We demonstrate a microwave imaging system that combines advances in metamaterial aperture design with emerging computational imaging techniques. The flexibility inherent to guided-wave, complementary metamaterials enables the design of a planar antenna that illuminates a scene with dramatically varying radiation patterns as a function of frequency. As frequency is swept over the K-band (17.5-26.5 GHz), a sequence of pseudorandom radiation patterns interrogates a scene. Measurements of the return signal versus frequency are then acquired and the scene is reconstructed using computational imaging methods. The low-cost, frequency-diverse static aperture allows three-dimensional images to be formed without mechanical scanning or dynamic beam-forming elements. The metamaterial aperture is complementary to a variety of computational imaging schemes, and can be used in conjunction with other sensors to form a multifunctional imaging platform. We illustrate the potential of multisensor fusion by integrating an infrared structured-light and optical image sensor to accelerate the microwave scene reconstruction and to provide a simultaneous visualization of the scene.
Cerebrospinal fluid (CSF) amyloid-? (A?) and tau have been studied as markers of Alzheimer's disease (AD). Combined A?42 and t-tau distinguishes AD from healthy controls with a sensitivity and specificity (sens/spec) near 89% across studies. This study examined these markers in the homogeneous OPTIMA cohort, using extensive longitudinal follow up and postmortem evaluation to confirm clinicopathological status. Baseline CSF was analyzed from 227 participants with AD (97% autopsy-confirmed), mild cognitive impairment (MCI; 73% confirmed), other dementia syndrome (ODS; 100% confirmed), and controls (CTL; 27% confirmed, follow up 9-13 years). Biomarker concentrations were analyzed using validated ELISAs. AD patients had lower CSF A?42 and higher t-tau, p-tau, t-tau/A?42, and t-tau/A?40 compared to CTLs, with MCI intermediate. CTL and MCI participants who progressed to AD demonstrated more AD-like profiles. A?40, sA?PP?, and sA?PP? were lower in AD compared to CTL. High-level discriminators of AD from CTL were t-tau/A?40 (AUROC 0.986, sens/spec of 92%/94%), p-tau/A?42 (AUROC 0.972, sens/spec of 94%/90%), and A?42 (AUROC 0.941, sens/spec of 88%). For discriminating AD from ODS, p-tau/A?42 demonstrated sens/spec of 88%/100% (95%/86% at the AD versus CTL cutoff) and A?42 demonstrated sens/spec of 84%/100% (88%/100% at the AD versus CTL cutoff). In a well-characterized, homogeneous population, a single cutoff for baseline CSF A? and tau markers can distinguish AD with a high level of sens/spec compared to other studies. It may be important to characterize sources of demographic and biological variability to support the effective use of CSF diagnostic assays in the broader AD population.
Shiga toxin-producing Escherichia coli (STEC), particularly STEC O157, cause rare but potentially serious human infections. Infection with STEC occurs by fecal-oral transmission, most commonly through food. Cattle are the most important reservoir for human STEC exposure, and efforts to control the flow of STEC through beef processing have reduced rates of human illness. However, further reduction in human incidence of STEC may require control of the pathogen in cattle populations. The ecology of STEC in cattle production systems is complex and explained by factors that favor (a) colonization in the gut, (b) survival in the environment, and (c) ingestion by another cattle host. Although nature creates seasonal environmental conditions that do not favor STEC transmission in cattle, human efforts to control STEC by environmental manipulation have not succeeded. Vaccines and direct-fed microbial products have reduced the carriage of STEC by cattle, and other interventions are under investigation.
Previous studies have indicated that rhesus monkeys (Macaca mulatta) but not capuchin monkeys (Cebus apella) respond to difficult or ambiguous situations by choosing not to respond or by seeking more information. Here we assessed whether a task with very low chance accuracy could diminish this species difference, presumably indicating that capuchins-compared to macaques-are less risk averse as opposed to less sensitive to signals of uncertainty. Monkeys searched for the largest of six stimuli on a computer screen. Trial difficulty was varied, and monkeys could choose to opt out of any trial. All rhesus monkeys, including some with no prior use of the uncertainty response, selectively avoided the most difficult trials. The majority of capuchins sometimes made uncertainty responses, but at lower rates than rhesus monkeys. Nonetheless, the presence of some adaptive uncertainty responding suggests that capuchins also experience uncertainty and can respond to it, though with less proficiency than macaque monkeys.
Field disease investigations can help to identify patterns of disease that lead to causal hypotheses and, hopefully, effective disease risk management strategies. The most common way of doing this would be to characterize the outbreak by subject, time, and space. One of the perplexing animal health problems on some beef cattle ranches is the occurrence of pneumonia in calves prior to weaning in conditions of little stress and relative isolation. Field investigation of outbreaks of pneumonia in ranch calves prior to weaning has revealed patterns of sporadic illness in calves less than 30 days of age, and rapidly occurring outbreaks in calves 90-150 days of age. We speculate that the causes of these two patterns may be failure of passive transfer resulting in more sporadic cases in very young calves, or a large proportion of the population losing maternal antibody protection (i.e. losing herd immunity) resulting in rapid and widespread onset of pneumonia in older calves.
Natural resource managers are developing assessments of selenium (Se) contamination in freshwater ecosystems based on fish tissue concentrations. We evaluated the effects of sample size (i.e., number of fish per site) on the probability of correctly detecting mean whole-body Se values above a range of potential management thresholds. We modeled Se concentrations as gamma distributions with shape and scale parameters fitting an empirical mean-to-variance relationship in data from southwestern West Virginia, USA (63 collections, 382 individuals). We used parametric bootstrapping techniques to calculate statistical power as the probability of detecting true mean concentrations up to 3?mg Se/kg above management thresholds ranging from 4 to 8?mg Se/kg. Sample sizes required to achieve 80% power varied as a function of management thresholds and Type I error tolerance (?). Higher thresholds required more samples than lower thresholds because populations were more heterogeneous at higher mean Se levels. For instance, to assess a management threshold of 4?mg Se/kg, a sample of eight fish could detect an increase of approximately 1?mg Se/kg with 80% power (given ??=?0.05), but this sample size would be unable to detect such an increase from a management threshold of 8?mg Se/kg with more than a coin-flip probability. Increasing ? decreased sample size requirements to detect above-threshold mean Se concentrations with 80% power. For instance, at an ?-level of 0.05, an 8-fish sample could detect an increase of approximately 2 units above a threshold of 8?mg Se/kg with 80% power, but when ? was relaxed to 0.2, this sample size was more sensitive to increasing mean Se concentrations, allowing detection of an increase of approximately 1.2 units with equivalent power. Combining individuals into 2- and 4-fish composite samples for laboratory analysis did not decrease power because the reduced number of laboratory samples was compensated for by increased precision of composites for estimating mean conditions. However, low sample sizes (<5 fish) did not achieve 80% power to detect near-threshold values (i.e., <1?mg Se/kg) under any scenario we evaluated. This analysis can assist the sampling design and interpretation of Se assessments from fish tissue by accounting for natural variation in stream fish populations. Integr Environ Assess Manag 2014;9999:1-7. Published 2014 SETAC.
Environmental pollution often accompanies the expansion and urbanisation of human populations where sewage and wastewaters commonly have an impact on the marine environments. Here we explored the potential for faecal bacterial pathogens, of anthropic origin, to spread to marine wildlife in coastal areas. The common zoonotic bacterium Campylobacter was isolated from grey seals (Halichoerus grypus), an important sentinel species for environmental pollution, and compared to isolates from wild birds, agricultural sources and clinical samples to characterize possible transmission routes. Campylobacter jejuni was present in half of all grey seal pups sampled (24/50 dead and 46/90 live pups) in the breeding colony on the Isle of May (Scotland), where it was frequently associated with histological evidence of disease. Returning yearling animals (19/19) were negative for C. jejuni suggesting clearance of infection whilst away from the localised colony infection source. The genomes of 90 isolates from seals were sequenced and characterized using a whole-genome multilocus sequence typing (MLST) approach, and compared to 192 published genomes from multiple sources using population genetic approaches and a probabilistic genetic attribution model to infer the source of infection from MLST data. The strong genotype-host association has enabled the application of source attribution models in epidemiological studies of human campylobacteriosis, and here assignment analyses consistently grouped seal isolates with those from human clinical samples. These findings are consistent with either a common infection source or direct transmission of human campylobacter to grey seals, raising concerns about the spread of human pathogens to wildlife marine sentinel species in coastal areas. This article is protected by copyright. All rights reserved.
The radiative processes associated with fluorophores and other radiating systems can be profoundly modified by their interaction with nanoplasmonic structures. Extreme electromagnetic environments can be created in plasmonic nanostructures or nanocavities, such as within the nanoscale gap region between two plasmonic nanoparticles, where the illuminating optical fields and the density of radiating modes are dramatically enhanced relative to vacuum. Unraveling the various mechanisms present in such coupled systems, and their impact on spontaneous emission and other radiative phenomena, however, requires a suitably reliable and precise means of tuning the plasmon resonance of the nanostructure while simultaneously preserving the electromagnetic characteristics of the enhancement region. Here, we achieve this control using a plasmonic platform consisting of colloidally synthesized nanocubes electromagnetically coupled to a metallic film. Each nanocube resembles a nanoscale patch antenna (or nanopatch) whose plasmon resonance can be changed independent of its local field enhancement. By varying the size of the nanopatch, we tune the plasmonic resonance by ? 200 nm, encompassing the excitation, absorption, and emission spectra corresponding to Cy5 fluorophores embedded within the gap region between nanopatch and film. By sweeping the plasmon resonance but keeping the field enhancements roughly fixed, we demonstrate fluorescence enhancements exceeding a factor of 30,000 with detector-limited enhancements of the spontaneous emission rate by a factor of 74. The experiments are supported by finite-element simulations that reveal design rules for optimized fluorescence enhancement or large Purcell factors.
Specific Escherichia coli strains associated with bovine postpartum uterine infection have recently been described. Many recognized virulence factors are absent in these strains; therefore, to define a prototypic strain, we report here the genome sequence of E. coli isolate MS499 from a cow with the postpartum disease metritis.
Kornell (2014, pp. 143-149) considers whether, and in what sense, animals may be considered metacognitive. He questions whether tests that rely on animals assessing their internal memory strength can provide useful data. He offers his own strategies for determining what internal cues animals use in making metacognitive judgments. We endorse his call for an increased focus on animals' metacognitive errors as true reflections of metacognitive states shorn of associative bases. We endorse a sharper focus on information-processing analyses of the executive or attentional level that metacognitive responses may occupy in animals' cognitive systems. Some of these analyses are being implemented in contemporary research, with positive results. Finally, we endorse the possibility that metacognition may not be an all-or-none thing, so that animals may share some facets--but not all facets--of metacognitive experience with humans. Kornell's interesting contribution makes clear that, in this area, the animal-metacognition literature needs further theoretical sharpening.
BackgroundResearch has increasingly highlighted the role of serotonin in behavior. However, few researchers have examined serotonin in an evolutionary context, although such research could provide insight into the evolution of important behaviors. The genus Macaca represents a useful model to address this, as this genus shows a wide range of behavioral variation. In addition, many genetic features of the macaque serotonin system are similar to those of humans, and as common models in biomedical research, knowledge of the genetic variation and evolution of serotonin functioning in macaques are particularly relevant for studies of human evolution. Here, we examine the role of selection in the macaque serotonin system by comparing patterns of genetic variation for two genes that code for two types of serotonin receptors ¿ HTR1A and HTR1B ¿ across five species of macaques.ResultsThe pattern of variation is significantly different for HTR1A compared to HTR1B. Specifically, there is an increase in between-species variation compared to within-species variation for HTR1A. Phylogenetic analyses indicate that portions of HTR1A show an elevated level of nonsynonymous substitutions. Together these analyses are indicative of positive selection acting on HTR1A, but not HTR1B. Furthermore, the haplotype network for HTR1A is inconsistent with the species tree, potentially due to both deep coalescence and selection.ConclusionsThe results of this study indicate distinct evolutionary histories for HTR1A and HTR1B, with HTR1A showing evidence of selection and a high level of divergence among species, a factor which may have an impact on biomedical research that uses these species as models. The wide genetic variation of HTR1A may also explain some of the species differences in behavior, although further studies on the phenotypic effect of the sequenced polymorphisms are needed to confirm this.
Trueperella pyogenes is a common commensal bacterium and an opportunistic pathogen associated with chronic purulent disease, particularly in ruminants. We report here the genome sequence of a T. pyogenes isolate from a severe case of bovine metritis. This is the first full record of a T. pyogenes genome.
An influential theoretical perspective describes an implicit category-learning system that associates regions of perceptual space with response outputs by integrating information preattentionally and predecisionally across multiple stimulus dimensions. In this study, we tested whether this kind of implicit, information-integration category learning is possible across stimulus dimensions lying in different sensory modalities. Humans learned categories composed of conjoint visual-auditory category exemplars comprising a visual component (rectangles varying in the density of contained lit pixels) and an auditory component (in Exp. 1, auditory sequences varying in duration; in Exp. 2, pure tones varying in pitch). The categories had either a one-dimensional, rule-based solution or a two-dimensional, information-integration solution. Humans could solve the information-integration category tasks by integrating information across two stimulus modalities. The results demonstrated an important cross-modal form of sensory integration in the service of category learning, and they advance the field's knowledge about the sensory organization of systems for categorization.
Mammalian toll-like receptor 5 (TLR5) senses flagellin of several bacterial species and has been described to activate the innate immune system. To assess the role of bovine TLR5 (boTLR5) in the cattle system, we cloned and successfully expressed boTLR5 in human embryonic kidney (HEK) 293 cells, as indicated by quantitative PCR and confocal microscopy. However, in contrast to huTLR5-transfected cells, exposure of boTLR5-transfected cells to flagellin neither activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) nor CXCL8 production. Subsequent comparison of the flagellin response induced in human and bovine primary macrophages revealed that flagellin did not lead to phosphorylation of major signalling molecules. Furthermore, the CXCL8 and TNF? response of primary bovine macrophages stimulated with flagellin was very low compared to that observed in human primary macrophages. Our results indicate that cattle express a functional TLR5 albeit with different flagellin sensing qualities compared to human TLR5. However, boTLR5 seemed to play a different role in the bovine system compared to the human system in recognizing flagellin, and other potentially intracellular expressed receptors may play a more important role in the bovine system to detect flagellin.
Synergistic integration of electromagnetic (EM) and mechanical properties of metamaterials, a concept known as smart metamaterials, promises new applications across the spectrum, from flexible waveguides to shape-conforming cloaks. These applications became possible thanks to smart transformation optics (STO), a design methodology that utilizes coordinate transformations to control both EM wave propagation and mechanical deformation of the device. Here, we demonstrate several STO devices based on extremely auxetic (Poisson ratio -1) elasto-electromagnetic metamaterials, both of which exhibit enormous flexibility and sustain efficient operation upon a wide range of deformations. Spatial maps of microwave electric fields across these devices confirm our ability to deform carpet cloaks, bent waveguides, and potentially other quasi-conformal TO-based devices operating at 7 ~ 8 GHz. These devices are each fabricated from a single sheet of initially uniform (double-periodic) square-lattice metamaterial, which acquires the necessary distribution of effective permittivity entirely from the mechanical deformation of its boundary. By integrating transformation optics and continuum mechanics theory, we provide analytical derivations for the design of STO devices. Additionally, we clarify an important point relating to two-dimensional STO devices: the difference between plane stress and plane strain assumptions, which lead to elastic metamaterials with Poisson ratio -1 and -?, respectively.
Cryptomonads, are a lineage of unicellular and mostly photosynthetic algae, that acquired their plastids through the "secondary" endosymbiosis of a red alga - and still retain the nuclear genome (nucleomorph) of the latter. We find that the genome of the cryptomonad Guillardia theta comprises genes coding for 13 globin domains, of which 6 occur within two large chimeric proteins. All the sequences adhere to the vertebrate 3/3 myoglobin fold. Although several globins have no introns, the remainder have atypical intron locations. Bayesian phylogenetic analyses suggest that the G. theta Hbs are related to the stramenopile and chlorophyte single domain globins.
The ability to wirelessly power electrical devices is becoming of greater urgency as a component of energy conservation and sustainability efforts. Due to health and safety concerns, most wireless power transfer (WPT) schemes utilize very low frequency, quasi-static, magnetic fields; power transfer occurs via magneto-inductive (MI) coupling between conducting loops serving as transmitter and receiver. At the "long range" regime - referring to distances larger than the diameter of the largest loop - WPT efficiency in free space falls off as (1/d)(6); power loss quickly approaches 100% and limits practical implementations of WPT to relatively tight distances between power source and device. A "superlens", however, can concentrate the magnetic near fields of a source. Here, we demonstrate the impact of a magnetic metamaterial (MM) superlens on long-range near-field WPT, quantitatively confirming in simulation and measurement at 13-16 MHz the conditions under which the superlens can enhance power transfer efficiency compared to the lens-less free-space system.
Subclinical endometritis (SCE) is an important postpartum disease in dairy cows, but conventional cytobrush diagnosis often gives imprecise results. The aim of this study was to analyze disease-associated changes in peripheral blood as potential diagnostic parameters. Cellular subpopulations of blood leukocytes from cows with or without SCE (45-55 days postpartum) were flow-cytometrically quantified. Gene expression of whole blood leukocytes was assessed by PAXgene analysis. Subclinical endometritis cows showed significantly higher number of blood mononuclear cells and neutrophils. Among mononuclear cells, numbers of B-cells, NK-cells, and CD172a-positive monocytes were significantly elevated. Compared with non-SCE cows, blood leukocytes of SCE cows significantly expressed higher copy numbers of CXCL8, TNF, and IL12. To test whether circulating plasma factors are responsible for these changes, leukocytes, polymorphonuclear cells, and monocyte subpopulations (classical, intermediate, nonclassical) of healthy cows were stimulated with plasma of SCE and non-SCE cows. Although gene expression of whole leukocytes and polymorphonuclear cells remained unaltered, plasma from SCE animals significantly elevated expressed messenger RNA copy numbers of CXCL8, CXCL1, and IL1B in intermediate monocytes. In conclusion, elevated number of selected mononuclear subpopulations in peripheral blood and enhanced expression of distinct genes encoding for inflammatory mediators in blood leukocytes reflect the subclinical uterine inflammatory process in cows. Whether the observed changes in the periphery of SCE cows are the consequence of the uterine inflammatory process, or whether they affect the pathogenesis of the disease is currently unknown.
Previous mass spectrometry analysis of cerebrospinal fluid (CSF) has allowed the identification of a panel of molecular markers that are associated with Alzheimer's disease (AD). The panel comprises Amyloid beta, Apolipoprotein E, Fibrinogen alpha chain precursor, Keratin type I cytoskeletal 9, Serum albumin precursor, SPARC-like 1 protein and Tetranectin. Here we report the development and implementation of immunoassays to measure the abundance and diagnostic capacity of these putative biomarkers in matched lumbar CSF and blood plasma samples taken in life from individuals confirmed at post-mortem as suffering from AD (n = 10) and from screened 'cognitively healthy' subjects (n = 18). The inflammatory components of Alzheimer's disease were also investigated. Employment of supervised learning techniques permitted examination of the interrelated expression patterns of the putative biomarkers and identified inflammatory components, resulting in biomarker panels with a diagnostic accuracy of 87.5% and 86.7% for the plasma and CSF datasets respectively. This is extremely important as it offers an ideal high-throughput and relatively inexpensive population screening approach. It appears possible to determine the presence or absence of AD based on our biomarker panel and it seems likely that a cheap and rapid blood test for AD is feasible.
Purulent disease of the uterus develops in 40% of dairy cows after parturition, when the epithelium of the endometrium is disrupted to expose the underlying stroma to bacteria. The severity of endometrial pathology is associated with isolation of Trueperella pyogenes. In the present study, T. pyogenes alone caused uterine disease when infused into the uterus of cattle where the endometrial epithelium was disrupted. The bacterium secretes a cholesterol-dependent cytolysin, pyolysin (PLO), and the plo gene was identical and the plo gene promoter was highly similar amongst 12 clinical isolates of T. pyogenes. Bacteria-free filtrates of the T. pyogenes cultures caused hemolysis and endometrial cytolysis, and PLO was the main cytolytic agent, because addition of anti-PLO antibody prevented cytolysis. Similarly, a plo-deletion T. pyogenes mutant did not cause hemolysis or endometrial cytolysis. Endometrial stromal cells were notably more sensitive to PLO-mediated cytolysis than epithelial or immune cells. Stromal cells also contained more cholesterol than epithelial cells, and reducing stromal cell cholesterol content using cyclodextrins protected against PLO. Although T. pyogenes or plo-deletion T. pyogenes stimulated accumulation of inflammatory mediators, such as IL-1beta, IL-6, and IL-8, from endometrium, PLO did not stimulate inflammatory responses by endometrial or hematopoietic cells, or in vitro organ cultures of endometrium. The marked sensitivity of stromal cells to PLO-mediated cytolysis provides an explanation for how T. pyogenes acts as an opportunistic pathogen to cause pathology of the endometrium once the protective epithelium is lost after parturition.
The controversy over multiple category-learning systems is reminiscent of the controversy over multiple memory systems. Researchers continue to seek paradigms to sharply dissociate explicit category-learning processes (featuring category rules that can be verbalized) from implicit category-learning processes (featuring learned stimulus-response associations that lie outside declarative cognition). We contribute a new dissociative paradigm, adapting the technique of deferred-rearranged reinforcement from comparative psychology. Participants learned matched category tasks that had either a one-dimensional, rule-based solution or a multidimensional, information-integration solution. They received feedback either immediately or after each block of trials, with the feedback organized such that positive outcomes were grouped and negative outcomes were grouped (deferred-rearranged reinforcement). Deferred reinforcement qualitatively eliminated implicit, information-integration category learning. It left intact explicit, rule-based category learning. Moreover, implicit-category learners facing deferred-rearranged reinforcement turned by default and information-processing necessity to rule-based strategies that poorly suited their nominal category task. The results represent one of the strongest explicit-implicit dissociations yet seen in the categorization literature.
We introduce the concept of a metamaterial aperture, in which an underlying reference mode interacts with a designed metamaterial surface to produce a series of complex field patterns. The resonant frequencies of the metamaterial elements are randomly distributed over a large bandwidth (18-26 GHz), such that the aperture produces a rapidly varying sequence of field patterns as a function of the input frequency. As the frequency of operation is scanned, different subsets of metamaterial elements become active, in turn varying the field patterns at the scene. Scene information can thus be indexed by frequency, with the overall effectiveness of the imaging scheme tied to the diversity of the generated field patterns. As the quality (Q-) factor of the metamaterial resonators increases, the number of distinct field patterns that can be generated increases-improving scene estimation. In this work we provide the foundation for computational imaging with metamaterial apertures based on frequency diversity, and establish that for resonators with physically relevant Q-factors, there are potentially enough distinct measurements of a typical scene within a reasonable bandwidth to achieve diffraction-limited reconstructions of physical scenes.
Background:Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva. Methods:To understand the horizontal transmission of HHV-8 within households to children we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV-1 and health and behavioral questionnaires were completed. Multi-level logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children. Results:Risk factors for HHV-8 infection included increasing number of HHV-8 positive household members [OR 2.5 (95% CI: 1.9, 3.3) P < 0.01] and having a primary caregiver who tested the temperature of food with their tongue prior to feeding the child [OR 2.4 (95% CI: 1.93, 3.30) P =0.01]. Breastfeeding was protective against infection with HHV-8 for children [OR 0.3 (95% CI: 0.16, 0.72) P <0.01]. Conclusions:These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection with specific feeding behaviors likely playing a role in transmission. Impact:Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods.
This paper presents an optical element capable of multiplexing two diffraction patterns for two orthogonal linear polarizations, based on the use of non-resonant metamaterial cross elements. The metamaterial cross elements provide unique building blocks for engineering arbitrary birefringence. As a proof-of-concept demonstration, we present the design and experimental characterization of a polarization multiplexed blazed diffraction grating and a polarization multiplexed computer-generated hologram, for the telecommunication wavelength of ? = 1.55 ?m. A quantitative study of the polarization multiplexed grating reveals that this approach yields a very large polarization contrast ratio. The results show that metamaterials can form the basis for a versatile and compact platform useful in the design of multi-functional photonic devices.
A metallic nanoparticle positioned over a metal film offers great advantages as a highly controllable system relevant for probing field-enhancement and other plasmonic effects. Because the size and shape of the gap between the nanoparticle and film can be controlled to subnanometer precision using relatively simple, bottom-up fabrication approaches, the film-coupled nanoparticle geometry has recently been applied to enhancing optical fields, accessing the quantum regime of plasmonics, and the design of surfaces with controlled reflectance. In the present work, we examine the plasmon modes associated with a silver nanocube positioned above a silver or gold film, separated by an organic, dielectric spacer layer. The film-coupled nanocube is of particular interest due to the formation of waveguide cavity-like modes between the nanocube and film. These modes impart distinctive scattering characteristics to the system that can be used in the creation of controlled reflectance surfaces and other applications. We perform both experimental spectroscopy and numerical simulations of individual nanocubes positioned over a metal film, finding excellent agreement between experiment and simulation. The waveguide mode description serves as a starting point to explain the optical properties observed.
A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-?4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.
The military unit is a critical center of gravity in the militarys efforts to enhance resilience and the health of the force. The purpose of this article is to augment the militarys Total Force Fitness (TFF) guidance with a framework of TFF in units. The framework is based on a Military Demand-Resource model that highlights the dynamic interactions across demands, resources, and outcomes. A joint team of subject-matter experts identified key variables representing unit fitness demands, resources, and outcomes. The resulting framework informs and supports leaders, support agencies, and enterprise efforts to strengthen TFF in units by (1) identifying TFF unit variables aligned with current evidence and operational practices, (2) standardizing communication about TFF in units across the Department of Defense enterprise in a variety of military organizational contexts, (3) improving current resources including evidence-based actions for leaders, (4) identifying and addressing of gaps, and (5) directing future research for enhancing TFF in units. These goals are intended to inform and enhance Service efforts to develop Service-specific TFF models, as well as provide the conceptual foundation for a follow-on article about TFF metrics for units.
Optical microscopy has played a critical role for discovery in biomedical sciences since Hookes introduction of the compound microscope. Recent years have witnessed explosive growth in optical microscopy tools and techniques. Information in microscopy is garnered through contrast mechanisms, usually absorption, scattering, or phase shifts introduced by spatial structure in the sample. The emergence of nonlinear optical contrast mechanisms reveals new information from biological specimens. However, the intensity dependence of nonlinear interactions leads to weak signals, preventing the observation of high-speed dynamics in the 3D context of biological samples. Here, we show that for second harmonic generation imaging, we can increase the 3D volume imaging speed from sub-Hertz speeds to rates in excess of 1,500 volumes imaged per second. This transformational capability is possible by exploiting coherent scattering of second harmonic light from an entire specimen volume, enabling new observational capabilities in biological systems.
Planar plasmonic devices are becoming attractive for myriad applications, owing to their potential compatibility with standard microelectronics technology and the capability for densely integrating a large variety of plasmonic devices on a chip. Mitigating the challenges of using plasmonics in on-chip configurations requires precise control over the properties of plasmonic modes, in particular their shape and size. Here we achieve this goal by demonstrating a planar plasmonic graded-index lens focusing surface plasmons propagating along the device. The plasmonic mode is manipulated by carving subwavelength features into a dielectric layer positioned on top of a uniform metal film, allowing the local effective index of the plasmonic mode to be controlled using a single binary lithographic step. Focusing and divergence of surface plasmons is demonstrated experimentally. The demonstrated approach can be used for manipulating the propagation of surface plasmons, e.g., for beam steering, splitting, cloaking, mode matching, and beam shaping applications.
Addition of one equivalent of selenium to a germanium-phosphanide complex results in insertion of selenium into the Ge-P bond, not oxidation at germanium or phosphorus. Addition of excess selenium results in oxidation at phosphorus, although of germanium oxidation is still observed.
A bioinformatics survey of about 120 protist and 240 fungal genomes and transcriptomes revealed a broad array of globins, representing five of the eight subfamilies identified in bacteria. Most conspicuous is the absence of protoglobins and globin-coupled sensors, except for a two-domain globin in Leishmanias, that comprises a nucleotidyl cyclase domain, and the virtual absence of truncated group 3 globins. In contrast to bacteria, co-occurrence of more than two globin subfamilies appears to be rare in protists. Although globins were lacking in the Apicomplexa and the Microsporidia intracellular pathogens, they occurred in the pathogenic Trypanosomatidae, Stramenopiles and certain fungi. Flavohaemoglobins (FHbs) and related single-domain globins occur across the protist groups. Fungi are unique in having FHbs co-occurring with sensor single-domain globins (SSDgbs). Obligately biotrophic fungi covered in our analysis lack globins. Furthermore, SSDgbs occur only in a heterolobosean amoeba, Naegleria and the stramenopile Hyphochytrium. Of the three subfamilies of truncated Mb-fold globins, TrHb1s appear to be the most widespread, occurring as multiple copies in chlorophyte and ciliophora genomes, many as multidomain proteins. Although the ciliates appear to have only TrHb1s, the chlorophytes have Mb-like globins and TrHb2s, both closely related to the corresponding plant globins. The presently available number of protist genomes is inadequate to provide a definitive census of their globins. Bayesian molecular analyses of single-domain 3/3 Mb-fold globins suggest a close relationship of chlorophyte and haptophyte globins, including choanoflagellate and Capsaspora globins to land plant symbiotic and non-symbiotic haemoglobins and to vertebrate neuroglobins.
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm) is a severe cattle disease, present in many countries in sub-Saharan Africa. The development of improved diagnostic tests and vaccines for CBPP control remains a research priority. Polyacrylamide gel electrophoresis and mass spectrometry were used to characterize the Triton X-114 soluble proteome of nine Mmm strains isolated from Europe or Africa. Of a total of 250 proteins detected, 67 were present in all strains investigated. Of these, 44 were predicted to be lipoproteins or cytoplasmic membrane-associated proteins and are thus likely to be members of the core in vitro surface membrane-associated proteome of Mmm. Moreover, the presence of all identified proteins in other ruminant Mycoplasma pathogens were investigated. Two proteins of the core proteome were identified only in other cattle pathogens of the genus Mycoplasma pointing towards a role in host-pathogen interactions. The data generated will facilitate the identification and prioritization of candidate Mycoplasma antigens for improved control measures, as it is likely that surface-exposed membrane proteins will include those that are involved in host-pathogen interactions.
A growing literature considers whether animals have capacities that are akin to human metacognition (i.e., humans capacity to monitor their states of uncertainty and knowing). Comparative psychologists have approached this question by testing a dolphin, pigeons, rats, monkeys, and apes using perception, memory, and food-concealment paradigms. As part of this consideration, some associative modelers have attempted to describe animals "metacognitive" performances in low-level, associative terms-an important goal if achievable. The authors summarize the empirical and theoretical situation regarding these associative descriptions. The associative descriptions in the animal-metacognition literature fail to encompass important phenomena. The sharp focus on abstract, mathematical associative models creates serious interpretative problems. The authors compare these failed associative descriptions with an alternative theoretical approach within contemporary comparative psychology. The alternative approach has the potential to strengthen comparative psychology as an empirical science and integrate it more fully within the mainstream of experimental psychology and cognitive science. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
We report stereolithographic polymer-based fabrication and experimental operation of a microwave X-band cloaking device. The device is a relatively thin (about one wavelength thick) shell of an air-dielectric composite, in which the dielectric component has negligible loss and dispersion. In a finite band (9.7-10.1 GHz), the shell eliminates the shadow and strongly suppresses scattering from a conducting cylinder of six-wavelength diameter for TE-polarized free-space plane waves. The device does not require an immersion liquid or conducting ground planes for its operation. The dielectric constant of the polymer is low enough (?=2.45) to suggest that this cloaking technique would be suitable for higher frequency radiation, including visible light.
Most cultures have respect for and respond positively to individuals who make significant literary contributions to the way that people understand life and society. While the impact of literature may vary widely, those individuals deemed to have added important perspectives through their writing are often elevated to positions of high regard and influence. Thus, their work becomes important to our understanding of the human condition, including the meaning of disability.
Preharvest control of Escherichia coli O157:H7 (STEC O157) may prevent human illness by reducing the presence of STEC O157 throughout the beef production chain. Immunization of cattle with a type III secreted protein vaccine inhibits colonization of cattle with STEC O157 and reduces the probability of fecal shedding and hide contamination. Our objectives were to perform a meta-analysis to estimate efficacy of a three-dose regimen of TTSP vaccine at reducing the presence of STEC O157 in the feces of feedlot cattle and to test factors that might modify vaccine efficacy. Pen-level data (n=184 pens, 1462 cattle) from four randomized controlled vaccine trials conducted from 2002 to 2008 at the University of Nebraska-Lincoln were analyzed. Factors explaining a culture-positive fecal sample were tested in generalized estimating equations logistic regression and log-binomial models. An autoregressive correlation structure was defined to account for clustering of repeated test-periods within block. Clustering or potential confounding by study was accounted for by treating study as a fixed effect. STEC O157 was detected from 661 of 5451 postvaccination fecal samples. The probability to detect STEC O157 postvaccination was 8.4% and 15.8% in vaccinated and unvaccinated cattle, respectively. Interactions between vaccination and (1) study; (2) prevalence of control pens within each time-place cluster; and (3) days from vaccination were not significant or fit poorly with observed data. Adjusting for study, cattle in pens receiving three doses of vaccine were less likely to shed STEC O157 (odds ratio=0.46, p<0.0001). Model-adjusted vaccine efficacy was 48% (95% confidence interval: 0.37-0.57). We concluded that a three-dose regimen type III secreted protein vaccine was efficacious at reducing the probability of detecting STEC O157 in the feces of cattle and that vaccine efficacy was not modified by study or level of prevalence observed in control pens.
Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimers disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.
Axisymmetric radiating and scattering structures whose rotational invariance is broken by non-axisymmetric excitations present an important class of problems in electromagnetics. For such problems, a cylindrical wave decomposition formalism can be used to efficiently obtain numerical solutions to the full-wave frequency-domain problem. Often, the far-field, or Fraunhofer region is of particular interest in scattering cross-section and radiation pattern calculations; yet, it is usually impractical to compute full-wave solutions for this region. Here, we propose a generalization of the Stratton-Chu far-field integral adapted for 2.5D formalism. The integration over a closed, axially symmetric surface is analytically reduced to a line integral on a meridional plane. We benchmark this computational technique by comparing it with analytical Mie solutions for a plasmonic nanoparticle, and apply it to the design of a three-dimensional polarization-insensitive cloak.
Despite reverence afforded the therapeutic relationship construct in occupational therapy, many occupational therapists feel ill equipped to use themselves therapeutically to enhance the relationship with their clients. Furthermore, although occupational therapists often link the strength of the therapeutic relationship to therapy outcomes, related occupational therapy specific research has been limited. According to the psychotherapy literature, the working alliance is one element of the therapeutic relationship which has in fact been linked to therapy outcomes.
Southeast Asias lowland dipterocarp forests experience supra-annual "mast" fruiting and flowering events, in which the majority of trees reproduce simultaneously at irregular intervals, with extensive intervening periods of very low primate food availability. This scarcity of food results in a negative energy balance and a reliance on "fallback foods" in some primate species. By contrast, ombrogenous tropical peat-swamp forests are non-masting, and show lower variability of food availability. We sought to test the influence of fruit availability on primate diet and preference in peat-swamp habitats and assess whether it differs from masting forests. We collected behavioral-dependent feeding data on three adult females in a group of red langurs (Presbytis rubicunda: Colobinae) between January and December 2011 in Sabangau tropical peat-swamp forest, Central Kalimantan, Indonesia, as colobine monkeys are adaptated for folivory, and are therefore generally considered less reliant on temporally variable fruits than monogastric primates. We documented the highest level of granivory recorded to date in colobine monkeys: mean annual diet comprised 76.4% seeds and 7.3% other fruit parts; 7.7% young and 2.5% mature leaves; 2.8% flowers; 2.6% piths, and <1% on other minor food items. Fruit availability was fairly constant throughout the year and fruit parts were consumed at consistently higher levels than expected based on availability, confirming that fruit is preferred. Leaves and flowers were consumed consistently less than expected and thus are not preferred. There were no significant correlations between preferred food availability and consumption of potential fallback foods, suggesting that reliance on fallback foods did not occur in Sabangau during the study period. Furthermore, consumption of fruit was not significantly correlated with its availability. Our findings suggest that the relatively constant availability of fruit in this habitat affords P. rubicunda regular access to a nutritionally superior food, and that reliance on fallback foods is therefore not required.
Neuronal glucose uptake was thought to be independent of insulin, being facilitated by glucose transporters GLUT1 and GLUT3, which do not require insulin signaling. However, it is now known that components of the insulin-mediated glucose uptake pathway, including neuronal insulin synthesis and the insulin-dependent glucose transporter GLUT4, are present in brain tissue, particularly in the hippocampus. There is considerable recent evidence that insulin signaling is crucial to optimal hippocampal function. The physiological basis, however, is not clear. We propose that while noninsulin-dependent GLUT1 and GLUT3 transport is adequate for resting needs, the surge in energy use during sustained cognitive activity requires the additional induction of insulin-signaled GLUT4 transport. We studied hippocampal high-energy phosphate metabolism in eight healthy volunteers, using a lipid infusion protocol to inhibit insulin signaling. Contrary to conventional wisdom, it is now known that free fatty acids do cross the blood-brain barrier in significant amounts. Energy metabolism within the hippocampus was assessed during standardized cognitive activity. (31)Phosphorus magnetic resonance spectroscopy was used to determine the phosphocreatine (PCr)-to-adenosine triphosphate (ATP) ratio. This ratio reflects cellular energy production in relation to concurrent cellular energy expenditure. With lipid infusion, the ratio was significantly reduced during cognitive activity (PCr/ATP 1.0 ± 0.4 compared with 1.4 ± 0.4 before infusion, P = 0.01). Without lipid infusion, there was no reduction in the ratio during cognitive activity (PCr/ATP 1.5 ± 0.3 compared with 1.4 ± 0.4, P = 0.57). This provides supporting evidence for a physiological role for insulin signaling in facilitating increased neuronal glucose uptake during sustained cognitive activity. Loss of this response, as may occur in type 2 diabetes, would lead to insufficient neuronal energy availability during cognitive activity.
In this concept, we present the basic assumptions and techniques underlying the hydrodynamic model of electron response in metals and demonstrate that the model can be easily incorporated into computational models. We discuss the role of the additional boundary conditions that arise due to nonlocal terms in the modified equation of motion and the ultimate impact on nanoplasmonic systems. The hydrodynamic model captures much of the microscopic dynamics relating to the fundamental quantum mechanical nature of the electrons and reveals intrinsic limitations to the confinement and enhancement of light around nanoscale features. The presence of such limits is investigated numerically for different configurations of plasmonic nanostructures.
Because of the large-scale destruction of Borneos rainforests on mineral soils, tropical peat-swamp forests (TPSFs) are increasingly essential for conserving remnant biodiversity, particularly in the lowlands where the majority of habitat conversion has occurred. Consequently, effective strategies for biodiversity conservation are required, which rely on accurate population density and distribution estimates as a baseline. We sought to establish the first population density estimates of the endemic red langur (Presbytis rubicunda) in Sabangau TPSF, the largest remaining contiguous lowland forest-block on Borneo. Using Distance sampling principles, we conducted line transect surveys in two of Sabangaus three principle habitat sub-classes and calculated group density at 2.52 groups km?² (95% CI 1.56-4.08) in the mixed-swamp forest sub-class. Based on an average recorded group size of 6.95 individuals, population density was 17.51 ind km?², the second highest density recorded in this species. The accessible area of the tall-interior forest, however, was too disturbed to yield density estimates representative of the entire sub-class, and P. rubicunda was absent from the low-pole forest, likely as a result of the low availability of the species preferred foods. This absence in 30% of Sabangaus total area indicates the importance of in situ population surveys at the habitat-specific level for accurately informing conservation strategies. We highlight the conservation value of TPSFs for P. rubicunda given the high population density and large areas remaining, and recommend 1) quantifying the response of P. rubicunda to the logging and burning of its habitats; 2) surveying degraded TPSFs for viable populations, and 3) effectively delineating TPSF sub-class boundaries from remote imagery to facilitate population estimates across the wider peat landscape, given the stark contrast in densities found across the habitat sub-classes of Sabangau.
When both electric and magnetic mechanisms contribute to a particular nonlinear optical process, there exists the possibility for nonlinear interference, often characterized by constructive or destructive interference in the radiation pattern of harmonics and mix waves. However, observation of a significant effect from nonlinear interference requires careful balancing of the various contributions. For this purpose, we propose an artificial metamaterial, using the formalism of nonlinear magnetoelectric coupling to simultaneously engineer the nonlinear polarization and magnetization. We confirm our predictions of nonlinear interference with both simulations and experiment, demonstrating unidirectional wave mixing in two microwave metamaterials. Our results point toward an ever wider range of nonlinear properties, in which nonlinear interference is just one of many potential applications.
Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimers disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG=1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor=1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions ,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.European Journal of Human Genetics advance online publication, 5 June 2013; doi:10.1038/ejhg.2013.116.
By leveraging metamaterials and compressive imaging, a low-profile aperture capable of microwave imaging without lenses, moving parts, or phase shifters is demonstrated. This designer aperture allows image compression to be performed on the physical hardware layer rather than in the postprocessing stage, thus averting the detector, storage, and transmission costs associated with full diffraction-limited sampling of a scene. A guided-wave metamaterial aperture is used to perform compressive image reconstruction at 10 frames per second of two-dimensional (range and angle) sparse still and video scenes at K-band (18 to 26 gigahertz) frequencies, using frequency diversity to avoid mechanical scanning. Image acquisition is accomplished with a 40:1 compression ratio.
Volvocalean green algae have among the most diverse mitochondrial and plastid DNAs (mtDNAs and ptDNAs) from the eukaryotic domain. However, nearly all of the organelle genome data from this group are restricted to unicellular species, like Chlamydomonas reinhardtii, and presently only one multicellular species, the ?4,000-celled Volvox carteri, has had its organelle DNAs sequenced. The V. carteri organelle genomes are repeat rich, and the ptDNA is the largest plastome ever sequenced. Here, we present the complete mtDNA and ptDNA of the colonial volvocalean Gonium pectorale, which is comprised of ?16 cells and occupies a phylogenetic position closer to that of V. carteri than C. reinhardtii within the volvocine line. The mtDNA and ptDNA of G. pectorale are circular-mapping AT-rich molecules with respective lengths and coding densities of 16 and 222.6 kilobases and 73 and 44%. They share some features with the organelle DNAs of V. carteri, including palindromic repeats within the plastid compartment, but show more similarities with those of C. reinhardtii, such as a compact mtDNA architecture and relatively low organelle DNA intron contents. Overall, the G. pectorale organelle genomes raise several interesting questions about the origin of linear mitochondrial chromosomes within the Volvocales and the relationship between multicellularity and organelle genome expansion.
The development of disease-modifying therapies for Alzheimers disease is hampered by our lack of understanding of the early pathogenic mechanisms and the lack of early biomarkers and risk factors.We have documented the expression pattern of mTOR regulated genes in the frontal cortex of Alzheimers disease patients. We have also examined the functional integrity of mTOR signaling in peripheral lymphocytes in Alzheimers disease patients relative to healthy controls.
Lawsonia intracellularis is the etiological agent of proliferative enteropathy (PE), causing mild or acute hemorrhagic diarrhea in infected animals. Here we report the genome sequence of strain N343, isolated from a sow that died of hemorrhagic PE. N343 contains 24 single nucleotide polymorphisms and 90 indels compared to the reference strain PHE/MN1-00.
Microsporidia from the Encephalitozoonidae are obligate intracellular parasites with highly conserved and compacted nuclear genomes: they have few introns, short intergenic regions, and almost identical gene complements and chromosome arrangements. Comparative genomics of Encephalitozoon and microsporidia in general have focused largely on the genomic diversity between different species, and we know very little about the levels of genetic diversity within species. Polymorphism studies with Encephalitozoon are so far restricted to a small number of genes, and a few genetically distinct strains have been identified; most notably, three genotypes (ECI, ECII, and ECIII) of the model species E. cuniculi have been identified based on variable repeats in the rRNA internal transcribed spacer (ITS). To determine if E. cuniculi genotypes are genetically distinct lineages across the entire genome and at the same time to examine the question of intraspecies genetic diversity in microsporidia in general, we sequenced de novo genomes from each of the three genotypes and analyzed patterns of single nucleotide polymorphisms (SNPs) and insertions/deletions across the genomes. Although the strains have almost identical gene contents, they harbor large numbers of SNPs, including numerous nonsynonymous changes, indicating massive intraspecies variation within the Encephalitozoonidae. Based on this diversity, we conclude that the recognized genotypes are genetically distinct and propose new molecular markers for microsporidian genotyping.
We demonstrate the design, fabrication and characterization of an artificially structured, gradient index metamaterial with a linear index variation of ?n ~ 3.0. The linear gradient profile is repeated periodically to form the equivalent of a blazed grating, with the gradient occurring across a spatial distance of 61 ?m. The grating, which operates at a wavelength of 10.6 ?m, is composed of non-resonant, progressively modified "I-beam" metamaterial elements and approximates a linear phase shift gradient using 61 distinguishable phase levels. The grating structure consists of four layers of lithographically patterned metallic I-beam elements separated by dielectric layers of SiO(2). The index gradient is confirmed by comparing the measured magnitudes of the -1, 0 and +1 diffracted orders to those obtained from full wave simulations incorporating all material properties of the metals and dielectrics of the structures. The large index gradient has the potential to enable compact infrared diffractive and gradient index optics, as well as more exotic transformation optical media.
Current theories of human categorization differentiate an explicit, rule-based system of category learning from an implicit system that slowly associates regions of perceptual space with response outputs. The researchers extended this theoretical differentiation to the category learning of New World primates. Four capuchins (Cebus apella) learned categories of circular sine-wave gratings that varied in bar spatial frequency and orientation. The rule-based and information-integration tasks, respectively, had one-dimensional and two-dimensional solutions. Capuchins, like humans, strongly dimensionalized the stimuli and learned the rule-based task more easily. The results strengthen the suggestion that nonhuman primates have some structural components of humans capacity for explicit categorization, which in humans is linked to declarative cognition and consciousness. The results also strengthen the primate contrast to other vertebrate species that may lack the explicit system. Therefore, the results raise important questions about the origins of the explicit categorization system during cognitive evolution and about its overall phylogenetic distribution.
Research in non-human animal (hereafter, animal) cognition has found strong evidence that some animal species are capable of meta-cognitively monitoring their mental states. They know when they know and when they do not know. In contrast, animals have generally not shown robust theory of mind (ToM) capabilities. Comparative research uses methods that are non-verbal, and thus might easily be labelled implicit using the terminology of traditional human cognition. However, comparative psychology has developed several non-verbal methods that are designed to test for aspects of meta-cognition that - while perhaps not fully explicit - go beyond the merely implicit or associative. We believe similar methods might be useful to developmental researchers who work with young children, and may provide a sound empirical alternative to verbal reports. Comparative psychology has moved away from all-or-none categorical labels (e.g., implicit vs. explicit) towards a theoretical framework that contains a spectrum of mental abilities ranging from implicit to explicit, and from associative to cognitive to fully conscious. We discuss how this same framework might be applied to developmental psychology when it comes to implicit versus explicit processing and ToM.
Using a finite-element, full-wave modeling approach, we present a flexible method of analyzing and simulating dielectric and plasmonic waveguide structures as well as their mode coupling. This method is applied to an integrated plasmonic circuit where a straight dielectric waveguide couples through a straight hybrid long-range plasmon waveguide to a uniformly bent hybrid one. The hybrid waveguide comprises a thin metal core embedded in a two-dimensional dielectric waveguide. The performance of such plasmonic circuits in terms of insertion losses is discussed.
Circulating vitamin B(12) (cobalamin/B(12)) and total transcobalamin (tTC) have been associated with increased and reduced risk, respectively, of prostate cancer. Mendelian randomization has the potential to determine whether these are causal associations. We estimated associations of single nucleotide polymorphisms in B(12)-related genes (MTR, MTRR, FUT2, TCN2, TCN1, CUBN, and MUT) with plasma concentrations of B(12), tTC, holo-transcobalamin, holo-haptocorrin, folate, and homocysteine and with prostate cancer risk in a case-control study (913 cases, 895 controls) nested within the UK-wide population-based ProtecT study of prostate cancer in men age 45-69 years. Instrumental variable (IV) analysis was used to estimate odds ratios for effects of B(12) and tTC on prostate cancer. We observed that B(12) was lower in men with FUT2 204G>A (rs492602), CUBN 758C>T (rs1801222) and MUT 1595G>A (rs1141321) alleles (P(trend)<0.001); tTC was lower in men with the TCN2 776C>G (rs1801198) allele (P(trend)<0.001). FUT2 204G>A and CUBN 758C>T were selected as instruments for B(12); TCN2 776C>G for tTC. Conventional and IV estimates for the association of log(e)(B(12)) with prostate cancer were: OR=1.17 (95% CI 0.90-1.51), P=0.2 and OR=0.60 (0.16-2.15), P=0.4, respectively. Conventional and IV estimates for the association of loge(tTC) with prostate cancer were: OR=0.81 (0.54-1.20), P=0.3 and OR=0.41 (0.13-1.32), P=0.1, respectively. Confidence intervals around the IV estimates in our study were too wide to allow robust inference. Sample size estimates based on our data indicated that Mendelian randomization in this context requires much larger studies or multiple genetic variants that explain all of the variance in the intermediate phenotype.
The Luneburg lens is a powerful imaging device, exhibiting aberration free focusing for parallel rays incident from any direction. However, its advantages are offset by a focal surface that is spherical and thus difficult to integrate with standard planar detector and emitter arrays. Using the recently developed technique of transformation optics, it is possible to transform the curved focal surface to a flat plane while maintaining the perfect focusing behavior of the Luneburg over a wide field of view. Here we apply these techniques to a lesser-known refractive Luneburg lens and implement the design with a metamaterial composed of a semi-crystalline distribution of holes drilled in a dielectric. In addition, we investigate the aberrations introduced by various approximations made in the implementation of the lens. The resulting design approach has improved mechanical strength with small aberrations and is ideally suited to implementation at infrared and visible wavelengths.
Altered glucose metabolism has been described in Alzheimers disease (AD). We re-investigated the interaction of the insulin (INS) and the peroxisome proliferator-activated receptor alpha (PPARA) genes in AD risk in the Epistasis Project, including 1,757 AD cases and 6,294 controls. Allele frequencies of both SNPs (PPARA L162V, INS intron 0 A/T) differed between Northern Europeans and Northern Spanish. The PPARA 162LL genotype increased AD risk in Northern Europeans (p = 0.04), but not in Northern Spanish (p = 0.2). There was no association of the INS intron 0 TT genotype with AD. We observed an interaction on AD risk between PPARA 162LL and INS intron 0 TT genotypes in Northern Europeans (Synergy factor 2.5, p = 0.016), but not in Northern Spanish. We suggest that dysregulation of glucose metabolism contributes to the development of AD and might be due in part to genetic variations in INS and PPARA and their interaction especially in Northern Europeans.
Investigation of antigenic determinants of the microaerophilic obligate intracellular bacterium Lawsonia intracellularis using a mass spectrometry approach identified a novel bacterial protein present in an extract of cell culture medium aspirated from heavily infected in vitro cell cultures. Western immunoblotting analysis of SDS-PAGE-resolved proteins using immune sera pooled from L. intracellularis-infected pigs revealed the presence of a strongly immunoreactive band of ? 72 kDa. Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of this component and database mining using a fully annotated L. intracellularis genome sequence and the comprehensive GenBank prokaryotic genomic database highlighted the presence of a protein that shares little sequence similarity with other prokaryotic proteins and appears to be highly species specific. Detailed bioinformatic analyses identified the protein as member of the autotransporter protein family of surface-exposed proteins, and the designation LatA (Lawsonia autotransporter protein A) is suggested. Recognition of recombinant LatA on Western blots by a panel of sera from infected and control pigs corresponded 100% with a commercial serodiagnostic that relies on in vitro culture of this fastidious organism. LatA therefore represents a potential candidate for the development of a rapid and species-specific serodiagnostic reagent.
Chlamydophila abortus is a common cause of ruminant abortion. Here we report the genome sequence of strain LLG, which differs genotypically and phenotypically from the wild-type strain S26/3. Genome sequencing revealed differences between LLG and S26/3 to occur in pseudogene content, in transmembrane head/inc family proteins, and in biotin biosynthesis genes.
We introduce a new concept for the manipulation of fluid flow around three-dimensional bodies. Inspired by transformation optics, the concept is based on a mathematical idea of coordinate transformations and physically implemented with anisotropic porous media permeable to the flow of fluids. In two situations-for an impermeable object placed either in a free-flowing fluid or in a fluid-filled porous medium-we show that the object can be coated with an inhomogeneous, anisotropic permeable medium, such as to preserve the flow that would have existed in the absence of the object. The proposed fluid flow cloak eliminates downstream wake and compensates viscous drag, hinting at the possibility of novel propulsion techniques.
Image and spectral intensity from bicarbonate-selective europium(III) probes localised in the mitochondria of cells is modulated reversibly by variation of external pCO(2), and is suppressed by addition of the carbonic anhydrase inhibitor, acetazolomide.
Nonlinear metamaterials have been predicted to support new and exciting domains in the manipulation of light, including novel phase-matching schemes for wave mixing. Most notable is the so-called nonlinear-optical mirror, in which a nonlinear negative-index medium emits the generated frequency towards the source of the pump. In this Letter, we experimentally demonstrate the nonlinear-optical mirror effect in a bulk negative-index nonlinear metamaterial, along with two other novel phase-matching configurations, utilizing periodic poling to switch between the three phase-matching domains.
Vitamin D may have a role in brain function. Low levels have been frequently associated with cognitive decline and may contribute to diseases of the nervous system. The vitamin D receptor (VDR) is widely expressed in human brain. Vitamin D appears to be neuroprotective and may regulate inflammation in the brain. We examined two VDR polymorphisms, Apa1 and Taq1. We used DNA from 255 Alzheimers disease (AD) cases and 260 cognitively screened elderly controls from the longitudinal cohort of the Oxford Project to Investigate Memory and Ageing (OPTIMA). The presence of each of the linked alleles, Apa1 T and Taq1 G, was associated with the risk of AD, particularly in people <75 years old: odds ratios ?3.0 and p?0.005. We also found preliminary evidence of interactions associated with AD between these polymorphisms and two other genes involved in the regulation of inflammation, interleukin-10 (IL10) and dopamine ?-hydroxylase (DBH): synergy factors ?3.4, uncorrected p<0.05. These associations are biologically plausible and are consistent with a role for vitamin D in AD. Nevertheless, we consider this to be a hypothesis-generating study, which needs to be replicated in a larger dataset.
Cell wall-associated (CWA) proteins made by Gram-positive pathogens play a fundamental role in pathogenesis. Staphylococcus pseudintermedius is a major animal pathogen responsible for the canine skin disease bacterial pyoderma. Here, we describe the bioinformatic analysis of the family of 18 predicted CWA proteins encoded in the genome of S. pseudintermedius strain ED99 and determine their distribution among a phylogenetically diverse panel of S. pseudintermedius clinical isolates and closely related species of the Staphylococcus intermedius group. In parallel, we employed a proteomic approach to identify proteins presented on the surface of strain ED99 in vitro, revealing a total of 60 surface-localized proteins in one or more phases of growth, including 6 of the 18 genome-predicted CWA proteins. Based on these analyses, we selected two CWA proteins (SpsD and SpsL) encoded by all strains examined and investigated their capacity to mediate adherence to extracellular matrix proteins. We discovered that SpsD and SpsL mediated binding of a heterologous host, Lactococcus lactis, to fibrinogen and fibronectin and that SpsD mediated binding to cytokeratin 10, a major constituent of mammalian skin. Of note, the interaction with fibrinogen was host-species dependent, suggestive of a role for SpsD and SpsL in the host tropism of S. pseudintermedius. Finally, we identified IgG specific for SpsD and SpsL in sera from dogs with bacterial pyoderma, implying that both proteins are expressed during infection. The combined genomic and proteomic approach employed in the current study has revealed novel host-pathogen interactions which represent candidate therapeutic targets for the control of bacterial pyoderma.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.