Search

Biological cells display complex internal architectures, with distinct micro environments that establish the chemical heterogeneity needed to sustain cellular functions. The continued efforts to create advanced cell mimics –artificial cells– demands strategies to construct similarly heterogeneous structures with localized functionalities. Here, we introduce a platform for constructing membrane-less artificial cells from the self-assembly of synthetic DNA nanostructures, in which internal domains can be established thanks to prescribed reaction-diffusion waves. The method, rationalized through numerical modeling, enables the formation of up to five distinct, concentric environments, in which functional moieties can be localized. As a proof-of-concept, we apply this platform to build DNA-based artificial cells in which a prototypical nucleus synthesizes fluorescent RNA aptamers, which then accumulate in a surrounding storage shell, thus demonstrating spatial segregation of functionalities reminiscent of that observed in biological cells.

Thanks to its biocompatibility, versatility and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering and drug delivery. Of particular importance for in vivo applications is the possibility of making such nano-materials responsive to physiological stimuli. Here we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the hydrogel aggregates can be photodisassembled upon near-UV irradiation in the presence of a porphyrin photosensitiser. The combined reversibility of assembly, responsiveness and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.

Thanks to its biocompatibility, versatility and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering and drug delivery. Of particular importance for in vivo applications is the possibility of making such nano-materials responsive to physiological stimuli. Here we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the frameworks can be rendered responsive to near-UV light through the addition of a porphyrin photosensitiser. The combined reversibility of assembly, responsiveness and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.

BACKGROUND Dyslipidemia has been documented in youth with type 2 diabetes. There is a paucity of studies examining dyslipidemia over time in youth with type 2 diabetes and associated risk factors. OBJECTIVE To evaluate lipids at baseline and follow-up and associated risk factors in youth with type 2 diabetes. METHODS We studied 212 youth with type 2 diabetes at baseline and after an average of 7 years of follow-up in the SEARCH for Diabetes in Youth Study. Abnormal lipids were defined as high-density lipoprotein cholesterol (HDL-C) 100, or triglycerides >150 (all mg/dl). We evaluated participants for progression to abnormal lipids (normal lipids at baseline and abnormal at follow-up), regression (abnormal lipids at baseline and normal at follow-up), stable normal, and stable abnormal lipids over time for HDL-C, LDL-C, and triglycerides. Associations between hemoglobin A1c (HbA1c) and adiposity over time (area under the curve [AUC]) with progression and stable abnormal lipids were evaluated. RESULTS HDL-C progressed, regressed, was stable normal, and stable abnormal in 12.3%, 11.3%, 62.3%, and 14.2% of participants, respectively. Corresponding LDL-C percentages were 15.6%, 12.7%, 42.9%, and 28.8% and triglycerides were 17.5%, 10.8%, 55.7%, and 16.0%. Each 1% increase in HbA1c AUC was associated with a 13% higher risk of progression and stable abnormal triglycerides and a 20% higher risk of progression and stable abnormal LDL-C. Higher adiposity AUC was marginally (p = 0.049) associated with abnormal HDL-C. CONCLUSIONS Progression and stable abnormal LDL-C and triglycerides occur in youth with type 2 diabetes and are associated with higher HbA1c.

Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecular cue, exposing the ‘sticky’ core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria., Lipid membrane disruption is often associated with disease but is also essential to a range of biosensing and therapeutic techniques. Here, the authors report on the development of DNA-based particles that, upon exposure to an external cue, can aggregate, disrupt lipid membranes, and arrest the motion of bacteria.

In this paper we exploit naturally occurring randomized settings within a very large dataset of golf shots to test whether order of play matters in professional golf tournaments. We isolate two settings where professional golf competitors find themselves with virtually identical shots, implying the order of play is effectively random. These settings allow us to identify unbiased, causal estimates of the relevance of moving first or second in competition. We find robust evidence that the second-mover has a statistically (and economically) significant advantage, which we argue is consistent with a learning effect in competition.

Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with shared genetic risk and are increasing in prevalence in the US. As CD is often under-diagnosed in the setting of T1D, additional data on the prevalence and characteristics of CD and potentially undiagnosed CD in youth with T1D is needed. In 2,442 youth with T1D in the SEARCH for Diabetes in Youth study we assessed self-reported CD via questionnaire and potentially undiagnosed CD by IgA tissue transglutaminase autoantibody assays (TGA). Groups were defined as 1) CD (based on self-reported CD), 2) potentially undiagnosed CD, (no self-reported CD and elevated TGA), 3) no CD (T1D controls). Patient characteristics were compared between CD and controls, and between potentially undiagnosed CD and controls. Coexisting autoimmune diseases were also assessed. The prevalence of self-reported CD was 6.9% and potentially undiagnosed CD was 4.1%. Youth with T1D and CD or potentially undiagnosed CD were more likely to be younger at T1D diagnosis and female compared with controls. Youth with T1D and CD were more likely to be Non-Hispanic white and to have co-existing autoimmune diseases compared with controls, all p CD and, importantly, undiagnosed CD are seen in youth with T1D. Youth with combined disease are at high risk for additional co-autoimmune diseases. Disclosure R. Brady: None. A. Honor: None. D. J. Pettitt: None. L. Merjaneh: None. D. Dabelea: None. A. S. Shah: None. E. T. Jensen: None. J. Rigdon: None. N. A. Crimmins: None. D. Mallon: Other Relationship; Self; Total Travel and Events. L. M. Dolan: None. G. Imperatore: None. A. Kahkoska: Other Relationship; Self; Novo Nordisk A/S. A. K. Mottl: Advisory Panel; Self; Bayer U. S.

Adaptive decision making in humans depends on feedback between monitoring, which assesses mental states, and control, by which cognitive processes are modified. We investigated the extent to which monitoring and control interact iteratively in monkeys. Monkeys classified images as birds, fish, flowers, or people. At the beginning of each trial, to-be-classified images were not visible. Monkeys touched the image area to incrementally brighten the image, referred to as the brighten response. The amount by which brightness increased with each brighten response was unpredictable, and the monkeys could choose to classify the images at any time during a trial. We hypothesized that if monkeys monitored the status of their classification decision then they would seek information depending on the amount of information available. In Experiment 1, monkeys rarely used the brighten response when images were bright initially, and they used the brighten response more when earlier uses in a given trial yielded smaller amounts of information. In Experiment 2, monkeys made more brighten responses when the presented image did not belong in any of the trained categories, suggesting monkeys were sensitive to the fact that they could not reach a classification decision despite the image brightening. In Experiment 3, we found that the probability that monkeys used the brighten response correlated with their ability to correctly classify when the brighten response was not available. These findings add to the literature documenting the metacognitive skills of nonhuman primates by demonstrating an iterative feedback loop between cognitive monitoring and cognitive control that allows for adaptive information-seeking behavior.

Limited information exists regarding the evolution of dyslipidemia in youth with type 2 diabetes (T2D). Understanding dyslipidemia risk factors may influence treatment. We studied 212 youth with T2D not on lipid lowering therapy (68% female, 43% non-Hispanic black, mean age 14.9±2.7y at baseline, mean follow-up 7.0±2.0y). Dyslipidemia was defined as HDL-C100mg/dL, or triglycerides (TG)>150mg/dL. Progression was defined as normal lipids at baseline, dyslipidemia at follow-up; regression as dyslipidemia at baseline, normal at follow-up; stable abnormal as dyslipidemia at both; stable normal as normal at both. Associations of A1c and abdominal adiposity (waist to height ratio, WHtR) over time (area under the curve, AUC) with progression and stable abnormal were examined and relative risks estimated. HDL-C progressed, regressed, was stable normal and stable abnormal in 12%, 11%, 62%, and 14%, respectively. Corresponding LDL-C values were 16%, 13%, 43% and 29%; TG were 17%, 11%, 56% and 16%. Each 1% increase in A1c AUC was associated with 13% higher risk of TG>150mg/dL and 22% higher risk of LDL-C>100mg/dL, after adjusting for WHtR (Table). There were no significant associations with WHtR. In youth with T2D, 33% and 45% had progression or stable dyslipidemia of TG and LDL-C, respectively. Higher A1c over time is associated with worse TG and LDL-C, highlighting the importance of glycemic control. Disclosure R.P. Brady: None. A.S. Shah: None. E.T. Jensen: None. J.M. Stafford: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.M. Dolan: None. L.M. Knight: None. G. Imperatore: None. C.B. Turley: None. A.D. Liese: None. E.M. Urbina: None. J.M. Lawrence: None. C. Pihoker: None. S.M. Marcovina: None. D. Dabelea: None. Funding Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)

The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA nanotechnology is widely acknowledged as a prime route for the rational design of nanostructured materials. Yet, the preparation of crystalline DNA frameworks with programmable structure and functionality remains a challenge. Here we demonstrate the potential of simple amphiphilic DNA motifs, dubbed “C-stars”, as a versatile platform for the design of programmable DNA crystals. In contrast to all-DNA materials, in which structure depends on the precise molecular details of individual building blocks, the self-assembly of C-stars is controlled uniquely by their topology and symmetry. Exploiting this robust self-assembly principle, we design a range of topologically identical, but structurally and chemically distinct C-stars that following a one-pot reaction self-assemble into highly porous, functional, crystalline frameworks. Simple design variations allow us to fine-tune the lattice parameter and thus control the partitioning of macromolecules within the frameworks, embed responsive motifs that can induce isothermal disassembly, and include chemical moieties to capture target proteins specifically and reversibly.

Working memory is a system by which a limited amount of information can be kept available for processing after the cessation of sensory input. Because working memory resources are limited, it is adaptive to focus processing on the most relevant information. We used a retro-cue paradigm to determine the extent to which monkey working memory possesses control mechanisms that focus processing on the most relevant representations. Monkeys saw a sample array of images, and shortly after the array disappeared, they were visually cued to a location that had been occupied by one of the sample images. The cue indicated which image should be remembered for the upcoming recognition test. By determining whether the monkeys were more accurate and quicker to respond to cued images compared to un-cued images, we tested the hypothesis that monkey working memory focuses processing on relevant information. We found a memory benefit for the cued image in terms of accuracy and retrieval speed with a memory load of two images. With a memory load of three images, we found a benefit in retrieval speed but only after shortening the onset latency of the retro-cue. Our results demonstrate previously unknown flexibility in the cognitive control of memory in monkeys, suggesting that control mechanisms in working memory likely evolved in a common ancestor of humans and monkeys more than 32 million years ago. Future work should be aimed at understanding the interaction between memory load and the ability to control memory resources, and the role of working memory control in generating differences in cognitive capacity among primates.

Existing peer effects studies produce contradictory findings, including positive, negative, large, and small effects, despite similar contexts. We explore these results using U.S. Naval Academy data covering a 17-year history of the random assignment of students to peer groups. Coupled with students’ limited discretion over freshman-year courses, our setting affords an opportunity to better understand peer effects in different social contexts. We find negative effects at the broader “company” level – students’ social and residential group – and positive effects at the narrower course-company level within small peer groups. We suggest that peer spillovers change direction because of differences in the underlying mechanism of peer influence.

Fragmented by policies, united by outcomes: This is the picture of the United States that emerges from our analysis of the spatial diffusion of COVID-19 and the scattered lock-down policies introduced by individual states to contain it. We first use spatial econometric techniques to document direct and indirect spillovers of new infections across county and state lines, as well as the impact of individual states' lock-down policies on infections in neighboring states. We find consistent statistical evidence that new cases diffuse across county lines, holding county level factors constant, and that the diffusion across counties was affected by the closure policies of adjacent states. Spatial impulse response functions reveal that the diffusion across counties is persistent for up to ten days after an increase in adjacent counties. We then develop a spatial version of the epidemiological SIR model where new infections arise from interactions between infected people in one state and susceptible people in the same or in neighboring states. We incorporate lock-down policies into our model and calibrate the model to match both the cumulative and the new infections across the 48 contiguous U.S. states and DC. Our results suggest that, had the states with the less restrictive social distancing measures tightened them by one level, the cumulative infections in other states would be about 5% smaller. In our spatial SIR model, the spatial containment policies such as border closures have a bigger impact on flattening the infection curve in the short-run than on the cumulative infections in the long-run.

Target-induced DNA strand displacement is an excellent candidate for developing analyte-responsive DNA circuitry to be used in clinical diagnostics and synthetic biology. While most available technologies rely on DNA circuitry free to diffuse in bulk, here we explore the use of liposomes as scaffolds for DNA-based sensing nanodevices. Our proof-of-concept sensing circuit responds to the presence of a model target analyte by releasing a DNA strand, which in turn activates a fluorescent reporter. Through a combination of experiments and coarse-grained Monte Carlo simulations, we demonstrate that the presence of the membrane scaffold accelerates the process of oligonucleotide release and suppresses undesired leakage reactions, making the sensor both more responsive and robust.

Monkeys with selective damage to the hippocampus are often unimpaired in matching-to-sample tests but are reportedly impaired in visual paired comparison. While both tests assess recognition of previously seen images, delayed matching-to-sample may engage active memory maintenance whereas visual paired comparison may not. Passive memory tests that are not rewarded with food and that do not require extensive training may provide more sensitive measures of hippocampal function. To test this hypothesis, we assessed memory in monkeys with hippocampal damage and matched controls by providing them the opportunity to repeatedly view small sets of videos. Monkeys pressed a button to play each video. The same 10 videos were used for six consecutive days, after which 10 new videos were introduced in each of seven cycles of testing. Our measure of memory was the extent to which monkeys habituated with repeated presentations, watching fewer videos per session over time. Monkeys with hippocampal lesions habituated more slowly than did control monkeys, indicating poorer memory for previous viewings. Both groups dishabituated each time new videos were introduced. These results, like those from preferential viewing, suggest that the hippocampus may be especially important for memory of incidentally encoded events.

The binding of imidazolium salts to cucurbit[8]uril, CB[8], triggers a stepwise self-assembly process with semiflexible polymer chains and crystalline nanostructures as early- and late-stage species, respectively. In such a process, which involves the crystallization of the host–guest complexes, the guest plays a critical role in directing self-assembly toward desirable morphologies. These include platelet-like aggregates and two-dimensional (2D) fibers, which, moreover, exhibit viscoelastic and lyotropic properties. Our observations provide a deeper understanding of the self-assembly of CB[8] complexes, with fundamental implications in the design of functional 2D systems and crystalline materials., This work was supported by the EPSRC (reference no. EP/G060649/1), an ERC Starting Investigator Grant (project no. 240629, ASPiRe) and a Next Generation Fellowship from the Walters-Kundert Foundation. J.d.B. acknowledges the MINECO, the FSE and the FEDER for funding through projects RYC-2015-18471 (Ramón y Cajal program) and CTQ2017-84087-R. L.D.M. acknowledges support from a Royal Society University Research Fellowship UF160152. R.A.B. acknowledges support from the EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC), grant number EP/L015978/1.

Taxonomies of human memory, influenced heavily by Endel Tulving, make a fundamental distinction between explicit and implicit memory. Humans are aware of explicit memories, whereas implicit memories control behavior even though we are not aware of them. Efforts to understand the evolution of memory, and to use nonhuman animals to model human memory, will be facilitated by better understanding the extent to which this critical distinction exists in nonhuman animals. Work with metacognition paradigms in the past 20 years has produced a strong case for the existence of explicit memory in nonhuman primates and possibly other nonhuman animals. Clear dissociations of explicit and implicit memory by metacognition have yet to be demonstrated in nonhumans, although dissociations between memory systems by other behavioral techniques, and by brain manipulations, suggest that the explicit-implicit distinction applies to nonhumans. Neurobehavioral studies of metamemory are beginning to identify neural substrates for memory monitoring in the frontal cortex of monkeys. We have strong evidence that at least some memory systems are explicit in rhesus monkeys, but we need to learn more about the distribution of explicit processes across cognitive systems within monkeys, and across species.

Summary Human working memory is greatly facilitated by linguistic representations—for example, by verbal rehearsal and by verbal recoding of novel stimuli. The absence of language in nonhumans raises questions about the extent to which nonhuman working memory includes similar mechanisms. There is strong evidence for rehearsal-like active maintenance in working memory when monkeys are tested with highly familiar stimuli, but not when tested with novel stimuli, suggesting that working memory depends on the existence of previously encoded representations. This difference in working memory for familiar and novel images may exist because, lacking language, monkeys cannot recode novel stimuli in a way that permits active maintenance in working memory. Alternatively, working memory for novel images may have been present, but behaviorally silent, in earlier studies. In tests with novel images, the high familiarity of to-be-remembered stimuli compared to never-before-seen distractors may be such a strong determinant of recognition performance that evidence of working memory is obscured. In the current study, we developed a technique for attenuating the utility of relative familiarity as a mnemonic signal in recognition tests with novel stimuli. In tests with novel images, we observed impairments of memory by concurrent cognitive load and delay interval that indicate actively maintained working memory. This flexibility in monkey working memory suggests that monkeys may recode unfamiliar stimuli to facilitate working memory and establishes new parallels between verbal human working memory and nonverbal nonhuman primate working memory.

The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA Nanotechnology is widely acknowledged as a prime route for the rational design of nanostructured materials. Yet, the preparation of crystalline DNA frameworks with programmable structure and functionality remains a challenge. Here we demonstrate the potential of simple amphiphilic DNA motifs, dubbed C-stars, as a versatile platform for the design of programmable DNA crystals. In contrast to all-DNA materials, in which structure depends on the precise molecular details of individual building blocks, the self-assembly of C-stars is controlled uniquely by their topology and symmetry. Exploiting this robust self-assembly principle we design a range of topologically identical, but structurally and chemically distinct C-stars that following a one-pot reaction self- assemble into highly porous, functional, crystalline frameworks. Simple design variations allow us to fine-tune the lattice parameter and thus control the partitioning of macromolecules within the frameworks, embed responsive mo- tifs that can induce isothermal disassembly, and include chemical moieties to capture target proteins specifically and reversibly.

Purpose The aim of this report is to provide a five-year summary of the Minnesota Radiological Society's initiative to send first-year radiology residents to the ACR at the AMCLC. The authors provide an update of the survey data for the first five years (2009-2013) and a report of the ACR membership status of the original 2009 cohort (class of 2012) five years after their conference experience. Methods Participating residents from 2009 to 2013 completed pre- and postconference surveys assessing their knowledge of ACR-related topics, conference satisfaction, and intention to join the ACR. ACR membership status of the first cohort was determined using the ACR membership database and compared with both the previous five graduating classes and the national average for practicing radiologists. Results Seventy first-year Minnesota radiology residents attended the conference from 2009 to 2013. Knowledge of the ACR significantly increased after the conference. Most residents were highly satisfied or satisfied with their conference experience and highly likely or likely to join the ACR in the future. Two years after residency, 87% of the first cohort (13 of 15) were ACR members, compared with an average membership rate of 57% (63 of 110) for the previous five graduating classes. Conclusions Exposing radiology residents early to the ACR at the AMCLC leads to a significant increase in knowledge pertaining to the professional organization. This exposure likely leads to increased ACR membership when residents enter practice. This early engagement in radiology affairs can lead to a higher rate of ACR membership and to a better informed membership.

Resting metabolic rate (RMR) represents a significant component of an animal’s energy budget and is correlated with ecological, physiological, and life-history parameters. We measured resting metabolic rates of 14 adult Northern Shrikes (Lanius excubitor) wintering in northern Wisconsin (Ashland and Bayfield Counties) over a 2-year period (Jan–Apr 2008 and 2009). The average (±SE) RMR was 3.09 ± 0.45 ml O2/g/hr (range 2.46–3.83) from the first reported RMR values for adults of this species from the Neartic. Our RMR values were 50% higher than RMRs gathered from summer adult Northern Shrikes in the Paleartic. These data suggest Northern Shrikes exhibit seasonal variation in their RMR as a potential means of winter acclimatization.

Wetland loss, biological invasions, and ecological restoration are major factors altering wetland resources in the Midwestern United States. Large-scale plant-community change associated with these factors is an under-investigated, potentially strong driver of habitat suitability for wetland-dependent wildlife, such as secretive marsh birds (SMBs), which are of widespread conservation concern. We employed multi-year, hierarchical Bayesian occupancy modeling to investigate sensitivity of 3 SMB species (American bittern, sora, and Virginia rail) to habitat and vegetation characteristics in Wisconsin, USA. We contrasted habitat characteristics and SMB occupancy in natural wetlands with those restored under the federally funded Wetlands Reserve Program (WRP). We also examined the extent to which SMB occupancy was explained by 3 levels of habitat assessment that encompassed different spatial scales and levels of sampling effort (landscape, rapid, and intensive). All species were significantly associated with variables derived from intensive assessment, and showed high sensitivity to differences in plant-community composition and vegetation quality. Both American bittern and Virginia rail were negatively associated with abundance of the invasive wetland grass, Phalaris arundinacea (reed canarygrass), and were positively associated with an indicator of plant-community quality (mean coefficient of conservatism, or C-value). Sora occupancy was positively associated with Typha (cattail) abundance. For all 3 species, occupancy was greater in natural sites than in restored sites, which were characterized by greater Phalaris abundance and lower mean C-values. Our results show broad agreement between botanical and avian indicators of wetland quality, suggesting that enhancing the condition of wetland vegetation can yield ancillary benefits for SMBs. In this region, efforts to control Phalaris and restore diverse, native-dominated plant communities are likely to increase wetlands’ capacity to support SMBs. © 2015 The Wildlife Society.

Many emerging technologies require materials with well-defined three-dimensional nanoscale architectures. Production of these structures is currently underpinned by self-assembling amphiphilic macromolecules or engineered all-DNA building blocks. Both of these approaches produce restricted ranges of crystal geometries due to synthetic amphiphiles' simple shape and limited specificity, or the technical difficulties in designing space-filling DNA motifs with targeted shapes. We have overcome these limitations with amphiphilic DNA nanostructures, or "C-Stars", that combine the design freedom and facile functionalization of DNA-based materials with robust hydrophobic interactions. C-Stars self-assemble into single crystals exceeding 40 μm in size with lattice parameters exceeding 20 nm.

In this paper I estimate the spatial diffusion of housing prices across U.S. states over a period from 1975 to 2011, showing how long and to what magnitude state-level housing prices are affected by a price shock emanating from surrounding states. I capture the spatial diffusion of regional housing prices with impulse response functions estimated directly from a single equation spatial autoregressive model. In addition, I compare and contrast spatial impulse response estimates over sub-periods. Results show that for the 1975 to 2011 period spatial diffusion of housing prices is statistically significant and persistent across states. This conclusion is robust to whether the model is estimated in levels or in first differences controlling for cointegration. Sub-period estimation, too, suggests the magnitude and persistence of spatial diffusion may be more pronounced after 1999 than before.

This paper examines the effect of financial frictions on the strength of the monetary transmission mechanism. Credit channel theory implies that the transmission mechanism of monetary policy should be stronger in countries with high levels of financial frictions, all else equal. The intuition is that in these countries, external finance premiums are more sensitive to firms' financial leverage. By affecting asset prices, therefore, monetary policy has greater impact on external finance premiums and output. We test this theoretical prediction by estimating SVAR models on cross-country data to generate indicators for the strength of monetary transmission. We find a positive relationship between various measures of financial frictions and the strength of monetary transmission, supporting the predictions of credit channel theory.

The migratory population of the King Rail (Rallus elegans) has declined dramatically during the past 50 years, emphasizing the need to document the distribution and status of this species to help guide conservation efforts. In an effort to guide King Rail breeding habitat protection and restoration, a landscape suitability index (LSI) model was developed for the Upper Mississippi River and Great Lakes Region Joint Venture (JV). To validate this model, 264 sites were surveyed across the JV region in 2008 and 2009 using the National Marshbird Monitoring protocol. Two other similarly collected data sets from Wisconsin (250 sites) and Ohio (259 sites) as well as data from the Cornell Laboratory of Ornithology's eBird database were added to our data set. Sampling effort was not uniform across the study area. King Rails were detected at 29 sites with the greatest concentration in southeastern Wisconsin and northeastern Illinois. Too few detections were made to validate the LSI model. King Rail detecti...

DNA nanostructures with programmable shape and interactions can be used as building blocks for the self-assembly of crystalline materials with prescribed nanoscale features, holding a vast technological potential. Structural rigidity and bond directionality have been recognised as key design features for DNA motifs to sustain long-range order in 3D, but the practical challenges associated with prescribing building-block geometry with sufficient accuracy have limited the variety of available designs. We have recently introduced a novel platform for the one-pot preparation of crystalline DNA frameworks supported by a combination of Watson-Crick base pairing and hydrophobic forces (Brady et al 2017 Nano Lett. 17 3276-81). Here we use small angle x-ray scattering and coarse-grained molecular simulations to demonstrate that, as opposed to available all-DNA approaches, amphiphilic motifs do not rely on structural rigidity to support long-range order. Instead, the flexibility of amphiphilic DNA building-blocks is a crucial feature for successful crystallisation.

I. INTRODUCTION In this article, we test for structural breaks in U.S. defense industry and spending data over the last five decades. The defense industry data, which include various measures of market concentration, capture trends in consolidation; the spending data, defined broadly to include measures of contract awards, budget authority, and expenditures and investment, capture trends in market size. We identify structural breaks in those data and compare them to structural breaks found in data relating to the rest of the economy to address a lingering debate among defense analysts, policy practitioners, and executives as to the forces behind the consolidation of the defense industry in the 1990s. Was the consolidation the result of an explicit directive of the U.S. Department of Defense (DOD) or was it driven by the same forces that led to consolidation in many sectors of the U.S. economy in the 1990s? In an era in which concerns about the future of the defense industry are again prominent, the answer bears directly on whether and how the DOD might choose to engage as a policymaking and procuring agency. If broader economic forces drive industry behavior, the DOD may face limitations in promoting competition, spurring innovation, or otherwise shaping the defense industry. We interpret structural breaks in the data as indicative of changes in defense spending, the defense industry at large, and the broader economy, which, in the context of two stylized narratives, provides a statistical approach to explaining defense-industry consolidation. The first stylized narrative, representing what we refer to as the "DOD-policy-centric" view, describes the DOD as the primary engineer of defense industry consolidation in the 1990s. The defense budget had been declining steadily since the mid-1980s and the DOD was seeking to reduce excess capacity and check rising costs. In response, at a 1993 dinner now referred to as the "Last Supper," the DOD asserted its support for industry-wide consolidation [see Augustine (1997, 2006) for an eyewitness account]. The DOD backed its assertion by agreeing to reimburse firms for some merger-related costs and, later, through antitrust oversight [for discussions see Gholz and Sapolsky (1999-2000), Markusen and Costigan (1999), and Markusen (1997)]. Without explicitly denying the relevance of economy-wide factors, this narrative claims DOD policy as the dominant factor in the consolidation process. For example, the former chairman of the Lockheed Martin Corporation, Norman R. Augustine, characterizes the Last Supper as perhaps "the most critical moment in the defense industry's consolidation" (Augustine, 1997). His comments suggest that the defense industry was hesitant to consolidate, even when faced with a declining budget, without encouragement from its largest purchaser, the DOD. (1) In contrast, a stylized "economy-centric" view places economy-wide phenomenon at the center of a story in which the same forces that drove the large number of mergers in the rest of U.S. economy also drove the consolidation of the defense industry in the 1990s. Such forces included developments in capital markets, innovation in technology, and deregulation [see Holmstrom and Kaplan (2001) and Andrade, Mitchell, and Stafford (2001) for details on merger activity in the U.S. economy]. Although the economy-centric view does not dismiss the impact of the decline in the defense budget, or the response of the DOD to that decline, it suggests that other forces provide a more telling explanation of defense-industry consolidation. Hensel (2007), for example, offers evidence that defense industry mergers in the 1990s are more correlated with economy-wide mergers than with DOD spending [see also Flamm (1998) and Oden (1998) for relevant discussions of evidence that is supportive of an economy-wide perspective]. We use the methods of Bai and Perron (1998, 2003) to estimate structural breaks in data that measure defense industry consolidation, defense spending, and economy-wide trends. …

How fast and how long (and to what magnitude) does a change in housing prices in one region affect its neighbors? In this paper, I apply a time series technique for measuring impulse response functions from local projections to a spatial autoregressive model of housing prices. For a dynamic panel of California counties, the data reveal that the diffusion of regional housing prices across space lasts up to two and half years. This result, and the econometric techniques employed, should be of interest not only to housing and regional economists, but to a variety of applied econometricians as well. Copyright © 2009 John Wiley & Sons, Ltd.

Northern Shrikes {Lanius excubitor) are predatory songbirds found primarily in taiga regions throughout their Holarctic breeding range. The species is poorly known, especially in North America, and is generally thought to be sexually monomorphic. From 2004 to 2007, we captured 50 adults in northern Wisconsin during the nonbreeding season (December-March) and determined sex using DNA extracted from feather samples. Males had significantly longer wings, longer tails, and less black in the outer rectrix than females, but body mass did not differ between the sexes. A discriminant function equation using tail length and extent of black on the outer rectrix correctly assigned the sex of 97.4% of captured adults. Plumage dimorphism was also evident, with males having paler gray heads and backs without brown tones, whiter underparts with lighter barring, and a more distinct and horizontal border at the base of the sixth primary feather. The ability to accurately determine sex will provide opportunities to examine possible inter- and intrasexual differences in the behavior and ecology of adult Northern Shrikes. RESUMEN. El uso del ADN, morfometr?a y plumaje para sexar adultos de Lanius excubitor La especie Lanius excubitor es un depredador (Passeriformes) encontrado principalmente en las regiones del taiga a trav?s de su distribuci?n reproductiva en el Hol?rtico. Esta especie es poco conocida, especialmente en Norteam?rica, y es generalmente considerada sexualmente monom?rfico. Desde 2004-2007 capturamos a 50 adultos en el norte de Wisconsin durante la ?poca no-reproductiva (Dic-Mar) y determinamos el sexo usando ADN extra?do de muestras de las plumas. Los machos tuvieron alas significativamente mas largas, colas mas largas y menos negro en el retrice exterior que las hembras, pero no hubo una diferencia en el peso entre los sexos. Una ecuaci?n de funci?n discriminativa usando el largo de cola y la cantidad de negro en el retrice exterior pudo asignar correctamente el sexo de 97.4% de los adultos capturados. Un dimorfismo en el plumaje tambi?n era evidente, en la cual los machos tuvieron cabezas de color gris m?s p?lidas y espaldas sin tonos pardos, con m?s blanco por debajo y barras m?s leves por debajo. Los machos tambi?n tuvieron un borde a la base de la sexta primaria m?s distinta y horizontal. Nuestra habilidad de determinar precisamente el sexo proveer? oportunidades para examinar las posibles diferencias inter- y intrasexuales en el comportamiento y ecolog?a de Lanius excubitor.

Has structural change in consumer credit made consumption smoother? Given recent empirical analysis the consumer’s inability to smooth consumption appears as prevalent as ever. In this paper, however, I show that structural change in consumer credit appears to have made consumption smoothing a reality. First, using the statistical methods of Bai and Perron [Bai, J., Perron, P., 1998. Estimating and testing linear models with multiple structural changes. Econometrica 66(1), 47–78; Bai, J., Perron, P., 2003. Computation and analysis of multiple structural change models. Journal of Applied Econometrics 18(1), 1–22], I find structural breaks in the series for consumer credit and consumption at various points from 1959 to 2005. Most notably, structural breaks occur in total consumer credit and revolving consumer credit in the 1990s. Based on the break date estimates, I estimate a structural equation of consumption growth in line with previous empirical tests of the permanent-income hypothesis. Consumption smoothing is evident in the data after the mid-1980s and into the 2000s. The findings of this paper have important implications for a variety of economic research. The evidence for consumption smoothing bears directly on the efficacy of monetary policy and fiscal policy, as well as on the recent discussion of the decline in macroeconomic volatility since the 1980s.

Western burrowing owls (Athene cunicularia hypugaea) are endangered in Canada and several western U.S. states. Population declines have been linked with control measures aimed at burrowing mammals and loss of nesting habitat. The owls frequently associate with irrigated agriculture throughout portions of their western U.S. range. To determine potential factors driving the association of burrowing owls with agriculture, we examined availability of suitable nest burrows (burrow availability hypothesis), abundance of potential prey (prey availability hypothesis), and predation of nest burrows (predation hypothesis) for owls nesting in the Snake River Birds of Prey National Conservation Area in southwestern Idaho during 2001–2002. Nest burrow availability did not differ between agricultural and nonagricultural habitats, and occupancy rates of owls in artificial burrows were greater near agriculture. More rodent prey species were live-trapped in agricultural habitat compared with nonagricultural habit...

Bovine respiratory syncytial virus (BRSV) is an etiological component of the bovine respiratory tract disease complex. Infection with BRSV following vaccination, or re-infection following natural infection is common since protection is incomplete. The objectives of this study were to create plasmid DNA constructs encoding single or multiple N-glycosylation-site deletion BRSV fusion (F) proteins, and evaluate their expression in cell culture, and potential to induce anti-BRSV F antibody responses in BALB/c mice. Four plasmid DNAs were constructed, each encoding 1-4 N-glycosylation-site deletions: Gly4, Gly2/4, Gly1/2/4 and Gly1/2/3/4. Each of the N-glycosylation-site deletion BRSV F proteins were expressed in COS-7 cells following transfection with plasmid DNA. Inoculation of BALB/c mice with plasmid DNA, resulted in a significant anti-BRSV F IgG response to the wild-type (WT) F and glycosylation-site deletion protein Gly2/4. Gly2/4 elicited a higher antibody titer than the fully glycosylated WT F protein. Significant neutralizing antibody titers were detected following immunization with the Gly2/4 plasmid DNA. These glycosylation-site deletion BRSV F proteins will be useful to characterize the effects of glycosylation on immunogenicity in the natural host, and may lead to a new approach for the generation of BRSV vaccines.

Bovine respiratory syncytial virus (BRSV) is a primary cause of lower respiratory tract disease in calves. Protection is incomplete following vaccination or natural infection, as re-infections are common. The objectives of this study were to create plasmid DNA constructs encoding the full-length, secreted, or conserved region of the BRSV G glycoprotein, and to compare and evaluate their expression in cell culture and potential to induce antibody responses in BALB/c mice. Transfection of COS-7 cells with plasmid DNA resulted in expression of the BRSV G region from each of the plasmid DNA constructs. Following inoculation of BALB/c mice with plasmid DNA, a significant and equivalent anti-BRSV G IgG response was elicited to the full-length and truncated BRSV G proteins. These constructs may be used to study host pathological and immunological responses.

To investigate the potential expression of territorial behavior of Burrowing Owls (Athene cunicularia) in southwestern Idaho, we used a playback protocol to determine if Burrowing Owls actively defended their nesting site from conspecifics, and if so, to determine the extent of their territorial boundaries. Eighty-eight percent of male Burrowing Owls responded to the broadcast of conspecific primary calls. All responsive males uttered primary calls, and many owls approached the broadcast speaker, exhibited white-and-tall stances, and bobbed. Females responded less frequently than males, but one female whose mate was presumably dead exhibited an intense response to the playback trial. There were no differences in number of primary calls uttered, number of white-and-tall stances performed, or number of bobs of focal males among three broadcast distances: (0 m, 50 m, and 100 m) from the active nest burrows. However, focal owls approached the broadcast speaker more closely at broadcast distances of 0...

This paper tests for the direct wealth effect versus an indirect wealth effect in aggregate data on U.S. households over four distinct sub-periods from 1952 through 2011. We use recent time series techniques to distinguish between the direct wealth effect from indirect channels which may operate through personal disposable income or liabilities. We find evidence of a direct wealth effect for housing wealth, in particular, from 1998 to 2011. The responses of consumption in the 1998 to 2011 period are in contrast to an indirect or ¡°common cause¡± explanation of the wealth effect. For financial wealth, there is some evidence of a direct wealth effect for the 1998 to 2011 period, but the effect overall is smaller than for tangible wealth. Also, before 1998 the evidence for a direct wealth effect from either housing wealth or financial wealth is weak.

The European sovereign-debt crisis began in Greece when the government announced in December, 2009, that its debt reached 121% of GDP (or 300 billion euros) and its 2009 budget deficit was 12.7% of GDP, four times the level allowed by the Maastricht Treaty. The Greek crisis soon spread to other Economic and Monetary Union (EMU) countries, notably Ireland, Portugal, Spain and Italy. Using quarterly data for the 2000–2011 period, we implement a panel-vector autoregressive (PVAR) model for 11 EMU countries to examine the extent to which a rise in a country’s bond-yield spread or debt-to-GDP ratio affects another EMU countries’ fiscal and macroeconomic outcomes. To distinguish between interdependence and contagion among EMU countries, we compare results obtained for the pre-crisis period (2000–2007) with the crisis period (2008–2011) and control for global risk aversion.

In this paper, we test for the direct wealth effect in aggregate data on U.S. households over four distinct sub-periods from 1952 through 2011. We use recent time series techniques to distinguish between the direct wealth effect from indirect channels which may operate through personal disposable income or liabilities. We find evidence of a direct wealth effect for housing wealth, in particular, from 1998 to 2011. The responses of consumption in the 1998 to 2011 period are in contrast to an indirect or “common cause” explanation of the wealth effect. For financial wealth, there is some evidence of a direct wealth effect for the 1998 to 2011 period, but the effect overall is smaller than for tangible wealth. Also, before 1998 evidence for a direct wealth effect from either housing wealth or financial wealth is weak.

Purpose This study was designed to determine if first-year radiology resident attendance at the ACR AMCLC over a period of 3 years from 2009 to 2011 led to increased resident knowledge regarding the ACR and Minnesota Radiological Society (MRS), and whether resident involvement in the conference would influence their decisions to participate in the ACR and state radiological societies in the future. Methods All first-year radiology residents from the University of Minnesota and the Mayo Clinic residency programs were invited to attend the ACR AMCLC from 2009 to 2011. Local radiology and radiation oncology groups provided funding for travel and hotel expenses, and both residency programs granted residents one day off from clinical duties to travel. Preconference and postconference questionnaires were used to assess residents' knowledge of the general structure and function of the ACR and MRS. Postconference questionnaires were also used to assess residents' satisfaction with the conference and determine their likelihood of joining the ACR and MRS in the future. Results A total of 46 residents from the residency programs attended the conference over this time period. Residents' knowledge regarding the ACR and MRS increased after the conference, with improved performance on postconference objective and subjective responses. The number of issues residents identified as important to radiology increased after the conference. The vast majority of residents had a very positive experience at the conference and were "highly likely" or "likely" to join the ACR and MRS in the future. Conclusions Results from the first 3 years of this ongoing study indicate that attending the ACR AMCLC has been an overwhelmingly positive experience for first-year radiology residents from the University of Minnesota and the Mayo Clinic programs. Residents' knowledge regarding the ACR and MRS increased nearly 2-fold following the conference. Future state radiological society and ACR membership rates among the participants in our study could potentially be higher than the current national average. Furthermore, we believe the residents' experiences at the conference play an important role in their development as more connected, informed, and politically active radiologists in the future.

Wetlands play a major role in the export of methylmercury (MeHg) to a watershed. The large contribution of wetlands to watersheds in northern Wisconsin, coupled with the acidic environment of this area, makes these habitats especially vulnerable to mercury (Hg) accumulation by biota. The purpose of this study was to compare Hg accumulation between northern Wisconsin wetlands and southern Wisconsin wetlands using the swamp sparrow (Melospiza georgiana) as a representative species. The swamp sparrow was selected as a representative passerine species in which to examine Hg in these habitats, because during their breeding season, they feed at a higher trophic level than many of their counterparts. During the breeding seasons of 2007 and 2008, blood samples were collected from swamp sparrows inhabiting wetlands in both northern and southern Wisconsin and analyzed for total Hg. The mean concentration of total Hg in swamp sparrows from northern wetlands was 0.135 ± 0.064 μg/ml while the mean concentration of total Hg in swamp sparrows from southern wetlands was 0.187 ± 0.106 μg/ml. Results revealed no significant difference (P = 0.17) between Hg accumulation in swamp sparrows from less-acidic wetlands in southern Wisconsin and Hg in swamp sparrows from acidic wetlands in northern Wisconsin. The results are contrary to those observed in other species such as common loon, tree swallow and river otter where higher accumulation has been observed in individuals from acidic habitats. Reasons for the lack of this accumulation pattern in swamp sparrows are unclear and warrant further study.

Purpose To measure and compare temperature changes in a recently developed gel phantom for thermochemical ablation as a function of reagent strength and concentration with several acids and bases. Materials and Methods Aliquots (0.5–1 mL) of hydrochloric acid or acetic acid and sodium hydroxide or aqueous ammonia were injected for 5 seconds into a hydrophobic gel phantom. Stepwise increments in concentration were used to survey the temperature changes caused by these reactions. Injections were performed in triplicate, measured with a thermocouple probe, and plotted as functions of concentration and time. Results Maximum temperatures were reached almost immediately in all cases, reaching 75°C–110°C at the higher concentrations. The highest temperatures were seen with hydrochloric acid and either base. More concentrated solutions of sodium hydroxide tended to mix incompletely, such that experiments at 9 M and higher were difficult to perform consistently. Conclusions Higher concentrations for any reagent resulted in higher temperatures. Stronger acid and base combinations resulted in higher temperatures versus weak acid and base combinations at the same concentration. Maximum temperatures obtained are in a range known to cause tissue coagulation, and all combinations tested therefore appeared suitable for further investigation in thermochemical ablation. Because of the loss of the reaction chamber shape at higher concentrations of stronger agents, the phantom does not allow complete characterization under these circumstances. Adequate mixing of reagents to maximize heating potential and avoid systemic exposure to unreacted acid and base must be addressed if the method is to be safely employed in tissues. In addition, understanding factors that control lesion shape in a more realistic tissue model will be critical.

I. INTRODUCTION Despite calls for its obsolescence, the lending channel of the monetary transmission mechanism continues to generate interest among monetary economists. Recently, Den Haan, Sumner, and Yamashiro (2007) find the loan-supply effect is evident for consumer lending and real estate loans in data up to 2004. The loan-supply effect, or lending channel, arises in the transmission mechanism if tight monetary policy forces banks to contract the supply of loans independent of a direct interest rate-effect (i.e., the "liquidity effect"), and such a contraction has real effects for bank-dependent borrowers. Although some, such as Perez (1998) and Ashcraft (2006), have emphasized the lending channel's lack of relevance for the monetary transmission mechanism, Den Haan, Sumner, and Yamashiro's (2007) results support a number of recent papers that offer detailed and disaggregated reasons why the channel is alive and well for certain lenders and borrowers (for recent examples, see Nilsen 2004 and Peek, Rosengren, and Tootell 2003). Den Haan, Sumner, and Yamashiro's (2007) findings suggest that the role of the consumer in the lending channel may be deserving of more attention. (1) This paper asks whether consumer lending is, or has become, a significant component of the lending channel (even if it was not thought crucial in lending channel studies published in the 1990s). Specifically, I take a closer look at the statistical and possible economic significance of the consumer loan-supply effect with disaggregated monthly consumer credit data from both commercial bank and nonbank sources, and for the nonrevolving and revolving components of consumer credit from each source. With this array of data, I test the assumptions of the channel by considering whether households are forced to use more expensive nonbank credit as bank credit declines, or that a household might switch into more costly revolving credit as installment loans decline. To examine the consumer lending channel, I estimate impulse response functions for the disaggregated consumer loan components mentioned above, with the monthly data spanning 1968-2006 (the sources of which are discussed later). This strategy follows the examples of numerous lending channel studies that analyze the responses of disaggregated data to a monetary policy shock to discern evidence of the loan-supply effect (Den Haan, Sumner, and Yamashiro 2007, e.g., compare the behavior of commercial and industrial loans with real estate and consumer loans). I follow the methods of previous studies in order to compare as closely as possible the results of this paper with the rich body of lending channel literature. For robustness, this paper estimates the impulse response functions from both a typical vector autoregression (VAR) model and using Jorda's (2005) linear projection technique. The latter method provides impulse response functions less-prone to misspecification (than in a VAR) along with conditional standard errors to aid in the statistical inference of the responses (see also Jorda 2009 and further discussion in Section III). Finally, for additional robustness, I employ Den Haan, Sumner, and Yamashiro's (2007) identification strategy for isolating the loan-supply effect. In preview of the results, ultimately the consumer credit data analyzed in this paper suggest that both the statistical (and by extension, the economic) significance of the consumer loan-supply effect is weak; in the least, the effect has weakened over time. Although monthly consumer credit data from commercial banks from 1968 through 2006 substantiate previous research on consumer lending--matching the decline documented by Gertler and Gilchrist (1993) and Den Haan, Sumner, and Yamashiro (2007)--after 1984, the responses of both nonrevolving and revolving consumer bank credit are not consistent with the lending channel. Instead, both series increase, similar to the result found by Den Haan, Sumner, and Yamashiro (2007) for commercial lending (in fact, total nonrevolving and revolving consumer credit increase for 2 yr after the monetary shock). …