digital rectal examination (DRE) remains an essential part of a routine physical examination, it is important to understand its diagnostic value in different circumstances. AIM: To quantify sensitivity, specificity and predictive value of DRE as a predictor of biopsy-confirmed prostate cancer in the US Veteran population. METHODS: The study group included 628 consecutive patients who underwent transrectal biopsy for suspected prostate cancer due to abnormal digital examination of the prostate, elevated serum prostate specific antigen (PSA) or both. The DRE results reported in this study are documented during physical examinations that were performed after referral for biopsy. The relation between DRE results and positive biopsy was examined while taking into consideration demographic and clinical patient characteristics. RESULTS: Among men with normal PSA the adjusted odds ratio (OR) reflecting the association between abnormal DRE and positive prostate biopsy was 0.53 with a 95% confidence interval (CI) from 0.27 to 1.06. In the presence of a moderately elevated (4.1-10 ng/mL) PSA, the OR was 1.07 (0.72-1.60). When serum PSA exceeded 10 ng/mL, the OR was 2.15 (1.12-4.43). The positive predictive value of an abnormal DRE varied widely from as high as 81% to as low as 14% depending on the other patient characteristics. DISCUSSION: These results indicate that DRE results are most informative when evaluated in conjunction with other clinical and demographic information.

Role of transrectal ultrasonography in diagnosis and treatment of retained Foley catheter.

Retention of Foley balloon in the bladder or urethra is a troublesome complication that presents a challenge to the urologist. We describe a complicated case of Foley catheter balloon retention (and trauma) within the urethra in an orthopedic patient undergoing hemiarthroplasty. The Foley balloon failed to deflate with standard methods. We used transrectal ultrasonography to successfully diagnose and manage the case.

Morphology of the prometamorphic larva of the spadefoot toad, Scaphiopus intermontanus (Anura: Pelobatidae), with an emphasis on the lateral line system and mouthparts.

We provide a detailed description of the larval morphology of the Great Basin spadefoot toad (Scaphiopus intermontanus), a species with documented morphological variability in larval structures associated with feeding. We based our findings on laboratory-raised individuals fed a herbivorous diet. We characterized the morphology of the prometamorphic larva (limited to developmental stages 37 and 38) and then related our findings to the larval ecology of the species. Based on its morphology, such as slightly depressed body, dorsally positioned eyes, anteroventrally oriented oral disc, intermediate tail fin height and slightly attenuated tail tip, relative lack of ventral neuromasts (compared to Xenopus laevis), and pigmentation banding patterns, and habits, such as selection of breeding sites by adults and larval foraging behavior, S. intermontanus can be characterized best as belonging to a (lentic-) benthic guild of anuran larvae. Nevertheless, the larvae are capable of occupying a broader array of ecological niches. Because we characterized individuals raised on a herbivorous diet, our morphological descriptions apply only to the herbivorous S. intermontanus larva (and perhaps to those larvae that are dietary generalists and may feed carnivorously only infrequently). Our findings can serve as a baseline for future morphological and developmental comparisons with the carnivorous morphological variant of this species.

Aetiology of diabetic neuropathy - abstract

The diverse disorder of diabetic neuropathy seems to be due to a plethora of factors. No one factor seems to be solely reposible. There is a spectrum of probabilities which include mechanical and environmental factors as well as the milieu interieur which embraces chemical, genetic, metabolic, biochemical, toxic and vascular entities. This paper attempts to explore these probabilities with a view to their relevance to the pathogenesis of diabetics neuropathy (AU)

Effects of Diet and Exercise on Peripheral Vascular Disease.

In brief A 46-year-old man presented with symptoms of peripheral vascular disease in 1966. In 1976 arteriography revealed 100% occlusion of both femoral arteries at midthigh and some reconstitution of flow via collaterals into the popliteal region. His cholesterol level was initially 407 mg/100 ml, and his walking tolerance was 100 yards. After a 26-day stay at the Pritikin Longevity Center, his cholesterol dropped from 230 mg/100 ml to 130 mg/100 ml, and his walking tolerance increased to 3 miles in one hour with little leg pain. He has run more than 20 road races and completed a marathon. A recent exercise Doppler exam and a second arteriogram indicated a significant increase in blood flow due to dilation of deep femoral arteries and existing collateral vessels.

Subacute sclerosing panencephalitis

The case is described of a 13-year-old Jamaican boy with subacute sclerosing panencephalitis. There have been no previous reports of this condition in Jamaica. Review of the literature has shown that the measles virus involved in the pathogenesis of this disorder (AU)

Neurosyphilis in Jamaica - abstract

This report reviews 105 consecutive cases of neurospyphilis seen at the Kingston Public Hospital over the past 10 years. The diagnostic criteria used were the clinical picture, blood and CSF serology and the lange colloidal gold curve. There were 51 males and 54 females with ages ranging from 17 to 84 years. Only 7 cases (6.6 percent) occurred before the age of 30 years. Syphilis serology was positive in blood in 65.7 percent and in CSF in 45.7 percent of cases, in 23.8 percent there was negative blood serology, in 51.4 percent negative CSF serology, while blood and CSF were negative in 20.9 percent of cases. In the 22 cases with negative blood and CSF serology 19 had a paretic lange curve. In the series as a whole, 62.8 percent had a paretic curve, 3.8 percent a tabetic curve and 33.3 percent were non-reactive. There was a strong correlation between a wide range of neuroluetic manifestations and a positive Lange curve. It also appeared that the best indices of neuroluetic activity were a reactive Lange curve, hyperproteinaemia lymphocytosis and a positive CSF serology. Among the neuroluetic manifestations found were personality changes, spastic paraplegia, hemiplegia, speech disturbances, ocular disturbances, epilepsy, headaches and subarachnoid haemorrhage. It is noted that epilepsy was a presenting feature in 17 percent of cases and the headaches which occurred in 14 cases closely resembled those seen in other clinical situations such as hypertension, anxiety states and migraine. Subarachnoid haemorrhage occurred in 17 percent of cases and 55 percent of these were under 55 years of age. On the basis of the present series 4 clinical groups emerge. They are (a) the catastrophic (b) the acute, (c) the chronic, (d) the remittent (AU)