Structure of the Reston ebolavirus VP30 C-terminal domain.

PubMed

Clifton, Matthew C; Kirchdoerfer, Robert N; Atkins, Kateri; Abendroth, Jan; Raymond, Amy; Grice, Rena; Barnes, Steve; Moen, Spencer; Lorimer, Don; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

2014-04-01

The ebolaviruses can cause severe hemorrhagic fever. Essential to the ebolavirus life cycle is the protein VP30, which serves as a transcriptional cofactor. Here, the crystal structure of the C-terminal, NP-binding domain of VP30 from Reston ebolavirus is presented. Reston VP30 and Ebola VP30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface.

SUBTLE: Situation Understanding Bot through Language and Environment

DTIC Science & Technology

2016-01-06

a 4 day “hackathon” by Stuart Young’s small robots group which successfully ported the SUBTLE MURI NLP robot interface to the Packbot platform they...null element restoration, a step typically ig- nored in NLP systems, allows for correct parsing of im- peratives and questions, critical structures

Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ponomarenko, Natalia; Chatziefthimiou, Spyros D.; Kurkova, Inna

2014-03-01

Catalytic antibody variants with κ and λ light-chain constant domains show differences in their crystal structures which lead to subtle changes in catalytic efficiency and thermodynamic parameters as well as in their affinity for peptide substrates. The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was foundmore » that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the V{sub L} and V{sub H} domains. These V{sub L}/V{sub H} domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.« less

Molecular mechanisms of conformational specificity: A study of Hox in vivo target DNA binding specificities and the structure of a Ure2p mutation that affects fibril formation rates

NASA Astrophysics Data System (ADS)

Bauer, William Joseph, Jr.

The fate of an individual cell, or even an entire organism, is often determined by minute, yet very specific differences in the conformation of a single protein species. Very often, proteins take on alternate folds or even side chain conformations to deal with different situations present within the cell. These differences can be as large as a whole domain or as subtle as the alteration of a single amino acid side chain. Yet, even these seemingly minor side chain conformational differences can determine the development of a cell type during differentiation or even dictate whether a cell will live or die. Two examples of situations where minor conformational differences within a specific protein could lead to major differences in the life cycle of a cell are described herein. The first example describes the variations seen in DNA conformations which can lead to slightly different Hox protein binding conformations responsible for recognizing biologically relevant regulatory sites. These specific differences occur in the minor groove of the bound DNA and are limited to the conformation of only two side chains. The conformation of the bound DNA, however, is not solely determined by the sequence of the DNA, as multiple sequences can result in the same DNA conformation. The second example takes place in the context of a yeast prion protein which contains a mutation that decreases the frequency at which fibrils form. While the specific interactions leading to this physiological change were not directly detected, it can be ascertained from the crystal structure that the structural changes are subtle and most likely involve another binding partner. In both cases, these conformational changes are very slight but have a profound effect on the downstream processes.

Raman Spectroscopy Adds Complementary Detail to the High-Resolution X-Ray Crystal Structure of Photosynthetic PsbP from Spinacia oleracea

PubMed Central

Lapkouski, Mikalai; Hofbauerova, Katerina; Sovova, Zofie; Ettrichova, Olga; González-Pérez, Sergio; Dulebo, Alexander; Kaftan, David; Kuta Smatanova, Ivana; Revuelta, Jose L.; Arellano, Juan B.; Carey, Jannette; Ettrich, Rüdiger

2012-01-01

Raman microscopy permits structural analysis of protein crystals in situ in hanging drops, allowing for comparison with Raman measurements in solution. Nevertheless, the two methods sometimes reveal subtle differences in structure that are often ascribed to the water layer surrounding the protein. The novel method of drop-coating deposition Raman spectropscopy (DCDR) exploits an intermediate phase that, although nominally “dry,” has been shown to preserve protein structural features present in solution. The potential of this new approach to bridge the structural gap between proteins in solution and in crystals is explored here with extrinsic protein PsbP of photosystem II from Spinacia oleracea. In the high-resolution (1.98 Å) x-ray crystal structure of PsbP reported here, several segments of the protein chain are present but unresolved. Analysis of the three kinds of Raman spectra of PsbP suggests that most of the subtle differences can indeed be attributed to the water envelope, which is shown here to have a similar Raman intensity in glassy and crystal states. Using molecular dynamics simulations cross-validated by Raman solution data, two unresolved segments of the PsbP crystal structure were modeled as loops, and the amino terminus was inferred to contain an additional beta segment. The complete PsbP structure was compared with that of the PsbP-like protein CyanoP, which plays a more peripheral role in photosystem II function. The comparison suggests possible interaction surfaces of PsbP with higher-plant photosystem II. This work provides the first complete structural picture of this key protein, and it represents the first systematic comparison of Raman data from solution, glassy, and crystalline states of a protein. PMID:23071614

Evolution of Precipitation Structure During the November DYNAMO MJO Event: Cloud-Resolving Model Intercomparison and Cross Validation Using Radar Observations

NASA Astrophysics Data System (ADS)

Li, Xiaowen; Janiga, Matthew A.; Wang, Shuguang; Tao, Wei-Kuo; Rowe, Angela; Xu, Weixin; Liu, Chuntao; Matsui, Toshihisa; Zhang, Chidong

2018-04-01

Evolution of precipitation structures are simulated and compared with radar observations for the November Madden-Julian Oscillation (MJO) event during the DYNAmics of the MJO (DYNAMO) field campaign. Three ground-based, ship-borne, and spaceborne precipitation radars and three cloud-resolving models (CRMs) driven by observed large-scale forcing are used to study precipitation structures at different locations over the central equatorial Indian Ocean. Convective strength is represented by 0-dBZ echo-top heights, and convective organization by contiguous 17-dBZ areas. The multi-radar and multi-model framework allows for more stringent model validations. The emphasis is on testing models' ability to simulate subtle differences observed at different radar sites when the MJO event passed through. The results show that CRMs forced by site-specific large-scale forcing can reproduce not only common features in cloud populations but also subtle variations observed by different radars. The comparisons also revealed common deficiencies in CRM simulations where they underestimate radar echo-top heights for the strongest convection within large, organized precipitation features. Cross validations with multiple radars and models also enable quantitative comparisons in CRM sensitivity studies using different large-scale forcing, microphysical schemes and parameters, resolutions, and domain sizes. In terms of radar echo-top height temporal variations, many model sensitivity tests have better correlations than radar/model comparisons, indicating robustness in model performance on this aspect. It is further shown that well-validated model simulations could be used to constrain uncertainties in observed echo-top heights when the low-resolution surveillance scanning strategy is used.

On the Perception of Religious Group Membership from Faces

PubMed Central

Rule, Nicholas O.; Garrett, James V.; Ambady, Nalini

2010-01-01

Background The study of social categorization has largely been confined to examining groups distinguished by perceptually obvious cues. Yet many ecologically important group distinctions are less clear, permitting insights into the general processes involved in person perception. Although religious group membership is thought to be perceptually ambiguous, folk beliefs suggest that Mormons and non-Mormons can be categorized from their appearance. We tested whether Mormons could be distinguished from non-Mormons and investigated the basis for this effect to gain insight to how subtle perceptual cues can support complex social categorizations. Methodology/Principal Findings Participants categorized Mormons' and non-Mormons' faces or facial features according to their group membership. Individuals could distinguish between the two groups significantly better than chance guessing from their full faces and faces without hair, with eyes and mouth covered, without outer face shape, and inverted 180°; but not from isolated features (i.e., eyes, nose, or mouth). Perceivers' estimations of their accuracy did not match their actual accuracy. Exploration of the remaining features showed that Mormons and non-Mormons significantly differed in perceived health and that these perceptions were related to perceptions of skin quality, as demonstrated in a structural equation model representing the contributions of skin color and skin texture. Other judgments related to health (facial attractiveness, facial symmetry, and structural aspects related to body weight) did not differ between the two groups. Perceptions of health were also responsible for differences in perceived spirituality, explaining folk hypotheses that Mormons are distinct because they appear more spiritual than non-Mormons. Conclusions/Significance Subtle markers of group membership can influence how others are perceived and categorized. Perceptions of health from non-obvious and minimal cues distinguished individuals according to their religious group membership. These data illustrate how the non-conscious detection of very subtle differences in others' appearances supports cognitively complex judgments such as social categorization. PMID:21151864

Probing the electronic and local structural changes across the pressure-induced insulator-to-metal transition in VO2

NASA Astrophysics Data System (ADS)

Marini, C.; Bendele, M.; Joseph, B.; Kantor, I.; Mitrano, M.; Mathon, O.; Baldini, M.; Malavasi, L.; Pascarelli, S.; Postorino, P.

2014-11-01

Local and electronic structures of vanadium in \\text{VO}2 are studied across the high-pressure insulator-to-metal (IMT) transition using V K-edge x-ray absorption spectroscopy. Unlike the temperature-induced IMT, pressure-induced metallization leads to only subtle changes in the V K-edge prepeak structure, indicating a different mechanism involving smaller electronic spectral weight transfer close to the chemical potential. Intriguingly, upon application of the hydrostatic pressure, the electronic structure begins to show substantial changes well before the occurrence of the IMT and the associated structural transition to an anisotropic compression of the monoclinic metallic phase.

Culture Wires the Brain: A Cognitive Neuroscience Perspective

PubMed Central

Park, Denise C.; Huang, Chih-Mao

2012-01-01

There is clear evidence that sustained experiences may affect both brain structure and function. Thus, it is quite reasonable to posit that sustained exposure to a set of cultural experiences and behavioral practices will affect neural structure and function. The burgeoning field of cultural psychology has often demonstrated the subtle differences in the way individuals process information—differences that appear to be a product of cultural experiences. We review evidence that the collectivistic and individualistic biases of East Asian and Western cultures, respectively, affect neural structure and function. We conclude that there is limited evidence that cultural experiences affect brain structure and considerably more evidence that neural function is affected by culture, particularly activations in ventral visual cortex—areas associated with perceptual processing. PMID:22866061

Subtle In-Scanner Motion Biases Automated Measurement of Brain Anatomy From In Vivo MRI

PubMed Central

Alexander-Bloch, Aaron; Clasen, Liv; Stockman, Michael; Ronan, Lisa; Lalonde, Francois; Giedd, Jay; Raznahan, Armin

2016-01-01

While the potential for small amounts of motion in functional magnetic resonance imaging (fMRI) scans to bias the results of functional neuroimaging studies is well appreciated, the impact of in-scanner motion on morphological analysis of structural MRI is relatively under-studied. Even among “good quality” structural scans, there may be systematic effects of motion on measures of brain morphometry. In the present study, the subjects’ tendency to move during fMRI scans, acquired in the same scanning sessions as their structural scans, yielded a reliable, continuous estimate of in-scanner motion. Using this approach within a sample of 127 children, adolescents, and young adults, significant relationships were found between this measure and estimates of cortical gray matter volume and mean curvature, as well as trend-level relationships with cortical thickness. Specifically, cortical volume and thickness decreased with greater motion, and mean curvature increased. These effects of subtle motion were anatomically heterogeneous, were present across different automated imaging pipelines, showed convergent validity with effects of frank motion assessed in a separate sample of 274 scans, and could be demonstrated in both pediatric and adult populations. Thus, using different motion assays in two large non-overlapping sets of structural MRI scans, convergent evidence showed that in-scanner motion—even at levels which do not manifest in visible motion artifact—can lead to systematic and regionally specific biases in anatomical estimation. These findings have special relevance to structural neuroimaging in developmental and clinical datasets, and inform ongoing efforts to optimize neuroanatomical analysis of existing and future structural MRI datasets in non-sedated humans. PMID:27004471

Continuing the conversation in nursing on race and racism.

PubMed

Hall, Joanne M; Fields, Becky

2013-01-01

Nursing values include diversity and a commitment to the elimination of health disparities. However, nursing comprises predominantly white, female nurses. The authors explore structural and interpersonal sources of disparities experienced by black persons, including white privilege. Here, the authors advocate for a continuation of the racism conversation, specifically among white nurses. Racial disadvantages stem from structural inequalities from daily slights, and usually unintended subtle racism toward black people on the part of white people, including white nurses. By raising consciousness on how we propagate subtle racism, nursing can progress faster in eliminating health disparities. Topics include postracialism, colorblindness, institutional racism, white privilege, health disparities, clinical encounters, subtle racism, and racial microaggressions. Suggestions for open dialogue, historical awareness, education, research, and practice are highlighted. Difficulties involved in confronting racism and white privilege are explored. Copyright © 2013 Elsevier Inc. All rights reserved.

Overt and Subtle Racial Discrimination and Mental Health: Preliminary Findings for Korean Immigrants

PubMed Central

Noh, Samuel; Kaspar, Violet; Wickrama, K.A.S.

2007-01-01

Objectives. We examined differential effects of overt and subtle forms of racial discrimination on 2 dimensions of mental health—positive affect and depressive symptoms, and explored the mediating roles of emotional arousal and cognitive appraisal. Methods. Cross-sectional survey data were collected through face-to-face interviews with a sample (N=180) of adult Korean immigrants living in Toronto, Ontario. Maximum likelihood estimates of path coefficients were obtained using structural equation models. Results. Perceived racial discrimination was associated with both the erosion of positive affect and depressive symptoms. Overt discrimination was associated with the erosion of positive affect, and subtle discrimination was associated with depressive symptoms. Effects of subtle discrimination on depressive symptoms were mediated through cognitive appraisal. Conclusions. The results emphasize the salience of subtle discrimination for the mental health of Asian immigrants. Experiences of overt racial bias seemed to be of little importance for the levels of depressive symptoms among those in our sample, although the experience of blatant discrimination tended to reduce positive mood. PMID:17538066

Small differences in amylopectin fine structure may explain large functional differences of starch.

PubMed

Bertoft, Eric; Annor, George A; Shen, Xinyu; Rumpagaporn, Pinthip; Seetharaman, Koushik; Hamaker, Bruce R

2016-04-20

Four amylose-free waxy rice starches were found to give rise to gels with clearly different morphology after storage for seven days at 4°C. The thermal and rheological properties of these gels were also different. This was remarkable in light of the subtle differences in the molecular structure of the amylopectin in the samples. Addition of iodine to the amylopectin samples suggested that not only external chains, but also the internal chains of amylopectin, could form helical inclusion complexes. It is suggested that these internal helical segments participate in the retrogradation of amylopectin, thereby stabilising the gels through double helical structures with external chains of adjacent molecules. Albeit few in number, such interactions appear to have important influences on starch functional properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expression of Glycosaminoglycan Epitopes During Zebrafish Skeletogenesis

PubMed Central

Hayes, Anthony J; Mitchell, Ruth E; Bashford, Andrew; Reynolds, Scott; Caterson, Bruce; Hammond, Chrissy L

2013-01-01

Background: The zebrafish is an important developmental model. Surprisingly, there are few studies that describe the glycosaminoglycan composition of its extracellular matrix during skeletogenesis. Glycosaminoglycans on proteoglycans contribute to the material properties of musculo skeletal connective tissues, and are important in regulating signalling events during morphogenesis. Sulfation motifs within the chain structure of glycosaminoglycans on cell-associated and extracellular matrix proteoglycans allow them to bind and regulate the sequestration/presentation of bioactive signalling molecules important in musculo-skeletal development. Results: We describe the spatio-temporal expression of different glycosaminoglycan moieties during zebrafish skeletogenesis with antibodies recognising (1) native sulfation motifs within chondroitin and keratan sulfate chains, and (2) enzyme-generated neoepitope sequences within the chain structure of chondroitin sulfate (i.e., 0-, 4-, and 6-sulfated isoforms) and heparan sulfate glycosaminoglycans. We show that all the glycosaminoglycan moieties investigated are expressed within the developing skeletal tissues of larval zebrafish. However, subtle changes in their patterns of spatio-temporal expression over the period examined suggest that their expression is tightly and dynamically controlled during development. Conclusions: The subtle differences observed in the domains of expression between different glycosaminoglycan moieties suggest differences in their functional roles during establishment of the primitive analogues of the skeleton. Developmental Dynamics 242:778–789, 2013. © 2013 Wiley Periodicals, Inc. Key Findings The developing zebrafish skeleton expresses many different glycosaminoglycan modifications. Multiple different glycosaminoglycan epitopes are dynamically expressed in the craniofacial skeleton. Expression of chondroitin sulfate moieties are dynamically expressed in the vertebral column and precede mineralisation. PMID:23576310

Physiology modulates social flexibility and collective behaviour in equids and other large ungulates.

PubMed

Gersick, Andrew S; Rubenstein, Daniel I

2017-08-19

Though morphologically very similar, equids across the extant species occupy ecological niches that are surprisingly non-overlapping. Occupancy of these distinct niches appears related to subtle physiological and behavioural adaptations which, in turn, correspond to significant differences in the social behaviours and emergent social systems characterizing the different species. Although instances of intraspecific behavioural variation in equids demonstrate that the same body plan can support a range of social structures, each of these morphologically similar species generally shows robust fidelity to its evolved social system. The pattern suggests a subtle relationship between physiological phenotypes and behavioural flexibility. While environmental conditions can vary widely within relatively short temporal or spatial scales, physiological changes and changes to the behaviours that regulate physiological processes, are constrained to longer cycles of adaptation. Physiology is then the limiting variable in the interaction between ecological variation and behavioural and socio-structural flexibility. Behavioural and socio-structural flexibility, in turn, will generate important feedbacks that will govern physiological function, thus creating a coupled web of interactions that can lead to changes in individual and collective behaviour. Longitudinal studies of equid and other large-bodied ungulate populations under environmental stress, such as those discussed here, may offer the best opportunities for researchers to examine, in real time, the interplay between individual behavioural plasticity, socio-structural flexibility, and the physiological and genetic changes that together produce adaptive change.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

Identifying Structural Flow Defects in Disordered Solids Using Machine-Learning Methods

NASA Astrophysics Data System (ADS)

Cubuk, E. D.; Schoenholz, S. S.; Rieser, J. M.; Malone, B. D.; Rottler, J.; Durian, D. J.; Kaxiras, E.; Liu, A. J.

2015-03-01

We use machine-learning methods on local structure to identify flow defects—or particles susceptible to rearrangement—in jammed and glassy systems. We apply this method successfully to two very different systems: a two-dimensional experimental realization of a granular pillar under compression and a Lennard-Jones glass in both two and three dimensions above and below its glass transition temperature. We also identify characteristics of flow defects that differentiate them from the rest of the sample. Our results show it is possible to discern subtle structural features responsible for heterogeneous dynamics observed across a broad range of disordered materials.

Conceptual structure modulates structural priming in the production of complex sentences

PubMed Central

Griffin, Zenzi M.; Weinstein-Tull, Justin

2016-01-01

Speakers tend to reproduce syntactic structures that they have recently comprehended or produced. This structural or syntactic priming occurs despite differences in the particular conceptual or event roles expressed in prime and target sentences (Bock & Loebell, 1990). In two sentence recall studies, we used the tendency of speakers to paraphrase the finite complements of object-raising verbs as infinitive complements (e.g., “John believed that Mary was nice” as “John believed Mary to be nice”) to test whether an additional conceptual role would affect priming. Prime constructions with identical constituent orders as object-raising infinitives but an additional conceptual role (“John persuaded Mary to be nice”) resulted in fewer paraphrases. Contrasts with other constructions suggest that the critical difference between primes was this extra conceptual role. Thus, subtle differences in conceptual structures can affect how speakers grammatically encode message elements. PMID:28066128

Culture Wires the Brain: A Cognitive Neuroscience Perspective.

PubMed

Park, Denise C; Huang, Chih-Mao

2010-07-01

There is clear evidence that sustained experiences may affect both brain structure and function. Thus, it is quite reasonable to posit that sustained exposure to a set of cultural experiences and behavioral practices will affect neural structure and function. The burgeoning field of cultural psychology has often demonstrated the subtle differences in the way individuals process information-differences that appear to be a product of cultural experiences. We review evidence that the collectivistic and individualistic biases of East Asian and Western cultures, respectively, affect neural structure and function. We conclude that there is limited evidence that cultural experiences affect brain structure and considerably more evidence that neural function is affected by culture, particularly activations in ventral visual cortex-areas associated with perceptual processing. © The Author(s) 2010.

Investigating Subtle Colors on Iapetus

NASA Image and Video Library

2015-04-06

NASA Cassini spacecraft stared toward Saturn two-toned moon Iapetus for about a week in early 2015, in a campaign motivated in part to investigate subtle color differences within the moon bright terrain.

Detection of urea-induced internal denaturation of dsDNA using solid-state nanopores.

PubMed

Singer, Alon; Kuhn, Heiko; Frank-Kamenetskii, Maxim; Meller, Amit

2010-11-17

The ability to detect and measure dsDNA thermal fluctuations is of immense importance in understanding the underlying mechanisms responsible for transcription and replication regulation. We describe here the ability of solid-state nanopores to detect sub-nanometer changes in DNA structure as a result of chemically enhanced thermal fluctuations. In this study, we investigate the subtle changes in the mean effective diameter of a dsDNA molecule with 3-5 nm solid-state nanopores as a function of urea concentration and the DNA's AT content. Our studies reveal an increase in the mean effective diameter of a DNA molecule of approximately 0.6 nm at 8.7 M urea. In agreement with the mechanism of DNA local denaturation, we observe a sigmoid dependence of these effects on urea concentration. We find that the translocation times in urea are markedly slower than would be expected if the dynamics were governed primarily by viscous effects. Furthermore, we find that the sensitivity of the nanopore is sufficient to statistically differentiate between DNA molecules of nearly identical lengths differing only in sequence and AT content when placed in 3.5 M urea. Our results demonstrate that nanopores can detect subtle structural changes and are thus a valuable tool for detecting differences in biomolecules' environment.

The Human Pelvis: Variation in structure and function during gait

PubMed Central

Lewis, Cara L.; Laudicina, Natalie M.; Khuu, Anne; Loverro, Kari L.

2017-01-01

The shift to habitual bipedalism 4–6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. PMID:28297184

Epitaxially Grown Films of Standing and Lying Pentacene Molecules on Cu(110) Surfaces

PubMed Central

2011-01-01

Here, it is shown that pentacene thin films (30 nm) with distinctively different crystallographic structures and molecular orientations can be grown under essentially identical growth conditions in UHV on clean Cu(110) surfaces. By X-ray diffraction, we show that the epitaxially oriented pentacene films crystallize either in the “thin film” phase with standing molecules or in the “single crystal” structure with molecules lying with their long axes parallel to the substrate. The morphology of the samples observed by atomic force microscopy shows an epitaxial alignment of pentacene crystallites, which corroborates the molecular orientation observed by X-ray diffraction pole figures. Low energy electron diffraction measurements reveal that these dissimilar growth behaviors are induced by subtle differences in the monolayer structures formed by slightly different preparation procedures. PMID:21479111

Whole Proteome Analyses on Ruminiclostridium cellulolyticum Show a Modulation of the Cellulolysis Machinery in Response to Cellulosic Materials with Subtle Differences in Chemical and Structural Properties

PubMed Central

Badalato, Nelly; Guillot, Alain; Sabarly, Victor; Dubois, Marc; Pourette, Nina; Pontoire, Bruno; Robert, Paul; Bridier, Arnaud; Monnet, Véronique; Sousa, Diana Z.; Durand, Sylvie; Mazéas, Laurent; Buléon, Alain; Bouchez, Théodore; Mortha, Gérard

2017-01-01

Lignocellulosic materials from municipal solid waste emerge as attractive resources for anaerobic digestion biorefinery. To increase the knowledge required for establishing efficient bioprocesses, dynamics of batch fermentation by the cellulolytic bacterium Ruminiclostridium cellulolyticum were compared using three cellulosic materials, paper handkerchief, cotton discs and Whatman filter paper. Fermentation of paper handkerchief occurred the fastest and resulted in a specific metabolic profile: it resulted in the lowest acetate-to-lactate and acetate-to-ethanol ratios. By shotgun proteomic analyses of paper handkerchief and Whatman paper incubations, 151 proteins with significantly different levels were detected, including 20 of the 65 cellulosomal components, 8 non-cellulosomal CAZymes and 44 distinct extracytoplasmic proteins. Consistent with the specific metabolic profile observed, many enzymes from the central carbon catabolic pathways had higher levels in paper handkerchief incubations. Among the quantified CAZymes and cellulosomal components, 10 endoglucanases mainly from the GH9 families and 7 other cellulosomal subunits had lower levels in paper handkerchief incubations. An in-depth characterization of the materials used showed that the lower levels of endoglucanases in paper handkerchief incubations could hypothetically result from its lower crystallinity index (50%) and degree of polymerization (970). By contrast, the higher hemicellulose rate in paper handkerchief (13.87%) did not result in the enhanced expression of enzyme with xylanase as primary activity, including enzymes from the “xyl-doc” cluster. It suggests the absence, in this material, of molecular structures that specifically lead to xylanase induction. The integrated approach developed in this work shows that subtle differences among cellulosic materials regarding chemical and structural characteristics have significant effects on expressed bacterial functions, in particular the cellulolysis machinery, resulting in different metabolic patterns and degradation dynamics. PMID:28114419

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

PubMed Central

Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

2012-01-01

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

Electron crystallography reveals that substrate release from the PTS IIC glucose transporter is coupled to a subtle conformational change.

PubMed

Kalbermatter, David; Chiu, Po-Lin; Jeckelmann, Jean-Marc; Ucurum, Zöhre; Walz, Thomas; Fotiadis, Dimitrios

2017-07-01

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a structurally and functionally complex system that mediates sugar uptake in bacteria. Besides several soluble subunits, the glucose-specific PTS includes the integral membrane protein IICB that couples the transmembrane transport of glucose to its phosphorylation. Here, we used electron crystallography of sugar-embedded tubular crystals of the glucose-specific IIC transport domain from Escherichia coli (ecIIC glc ) to visualize the structure of the transporter in the presence and absence of its substrate. Using an in vivo transport assay and binding competition experiments, we first established that, while it transports d-glucose, ecIIC glc does not bind l-glucose. We then determined the projection structure of ecIIC glc from tubular crystals embedded in d- and l-glucose and found a subtle conformational change. From comparison of the ecIIC glc projection maps with crystal structures of other IIC transporters, we can deduce that the transporter adopts an inward-facing conformation, and that the maps in the presence and absence of the substrate reflect the transporter before and after release of the transported glucose into the cytoplasm. The transition associated with substrate release appears to require a subtle structural rearrangement in the region that includes hairpin 1. Copyright © 2017 Elsevier Inc. All rights reserved.

The association between discrimination and health: findings on Russian, Somali and Kurdish origin populations in Finland.

PubMed

Rask, Shadia; Elo, Irma T; Koskinen, Seppo; Lilja, Eero; Koponen, Päivikki; Castaneda, Anu E

2018-06-06

The Second European Union Minorities and Discrimination Survey recently demonstrated widespread discrimination across EU countries, with high discrimination rates observed in countries like Finland. Discrimination is known to negatively impact health, but fewer studies have examined how different types of perceived discrimination are related to health. This study examines (i) the prevalence of different types of perceived discrimination among Russian, Somali and Kurdish origin populations in Finland, and (ii) the association between different types of perceived discrimination (no experiences; subtle discrimination only; overt or subtle and overt discrimination) and health (self-rated health; limiting long-term illness (LLTI) or disability; mental health symptoms). Data are from the Finnish Migrant Health and Wellbeing Study (n = 1795). Subtle discrimination implies reporting being treated with less courtesy and/or treated with less respect than others, and overt discrimination being called names or insulted and/or threatened or harassed. The prevalence of discrimination and the associations between discrimination and health were calculated with predicted margins and logistic regression. Experiences of subtle discrimination were more common than overt discrimination in all the studied groups. Subtle discrimination was reported by 29% of Somali origin persons and 35% Russian and Kurdish origin persons. The prevalence of overt discrimination ranged between 22% and 24%. Experiences of discrimination increased the odds for poor self-reported health, LLTI and mental health symptoms, particularly among those reporting subtle discrimination only. To promote the health of diverse populations, actions against racism and discrimination are highly needed, including initiatives that promote shared belonging.

High-Throughput Biophysical Analysis and Data Visualization of Conformational Stability of an IgG1 Monoclonal Antibody (mAb) After Deglycosylation

PubMed Central

Alsenaidy, Mohammad A.; Kim, Jae Hyun; Majumdar, Ranajoy; Weis, David D.; Joshi, Sangeeta B.; Tolbert, Thomas J.; Middaugh, C. Russell; Volkin, David B.

2013-01-01

The structural integrity and conformational stability of an IgG1 monoclonal antibody (mAb), after partial and complete enzymatic removal of the N-linked Fc glycan, was compared to the untreated mAb over a wide range of temperature (10° to 90°C) and solution pH (3 to 8) using circular dichroism, fluorescence spectroscopy, and static light scattering combined with data visualization employing empirical phase diagrams (EPDs). Subtle to larger stability differences between the different glycoforms were observed. Improved detection of physical stability differences was then demonstrated over narrower pH range (4.0-6.0) using smaller temperature increments, especially when combined with an alternative data visualization method (radar plots). Differential scanning calorimetry and differential scanning fluorimetry were then utilized and also showed an improved ability to detect differences in mAb glycoform physical stability. Based on these results, a two-step methodology was used in which mAb glycoform conformational stability is first screened with a wide variety of instruments and environmental stresses, followed by a second evaluation with optimally sensitive experimental conditions, analytical techniques and data visualization methods. With this approach, high-throughput biophysical analysis to assess relatively subtle conformational stability differences in protein glycoforms is demonstrated. PMID:24114789

Southern high latitude squat lobsters II: description of Uroptychus macquariae sp. nov. from Macquarie Ridge.

PubMed

Schnabel, Kareen E; Burghardt, Ingo; Ahyong, Shane T

2017-11-23

Squat lobsters have only recently been recorded from the Macquarie Ridge, which extends south between New Zealand and Antarctica. Among these, Uroptychus insignis (Henderson, 1885) was recorded for the first time outside the western Indian Ocean, exhibiting only subtle morphological differences. Reexamination of the Macquarie Ridge and Indian Ocean specimens attributed to U. insignis using morphological and molecular data revealed the Macquarie Ridge form to represent a separate species. Subtle but consistent morphological differences are evident and partial CO1 sequence data indicates that the specimens collected on Macquarie Ridge differ from those collected in the Indian Ocean by more than 7%. The Macquarie Ridge species is described herein as Uroptychus macquariae n.sp. Subtle morphological differences between the new species and U. insignis are discussed.

Transverse Resonant Vibration of Non-Bearing Structures Caused by Wind

NASA Astrophysics Data System (ADS)

Jendzelovsky, Norbert; Antal, Roland

2017-10-01

Nowadays, there are increasing use of very thin, subtle and light structures in the field of building constructions. We can find such a structures as part of roofs or design facades. By using these lamellas like, non-bearing structures as a part of architectural design of buildings, it is necessary to consider wind effects on these structures. Subtle structures of this type are prone to vibration in the transverse direction of the wind flow. The fact that the vibration occurs depends on wind parameters (wind velocity, direction of an air flow) and it also depends on the properties of lamella (shape, length, mass, natural frequency, support type). The principal idea of this article is to show susceptibility of lamellae-like structures to transverse resonant vibration caused by the phenomenon called Von Karman effect. Comparison of susceptibility to transverse resonance vibration was analysed on the different shapes of lamellas loaded by different wind speed. Analysis was based on usage of empirically derived equations. Von Karman effect arise from wind flow past an object. Turbulence in the form of vortices are formed at the object and shed into the flowing stream intermittently. The potential problem is that this turbulence can induce vibrations into the lamella itself. In terms of this vibration problem, two frequencies are interesting. Von Karman shedding frequency is the frequency at which the vortices are formed and shed at the object. The vortex-shedding frequency increases with the velocity of the wind flow and decreases with the size of the object. Natural frequency of the object depends on the construction of the lamella itself. Parameters of lamella as a shape, mass, length, elasticity modulus of material and support types are directly involved in the calculation of natural frequency. Worst case scenario in the term of transverse resonant vibration occurs when the natural frequency of lamella is equal to the vortex-shedding frequency. In this case vibration rises and structure can be snapped or deformed permanently. In the long term vibration, fatigue stress can be significant. At the conclusion hazardous wind speed and recommendations for different shapes and parameters of lamellas are shown.

Self-consistent electronic structure of disordered Fe/sub 0. 65/Ni/sub 0. 35/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.D.; Pinski, F.J.; Stocks, G.M.

1985-04-15

We present the results of the first ab initio calculation of the electronic structure of the disordered alloy Fe/sub 0.65/Ni/sub 0.35/. The calculation is based on the multiple-scattering coherent-potential approach (KKR-CPA) and is fully self-consistent and spin polarized. Magnetic effects are included within local-spin-density functional theory using the exchange-correlation function of Vosko--Wilk--Nusair. The most striking feature of the calculation is that electrons of different spins experience different degrees of disorder. The minority spin electrons see a very large disorder, whereas the majority spin electrons see little disorder. Consequently, the minority spin density of states is smooth compared to the verymore » structured majority spin density of states. This difference is due to a subtle balance between exchange splitting and charge neutrality.« less

Self-consistent electronic structure of disordered Fe/sub 0/ /sub 65/Ni/sub 0/ /sub 35/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.D.; Pinski, F.J.; Stocks, G.M.

1984-01-01

We present the results of the first ab-initio calculation of the electronic structure of a disordered Fe/sub 0/ /sub 65/Ni/sub 0/ /sub 35/ alloy. The calculation is based on the multiple-scattering coherent-potential approach (KKR-CPA) and is fully self-consistent and spin-polarized. Magnetic effects are included within local-spin-density functional theory using the exchange-correlation function of Vosko-Wilk-Nusair. The most striking feature of the calculation is that electrons of different spins experience different degrees of disorder. The minority spin electrons see a very large disorder; whereas, the majority spin electrons see little disorder. Consequently, the minority spin density of states is smooth compared tomore » the very structured majority spin density of states. This difference is due to a subtle balance between exchange-splitting and charge neutrality. 15 references, 2 figures.« less

Modulating the single-molecule magnet behaviour in phenoxo-O bridged Dy2 systems via subtle structural variations

NASA Astrophysics Data System (ADS)

Wang, Wen-Min; Zhao, Xiao-Yu; Qiao, Hui; Bai, Li; Han, Hong-Fei; Fang, Ming; Wu, Zhi-Lei; Zou, Ji-Yong

2017-09-01

In search of simple approaches to rationally modulate the single-molecule magnet behaviour in polynuclear lanthanide compound, a new system containing two structurally closely related dinuclear dysprosium complexes, namely [Dy2(hfac)4L2] (1) and [Dy2(hfac)4L‧2] (2) (hfac = hexafluoroacetylacetonate, HL = 2-[4-methylaniline-imino]methyl]-8-hydroxyquinoline and HL' = 2-[(3,4-dimethylaniline)-imino]methyl]-8-hydroxyquinoline), are successfully synthesized and the structure-dependent magnetic properties are investigated. The two Dy2 compounds display only slight variations in the coordination geometries of the center Dy(III) ion but display remarkably different single-molecule magnet behaviors with the anisotropic barriers (ΔE/kB) of 9.91 K for 1 and 20.57 K for 2. The different magnetic relaxation behaviors of the two Dy2 complexes mainly originate from the different chemical environments of the central DyIII ions.

The Human Pelvis: Variation in Structure and Function During Gait.

PubMed

Lewis, Cara L; Laudicina, Natalie M; Khuu, Anne; Loverro, Kari L

2017-04-01

The shift to habitual bipedalism 4-6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. Anat Rec, 300:633-642, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Survey on Security Isolation of Virtualization, Containers, and Unikernels

DTIC Science & Technology

2017-05-01

this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents. Citation of...characteristics is necessary to understand the potential threats. Each of these technologies contains subtle differences in the methodology and...technologies contains subtle differences in the methodology and software architecture to provide secure isolation between guests. All 3 of these

Neural Measures Reveal Implicit Learning during Language Processing.

PubMed

Batterink, Laura J; Cheng, Larry Y; Paller, Ken A

2016-10-01

Language input is highly variable; phonological, lexical, and syntactic features vary systematically across different speakers, geographic regions, and social contexts. Previous evidence shows that language users are sensitive to these contextual changes and that they can rapidly adapt to local regularities. For example, listeners quickly adjust to accented speech, facilitating comprehension. It has been proposed that this type of adaptation is a form of implicit learning. This study examined a similar type of adaptation, syntactic adaptation, to address two issues: (1) whether language comprehenders are sensitive to a subtle probabilistic contingency between an extraneous feature (font color) and syntactic structure and (2) whether this sensitivity should be attributed to implicit learning. Participants read a large set of sentences, 40% of which were garden-path sentences containing temporary syntactic ambiguities. Critically, but unbeknownst to participants, font color probabilistically predicted the presence of a garden-path structure, with 75% of garden-path sentences (and 25% of normative sentences) appearing in a given font color. ERPs were recorded during sentence processing. Almost all participants indicated no conscious awareness of the relationship between font color and sentence structure. Nonetheless, after sufficient time to learn this relationship, ERPs time-locked to the point of syntactic ambiguity resolution in garden-path sentences differed significantly as a function of font color. End-of-sentence grammaticality judgments were also influenced by font color, suggesting that a match between font color and sentence structure increased processing fluency. Overall, these findings indicate that participants can implicitly detect subtle co-occurrences between physical features of sentences and abstract, syntactic properties, supporting the notion that implicit learning mechanisms are generally operative during online language processing.

Molecular differences between deuterated and protonated polystyrenes using reversed-phase high-performance liquid chromatography.

PubMed

Kayillo, Sindy; Gray, Michael J; Shalliker, R Andrew; Dennis, Gary R

2005-05-06

Isotopic substitution is a technique used to highlight particular bonds within a molecule for kinetic, spectroscopic and structure analysis. It is presumed that although some properties such as stretching frequencies will not be the same for substituted analogues, the chemical interactions will not vary appreciably as a function of labelling. Reversed-phase liquid chromatography has been used to demonstrate that there are significant differences between the chromatographic behaviour of a sequence of deuterated and protonated oligomeric polystyrenes. Two-dimensional reversed-phase liquid chromatography was used to show that even the diasteromers of the oligomers (n = 5) have retention mechanisms that are dependent on the subtle changes to the molecular conformation and electronic structure, which are a consequence of deuteration.

The brain map of gait variability in aging, cognitive impairment and dementia. A systematic review

PubMed Central

Tian, Qu; Chastan, Nathalie; Bair, Woei-Nan; Resnick, Susan M.; Ferrucci, Luigi; Studenski, Stephanie A.

2017-01-01

While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia. We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia. In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed. PMID:28115194

Heel-toe running: A new look at the influence of foot strike pattern on impact force.

PubMed

Mercer, John A; Horsch, Sarah

2015-06-01

It is important to understand the factors that influence the impact force observed during running, since the impact force is likely to be related to overuse injuries. The purpose of this study was to compare the impact force during running when participants were instructed to use different foot strike patterns: obvious heel strike (Obvious-HS), subtle heel strike (Subtle-HS), midfoot strike (Mid-FS), and fore foot strike (Fore-FS) patterns. Participants ( n  = 10, 25 ± 5.7 years, 70.2 ± 12.1 kg, 174.6 ± 7.2 cm) completed four foot strike patterns while running over ground: Obvious-HS, Subtle-HS, Mid-FS, and Fore-FS. Speed was controlled between conditions (random order). Vertical ground reaction forces were recorded (1000 Hz) along with the impact force, peak force, and stance time for analysis. A repeated measures analysis of variance was used to compare each variable across foot strike instructions, with post hoc comparisons contrasting Obvious-HS to each of the other conditions. Impact force was influenced by foot strike instructions, with Obvious-HS being greater than Subtle-HS and Fore-FS ( p  < 0.05) but not different from Mid-FS ( p  > 0.05). The peak force was not influenced by foot strike instructions ( p  > 0.05); stance time was longer during Obvious-HS than during Mid-FS or Fore-FS ( p  < 0.05), but not different from Subtle-HS ( p  > 0.05). The unique observation of this study was that impact force was different when participants were instructed to run with either an Obvious-HS or a Subtle-HS at contact. Both these foot strike patterns would have been considered rear foot strike patterns, suggesting that something other than which specific part of the foot strikes the ground initially influenced impact force.

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

PubMed Central

Duning, Thomas; Deppe, Michael; Brand, Eva; Stypmann, Jörg; Becht, Charlotte; Heidbreder, Anna; Young, Peter

2013-01-01

Background The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea. Patients and Methods Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis. Results In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem. Conclusion Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than conventional structural MRI and other advanced MR analyses tools in demonstrating these abnormalities. PMID:23637744

Dehydrogenation of methanol to formaldehyde catalyzed by pristine and defective ceria surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beste, Ariana; Overbury, Steven H.

We have explored the dehydrogenation of methoxy on pristine and defective (111), (100), and (110) ceria surfaces with density functional methods. Methanol conversion is used as a probe reaction to understand structure sensitivity of the oxide catalysis. Differences in reaction selectivity have been observed experimentally as a function of crystallographically exposed faces and degree of reduction. We find that the barrier for carbon-hydrogen cleavage in methoxy is similar for the pristine and defective (111), (100), and (110) surfaces. However, there are large differences in the stability of the surface intermediates on the different surfaces. The variations in experimentally observed productmore » selectivities are a consequence of the interplay between barrier controlled bond cleavage and desorption processes. Ultimately, subtle differences in activation energies for carbon-hydrogen cleavage on the different crystallographic faces of ceria could not be correlated with structural or electronic descriptors.« less

Dehydrogenation of methanol to formaldehyde catalyzed by pristine and defective ceria surfaces

DOE PAGES

Beste, Ariana; Overbury, Steven H.

2016-03-09

We have explored the dehydrogenation of methoxy on pristine and defective (111), (100), and (110) ceria surfaces with density functional methods. Methanol conversion is used as a probe reaction to understand structure sensitivity of the oxide catalysis. Differences in reaction selectivity have been observed experimentally as a function of crystallographically exposed faces and degree of reduction. We find that the barrier for carbon-hydrogen cleavage in methoxy is similar for the pristine and defective (111), (100), and (110) surfaces. However, there are large differences in the stability of the surface intermediates on the different surfaces. The variations in experimentally observed productmore » selectivities are a consequence of the interplay between barrier controlled bond cleavage and desorption processes. Ultimately, subtle differences in activation energies for carbon-hydrogen cleavage on the different crystallographic faces of ceria could not be correlated with structural or electronic descriptors.« less

Dehydrogenation of methanol to formaldehyde catalyzed by pristine and defective ceria surfaces.

PubMed

Beste, Ariana; Overbury, Steven H

2016-04-21

We have explored the dehydrogenation of methoxy on pristine and defective (111), (100), and (110) ceria surfaces with density functional methods. Methanol conversion is used as a probe reaction to understand structure sensitivity of the oxide catalysis. Differences in reaction selectivity have been observed experimentally as a function of crystallographically exposed faces and degree of reduction. We find that the barrier for carbon-hydrogen cleavage in methoxy is similar for the pristine and defective (111), (100), and (110) surfaces. However, there are large differences in the stability of the surface intermediates on the different surfaces. The variations in experimentally observed product selectivities are a consequence of the interplay between barrier controlled bond cleavage and desorption processes. Subtle differences in activation energies for carbon-hydrogen cleavage on the different crystallographic faces of ceria could not be correlated with structural or electronic descriptors.

Sensitivity to differences in the motor origin of drawings: from human to robot.

PubMed

De Preester, Helena; Tsakiris, Manos

2014-01-01

This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of "motor resonance".

Sensitivity to Differences in the Motor Origin of Drawings: From Human to Robot

PubMed Central

De Preester, Helena; Tsakiris, Manos

2014-01-01

This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of “motor resonance”. PMID:25014198

MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies.

PubMed

Raja, Rajikha; Rosenberg, Gary A; Caprihan, Arvind

2018-05-15

Blood-brain barrier (BBB) separates the systemic circulation and the brain, regulating transport of most molecules to protect the brain microenvironment. Multiple structural and functional components preserve the integrity of the BBB. Several imaging modalities are available to study disruption of the BBB. However, the subtle changes in BBB leakage that occurs in vascular cognitive impairment and Alzheimer's disease have been less well studied. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is the most widely adopted non-invasive imaging technique for evaluating BBB breakdown. It is used as a significant marker for a wide variety of diseases with large permeability leaks, such as brain tumors and multiple sclerosis, to more subtle disruption in chronic vascular disease and dementia. DCE-MRI analysis of BBB includes both model-free parameters and quantitative parameters using pharmacokinetic modelling. We review MRI studies of BBB breakdown in dementia. The challenges in measuring subtle BBB changes and the state of the art techniques are initially examined. Subsequently, a systematic review comparing methodologies from recent in-vivo MRI studies is presented. Various factors related to subtle BBB permeability measurement such as DCE-MRI acquisition parameters, arterial input assessment, T 1 mapping and data analysis methods are reviewed with the focus on finding the optimal technique. Finally, the reported BBB permeability values in dementia are compared across different studies and across various brain regions. We conclude that reliable measurement of low-level BBB permeability across sites remains a difficult problem and a standardization of the methodology for both data acquisition and quantitative analysis is required. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Copyright © 2017 Elsevier Ltd. All rights reserved.

ASSESSING HIPPOCAMPAL CHANGES INDICATIVE OF NEUROTOXIC EFFECTS.

EPA Science Inventory

Subtle changes in cognitive function are often the earliest indication of neurotoxic effects in humans. The hippocampus is a large forebrain structure subserving specific kinds of information encoding and consolidation in humans and other animals. Because of it laminar structur...

Expression intensity, gender and facial emotion recognition: Women recognize only subtle facial emotions better than men.

PubMed

Hoffmann, Holger; Kessler, Henrik; Eppel, Tobias; Rukavina, Stefanie; Traue, Harald C

2010-11-01

Two experiments were conducted in order to investigate the effect of expression intensity on gender differences in the recognition of facial emotions. The first experiment compared recognition accuracy between female and male participants when emotional faces were shown with full-blown (100% emotional content) or subtle expressiveness (50%). In a second experiment more finely grained analyses were applied in order to measure recognition accuracy as a function of expression intensity (40%-100%). The results show that although women were more accurate than men in recognizing subtle facial displays of emotion, there was no difference between male and female participants when recognizing highly expressive stimuli. Copyright © 2010 Elsevier B.V. All rights reserved.

Inference of Population Structure using Dense Haplotype Data

PubMed Central

Lawson, Daniel John; Hellenthal, Garrett

2012-01-01

The advent of genome-wide dense variation data provides an opportunity to investigate ancestry in unprecedented detail, but presents new statistical challenges. We propose a novel inference framework that aims to efficiently capture information on population structure provided by patterns of haplotype similarity. Each individual in a sample is considered in turn as a recipient, whose chromosomes are reconstructed using chunks of DNA donated by the other individuals. Results of this “chromosome painting” can be summarized as a “coancestry matrix,” which directly reveals key information about ancestral relationships among individuals. If markers are viewed as independent, we show that this matrix almost completely captures the information used by both standard Principal Components Analysis (PCA) and model-based approaches such as STRUCTURE in a unified manner. Furthermore, when markers are in linkage disequilibrium, the matrix combines information across successive markers to increase the ability to discern fine-scale population structure using PCA. In parallel, we have developed an efficient model-based approach to identify discrete populations using this matrix, which offers advantages over PCA in terms of interpretability and over existing clustering algorithms in terms of speed, number of separable populations, and sensitivity to subtle population structure. We analyse Human Genome Diversity Panel data for 938 individuals and 641,000 markers, and we identify 226 populations reflecting differences on continental, regional, local, and family scales. We present multiple lines of evidence that, while many methods capture similar information among strongly differentiated groups, more subtle population structure in human populations is consistently present at a much finer level than currently available geographic labels and is only captured by the haplotype-based approach. The software used for this article, ChromoPainter and fineSTRUCTURE, is available from http://www.paintmychromosomes.com/. PMID:22291602

Generalized Sheet Transition Conditions for a Metascreen—A Fishnet Metasurface

NASA Astrophysics Data System (ADS)

Holloway, Christopher L.; Kuester, Edward F.

2018-05-01

We used a multiple-scale homogenization method to derive generalized sheet transition conditions (GSTCs) for electromagnetic fields at the surface of a metascreen---a metasurface with a "fishnet" structure. These surfaces are characterized by periodically-spaced arbitrary-shaped apertures in an otherwise relatively impenetrable surface. The parameters in these GSTCs are interpreted as effective surface susceptibilities and surface porosities, which are related to the geometry of the apertures that constitute the metascreen. Finally, we emphasize the subtle but important difference between the GSTCs required for metascreens and those required for metafilms (a metasurface with a "cermet" structure, i.e., an array of isolated (non-touching) scatterers).

Rational protein engineering in action: The first crystal structure of a phenylalanine tRNA synthetase from Staphylococcus haemolyticus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evdokimov, Artem G.; Mekel, Marlene; Hutchings, Kim

2008-07-08

In this article, we describe for the first time the high-resolution crystal structure of a phenylalanine tRNA synthetase from the pathogenic bacterium Staphylococcus haemolyticus. We demonstrate the subtle yet important structural differences between this enzyme and the previously described Thermus thermophilus ortholog. We also explain the structure-activity relationship of several recently reported inhibitors. The native enzyme crystals were of poor quality -- they only diffracted X-rays to 3--5 {angstrom} resolution. Therefore, we have executed a rational surface mutagenesis strategy that has yielded crystals of this 2300-amino acid multidomain protein, diffracting to 2 {angstrom} or better. This methodology is discussed andmore » contrasted with the more traditional domain truncation approach.« less

From bacteria to elephants: Effects of land-use legacies on biodiversity and ecosystem structure in the Serengeti-Mara ecosystem: Chapter 8

USGS Publications Warehouse

Verchot, Louis V.; Ward, Naomi L.; Belnap, Jayne; Bossio, Deborah; Coughenour, Michael; Gibson, John; Hanotte, Olivier; Muchiru, Andrew N.; Phillips, Susan L.; Steven, Blaire; Wall, Diana H.; Reid, Robin S.

2015-01-01

Generally, ecological research has considered the aboveground and belowground components of ecosystems separately. Consequently, frameworks for integrating the two components are not well developed. Integrating the microbial components into ecosystem ecology requires different approaches from those offered by plant ecology, partly because of the scales at which microbial processes operate and partly because of measurement constraints. Studies have begun to relate microbial community structure to ecosystem function. results suggest that excluding people and livestock from the MMNR, or preventing heavier livestock from grazing around settlements, may not change the general structure of the ecosystem (soils, plant structure), but can change the numbers and diversity of wildlife, nematodes and microbes in this ecosystem in subtle ways.

Characterization of Isomeric Glycans by Reversed Phase Liquid Chromatography-Electronic Excitation Dissociation Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Tang, Yang; Wei, Juan; Costello, Catherine E.; Lin, Cheng

2018-04-01

The occurrence of numerous structural isomers in glycans from biological sources presents a severe challenge for structural glycomics. The subtle differences among isomeric structures demand analytical methods that can provide structural details while working efficiently with on-line glycan separation methods. Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool for mixture analysis, the commonly utilized collision-induced dissociation (CID) method often does not generate a sufficient number of fragments at the MS2 level for comprehensive structural characterization. Here, we studied the electronic excitation dissociation (EED) behaviors of metal-adducted, permethylated glycans, and identified key spectral features that could facilitate both topology and linkage determinations. We developed an EED-based, nanoscale, reversed phase (RP)LC-MS/MS platform, and demonstrated its ability to achieve complete structural elucidation of up to five structural isomers in a single LC-MS/MS analysis. [Figure not available: see fulltext.

Structure and Thermodynamics of Polyolefin Melts

NASA Astrophysics Data System (ADS)

Weinhold, J. D.; Curro, J. G.; Habenschuss, A.; Londono, J. D.

1997-03-01

Subtle differences in the intermolecular packing of various polyolefins can create dissimilar permeability and mixing behavior. We have used a combination of the Polymer Reference Interaction Site Model (PRISM) and Monte Carlo simulation to study the structural and thermodynamic properties of realistic models for polyolefins. Results for polyisobutylene and syndiotactic polypropylene will be presented along with comparisons to wide-angle x-ray scattering experiments and properties determined from previous studies of polyethylene and isotactic polypropylene. Our technique uses a Monte Carlo simulation on an isolated molecule to determine the polymer's intramolecular structure. With this information, PRISM theory can predict the intermolecular packing for any liquid density and/or mixture composition in a computationally efficient manner. This approach will then be used to explore the mixing behavior of these polyolefins.

Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.

PubMed

Mason, Emily J; Hussey, Erin P; Molitor, Robert J; Ko, Philip C; Donahue, Manus J; Ally, Brandon A

2017-01-01

Early detection may be the key to developing therapies that will combat Alzheimer's disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40-60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects' medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.

Cooperative hydrogen bonds and mobility of the non-aromatic ring as selectivity determinants for human acetylcholinesterase to similar anti-Alzheimer's galantaminics: a computational study.

PubMed

Rocha, Rafael E O; Lima, Leonardo H F

2018-05-17

Galantamine (Gnt) is a natural alkaloid inhibitor of acetylcholinesterase and is presently one of the most used drugs in the treatment against Alzheimer's disease during both the initial and intermediate stages. Among several natural Gnt derivatives, sanguinine (Sng) and lycoramine (Lyc) attract attention because of the way their subtle chemical differences from Gnt lead to drastic and opposite distinctions in inhibitory effects. However, to date, there is no solved structure for these natural derivatives. In the present study, we applied computational modeling and free energy calculation methods to better elucidate the molecular basis of the subtle distinctions between these derivatives and Gnt. The results showed that differences in the mobility of the non-aromatic ring carried by the Lyc-like sp 2 -sp 3 modification display drastic conformational, vibrational, and entropic penalties at binding compared to Gnt. Additionally, the establishment of a stronger hydrogen bond network added enthalpic advantages for the linkage of the Sng-like methoxy-hydroxy substituted ligands. These results, which suggest an affinity ranking in agreement with that found in the literature, provided insights that are helpful for future planning and development of new anti-Alzheimer's disease drugs.

Structure of the CLC-1 chloride channel from Homo sapiens.

PubMed

Park, Eunyong; MacKinnon, Roderick

2018-05-29

CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

VASP-E: Specificity Annotation with a Volumetric Analysis of Electrostatic Isopotentials

PubMed Central

Chen, Brian Y.

2014-01-01

Algorithms for comparing protein structure are frequently used for function annotation. By searching for subtle similarities among very different proteins, these algorithms can identify remote homologs with similar biological functions. In contrast, few comparison algorithms focus on specificity annotation, where the identification of subtle differences among very similar proteins can assist in finding small structural variations that create differences in binding specificity. Few specificity annotation methods consider electrostatic fields, which play a critical role in molecular recognition. To fill this gap, this paper describes VASP-E (Volumetric Analysis of Surface Properties with Electrostatics), a novel volumetric comparison tool based on the electrostatic comparison of protein-ligand and protein-protein binding sites. VASP-E exploits the central observation that three dimensional solids can be used to fully represent and compare both electrostatic isopotentials and molecular surfaces. With this integrated representation, VASP-E is able to dissect the electrostatic environments of protein-ligand and protein-protein binding interfaces, identifying individual amino acids that have an electrostatic influence on binding specificity. VASP-E was used to examine a nonredundant subset of the serine and cysteine proteases as well as the barnase-barstar and Rap1a-raf complexes. Based on amino acids established by various experimental studies to have an electrostatic influence on binding specificity, VASP-E identified electrostatically influential amino acids with 100% precision and 83.3% recall. We also show that VASP-E can accurately classify closely related ligand binding cavities into groups with different binding preferences. These results suggest that VASP-E should prove a useful tool for the characterization of specific binding and the engineering of binding preferences in proteins. PMID:25166865

Folding a Protein with Equal Probability of Being Helix or Hairpin

PubMed Central

Lin, Chun-Yu; Chen, Nan-Yow; Mou, Chung Yu

2012-01-01

We explore the possibility for the native structure of a protein being inherently multiconformational in an ab initio coarse-grained model. Based on the Wang-Landau algorithm, the complete free energy landscape for the designed sequence 2DX4: INYWLAHAKAGYIVHWTA is constructed. It is shown that 2DX4 possesses two nearly degenerate native structures: one is a helix structure with the other a hairpinlike structure, and their free energy difference is <2% of that of local minima. Two degenerate native structures are stabilized by an energy barrier of ∼10 kcal/mol. Furthermore, the hydrogen-bond and dipole-dipole interactions are found to be two major competing interactions in transforming one conformation into the other. Our results indicate that two degenerate native structures are stabilized by subtle balance between different interactions in proteins. In particular, for small proteins, balance between the hydrogen-bond and dipole-dipole interactions happens for proteins of sizes being ∼18 amino acids and is shown to the main driving mechanism for the occurrence of degeneracy. These results provide important clues to the study of native structures of proteins. PMID:22828336

Efficient subtle motion detection from high-speed video for sound recovery and vibration analysis using singular value decomposition-based approach

NASA Astrophysics Data System (ADS)

Zhang, Dashan; Guo, Jie; Jin, Yi; Zhu, Chang'an

2017-09-01

High-speed cameras provide full field measurement of structure motions and have been applied in nondestructive testing and noncontact structure monitoring. Recently, a phase-based method has been proposed to extract sound-induced vibrations from phase variations in videos, and this method provides insights into the study of remote sound surveillance and material analysis. An efficient singular value decomposition (SVD)-based approach is introduced to detect sound-induced subtle motions from pixel intensities in silent high-speed videos. A high-speed camera is initially applied to capture a video of the vibrating objects stimulated by sound fluctuations. Then, subimages collected from a small region on the captured video are reshaped into vectors and reconstructed to form a matrix. Orthonormal image bases (OIBs) are obtained from the SVD of the matrix; available vibration signal can then be obtained by projecting subsequent subimages onto specific OIBs. A simulation test is initiated to validate the effectiveness and efficiency of the proposed method. Two experiments are conducted to demonstrate the potential applications in sound recovery and material analysis. Results show that the proposed method efficiently detects subtle motions from the video.

Effect of ethnicity on performance in a final objective structured clinical examination: qualitative and quantitative study

PubMed Central

Wass, Val; Roberts, Celia; Hoogenboom, Ron; Jones, Roger; Van der Vleuten, Cees

2003-01-01

Objective To assess the effect of ethnicity on student performance in stations assessing communication skills within an objective structured clinical examination. Design Quantitative and qualitative study. Setting A final UK clinical examination consisting of a two day objective structured clinical examination with 22 stations. Participants 82 students from ethnic minorities and 97 white students. Main outcome measures Mean scores for stations (quantitative) and observations made using discourse analysis on selected communication stations (qualitative). Results Mean performance of students from ethnic minorities was significantly lower than that of white students for stations assessing communication skills on days 1 (67.0% (SD 6.8%) and 72.3% (7.6%); P=0.001) and 2 (65.2% (6.6%) and 69.5% (6.3%); P=0.003). No examples of overt discrimination were found in 309 video recordings. Transcriptions showed subtle differences in communication styles in some students from ethnic minorities who performed poorly. Examiners' assumptions about what is good communication may have contributed to differences in grading. Conclusions There was no evidence of explicit discrimination between students from ethnic minorities and white students in the objective structured clinical examination. A small group of male students from ethnic minorities used particularly poorly rated communicative styles, and some subtle problems in assessing communication skills may have introduced bias. Tests need to reflect issues of diversity to ensure that students from ethnic minorities are not disadvantaged. What is already known on this topicUK medical schools are concerned that students from ethnic minorities may perform less well than white students in examinationsIt is important to understand whether our examination system disadvantages themWhat this study addsMean performance of students from ethnic minorities was significantly lower than that of white students in a final year objective structured clinical examinationTwo possible reasons for the difference were poor communicative performance of a small group of male students from ethnic minorities and examiners' use of a textbook patient centred notion of good communicationIssues of diversity in test construction and implementation must be addressed to ensure that students from ethnic minorities are not disadvantaged PMID:12689978

Olfactory receptor neuron profiling using sandalwood odorants.

PubMed

Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

2004-07-01

The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

The new "new racism" thesis: limited government values and race-conscious policy attitudes.

PubMed

Gainous, Jason

2012-01-01

Some contend that Whites’ application of values to form opinions about race-conscious policy may constitute a subtle form of racism. Others challenge the new racism thesis, suggesting that racism and values are exclusive in their influence. Proponents of the thesis assert that many Whites’ attitudes about such policy are structured by a mix of racism and American individualism. The author suggests that an even more subtle form of racism may exist. Racism may actually be expressed in opposition to big government. The test results presented here indicate that the effects of limited-government values on attitudes about race-conscious policy are conditional on levels of racial prejudice for many Whites, whereas the effects on racially ambiguous social welfare policy attitudes are not. The author contends that these results provide support to the argument that racism still exists and has found a new subtle expression.

Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence

NASA Technical Reports Server (NTRS)

Caviness, V. S. Jr; Takahashi, T.; Nowakowski, R. S.

2000-01-01

Variations in the structure of the neocortex induced by single gene mutations may be extreme or subtle. They differ from variations in neocortical structure encountered across and within species in that these "normal" structural variations are adaptive (both structurally and behaviorally), whereas those associated with disorders of development are not. Here we propose that they also differ in principle in that they represent disruptions of molecular mechanisms that are not normally regulatory to variations in the histogenetic sequence. We propose an algorithm for the operation of the neuronogenetic sequence in relation to the overall neocortical histogenetic sequence and highlight the restriction point of the G1 phase of the cell cycle as the master regulatory control point for normal coordinate structural variation across species and importantly within species. From considerations based on the anatomic evidence from neocortical malformation in humans, we illustrate in principle how this overall sequence appears to be disrupted by molecular biological linkages operating principally outside the control mechanisms responsible for the normal structural variation of the neocortex. MRDD Research Reviews 6:22-33, 2000. Copyright 2000 Wiley-Liss, Inc.

Water: Communicator In Moon-Earth Relationships

NASA Astrophysics Data System (ADS)

Davis, Joan S.

The Moon's myriad effects upon Earth have been objects of fascination, and subjects for literary works and scientific speculation throughout history. Although many of Moon's influences upon Earth involve water, tidal movement is clearly the most readily associated effect. While very obvious, it however represents only one of a multitude of ways in which lunar forces effect this planet, and all life upon it. Much less apparent, though essential for all of life, is the wide spectrum of subtle fluctuating influences upon the water in the cells of living systems. Water's capacity to respond to extremely subtle changes in physical influences (such as gravitational fields), as associated with Moon phases (N.B. also with planetary constellations and sunspot activity), enables it to communicate such inputs to living systems. The periodicity of changes in natural systems has been of interest to man throughout history. However, only in more recent times has insight into water's behaviour led to its being recognised as a link between the periodicities seen in abiotic (Moon and other planetary) systems and biotic systems. Particular attention has long been paid to systematic fluctuations in agriculture and forestry: Different growth patterns are observed in connection with the Moon phases (and zodiac constellations) at planting time; different characteristics (e.g., fire resistance, pliability, firmness, etc.) of wood are seen in trees harvested at different phases and constellations. . The usefulness of such correlations has influenced planting and harvesting patterns in more traditional-oriented agriculture and forestry. Its acceptance by science has, however, been long in coming. The case similar, as regards physiological fluctuations observed in the medical field. A documented case in point is the correlation between the Moon-phase and risk of hemorrhage during surgery: This is one of many observations on periodicity in body functions, which deserve more research attention than they receive. . Direct measurements of physical parameters of water (such as surface tension, solution constants), which respond to subtle influences, such as weak magnetic fields, could concievably benefit insight into the role of water as communicator of `information' to both biotic and abiotic systems. The same approach would apply for research on other sources of subtle influences such as planetary constellations and sunspot activity (N.B. this is well documented in its effects upon aqueous reactions; the eleven year periodicity is clearly recognisable). . In turn, insight into water's role could lead to more recognition and acceptance of such significant, though subtle, effects upon living systems … and with this, a more appropriate consideration of their consequences and their relevance for many of man's activities. . The fact that science has been so reticent to recognize and accept the lunar effects upon the Earth and its inhabitants, is in part due to its insufficient understanding of water. Current research on its structure and its behaviour can help us understand how water can serve as communicator of information between Moon and Earth. And thus also to recognise the significance of the subtle, life-supporting regulation the Moon provides to our planet.

Managing Diversity.

ERIC Educational Resources Information Center

Geber, Beverly

1990-01-01

Demographic trends imply that organizations must learn to manage a diverse work force. Ways to change organizational systems, structures, and practices to eliminate subtle barriers are awareness training, attitude change, and valuing diversity. (SK)

Mega-geomorphology and neotectonics

NASA Technical Reports Server (NTRS)

Lattman, L. H.

1985-01-01

For several decades, subtle neotectonic effects involving several square kilometers have been studied in detail using remote sensing, primarily various types of stereo-aerial photographs at scales of 1:10,000 to 1:80,000. These subtle effects, especially local uplifts associated with growing structures of differential compaction, have been detected by the effect on drainage patterns, changes in hydraulic geometry of individuals channels or groups of channels, tonal halos (soil) and fracture patterns. The studies were extended with the advent of thermal IR imagery particularly in tonal analysis, and SLAR primarily in fracture pattern studies. Lately, quantitative efforts have begun attempting to link measured uplift over known structures with measured changes in hydraulic geometry and alluvial deposition. Thus, efforts are now underway attempting to quantify the relationship between neo- (micro-) tectonic changes and geomorphic parameters of drainage systems.

Geologic interpretation of Seasat SAR imagery near the Rio Lacantum, Mexico

NASA Technical Reports Server (NTRS)

Rebillard, PH.; Dixon, T.

1984-01-01

A mosaic of the Seasat Synthetic Aperture Radar (SAR) optically processed images over Central America is presented. A SAR image of the Rio Lacantum area (southeastern Mexico) has been digitally processed and its interpretation is presented. The region is characterized by low relief and a dense vegetation canopy. Surface is believed to be indicative of subsurface structural features. The Seasat-SAR system had a steep imaging geometry (incidence angle 23 + or - 3 deg off-nadir) which is favorable for detection of subtle topographic variations. Subtle textural features in the image corresponding to surface topography were enhanced by image processing techniques. A structural and lithologic interpretation of the processed images is presented. Lineaments oriented NE-SW dominate and intersect broad folds trending NW-SE. Distinctive karst topography characterizes one high relief area

Crystal Structures of Penicillin-Binding Protein 2 From Penicillin-Susceptible And -Resistant Strains of Neisseria Gonorrhoeae Reveal An Unexpectedly Subtle Mechanism for Antibiotic Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, A.J.; Tomberg, J.; Deacon, A.M.

Penicillin-binding protein 2 (PBP2) from N. gonorrhoeae is the major molecular target for {beta}-lactam antibiotics used to treat gonococcal infections. PBP2 from penicillin-resistant strains of N. gonorrhoeae harbors an aspartate insertion after position 345 (Asp-345a) and 4-8 additional mutations, but how these alter the architecture of the protein is unknown. We have determined the crystal structure of PBP2 derived from the penicillin-susceptible strain FA19, which shows that the likely effect of Asp-345a is to alter a hydrogen-bonding network involving Asp-346 and the SXN triad at the active site. We have also solved the crystal structure of PBP2 derived from themore » penicillin-resistant strain FA6140 that contains four mutations near the C terminus of the protein. Although these mutations lower the second order rate of acylation for penicillin by 5-fold relative to wild type, comparison of the two structures shows only minor structural differences, with the positions of the conserved residues in the active site essentially the same in both. Kinetic analyses indicate that two mutations, P551S and F504L, are mainly responsible for the decrease in acylation rate. Melting curves show that the four mutations lower the thermal stability of the enzyme. Overall, these data suggest that the molecular mechanism underlying antibiotic resistance contributed by the four mutations is subtle and involves a small but measurable disordering of residues in the active site region that either restricts the binding of antibiotic or impedes conformational changes that are required for acylation by {beta}-lactam antibiotics.« less

An evaluation of dynamic mutuality measurements and methods in cyclic time series

NASA Astrophysics Data System (ADS)

Xia, Xiaohua; Huang, Guitian; Duan, Na

2010-12-01

Several measurements and techniques have been developed to detect dynamic mutuality and synchronicity of time series in econometrics. This study aims to compare the performances of five methods, i.e., linear regression, dynamic correlation, Markov switching models, concordance index and recurrence quantification analysis, through numerical simulations. We evaluate the abilities of these methods to capture structure changing and cyclicity in time series and the findings of this paper would offer guidance to both academic and empirical researchers. Illustration examples are also provided to demonstrate the subtle differences of these techniques.

Rapid flow fractionation of particles combining liquid and particulate dielectrophoresis

NASA Technical Reports Server (NTRS)

King, Michael R. (Inventor); Lomakin, Oleg (Inventor); Jones, Thomas B. (Inventor); Ahmed, Rajib (Inventor)

2007-01-01

Rapid, size-based, deposition of particles from liquid suspension is accomplished using a nonuniform electric field created by coplanar microelectrode strips patterned on an insulating substrate. The scheme uses the dielectrophoretic force both to distribute aqueous liquid containing particles and, simultaneously, to separate the particles. Size-based separation is found within nanoliter droplets formed along the structure after voltage removal. Bioparticles or macromolecules of similar size can also be separated based on subtle differences in dielectric property, by controlling the frequency of the AC current supplied to the electrodes.

Anharmonic and Quantum Fluctuations in Molecular Crystals from Ab Initio Simulations

NASA Astrophysics Data System (ADS)

Rossi, Mariana; Gasparotto, Piero; Ceriotti, Michele

Molecular crystals often exist in multiple competing polymorphs which are challenging to be predicted computationally, but show significantly different physicochemical properties. This challenge is not due only to the combinatorial search space, but also to the complex interplay of subtle effects determine the relative stability of different structures. Here we estimate all contributions to the free energies of these systems with density-functional theory, including the oft-neglected anharmonic contributions and nuclear quantum effects, by using a series of different flavors of thermodynamic integration. As an example, for the two most stable forms of paracetamol we find that anharmonic contributions, different descriptions of van der Waals interactions, and nuclear quantum effects all matter to quantitatively determine the stability of different phases. Our studies indicate that anharmonic free energies could play an important role for molecular crystals composed by large molecules and opens the way for a systematic inclusion of these effects in order to obtain a predictive screening of structures.

Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thurman, Ryan D.; Kathir, Karuppanan Muthusamy; Rajalingam, Dakshinamurthy

Highlights: Black-Right-Pointing-Pointer The structural basis of the Kallmann syndrome is elucidated. Black-Right-Pointing-Pointer Kallmann syndrome mutation (A168S) induces a subtle conformational change(s). Black-Right-Pointing-Pointer Structural interactions mediated by beta-sheet G are most perturbed. Black-Right-Pointing-Pointer Ligand (FGF)-receptor interaction(s) is completely abolished by Kallmann mutation. Black-Right-Pointing-Pointer Kallmann mutation directly affects the FGF signaling process. -- Abstract: Kallmann syndrome (KS) is a developmental disease that expresses in patients as hypogonadotropic hypogonadism and anosmia. KS is commonly associated with mutations in the extracellular D2 domain of the fibroblast growth factor receptor (FGFR). In this study, for the first time, the molecular basis for the FGFR associatedmore » KS mutation (A168S) is elucidated using a variety of biophysical experiments, including multidimensional NMR spectroscopy. Secondary and tertiary structural analysis using far UV circular dichroism, fluorescence and limited trypsin digestion assays suggest that the KS mutation induces subtle tertiary structure change in the D2 domain of FGFR. Results of isothermal titration calorimetry experiments show the KS mutation causes a 10-fold decrease in heparin binding affinity and also a complete loss in ligand (FGF-1) binding. {sup 1}H-{sup 15}N chemical perturbation data suggest that complete loss in the ligand (FGF) binding affinity is triggered by a subtle conformational change that disrupts crucial structural interactions in both the heparin and the FGF binding sites in the D2 domain of FGFR. The novel findings reported in this study are expected to provide valuable clues toward a complete understanding of the other genetic diseases linked to mutations in the FGFR.« less

Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

PubMed

Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

2014-01-01

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

Use of the Primitive Unit Cell in Understanding Subtle Features of the Cubic Closest-Packed Structure

ERIC Educational Resources Information Center

Hawkins, John A.; Rittenhouse, Jeffrey L.; Soper, Linda M.; Rittenhouse, Robert C.

2008-01-01

One of the most important crystal structures adopted by metals is characterized by the "abcabc"...stacking of close-packed layers. This structure is commonly referred to in textbooks as the cubic close-packed (ccp) or face-centered cubic (fcc) structure, since the entire lattice can be generated by replication of a face-centered cubic unit cell…

Brief Report: CANTAB Performance and Brain Structure in Pediatric Patients with Asperger Syndrome

ERIC Educational Resources Information Center

Kaufmann, Liane; Zotter, Sibylle; Pixner, Silvia; Starke, Marc; Haberlandt, Edda; Steinmayr-Gensluckner, Maria; Egger, Karl; Schocke, Michael; Weiss, Elisabeth M.; Marksteiner, Josef

2013-01-01

By merging neuropsychological (CANTAB/Cambridge Neuropsychological Test Automated Battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group…

Crystallographic structure refinement with quadrupolar nuclei: a combined solid-state NMR and GIPAW DFT example using MgBr(2).

PubMed

Widdifield, Cory M; Bryce, David L

2009-09-07

Solid-state NMR spectroscopy and GIPAW DFT calculations reveal the pronounced sensitivity of (79/81)Br and (25)Mg quadrupolar coupling constants to subtle aspects of solid state structure which were not previously detected by pXRD methods.

A Study of Cognitive Linguistic Structure Based on the Four Conditions of the Mulamadhyamakakarika

ERIC Educational Resources Information Center

You, Hee Jong

2013-01-01

The main purpose of this study is to depict Nagarjuna's implication on how he redefined the Four Conditions ("atvarah pratyaya") as the cognitive linguistic structure by allocating 32 functional metadata throughout the texts of Mulamadhyamakakarika (MMK). Following subtle traces of "okasamvrtisatya" (the conventional truth) in…

Comparative studies of '1212' superconductors

NASA Astrophysics Data System (ADS)

Gapud, Albert Agcaoili

Several properties of highly isomorphic species of HgBa2CaCu 2O6+delta (Hg-1212) and TlBa2CaCu2O 7-delta (Tl-1212) were compared. The samples used were high-quality, c-oriented thin films with epitaxial growth. In particular, the Hg-1212 films were made from either Tl-2212 or Tl-1212 films using a novel method in which the Tl cations were surgically replaced by Hg cations, during which the 1212 structure was retained. Properties studied were: the irreversibility line, critical current density, the magnetic phase diagram, the normal-state Hall effect, and the mixed-state Hall effect. There are several indications that the most significant difference between the 1212 species is mostly in their superconducting charge carrier density. However, the subtle differences in their electronic band structure may have also been discerned.

Isospin symmetry breaking and large-scale shell-model calculations with the Sakurai-Sugiura method

NASA Astrophysics Data System (ADS)

Mizusaki, Takahiro; Kaneko, Kazunari; Sun, Yang; Tazaki, Shigeru

2015-05-01

Recently isospin symmetry breaking for mass 60-70 region has been investigated based on large-scale shell-model calculations in terms of mirror energy differences (MED), Coulomb energy differences (CED) and triplet energy differences (TED). Behind these investigations, we have encountered a subtle problem in numerical calculations for odd-odd N = Z nuclei with large-scale shell-model calculations. Here we focus on how to solve this subtle problem by the Sakurai-Sugiura (SS) method, which has been recently proposed as a new diagonalization method and has been successfully applied to nuclear shell-model calculations.

Principal coordinate analysis assisted chromatographic analysis of bacterial cell wall collection: A robust classification approach.

PubMed

Kumar, Keshav; Cava, Felipe

2018-04-10

In the present work, Principal coordinate analysis (PCoA) is introduced to develop a robust model to classify the chromatographic data sets of peptidoglycan sample. PcoA captures the heterogeneity present in the data sets by using the dissimilarity matrix as input. Thus, in principle, it can even capture the subtle differences in the bacterial peptidoglycan composition and can provide a more robust and fast approach for classifying the bacterial collection and identifying the novel cell wall targets for further biological and clinical studies. The utility of the proposed approach is successfully demonstrated by analysing the two different kind of bacterial collections. The first set comprised of peptidoglycan sample belonging to different subclasses of Alphaproteobacteria. Whereas, the second set that is relatively more intricate for the chemometric analysis consist of different wild type Vibrio Cholerae and its mutants having subtle differences in their peptidoglycan composition. The present work clearly proposes a useful approach that can classify the chromatographic data sets of chromatographic peptidoglycan samples having subtle differences. Furthermore, present work clearly suggest that PCoA can be a method of choice in any data analysis workflow. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular evidence confirms the taxonomic separation of Lutzomyia tihuiliensis from Lutzomyia pia (Diptera: Psychodidae) and the usefulness of pleural pigmentation patterns in species identification.

PubMed

Pérez-Doria, Alveiro; Bejarano, Eduar Elías; Sierra, Diana; Vélez, Iván Darío

2008-07-01

The phlebotomine sand flies Lutzomyia pia (Fairchild & Hertig 1961) and Lutzomyia tihuiliensis Le Pont, Torrez-Espejo & Dujardin 1997 (Diptera: Psychodidae) belong to the pia series of the Lu. verrucarum species group, which includes several species that bite humans in Andean foci of leishmaniasis. The females of these two species exhibit isometry and isomorphism in anatomical structures of the head and terminalia commonly used in taxonomic identification of sand flies. They can only be differentiated based on subtle differences in the pigmentation of the pleura. In Lu. tihuiliensis, this is restricted to the basal portions of the katepimeron and katepisternum, whereas in Lu. pia both structures are totally pigmented. Taking into account the subtle morphological differences between these species, the objective of the current study was to evaluate the specific taxonomic status of Lu. tihuiliensis with respect to Lu. pia. A 475-bp portion of the mitochondrial genome was sequenced, composed of the 3' end of the cytochrome b gene, intergenic spacer 1, the transfer RNA gene for serine, intergenic spacer 2, and the 3' end of the gene NAD dehydrogenase 1. Genetic analysis confirms that Lu. tihuiliensis and Lu. pia constitute two distinct species and this is supported by four strong lines of evidence, i.e., the paired genetic distances, size differences and amino acid composition of the cytochrome b protein, presence and absence of intergenic spacer one and divergence observed in the sequence of the transfer RNA gene for serine. It also confirms the validity of the pleural pigmentation pattern as a species diagnostic character and the importance of performing a detailed examination of this character during morphological determination of phlebotomine sand flies in the series pia.

Applications of ICA and fractal dimension in sEMG signal processing for subtle movement analysis: a review.

PubMed

Naik, Ganesh R; Arjunan, Sridhar; Kumar, Dinesh

2011-06-01

The surface electromyography (sEMG) signal separation and decphompositions has always been an interesting research topic in the field of rehabilitation and medical research. Subtle myoelectric control is an advanced technique concerned with the detection, processing, classification, and application of myoelectric signals to control human-assisting robots or rehabilitation devices. This paper reviews recent research and development in independent component analysis and Fractal dimensional analysis for sEMG pattern recognition, and presents state-of-the-art achievements in terms of their type, structure, and potential application. Directions for future research are also briefly outlined.

Selective incivility: immigrant groups experience subtle workplace discrimination at different rates.

PubMed

Krings, Franciska; Johnston, Claire; Binggeli, Steve; Maggiori, Christian

2014-10-01

Immigrants play an increasingly important role in local labor markets. Not only do they grow steadily in number but also in cultural, educational, and skill diversity, underlining the necessity to distinguish between immigrant groups when studying discrimination against immigrants. We examined immigrant employees' subtle discrimination experiences in a representative sample in Switzerland, controlling for dispositional influences. Results showed that mainly members of highly competitive immigrant groups, from immediate neighbor countries, experienced workplace incivility and that these incivility experiences were related to higher likelihoods of perceived discrimination at work. This research confirms recent accounts that successful but disliked groups are particularly likely to experience subtle interpersonal discrimination. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Altruists are trusted based on non-verbal cues.

PubMed

Oda, Ryo; Naganawa, Takuya; Yamauchi, Shinsaku; Yamagata, Noriko; Matsumoto-Oda, Akiko

2009-12-23

The identification of altruists based on non-verbal cues might offer a solution to the problem of subtle cheating. Previous studies have indicated that the ability to discriminate altruists from non-altruists emerges during evolution. However, behavioural differences with regard to social exchanges involving altruists and non-altruists have not been studied. We investigated differences in responses to videotaped altruists and non-altruists with the Faith Game. Participants tended to entrust real money to altruists more than to non-altruists, providing strong evidence that cognitive adaptations evolve as counter-strategies to subtle cheating.

Neurally Derived Tissues in Xenopus laevis Embryos Exhibit a Consistent Bioelectrical Left-Right Asymmetry

PubMed Central

Pai, Vaibhav P.; Vandenberg, Laura N.; Blackiston, Douglas; Levin, Michael

2012-01-01

Consistent left-right asymmetry in organ morphogenesis is a fascinating aspect of bilaterian development. Although embryonic patterning of asymmetric viscera, heart, and brain is beginning to be understood, less is known about possible subtle asymmetries present in anatomically identical paired structures. We investigated two important developmental events: physiological controls of eye development and specification of neural crest derivatives, in Xenopus laevis embryos. We found that the striking hyperpolarization of transmembrane potential (V mem) demarcating eye induction usually occurs in the right eye field first. This asymmetry is randomized by perturbing visceral left-right patterning, suggesting that eye asymmetry is linked to mechanisms establishing primary laterality. Bilateral misexpression of a depolarizing channel mRNA affects primarily the right eye, revealing an additional functional asymmetry in the control of eye patterning by V mem. The ATP-sensitive K+ channel subunit transcript, SUR1, is asymmetrically expressed in the eye primordia, thus being a good candidate for the observed physiological asymmetries. Such subtle asymmetries are not only seen in the eye: consistent asymmetry was also observed in the migration of differentiated melanocytes on the left and right sides. These data suggest that even anatomically symmetrical structures may possess subtle but consistent laterality and interact with other developmental left-right patterning pathways. PMID:23346115

Neurally Derived Tissues in Xenopus laevis Embryos Exhibit a Consistent Bioelectrical Left-Right Asymmetry.

PubMed

Pai, Vaibhav P; Vandenberg, Laura N; Blackiston, Douglas; Levin, Michael

2012-01-01

Consistent left-right asymmetry in organ morphogenesis is a fascinating aspect of bilaterian development. Although embryonic patterning of asymmetric viscera, heart, and brain is beginning to be understood, less is known about possible subtle asymmetries present in anatomically identical paired structures. We investigated two important developmental events: physiological controls of eye development and specification of neural crest derivatives, in Xenopus laevis embryos. We found that the striking hyperpolarization of transmembrane potential (V(mem)) demarcating eye induction usually occurs in the right eye field first. This asymmetry is randomized by perturbing visceral left-right patterning, suggesting that eye asymmetry is linked to mechanisms establishing primary laterality. Bilateral misexpression of a depolarizing channel mRNA affects primarily the right eye, revealing an additional functional asymmetry in the control of eye patterning by V(mem). The ATP-sensitive K(+) channel subunit transcript, SUR1, is asymmetrically expressed in the eye primordia, thus being a good candidate for the observed physiological asymmetries. Such subtle asymmetries are not only seen in the eye: consistent asymmetry was also observed in the migration of differentiated melanocytes on the left and right sides. These data suggest that even anatomically symmetrical structures may possess subtle but consistent laterality and interact with other developmental left-right patterning pathways.

[3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging in the diagnosis of focal cortical dysplasia in children].

PubMed

Alikhanov, A A; Sinitsyn, V E; Perepelova, E M; Mukhin, K Iu; Demushkina, A A; Omarova, M O; Piliia, S V

2001-01-01

Small dysplastic lesions of the cerebral cortex are often missed by conventional MRI methods. The identification of subtle structural abnormalities by traditional multiplanar rectilinear slices is often limited by the complex convolutional pattern of the brain. We used a method of FSPGR (fast spoiled gradient-echo) of three-dimensional MRI data that improves the anatomical display of the sulcal structure of the hemispheric convexities. It also reduces the asymmetric sampling of gray-white matter that may lead to false-positive results. We present 5 from 12 patients with dysplastic cortical lesions in whom conventional two-dimensional and three-dimensional MRI with multiplanar reformatting was initially considered normal. Subsequent studies using 3D FSPGR identified various types of focal cortical dysplasia in all. These results indicate that an increase in the detection of subtle focal dysplastic lesions may be accomplished when one improves the anatomical display of the brain sulcal structure by performing 3D FSPGR.

Medial Temporal Lobe Structures Contribute to On-Line Processing

ERIC Educational Resources Information Center

Warren, David

2009-01-01

For the last five decades, the medial temporal lobes have been generally understood to facilitate enduring representation of certain kinds of information. In particular, knowledge about the relations among items and concepts appears to rely on that region of the brain. Recent results suggest that those same structures also play a subtle role in…

The HD molecule in small and medium cages of clathrate hydrates: Quantum dynamics studied by neutron scattering measurements and computation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colognesi, Daniele; Celli, Milva; Ulivi, Lorenzo, E-mail: lorenzo.ulivi@isc.cnr.it

2014-10-07

We report inelastic neutron scattering (INS) measurements on molecular hydrogen deuteride (HD) trapped in binary cubic (sII) and hexagonal (sH) clathrate hydrates, performed at low temperature using two different neutron spectrometers in order to probe both energy and momentum transfer. The INS spectra of binary clathrate samples exhibit a rich structure containing sharp bands arising from both the rotational transitions and the rattling modes of the guest molecule. For the clathrates with sII structure, there is a very good agreement with the rigorous fully quantum simulations which account for the subtle effects of the anisotropy, angular and radial, of themore » host cage on the HD microscopic dynamics. The sH clathrate sample presents a much greater challenge, due to the uncertainties regarding the crystal structure, which is known only for similar crystals with different promoter, but nor for HD (or H{sub 2}) plus methyl tert-butyl ether (MTBE-d12)« less

Nanoscale Structure of Urethane/Urea Elastomeric Films

NASA Astrophysics Data System (ADS)

Reis, Dennys; Trindade, Ana C.; Godinho, Maria Helena; Silva, Laura C.; do Carmo Gonçalves, Maria; Neto, Antônio M. Figueiredo

2017-02-01

The nanostructure of urethane/urea elastomeric membranes was investigated by small-angle X-ray scattering (SAXS) in order to establish relationships between their structure and mechanical properties. The networks were made up of polypropylene oxide (PPO) and polybutadiene (PB) segments. The structural differences were investigated in two types of membranes with the same composition but with different thermal treatment after casting. Type I was cured at 70-80 °C and type II at 20 °C. Both membranes showed similar phase separation by TEM, with nanodomains rich in PB or PPO and 25 nm dimensions. The main difference between type I and type II membranes was found by SAXS. The type I membrane spectra showed, besides a broad band at a 27-nm q value (modulus of the scattering vector), an extra band at 6 nm, which was not observed in the type II membrane. The SAXS spectra were interpreted in terms of PPO, PB soft segments, and urethane/urea links, as well as hard moiety segregation in the reaction medium. This additional segregation ( q = 7 nm), although subtle, results in diverse mechanical behavior of in both membranes.

Petrology of Impact-Melt Rocks at the Chicxulub Multiring Basin, Yucatan, Mexico

NASA Technical Reports Server (NTRS)

Schuraytz, Benjamin C.; Sharpton, Virgil L.; Marin, Luis E.

1994-01-01

Compositions and textures of melt rocks from the upper part of the Chicxulub structure are typical of melt rocks at other large terrestrial impact structures. Apart from variably elevated iridium concentrations (less than 1.5 to 13.5 +/- 0.9 ppb) indicating nonuniform dissemination of a meteoritic component, bulk rock and phenocryst compositions imply that these melt rocks were derived exclusively from continental crust and platform-sediment target lithologies. Modest differences in bulk chemistry among samples from wells located approximately 40 km apart suggest minor variations in relative contributions of these target lithologies to the melts. Subtle variations in the compositions of early-formed pyroxene and plagioclase also support minor primary differences in chemistry between the melts. Evidence for pervasive hydrothermal alteration of the porous mesostasis includes albite, K-feldspar, quartz, epidote, chlorite, and other phyllosilicates, as well as siderophile element-enriched sulfides, suggesting the possibility that Chicxulub, like Sudbury, may host important ore deposits.

Colour thresholding and objective quantification in bioimaging

NASA Technical Reports Server (NTRS)

Fermin, C. D.; Gerber, M. A.; Torre-Bueno, J. R.

1992-01-01

Computer imaging is rapidly becoming an indispensable tool for the quantification of variables in research and medicine. Whilst its use in medicine has largely been limited to qualitative observations, imaging in applied basic sciences, medical research and biotechnology demands objective quantification of the variables in question. In black and white densitometry (0-256 levels of intensity) the separation of subtle differences between closely related hues from stains is sometimes very difficult. True-colour and real-time video microscopy analysis offer choices not previously available with monochrome systems. In this paper we demonstrate the usefulness of colour thresholding, which has so far proven indispensable for proper objective quantification of the products of histochemical reactions and/or subtle differences in tissue and cells. In addition, we provide interested, but untrained readers with basic information that may assist decisions regarding the most suitable set-up for a project under consideration. Data from projects in progress at Tulane are shown to illustrate the advantage of colour thresholding over monochrome densitometry and for objective quantification of subtle colour differences between experimental and control samples.

Crystal structures of η''-Cu3+xSi and η'''-Cu3+xSi.

PubMed

Corrêa, Cinthia Antunes; Perez, Olivier; Kopeček, Jaromír; Brázda, Petr; Klementová, Mariana; Palatinus, Lukáš

2017-08-01

The binary phase diagram of Cu-Si is unexpectedly complex in the vicinity of Cu 3+x Si. The low-temperature region contains three closely related incommensurately modulated phases denoted, in order of increasing temperature of stability, η''', η'' and η'. The structure analysis of η' has been reported previously [Palatinus et al. (2011). Inorg. Chem. 50, 3743]. Here the structure model for the phases η'' and η''' is reported. The structures could be solved in superspace, but no superspace structure model could be constructed due to the complexity of the modulation functions. Therefore, the structures were described in a supercell approximation, which involved a 4 × 4 × 3 supercell for the η'' phase and a 14 × 14 × 3 supercell for the η''' phase. Both structures are very similar and differ only by a subtle symmetry lowering from η'' to η'''. A comparison of the structure models of η'' and η''' with the reported structure of η' suggests that the reported structure model of η' contains an incorrect assignment of atomic types.

Microgravity

NASA Image and Video Library

1997-01-12

1 mm histone octamer crystal grown on STS-81. A very dynamic structure which functions in many aspects of gene regulation from control of gene activity to the more subtle mechanisms of genetic imprinting. Principle Investigator is Dan Carter of New Century Pharmaceuticals.

Spaceborne Potential for Examining Taiga-Tundra Ecotone Form and Vulnerability

NASA Technical Reports Server (NTRS)

Montesano, Paul M.; Sun, Guoqing; Dubayah, Ralph O.; Ranson, K. Jon

2016-01-01

In the taiga-tundra ecotone (TTE), site-dependent forest structure characteristics can influence the subtle and heterogeneous structural changes that occur across the broad circumpolar extent. Such changes may be related to ecotone form, described by the horizontal and vertical patterns of forest structure (e.g., tree cover, density and height) within TTE forest patches, driven by local site conditions, and linked to ecotone dynamics. The unique circumstance of subtle, variable and widespread vegetation change warrants the application of spaceborne data including high-resolution (less than 5m) spaceborne imagery (HRSI) across broad scales for examining TTE form and predicting dynamics. This study analyzes forest structure at the patch-scale in the TTE to provide a means to examine both vertical and horizontal components of ecotone form. We demonstrate the potential of spaceborne data for integrating forest height and density to assess TTE form at the scale of forest patches across the circumpolar biome by (1) mapping forest patches in study sites along the TTE in northern Siberia with a multi-resolution suite of spaceborne data, and (2) examining the uncertainty of forest patch height from this suite of data across sites of primarily diffuse TTE forms. Results demonstrate the opportunities for improving patch-scale spaceborne estimates of forest height, the vertical component of TTE form, with HRSI. The distribution of relative maximum height uncertainty based on prediction intervals is centered at approximately 40%, constraining the use of height for discerning differences in forest patches. We discuss this uncertainty in light of a conceptual model of general ecotone forms, and highlight how the uncertainty of spaceborne estimates of height can contribute to the uncertainty in identifying TTE forms. A focus on reducing the uncertainty of height estimates in forest patches may improve depiction of TTE form, which may help explain variable forest responses in the TTE to climate change and the vulnerability of portions of the TTE to forest structure change. structural changes.

Does Compound I Vary Significantly between Isoforms of Cytochrome P450?

PubMed Central

2011-01-01

The cytochrome P450 (CYP) enzymes are important in many areas, including pharmaceutical development. Subtle changes in the electronic structure of the active species, Compound I, have been postulated previously to account partly for the experimentally observed differences in reactivity between isoforms. Current predictive models of CYP metabolism typically assume an identical Compound I in all isoforms. Here we present a method to calculate the electronic structure and to estimate the Fe–O bond enthalpy of Compound I, and apply it to several human and bacterial CYP isoforms. Conformational flexibility is accounted for by sampling large numbers of structures from molecular dynamics simulations, which are subsequently optimized with density functional theory (B3LYP) based quantum mechanics/molecular mechanics. The observed differences in Compound I between human isoforms are small: They are generally smaller than the spread of values obtained for the same isoform starting from different initial structures. Hence, it is unlikely that the variation in activity between human isoforms is due to differences in the electronic structure of Compound I. A larger difference in electronic structure is observed between the human isoforms and P450cam and may be explained by the slightly different hydrogen-bonding environment surrounding the cysteinyl sulfur. The presence of substrate in the active site of all isoforms studied appears to cause a slight decrease in the Fe–O bond enthalpy, apparently due to displacement of water out of the active site, suggesting that Compound I is less stable in the presence of substrate. PMID:21863858

Groupwise shape analysis of the hippocampus using spectral matching

NASA Astrophysics Data System (ADS)

Shakeri, Mahsa; Lombaert, Hervé; Lippé, Sarah; Kadoury, Samuel

2014-03-01

The hippocampus is a prominent subcortical feature of interest in many neuroscience studies. Its subtle morphological changes often predicate illnesses, including Alzheimer's, schizophrenia or epilepsy. The precise location of structural differences requires a reliable correspondence between shapes across a population. In this paper, we propose an automated method for groupwise hippocampal shape analysis based on a spectral decomposition of a group of shapes to solve the correspondence problem between sets of meshes. The framework generates diffeomorphic correspondence maps across a population, which enables us to create a mean shape. Morphological changes are then located between two groups of subjects. The performance of the proposed method was evaluated on a dataset of 42 hippocampus shapes and compared with a state-of-the-art structural shape analysis approach, using spherical harmonics. Difference maps between mean shapes of two test groups demonstrates that the two approaches showed results with insignificant differences, while Gaussian curvature measures calculated between matched vertices showed a better fit and reduced variability with spectral matching.

On the structural affinity of macromolecules with different biological properties: molecular dynamics simulations of a series of TEM-1 mutants.

PubMed

Giampaolo, Alessia Di; Mazza, Fernando; Daidone, Isabella; Amicosante, Gianfranco; Perilli, Mariagrazia; Aschi, Massimiliano

2013-07-12

Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical-biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment. Copyright © 2013 Elsevier Inc. All rights reserved.

Complex networks: Effect of subtle changes in nature of randomness

NASA Astrophysics Data System (ADS)

Goswami, Sanchari; Biswas, Soham; Sen, Parongama

2011-03-01

In two different classes of network models, namely, the Watts Strogatz type and the Euclidean type, subtle changes have been introduced in the randomness. In the Watts Strogatz type network, rewiring has been done in different ways and although the qualitative results remain the same, finite differences in the exponents are observed. In the Euclidean type networks, where at least one finite phase transition occurs, two models differing in a similar way have been considered. The results show a possible shift in one of the phase transition points but no change in the values of the exponents. The WS and Euclidean type models are equivalent for extreme values of the parameters; we compare their behaviour for intermediate values.

Predicting helix orientation for coiled-coil dimers

PubMed Central

Apgar, James R.; Gutwin, Karl N.; Keating, Amy E.

2008-01-01

The alpha-helical coiled coil is a structurally simple protein oligomerization or interaction motif consisting of two or more alpha helices twisted into a supercoiled bundle. Coiled coils can differ in their stoichiometry, helix orientation and axial alignment. Because of the near degeneracy of many of these variants, coiled coils pose a challenge to fold recognition methods for structure prediction. Whereas distinctions between some protein folds can be discriminated on the basis of hydrophobic/polar patterning or secondary structure propensities, the sequence differences that encode important details of coiled-coil structure can be subtle. This is emblematic of a larger problem in the field of protein structure and interaction prediction: that of establishing specificity between closely similar structures. We tested the behavior of different computational models on the problem of recognizing the correct orientation - parallel vs. antiparallel - of pairs of alpha helices that can form a dimeric coiled coil. For each of 131 examples of known structure, we constructed a large number of both parallel and antiparallel structural models and used these to asses the ability of five energy functions to recognize the correct fold. We also developed and tested three sequenced-based approaches that make use of varying degrees of implicit structural information. The best structural methods performed similarly to the best sequence methods, correctly categorizing ∼81% of dimers. Steric compatibility with the fold was important for some coiled coils we investigated. For many examples, the correct orientation was determined by smaller energy differences between parallel and antiparallel structures distributed over many residues and energy components. Prediction methods that used structure but incorporated varying approximations and assumptions showed quite different behaviors when used to investigate energetic contributions to orientation preference. Sequence based methods were sensitive to the choice of residue-pair interactions scored. PMID:18506779

Chromatin Structure and the Cell Cycle

PubMed Central

Pederson, Thoru

1972-01-01

Pancreatic DNase I is used to probe the structure of chromatin isolated from synchronized HeLa cells. The degree to which DNA in chromatin is protected from DNase attack varies during the G1, S, and G2 phases of the cell cycle. In addition, the DNase sensitivity of chromatin from contact-inhibited African green monkey kidney cells differs from that of actively dividing, subconfluent cultures. These cell cycle-dependent chromatin changes were observed consistently at all enzyme concentrations (5000-fold range) and incubation times (15 min-2 hr) tested. The results indicate that the degree of complexing between DNA and chromosomal proteins changes during interphase, and they suggest that the chromosome coiling cycle of visible mitosis may extend in more subtle form over the entire cell cycle. PMID:4626402

Evolution of planetary lithospheres - Evidence from multiringed structures on Ganymede and Callisto

NASA Technical Reports Server (NTRS)

Mckinnon, W. B.; Melosh, H. J.

1980-01-01

The thickness and viscosity of a planetary lithosphere increase with time as the mantle cools, with a thicker lithosphere leading to the formation of one (or very few) irregular normal faults concentric to the crater. Since a gravity wave or tsunami induced by impact into a liquid mantle would result in both radial and concentric extension features, which are not observed in the case of the large impact structures on Ganymede and Callisto, an alternative mechanism is proposed in which the varying ice/silicate ratios, tectonic histories, and erosional mechanisms of the two bodies are considered to explain the subtle differences in thin lithosphere ring morphology between Ganymede and Callisto. It is concluded that the present lithosphere thickness of Ganymede is too great to permit the development of any rings.

Effect of fibril shape on adhesive properties

NASA Astrophysics Data System (ADS)

Soto, Daniel; Hill, Ginel; Parness, Aaron; Esparza, Noé; Cutkosky, Mark; Kenny, Tom

2010-08-01

Research into the gecko's adhesive system revealed a unique architecture for adhesives using tiny hairs. By using a stiff material (β-keratin) to create a highly structured adhesive, the gecko's system demonstrates properties not seen in traditional pressure-sensitive adhesives which use a soft, unstructured planar layer. In contrast to pressure sensitive adhesives, the gecko adhesive displays frictional adhesion, in which increased shear force allows it to withstand higher normal loads. Synthetic fibrillar adhesives have been fabricated but not all demonstrate this frictional adhesion property. Here we report the dual-axis force testing of single silicone rubber pillars from synthetic adhesive arrays. We find that the shape of the adhesive pillar dictates whether frictional adhesion or pressure-sensitive behavior is observed. This work suggests that both types of behavior can be achieved with structures much larger than gecko terminal structures. It also indicates that subtle differences in the shape of these pillars can significantly influence their properties.

2011 Rita Schaffer lecture: nanoparticles for intracellular nucleic acid delivery.

PubMed

Green, Jordan J

2012-07-01

Nanoparticles are a promising technology for delivery of new types of therapeutics. A polymer library approach has allowed engineering of polymeric particles that are particularly effective for the delivery of DNA and siRNA to human cells. Certain chemical structural motifs, degradable linkages, hydrophobicity, and biophysical properties are key for successful intracellular delivery. Small differences to biomaterial structure, and especially the type of degradable linkage in the polymers, can be critical for successful delivery of siRNA vs. DNA. Furthermore, subtle changes to biomaterial structure can facilitate cell-type gene delivery specificity between human brain cancer cells and healthy cells as well as between human retinal endothelial cells and epithelial cells. These polymeric nanoparticles are effective for nucleic acid delivery in a broad range of human cell types and have applications to regenerative medicine, ophthalmology, and cancer among many other biomedical research areas.

Designing cooperatively folded abiotic uni- and multimolecular helix bundles

NASA Astrophysics Data System (ADS)

de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

Improving the signal subtle feature extraction performance based on dual improved fractal box dimension eigenvectors

NASA Astrophysics Data System (ADS)

Chen, Xiang; Li, Jingchao; Han, Hui; Ying, Yulong

2018-05-01

Because of the limitations of the traditional fractal box-counting dimension algorithm in subtle feature extraction of radiation source signals, a dual improved generalized fractal box-counting dimension eigenvector algorithm is proposed. First, the radiation source signal was preprocessed, and a Hilbert transform was performed to obtain the instantaneous amplitude of the signal. Then, the improved fractal box-counting dimension of the signal instantaneous amplitude was extracted as the first eigenvector. At the same time, the improved fractal box-counting dimension of the signal without the Hilbert transform was extracted as the second eigenvector. Finally, the dual improved fractal box-counting dimension eigenvectors formed the multi-dimensional eigenvectors as signal subtle features, which were used for radiation source signal recognition by the grey relation algorithm. The experimental results show that, compared with the traditional fractal box-counting dimension algorithm and the single improved fractal box-counting dimension algorithm, the proposed dual improved fractal box-counting dimension algorithm can better extract the signal subtle distribution characteristics under different reconstruction phase space, and has a better recognition effect with good real-time performance.

Offering variety: a subtle manipulation to promote healthy food choice throughout the day.

PubMed

Burns, Rachel J; Rothman, Alexander J

2015-05-01

Providing a variety of food generally increases consumption and enjoyment. This effect is typically associated with unhealthy behavior (e.g., overindulgence at a buffet) and studied during a single meal. Two studies tested whether this effect can be leveraged in a subtle, simple manipulation to promote healthy food choices over the course of a day. In Studies 1 and 2, 188 and 187 participants, respectively, chose between a sweet and a piece of fruit in the afternoon. The fruit was either the same as or different from fruit that was selected in the morning; choice was not given in the morning. Study 1 tested this effect in the domain of expressed preferences and Study 2 examined actual choice. In both studies, a second piece of fruit was more likely to be selected in the afternoon if it was different from fruit that was selected in the morning. These results illustrate how a robust effect that is typically associated with unhealthy outcomes can be harnessed to promote healthy food choices and underscore the importance of conceptualizing eating as a series of interrelated behavioral decisions. This work has implications for applied settings, such as cafeterias, and is distinguished from other simple structural manipulations by its focus on sustaining healthy food choice over the course of the day. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

A successful development of subtle traps: Chihuido de la Sierra Negra, Neuquen Basin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comeron, R.; Valenzuela, M.W.

1996-08-01

Using new traps search concepts in the Chihuido de la Sierra Negra oil field, it was possible to substantially increase production from 4400 bbl/day in 1984 to 125,000 bbl/day in 1995. Oil reserves are located within an 8000 ha area situated on the Chihuido de la Sierra Negra anticlinal flank. Success was achieved by using different techniques for subtle traps detection, namely seismic amplitude mapping, individualization of different production facies and its predictive mapping. This reduced the search and development toward low structural areas which had not been considered before. The production layers are formed by two lower Cretaceous eolianmore » sandstones called the Avile Member and the Troncoso Lower Member, with thicknesses ranging from 5 to 30 meters. 2D seismic made it possible to individualize the thickest sand areas, some of which turned out to be productive. Using 3D seismic, by means of azimuth and dip maps, fractured areas were detected where fault throws range from 5 to 10 meters. In many of these fractured zones, thin igneous intrusives are emplaced forming seals. Such determinations make it possible for different oil-water contacts and static pressures to be delimited. Due to the small fault throws, the different blocks could not be detected by conventional mapping methods. The delineation of the field compartmentalization becomes important in the waterflooding stage as well as for the detection of new traps in surrounding areas. The combination of seismic and stratigraphic methods made it possible to discover and develop Argentina`s main oil field.« less

Microgravity

NASA Image and Video Library

1997-01-12

This is a large 2 mm crystal of histone octamer, grown on STS-81. A very dynamic structure which functions in many aspects of gene regulation from control of gene activity to the more subtle mechanisms of genetic imprinting. Principle Investigator is Dan Carter of New Century Pharmaceuticals.

Spaceborne potential for examining taiga-tundra ecotone form and vulnerability

NASA Astrophysics Data System (ADS)

Montesano, Paul M.; Sun, Guoqing; Dubayah, Ralph O.; Ranson, K. Jon

2016-07-01

In the taiga-tundra ecotone (TTE), site-dependent forest structure characteristics can influence the subtle and heterogeneous structural changes that occur across the broad circumpolar extent. Such changes may be related to ecotone form, described by the horizontal and vertical patterns of forest structure (e.g., tree cover, density, and height) within TTE forest patches, driven by local site conditions, and linked to ecotone dynamics. The unique circumstance of subtle, variable, and widespread vegetation change warrants the application of spaceborne data including high-resolution (< 5 m) spaceborne imagery (HRSI) across broad scales for examining TTE form and predicting dynamics. This study analyzes forest structure at the patch scale in the TTE to provide a means to examine both vertical and horizontal components of ecotone form. We demonstrate the potential of spaceborne data for integrating forest height and density to assess TTE form at the scale of forest patches across the circumpolar biome by (1) mapping forest patches in study sites along the TTE in northern Siberia with a multi-resolution suite of spaceborne data and (2) examining the uncertainty of forest patch height from this suite of data across sites of primarily diffuse TTE forms. Results demonstrate the opportunities for improving patch-scale spaceborne estimates of forest height, the vertical component of TTE form, with HRSI. The distribution of relative maximum height uncertainty based on prediction intervals is centered at ˜ 40 %, constraining the use of height for discerning differences in forest patches. We discuss this uncertainty in light of a conceptual model of general ecotone forms and highlight how the uncertainty of spaceborne estimates of height can contribute to the uncertainty in identifying TTE forms. A focus on reducing the uncertainty of height estimates in forest patches may improve depiction of TTE form, which may help explain variable forest responses in the TTE to climate change and the vulnerability of portions of the TTE to forest structure change.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voylov, D. N.; Griffin, P. J.; Mercado, B.

In this detailed analysis of the static structure factor S(Q) in several glass-forming liquids we show that the temperature variations of the width of the main diffraction peak Q(T ) correlate with the fragility of these liquids. Our observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We also show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, lc 2 /Q, and the size of cooperatively rearranging regions.

Understanding Two Different Structures in the Dark Stable State of the Oxygen‐Evolving Complex of Photosystem II: Applicability of the Jahn–Teller Deformation Formula

PubMed Central

Shoji, Mitsuo; Isobe, Hiroshi; Tanaka, Ayako; Fukushima, Yoshimasa; Kawakami, Keisuke; Umena, Yasufumi; Kamiya, Nobuo; Nakajima, Takahito

2017-01-01

Abstract Tanaka et al. (J. Am. Chem. Soc., 2017, 139, 1718) recently reported the three‐dimensional (3D) structure of the oxygen evolving complex (OEC) of photosystem II (PSII) by X‐ray diffraction (XRD) using extremely low X‐ray doses of 0.03 and 0.12 MGy. They observed two different 3D structures of the CaMn4O5 cluster with different hydrogen‐bonding interactions in the S1 state of OEC keeping the surrounding polypeptide frameworks of PSII the same. Our Jahn–Teller (JT) deformation formula based on large‐scale quantum mechanics/molecular mechanics (QM/MM) was applied for these low‐dose XRD structures, elucidating important roles of JT effects of the MnIII ion for subtle geometric distortions of the CaMn4O5 cluster in OEC of PSII. The JT deformation formula revealed the similarity between the low‐dose XRD and damage‐free serial femtosecond X‐ray diffraction (SFX) structures of the CaMn4O5 cluster in the dark stable state. The extremely low‐dose XRD structures were not damaged by X‐ray irradiation. Implications of the present results are discussed in relation to recent SFX results and a blue print for the design of artificial photocatalysts for water oxidation. PMID:29577075

Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring.

EPA Science Inventory

Severe thyroid hormone (TH) insufficiency during early development results in alterations in brain structure and function. Many environmental agents produce subtle alterations in TH status, but the dose-response relationships for such effects are unclear. We have previously demon...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hai, Yang; Christianson, David W.

Leishmaniaarginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiatesde novopolyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections. To this end, two X-ray crystal structures ofL. mexicanaarginase complexed with α,α-disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2-(S)-amino-6-boronohexanoic acidmore » are now reported. Structural comparisons with human and parasitic arginase complexes reveal interesting differences in the binding modes of the additional α-substituents,i.e.the D side chains, of these inhibitors. Subtle differences in the three-dimensional contours of the outer active-site rims among arginases from different species lead to different conformations of the D side chains and thus different inhibitor-affinity trends. The structures suggest that it is possible to maintain affinity while fine-tuning intermolecular interactions of the D side chain of α,α-disubstituted boronic amino-acid inhibitors in the search for isozyme-specific and species-specific arginase inhibitors.« less

Anharmonic and Quantum Fluctuations in Molecular Crystals: A First-Principles Study of the Stability of Paracetamol

NASA Astrophysics Data System (ADS)

Rossi, Mariana; Gasparotto, Piero; Ceriotti, Michele

2016-09-01

Molecular crystals often exist in multiple competing polymorphs, showing significantly different physicochemical properties. Computational crystal structure prediction is key to interpret and guide the search for the most stable or useful form, a real challenge due to the combinatorial search space, and the complex interplay of subtle effects that work together to determine the relative stability of different structures. Here we take a comprehensive approach based on different flavors of thermodynamic integration in order to estimate all contributions to the free energies of these systems with density-functional theory, including the oft-neglected anharmonic contributions and nuclear quantum effects. We take the two main stable forms of paracetamol as a paradigmatic example. We find that anharmonic contributions, different descriptions of van der Waals interactions, and nuclear quantum effects all matter to quantitatively determine the stability of different phases. Our analysis highlights the many challenges inherent in the development of a quantitative and predictive framework to model molecular crystals. However, it also indicates which of the components of the free energy can benefit from a cancellation of errors that can redeem the predictive power of approximate models, and suggests simple steps that could be taken to improve the reliability of ab initio crystal structure prediction.

``Sub-prime" Biophysics: Acoustic assessment of animal stress

NASA Astrophysics Data System (ADS)

Browning, David

2007-10-01

Animal welfare is of increasing concern. Vocalizations can be easily monitored and for some animals, such as the ``yip'' of a dog, stress is easily discernible. Unfortunately for many important farm animals, such as cows, sheep, and horses, the impact of stress on vocalizations appears to be more subtle. Our work is presently focused on the frequency spectra of horse whinnies. A whinny is comprised of two components; a tonal structure, and a varying frequency component or ``call.'' Results to date are presented on whether a horse can control this ``call'' so that there is a significant difference between a ``stressed'' whinny and a ``happy'' whinny.

Functional and Structural Impact of Target Uridine Substitutions on the H/ACA Ribonucleoprotein Particle Pseudouridine Synthase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jing; Liang, Bo; Li, Hong

2010-09-17

Box H/ACA ribonucleoprotein protein particles catalyze the majority of pseudouridylation in functional RNA. Different from stand alone pseudouridine synthases, the RNP pseudouridine synthase comprises multiple protein subunits and an RNA subunit. Previous studies showed that each subunit, regardless its location, is sensitive to the step of subunit placement at the catalytic center and potentially to the reaction status of the substrate. Here we describe the impact of chemical substitutions of target uridine on enzyme activity and structure. We found that 3-methyluridine in place of uridine inhibited its isomerization while 2{prime}-deoxyuridine or 4-thiouridine did not. Significantly, crystal structures of an archaealmore » box H/ACA RNP bound with the nonreactive and the two postreactive substrate analogues showed only subtle structural changes throughout the assembly except for a conserved tyrosine and a substrate anchoring loop of Cbf5. Our results suggest a potential role of these elements and the subunit that contacts them in substrate binding and product release.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demircioglu, F. Esra; Sosa, Brian A.; Ingram, Jessica

The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure atmore » 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.« less

Structural insights into μ-opioid receptor activation

PubMed Central

Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J.; Laeremans, Toon; Feinberg, Evan N.; Sanborn, Adrian L.; Kato, Hideaki E.; Livingston, Kathryn E.; Thorsen, Thor S.; Kling, Ralf; Granier, Sébastien; Gmeiner, Peter; Husbands, Stephen M.; Traynor, John R.; Weis, William I.; Steyaert, Jan; Dror, Ron O.; Kobilka, Brian K.

2015-01-01

Summary Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To understand the structural basis for μOR activation, we obtained a 2.1 Å X-ray crystal structure of the μOR bound to the morphinan agonist BU72 and stabilized by a G protein-mimetic camelid-antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β2 adrenergic receptor (β2AR) and the M2 muscarinic receptor (M2R). Comparison with active β2AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three GPCRs. PMID:26245379

Applications of Fault Detection in Vibrating Structures

NASA Technical Reports Server (NTRS)

Eure, Kenneth W.; Hogge, Edward; Quach, Cuong C.; Vazquez, Sixto L.; Russell, Andrew; Hill, Boyd L.

2012-01-01

Structural fault detection and identification remains an area of active research. Solutions to fault detection and identification may be based on subtle changes in the time series history of vibration signals originating from various sensor locations throughout the structure. The purpose of this paper is to document the application of vibration based fault detection methods applied to several structures. Overall, this paper demonstrates the utility of vibration based methods for fault detection in a controlled laboratory setting and limitations of applying the same methods to a similar structure during flight on an experimental subscale aircraft.

Structural and dynamical properties of chlorinated hydrocarbons studied with resonant inelastic x-ray scattering

NASA Astrophysics Data System (ADS)

Bohinc, R.; Žitnik, M.; Bučar, K.; Kavčič, M.; Carniato, S.; Journel, L.; Guillemin, R.; Marchenko, T.; Kawerk, E.; Simon, M.; Cao, W.

2016-04-01

We present a theoretical and experimental study of resonant inelastic x-ray scattering on a large group of chlorinated hydrocarbons: CH3Cl, CH2Cl2, CHCl3, CCl4, CH3CH2Cl, ClCH2CH2Cl, CH3CHCl2, CH3CCl3, C2H2Cl2-iso, C2H2Cl2-cis, C2H2Cl2-trans, and C6H5Cl. Differences in structural and dynamical properties of the molecules generated by diverse chemical environments are observed in the measured Cl(Kα) spectral maps as well as in the Cl(K) total fluorescence yield spectra. The energy position, relative intensity, and the width of the Franck-Condon distribution of low-lying σ∗ and π∗ resonances are extracted by a fitting procedure taking into account the experimental broadening. The theoretical values obtained with the transition potential and Δ Kohn-Sham methods are in good agreement with the experimental parameters indicating subtle differences due to variations in the molecular structure.

Structural and dynamical properties of chlorinated hydrocarbons studied with resonant inelastic x-ray scattering.

PubMed

Bohinc, R; Žitnik, M; Bučar, K; Kavčič, M; Carniato, S; Journel, L; Guillemin, R; Marchenko, T; Kawerk, E; Simon, M; Cao, W

2016-04-07

We present a theoretical and experimental study of resonant inelastic x-ray scattering on a large group of chlorinated hydrocarbons: CH3Cl, CH2Cl2, CHCl3, CCl4, CH3CH2Cl, ClCH2CH2Cl, CH3CHCl2, CH3CCl3, C2H2Cl2-iso, C2H2Cl2-cis, C2H2Cl2-trans, and C6H5Cl. Differences in structural and dynamical properties of the molecules generated by diverse chemical environments are observed in the measured Cl(K(α)) spectral maps as well as in the Cl(K) total fluorescence yield spectra. The energy position, relative intensity, and the width of the Franck-Condon distribution of low-lying σ* and π* resonances are extracted by a fitting procedure taking into account the experimental broadening. The theoretical values obtained with the transition potential and Δ Kohn-Sham methods are in good agreement with the experimental parameters indicating subtle differences due to variations in the molecular structure.

Reversible thermochromic response based on photonic crystal structure in butterfly wing

NASA Astrophysics Data System (ADS)

Wang, Wanlin; Wang, Guo Ping; Zhang, Wang; Zhang, Di

2018-01-01

Subtle responsive properties can be achieved by the photonic crystal (PC) nanostructures of butterfly based on thermal expansion effect. The studies focused on making the sample visually distinct. However, the response is restricted by limited thermal expansion coefficients. We herein report a new class of reversible thermochromic response achieved by controlling the ambient refractive index in butterfly PC structure. The photonic ethanol-filled nanoarchitecture sample is simply assembled by sealing liquid ethanol filling Papilio ulysses butterfly wing. Volatile ethanol is used to modulate the ambient refractive index. The sample is sealed with glasses to ensure reversibility. Liquid ethanol filling butterfly wing demonstrated significant allochroic response to ambient refractive index, which can be controlled by the liquefaction and vaporization of ethanol. This design is capable of converting thermal energy into visual color signals. The mechanism of this distinct response is simulated and proven by band theory. The response properties are performed with different filled chemicals and different structure parameters. Thus, the reversible thermochromic response design might have potential use in the fields such as detection, photonic switch, displays, and so forth.

Atomic Step Formation on Sapphire Surface in Ultra-precision Manufacturing

PubMed Central

Wang, Rongrong; Guo, Dan; Xie, Guoxin; Pan, Guoshun

2016-01-01

Surfaces with controlled atomic step structures as substrates are highly relevant to desirable performances of materials grown on them, such as light emitting diode (LED) epitaxial layers, nanotubes and nanoribbons. However, very limited attention has been paid to the step formation in manufacturing process. In the present work, investigations have been conducted into this step formation mechanism on the sapphire c (0001) surface by using both experiments and simulations. The step evolutions at different stages in the polishing process were investigated with atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM). The simulation of idealized steps was constructed theoretically on the basis of experimental results. It was found that (1) the subtle atomic structures (e.g., steps with different sawteeth, as well as steps with straight and zigzag edges), (2) the periodicity and (3) the degree of order of the steps were all dependent on surface composition and miscut direction (step edge direction). A comparison between experimental results and idealized step models of different surface compositions has been made. It has been found that the structure on the polished surface was in accordance with some surface compositions (the model of single-atom steps: Al steps or O steps). PMID:27444267

Atomic Step Formation on Sapphire Surface in Ultra-precision Manufacturing

NASA Astrophysics Data System (ADS)

Wang, Rongrong; Guo, Dan; Xie, Guoxin; Pan, Guoshun

2016-07-01

Surfaces with controlled atomic step structures as substrates are highly relevant to desirable performances of materials grown on them, such as light emitting diode (LED) epitaxial layers, nanotubes and nanoribbons. However, very limited attention has been paid to the step formation in manufacturing process. In the present work, investigations have been conducted into this step formation mechanism on the sapphire c (0001) surface by using both experiments and simulations. The step evolutions at different stages in the polishing process were investigated with atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM). The simulation of idealized steps was constructed theoretically on the basis of experimental results. It was found that (1) the subtle atomic structures (e.g., steps with different sawteeth, as well as steps with straight and zigzag edges), (2) the periodicity and (3) the degree of order of the steps were all dependent on surface composition and miscut direction (step edge direction). A comparison between experimental results and idealized step models of different surface compositions has been made. It has been found that the structure on the polished surface was in accordance with some surface compositions (the model of single-atom steps: Al steps or O steps).

The temporolimbic system theory of positive schizophrenic symptoms.

PubMed

Bogerts, B

1997-01-01

This article proposes that subtle structural and functional disturbance of limbic key structures in the medial temporal lobe-especially of the left hippocampal formation and parahippocampal gyrus-can explain the so-called positive symptoms of schizophrenia. After presenting pathophysiological considerations linking limbic dysfunction to schizophrenia, the article reviews evidence from structural, biochemical, and functional studies supporting the theory. Also discussed here are neurodevelopmental and laterality aspects, as well as predictions, questions, and future tasks derived from the theory.

Evaluation of the airborne visible-infrared imaging spectrometer for mapping subtle lithological variation

NASA Technical Reports Server (NTRS)

Kruse, Fred A.

1990-01-01

The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS), flown aboard the NASA ER-2 aircraft in 1987 and 1989, used four linear arrays and four individual spectrometers to collect data simultaneously from the 224 bands in a scanned 614 pixel-wide swath perpendicular to the aircraft direction. The research had two goals. One was to evaluate the AVIRIS data. The other was to look at the subtle lithological variation at the two test sites to develop a better understanding of the regional geology and surficial processes. The geometric characteristics of the data, adequacy of the spatial resolution, and adequacy of the spectral sampling interval are evaluated. Geologic differences at the test sites were mapped. They included lithological variation caused by primary sedimentary layering, facies variation, and weathering; and subtle mineralogical differences caused by hydrothermal alterations of igneous and sedimentary rocks. The investigation used laboratory, field, and aircraft spectral measurements; known properties of geological materials; digital image processing and spectrum processing techniques; and field geologic data to evaluate the selected characteristics of the AVIRIS data.

TAP score: torsion angle propensity normalization applied to local protein structure evaluation

PubMed Central

Tosatto, Silvio CE; Battistutta, Roberto

2007-01-01

Background Experimentally determined protein structures may contain errors and require validation. Conformational criteria based on the Ramachandran plot are mainly used to distinguish between distorted and adequately refined models. While the readily available criteria are sufficient to detect totally wrong structures, establishing the more subtle differences between plausible structures remains more challenging. Results A new criterion, called TAP score, measuring local sequence to structure fitness based on torsion angle propensities normalized against the global minimum and maximum is introduced. It is shown to be more accurate than previous methods at estimating the validity of a protein model in terms of commonly used experimental quality parameters on two test sets representing the full PDB database and a subset of obsolete PDB structures. Highly selective TAP thresholds are derived to recognize over 90% of the top experimental structures in the absence of experimental information. Both a web server and an executable version of the TAP score are available at . Conclusion A novel procedure for energy normalization (TAP) has significantly improved the possibility to recognize the best experimental structures. It will allow the user to more reliably isolate problematic structures in the context of automated experimental structure determination. PMID:17504537

The dynamics of interacting salt structures and associated fluid flow in the western Norwegian-Danish Basin

NASA Astrophysics Data System (ADS)

Olsen, Mikkel S.; Clausen, Ole R.; Andresen, Katrine J.; Korstgård, John A.

2015-04-01

Minor secondary structures observed along the flanks of major salt structures in the Norwegian-Danish Basin appear to be generated mainly during the early stages of halokinesis. Seismic anomalies in the cover sediments at the flanks of the major salt structures and in relation to one of the secondary structures show several circular patterns. The circular patterns are generally interpreted as faults related to collapsing salt, indicating a subtle and dynamic cannibalization relationship between the secondary structure and the main diapir. High-amplitude reflections interpreted as either entrapped gas along the circular faults or diagenetic changes induced by the fluids originating from the salt-sediment interface generally enhances the seismic appearance of the circular faults, but potentially also disturb the seismic imaging of the faults. Other secondary salt structures, with a similar geometry, do not show sign of collapse, apparently due to a greater distance from the main salt structures and therefore not within the reach of being cannibalized by these. The observations furthermore suggest a trend showing a more advanced development of the main salt structures when the secondary structures are cannibalized. The lateral distribution of the main salt structures thus appears to be controlled not only by the initial thickness of the Zechstein salt, and possible underlying structures, but also by subtle variations in the location and evolution of secondary structures. The secondary structures have a major impact on the drainage of the deep Mesozoic succession as indicated by the fluid flow pattern also observed in the study, which emphasizes that a detailed mapping of salt structures including secondary structures at the flanks is of major importance during evaluation of petroleum systems in areas dominated by halokinesis.

Resolving Structural Isomers of Monosaccharide Methyl Glycosides Using Drift Tube and Traveling Wave Ion Mobility Mass Spectrometry

PubMed Central

Li, Hongli; Giles, Kevin; Bendiak, Brad; Kaplan, Kimberly; Siems, William F.; Hill, Herbert H.

2013-01-01

Monosaccharide structural isomers including sixteen methyl-D-glycopyranosides and four methyl-N-acetylhexosamines were subjected to ion mobility measurements by electrospray ion mobility mass spectrometry. Two ion mobility-MS systems were employed: atmospheric pressure drift tube ion mobility time-of-flight mass spectrometry and a Synapt G2 HDMS system which incorporates a low pressure traveling wave ion mobility separator. All the compounds were investigated as [M+Na]+ ions in the positive mode. A majority of the monosaccharide structural isomers exhibited different mobility drift times in either system, depending on differences in their anomeric and stereochemical configurations. In general, drift time patterns (relative drift times of isomers) matched between the two instruments. Higher resolving power was observed using the atmospheric pressure drift tube. Collision cross section values of monosaccharide structural isomers were directly calculated from the atmospheric pressure ion mobility experiments and a collision cross section calibration curve was made for the traveling wave ion mobility instrument. Overall, it was demonstrated that ion mobility-mass spectrometry using either drift tube or traveling wave ion mobility is a valuable technique for resolving subtle variations in stereochemistry among the sodium adducts of monosaccharide methyl glycosides. PMID:22339760

Reverse engineering the ancient ceramic technology based on X-ray fluorescence spectromicroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sciau, Philippe; Leon, Yoanna; Goudeau, Philippe

2011-07-06

We present results of X-ray fluorescence (XRF) microprobe analyses of ancient ceramic cross-sections aiming at deciphering the different firing protocols used for their production. Micro-focused XRF elemental mapping, Fe chemical mapping and Fe K-edge X-ray absorption near edge structure spectroscopy were performed on pre-sigillata ceramics from southern Gaul, and terra Sigillata vessels from Italy and southern Gaul. Pieces from the different workshops and regions showed significant difference in the starting clay material, clay conditioning and kiln firing condition. By contrast, sherds from the same workshop exhibited more subtle differences and possible misfirings. Understanding the precise firing conditions and protocols wouldmore » allow recreation of kilns for various productions. Furthermore, evolution and modification of kiln design would shed some light on how ancient potters devised solutions to diverse technological problems they encountered.« less

Thermodynamic and structural effect of urea and guanidine chloride on the helical and on a hairpin fragment of GB1 from molecular simulations.

PubMed

Meloni, R; Tiana, G

2017-04-01

With the help of molecular-dynamics simulations, we studied the effect of urea and guanidine chloride on the thermodynamic and structural properties of the helical fragment of protein GB1, comparing them with those of its second beta hairpin. We showed that the helical fragment in different solvents populates an ensemble of states that is more complex than that of the hairpin, and thus the associated experimental observables (circular-dichroism spectra, secondary chemical shifts, m values), that we back-calculated from the simulations and compared with the actual data, are more difficult to interpret. We observed that in the case of both peptides, urea binds tightly to their backbone, while guanidine exerts its denaturing effect in a more subtle way, strongly affecting the electrostatic properties of the solution. This difference can have consequences in the way denaturation experiments are interpreted. Proteins 2017; 85:753-763. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A greedy-navigator approach to navigable city plans

NASA Astrophysics Data System (ADS)

Lee, Sang Hoon; Holme, Petter

2013-01-01

We use a set of four theoretical navigability indices for street maps to investigate the shape of the resulting street networks, if they are grown by optimizing these indices. The indices compare the performance of simulated navigators (having a partial information about the surroundings, like humans in many real situations) to the performance of optimally navigating individuals. We show that our simple greedy shortcut construction strategy generates the emerging structures that are different from real road network, but not inconceivable. The resulting city plans, for all navigation indices, share common qualitative properties such as the tendency for triangular blocks to appear, while the more quantitative features, such as degree distributions and clustering, are characteristically different depending on the type of metrics and routing strategies. We show that it is the type of metrics used which determines the overall shapes characterized by structural heterogeneity, but the routing schemes contribute to more subtle details of locality, which is more emphasized in case of unrestricted connections when the edge crossing is allowed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Soohaeng; Xantheas, Sotiris S.

Water's function as a universal solvent and its role in mediating several biological functions that are responsible for sustaining life has created tremendous interest in the understanding of its structure at the molecular level.1 Due to the size of the simulation cells and the sampling time needed to compute many macroscopic properties, most of the initial simulations are performed using a classical force field whereas several processes that involve chemistry are subsequently probed with electronic structure based methods. A significant effort has therefore been devoted towards the development of classical force fields for water.2 Clusters of water molecules are usefulmore » in probing the intermolecular interactions at the microscopic level as well as providing information about the subtle energy differences that are associated with different bonding arrangements within a hydrogen bonded network. They moreover render a quantitative picture of the nature and magnitude of the various components of the intermolecular interactions such as exchange, dispersion, induction etc. They can finally serve as a vehicle for the study of the convergence of properties with increasing size.« less

Geology of Utah and Nevada by ERTS-1 imagery

NASA Technical Reports Server (NTRS)

Jensen, M. L.

1973-01-01

Repetitive ERTS-1 imagery covering Utah and Nevada is studied as an aid in structural geology, mineral exploration, and limnological and hydrological aspects. Limnological features of algal blooms and varying biological activities in Utah Lake and the Great Salt Lake are grossly evident on the imagery with more subtle details detected on the different bands. Major structural breaks, lineages, or trends are abundant throughout the area of study. The correlation of positive aeromagnetic anomalies with the trends suggests near surface intrusive bodies, not yet exposed at the surface, that can be tested for possible associated mineralization by collecting soil-gas at the surface which is analyzed for mercury that is (1) apparently associated with mineralization, (2) escapes as a vapor, and (3) can be readily measured in extremely low amounts of less than 1 ppb by absorption.

Phase shift of oscillatory magnetoresistance in a double-cross thin film structure of La0.3Pr0.4Ca0.3MnO3 via strain-engineered elongation of electronic domains

NASA Astrophysics Data System (ADS)

Alagoz, H. S.; Prasad, B.; Jeon, J.; Blamire, M. G.; Chow, K. H.; Jung, J.

2018-02-01

The subtle balance between the competing electronic phases in manganites due to complex interplay between spin, charge, and orbital degrees of freedom could allow one to modify the properties of electronically phase separated systems. In this paper, we show that the phase shift in the oscillatory magnetoresistance ρ (θ ) can be modified by engineering strain driven elongation of electronic domains in La0.3Pr0.4Ca0.3MnO3 (LPCMO) thin films. Strain-driven elongation of magnetic domains can produce different percolation paths and hence different anisotropic magnetoresistance responses. This tunability provides a unique control that is unattainable in conventional 3 d ferromagnetic metals and alloys.

Quantitative comparison of structure and dynamics of elastin following three isolation schemes by 13C solid state NMR and MALDI mass spectrometry.

PubMed

Papaioannou, A; Louis, M; Dhital, B; Ho, H P; Chang, E J; Boutis, G S

2015-05-01

Methods for isolating elastin from fat, collagen, and muscle, commonly used in the design of artificial elastin based biomaterials, rely on exposing tissue to harsh pH levels and temperatures that usually denature many proteins. At present, a quantitative measurement of the modifications to elastin following isolation from other extracellular matrix constituents has not been reported. Using magic angle spinning (13)C NMR spectroscopy and relaxation methodologies, we have measured the modification in structure and dynamics following three known purification protocols. Our experimental data reveal that the (13)C spectra of the hydrated samples appear remarkably similar across the various purification methods. Subtle differences in the half maximum widths were observed in the backbone carbonyl suggesting possible structural heterogeneity across the different methods of purification. Additionally, small differences in the relative signal intensities were observed between purified samples. Lyophilizing the samples results in a reduction of backbone motion and reveals additional differences across the purification methods studied. These differences were most notable in the alanine motifs indicating possible changes in cross-linking or structural rigidity. The measured correlation times of glycine and proline moieties are observed to also vary considerably across the different purification methods, which may be related to peptide bond cleavage. Lastly, the relative concentration of desmosine cross-links in the samples quantified by MALDI mass spectrometry is reported. Copyright © 2015 Elsevier B.V. All rights reserved.

State Action and Labor Structure Change in Mexico.

ERIC Educational Resources Information Center

Fuller, Bruce; And Others

1990-01-01

Examines how the Mexican government's penetration into 299 rural and urban counties, 1900-40, was related to growth in trade and service jobs. Emphasizes the government's support for written literacy and mass schooling as subtle strategies for incorporating peasants into urban institutions. Contains 39 references. (SV)

Characterization and differentiation of rock varnish types from different environments by microanalytical techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macholdt, D. S.; Jochum, K. P.; Pöhlker, C.

We investigated rock varnishes collected from several locations and environments worldwide by a wide range of microanalytical techniques. These techniques were selected to address the challenges posed by the chemical and structural complexity within the micrometer- to nanometer-sized structures in these geological materials. Femtosecond laser ablation-inductively coupled plasma-mass spectrometry (fs LA-ICP-MS), scanning transmission X-ray microscopy-near edge X-ray adsorption fine structure spectroscopy (STXM-NEXAFS) in combination with scanning electron microscopy (SEM) of focused ion beam (FIB) ultra-thin (100–200 nm) sections, conventional and polarization microscopy, as well as electron paramagnetic resonance (EPR) measurements were used to obtain information about these rock varnishes. Rockmore » varnishes from different environments, which cannot readily be distinguished based on their macroscopic appearance, differ significantly in their constituent elemental mass fractions, e.g., of Mn, Fe, Ni, Co, Ba, and Pb, and their rare earth element (REE) patterns. Structural characteristics such as the particle sizes of embedded dust grains, internal structures such as layers of Mn-, Fe-, and Ca -rich material, and structures such as cavities varied between varnishes from different environments and regions in the world. The EPR spectra were consistent with aged biogenic Mn oxides in all samples, but showed subtle differences between samples of different origin. Our observations allow us to separate rock varnishes into different types, with differences that might be indicators of distinct geneses. Five different types of rock varnish could be distinguished, Type I–V, of which only Type I might be used as potential paleoclimate archive. Each varnish type has specific characteristics in terms of their elemental composition, element distribution, and structures. The combination of element ratios (Mn/Ba, Al/Ni, Mn/REY, Mn/Ce, Mn/Pb, La N /Yb N , and Ce/Ce*), total REE contents, and structures can be used to separate the different types of rock varnish from each other.« less

Microgravity

NASA Image and Video Library

2000-05-05

This computer graphic depicts the relative complexity of crystallizing large proteins in order to study their structures through x-ray crystallography. Insulin is a vital protein whose structure has several subtle points that scientists are still trying to determine. Large molecules such as insuline are complex with structures that are comparatively difficult to understand. For comparison, a sugar molecule (which many people have grown as hard crystals in science glass) and a water molecule are shown. These images were produced with the Macmolecule program. Photo credit: NASA/Marshall Space Flight Center (MSFC)

The impact of radiology expertise upon the localization of subtle pulmonary lesions

NASA Astrophysics Data System (ADS)

Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J.

2016-03-01

Rationale and objectives: This study investigates the influence of radiology expertise in the correct localization of lesions when radiologists are requested to complete an observer task. Specifically, the ability to detect pulmonary lesions of different subtleties is explored in relation to radiologists' reported specialty. Materials and Methods: Institutional ethics was granted. Ten radiologists (5 thoracic, 5 non-thoracic) interpreted 40 posterior-anterior (PA) chest x-rays (CXRs) consisting of 21 normal and 19 abnormal cases (solitary pulmonary nodule). The abnormal cases contained a solitary nodule with an established subtlety (subtlety 5 = obvious to subtlety 1 = extremely subtle). Radiologists read the test set and identified any pulmonary nodule using a 1-5 confidence scale (1=no pulmonary nodule to 5=highest confidence case contains a pulmonary lesion). The radiologists interpreted the image bank twice and the cases were randomized for each reader between reads. Results: The Kruskal-Wallis test identified that subtlety of nodules significantly influenced the sensitivity of nonthoracic radiologists (P=<0.0001) and thoracic radiologists (P=<0.0001). A Wilcoxon rank test demonstrated a significant difference in sensitivity for radiologist specialisation (P=0.013), with thoracic radiologists better compared to non-thoracic radiologists (mean sensitivity 0.479 and 0.389 respectively). The sensitivity of nodule detection decreased when comparing subtlety 4 to 3, 3 to 2 and 2 to 1 for non-thoracic and thoracic radiologists'with the subtlety 3 to subtlety 2 being significant (P=0.014) for non thoracic radiologists while thoracic radiologists' demonstrated a decrease but no transitions between subtlety were significant. The most noticeable, and interesting, effect was with the thoracic radiologists' with the average means of subtlety 2 and 1 being almost the same and closely comparable to level 3. Conclusion: Results from this study indicate that expertise in chest radiology does significantly impact upon the sensitivity of radiologists in detecting pulmonary lesions of varying subtlety. Thoracic radiologists had a consistently higher sensitivity with subtle, very subtle and extremely subtle nodules.

Reconciliation of local and long-range tilt correlations in underdoped La 2-xBa xCuO 4(0 ≤ x ≤ 0.155)

DOE PAGES

Bozin, Emil S.; Zhong, Ruidan; Knox, Kevin R.; ...

2015-02-26

A long standing puzzle regarding the disparity of local and long range CuO₆ octahedral tilt correlations in the underdoped regime of La₂₋ xBa xCuO₄ is addressed by utilizing complementary neutron powder diffraction and inelastic neutron scattering (INS) approaches. Long-range and static CuO₆ tilt order with orthogonally inequivalent Cu-O bonds in the CuO₂ planes in the low temperature tetragonal (LTT) phase is succeeded on warming through the low-temperature transition by one with orthogonally equivalent bonds in the low temperature orthorhombic (LTO) phase. In contrast, the signatures of LTT-type tilts in the instantaneous local atomic structure persist on heating throughout the LTOmore » crystallographic phase on the nanoscale, although becoming weaker as temperature increases. Analysis of the INS spectra for the x = 1/8 composition reveals the dynamic nature of the LTT-like tilt fluctuations within the LTO phase and their 3D character. The doping dependence of relevant structural parameters indicates that the magnitude of the Cu-O bond anisotropy has a maximum at x = 1/8 doping where bulk superconductivity is most strongly suppressed, suggesting that the structural anisotropy might be influenced by electron-phonon coupling and the particular stability of the stripe-ordered phase at this composition. The bond-length modulation that pins stripe order is found to be remarkably subtle, with no anomalous bond length disorder at low temperature, placing an upper limit on any in-plane Cu-O bondlength anisotropy. The results further reveal that although appreciable octahedral tilts persist through the high-temperature transition and into the high temperature tetragonal (HTT) phase, there is no significant preference between different tilt directions in the HTT regime. As a result, this study also exemplifies the importance of a systematic approach using complementary techniques when investigating systems exhibiting a large degree of complexity and subtle structural responses.« less

Friction of water on graphene and hexagonal boron nitride from ab initio methods: very different slippage despite very similar interface structures.

PubMed

Tocci, Gabriele; Joly, Laurent; Michaelides, Angelos

2014-12-10

Friction is one of the main sources of dissipation at liquid water/solid interfaces. Despite recent progress, a detailed understanding of water/solid friction in connection with the structure and energetics of the solid surface is lacking. Here, we show for the first time that ab initio molecular dynamics can be used to unravel the connection between the structure of nanoscale water and friction for liquid water in contact with graphene and with hexagonal boron nitride. We find that although the interface presents a very similar structure between the two sheets, the friction coefficient on boron nitride is ≈ 3 times larger than that on graphene. This comes about because of the greater corrugation of the energy landscape on boron nitride arising from specific electronic structure effects. We discuss how a subtle dependence of the friction on the atomistic details of a surface, which is not related to its wetting properties, may have a significant impact on the transport of water at the nanoscale, with implications for the development of membranes for desalination and for osmotic power harvesting.

Magnetically-induced ferroelectricity in the (ND4)2[FeCl5(D2O)] molecular compound

PubMed Central

Alberto Rodríguez-Velamazán, José; Fabelo, Óscar; Millán, Ángel; Campo, Javier; Johnson, Roger D.; Chapon, Laurent

2015-01-01

The number of magnetoelectric multiferroic materials reported to date is scarce, as magnetic structures that break inversion symmetry and induce an improper ferroelectric polarization typically arise through subtle competition between different magnetic interactions. The (NH4)2[FeCl5(H2O)] compound is a rare case where such improper ferroelectricity has been observed in a molecular material. We have used single crystal and powder neutron diffraction to obtain detailed solutions for the crystal and magnetic structures of (NH4)2[FeCl5(H2O)], from which we determined the mechanism of multiferroicity. From the crystal structure analysis, we observed an order-disorder phase transition related to the ordering of the ammonium counterion. We have determined the magnetic structure below TN, at 2 K and zero magnetic field, which corresponds to a cycloidal spin arrangement with magnetic moments contained in the ac-plane, propagating parallel to the c-axis. The observed ferroelectricity can be explained, from the obtained magnetic structure, via the inverse Dzyaloshinskii-Moriya mechanism. PMID:26417890

High-resolution charge carrier mobility mapping of heterogeneous organic semiconductors

NASA Astrophysics Data System (ADS)

Button, Steven W.; Mativetsky, Jeffrey M.

2017-08-01

Organic electronic device performance is contingent on charge transport across a heterogeneous landscape of structural features. Methods are therefore needed to unravel the effects of local structure on overall electrical performance. Using conductive atomic force microscopy, we construct high-resolution out-of-plane hole mobility maps from arrays of 5000 to 16 000 current-voltage curves. To demonstrate the efficacy of this non-invasive approach for quantifying and mapping local differences in electrical performance due to structural heterogeneities, we investigate two thin film test systems, one bearing a heterogeneous crystal structure [solvent vapor annealed 5,11-Bis(triethylsilylethynyl)anthradithiophene (TES-ADT)—a small molecule organic semiconductor] and one bearing a heterogeneous chemical composition [p-DTS(FBTTh2)2:PC71BM—a high-performance organic photovoltaic active layer]. TES-ADT shows nearly an order of magnitude difference in hole mobility between semicrystalline and crystalline areas, along with a distinct boundary between the two regions, while p-DTS(FBTTh2)2:PC71BM exhibits subtle local variations in hole mobility and a nanoscale domain structure with features below 10 nm in size. We also demonstrate mapping of the built-in potential, which plays a significant role in organic light emitting diode and organic solar cell operation.

Crystallinity of tellurium capping and epitaxy of ferromagnetic topological insulator films on SrTiO 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jihwey; Soh, Yeong-Ah; Aeppli, Gabriel

2015-06-30

Thin films of topological insulators are often capped with an insulating layer since topological insulators are known to be fragile to degradation. However, capping can hinder the observation of novel transport properties of the surface states. To understand the influence of capping on the surface states, it is crucial to understand the crystal structure and the atomic arrangement at the interfaces. Here, we use x-ray diffraction to establish the crystal structure of magnetic topological insulator Cr-doped (Bi,Sb) 2Te 3 (CBST) films grown on SrTiO 3 (1 1 1) substrates with and without a Te capping layer. We find that bothmore » the film and capping layer are single crystal and that the crystal quality of the film is independent of the presence of the capping layer, but that x-rays cause sublimation of the CBST film, which is prevented by the capping layer. Our findings show that the different transport properties of capped films cannot be attributed to a lower crystal quality but to a more subtle effect such as a different electronic structure at the interface with the capping layer. Our results on the crystal structure and atomic arrangements of the topological heterostructure will enable modelling the electronic structure and design of topological heterostructures.« less

Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies*

PubMed Central

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; Goger, Michael; Wang, Xiaobo; Fries, Bettina C.

2015-01-01

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

Mechanisms mediating enhanced neutralization efficacy of Staphylococcal enterotoxin B by combinations of monoclonal antibodies

DOE PAGES

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; ...

2015-01-08

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used tomore » validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Lastly structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.« less

Effects of Participant Engagement on Prosodic Prominence

ERIC Educational Resources Information Center

Buxó-Lugo, Andrés; Toscano, Joseph C.; Watson, Duane G.

2018-01-01

It is generally assumed that prosodic cues that provide linguistic information, like discourse status, are driven primarily by the information structure of the conversation. This article investigates whether speakers have the capacity to adjust subtle acoustic-phonetic properties of the prosodic signal when they find themselves in contexts in…

Instructional Television: Do We Have the Courage to Succeed?

ERIC Educational Resources Information Center

Bosner, Paul

1976-01-01

A discussion of instructional television's implementation in terms of massiveness of the system; the decentralization of the system; and the fragmented, overlapping funding structure of the system, which results in obscured centers of power resting somewhere between state and local control, with subtle direction by the federal government.…

Cell Signaling and Neurotoxicity: Protein Kinase C in vitro and in vivo

EPA Science Inventory

There is a growing concern about the effects of chemicals on the developing nervous system. Chemical exposure at critical periods of development can be associated with effects ranging from subtle to profound on the structure and/or function of the nervous system. Understanding cr...

Making quantitative morphological variation from basic developmental processes: where are we? The case of the Drosophila wing

PubMed Central

Alexis, Matamoro-Vidal; Isaac, Salazar-Ciudad; David, Houle

2015-01-01

One of the aims of evolutionary developmental biology is to discover the developmental origins of morphological variation. The discipline has mainly focused on qualitative morphological differences (e.g., presence or absence of a structure) between species. Studies addressing subtle, quantitative variation are less common. The Drosophila wing is a model for the study of development and evolution, making it suitable to investigate the developmental mechanisms underlying the subtle quantitative morphological variation observed in nature. Previous reviews have focused on the processes involved in wing differentiation, patterning and growth. Here, we investigate what is known about how the wing achieves its final shape, and what variation in development is capable of generating the variation in wing shape observed in nature. Three major developmental stages need to be considered: larval development, pupariation, and pupal development. The major cellular processes involved in the determination of tissue size and shape are cell proliferation, cell death, oriented cell division and oriented cell intercalation. We review how variation in temporal and spatial distribution of growth and transcription factors affects these cellular mechanisms, which in turn affects wing shape. We then discuss which aspects of the wing morphological variation are predictable on the basis of these mechanisms. PMID:25619644

Deconstructing Planning Ability in Children and Adolescents with Anorexia Nervosa.

PubMed

Rose, Mark; Reville, Marie-Claire; Iszatt, Amber; Levinson, Simon; Frampton, Ian; Lask, Bryan

2017-01-01

Weaknesses in planning by patients with anorexia nervosa (AN) have been noted (e.g., Zakzanis, Campbell, & Polsinelli, 2010 ) and are generally based on adults. This study explored D-KEFS Tower Test performance to better understand learning styles and strategies used by child and adolescent patients with AN compared to healthy controls. Overall, no significant differences were found in achievement; however, Item 5 predicted performance across harder items. The AN group was significantly faster to move their first disc suggesting patients with AN did not spend as much time planning their strategies for item completion. The findings of this study in conjunction with other studies investigating planning in AN may suggest the existence of subtle differences in learning style and strategy, such as faster initiation times, rather than gross planning differences. Further research is required to better understand the relationship between these subtle differences and clinical presentations.

Indirect effects in community ecology: Their definition, study and importance.

PubMed

Strauss, S Y

1991-07-01

The diversity of indirect interactions that can occur within communities is large. Recent research on indirect interactions is scattered in the literature under numerous labels. The definition of indirect effects is an important aspect of their study, and clarifies some of the subtle differences among indirect effects found in natural communities. Choosing which species to study, how to manipulate species and for what duration, which attributes to measure and, finally, which analytical techniques to use are all problems facing the community ecologist. Ultimately, we are striving for the best means of determining the relative importance of direct and indirect effects in structuring communities. Copyright © 1991. Published by Elsevier Ltd.

Competition and compensation

PubMed Central

Manor, Uri; Grati, M'hamed; Yengo, Christopher M.; Kachar, Bechara; Gov, Nir S.

2012-01-01

Stereocilia are actin protrusions with remarkably well-defined lengths and organization. A flurry of recent papers has reported multiple myosin motor proteins involved in regulating stereocilia structures by transporting actin-regulatory cargo to the tips of stereocilia.1-13 In our recent paper, we show that two paralogous class 3 myosins — Myo3a and Myo3b — both transport the actin-regulatory protein Espin 1 (Esp1) to stereocilia and filopodia tips in a remarkably similar, albeit non-identical fashion.1 Here we present experimental and computational data that suggests that subtle differences between these two proteins’ biophysical and biochemical properties can help us understand how these myosin species target and regulate the lengths of actin protrusions. PMID:22954581

Lymphocyte signaling: beyond knockouts.

PubMed

Saveliev, Alexander; Tybulewicz, Victor L J

2009-04-01

The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.

Near-Unity Quantum Yields of Biexciton Emission from CdSe=CdS Nanocrystals Measured Using Single-Particle Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Young-Shin; Malko, Anton V.; Vela, Javier

2011-05-03

Biexciton photoluminescence (PL) quantum yields (Q 2X) of individual CdSe/CdS core-shell nanocrystal quantum dots with various shell thicknesses are derived from independent PL saturation and two-photon correlation measurements. We observe a near-unity Q{sub 2X} for some nanocrystals with an ultrathick 19-monolayer shell. High Q 2X’s are, however, not universal and vary widely among nominally identical nanocrystals indicating a significant dependence of Q 2X upon subtle structural differences. Interestingly, our measurements indicate that high Q 2X’s are not required to achieve complete suppression of PL intensity fluctuations in individual nanocrystals.

Halogenated Alkyltetrazoles for the Rational Design of FeII Spin-Crossover Materials: Fine-Tuning of the Ligand Size.

PubMed

Müller, Danny; Knoll, Christian; Seifried, Marco; Welch, Jan M; Giester, Gerald; Reissner, Michael; Weinberger, Peter

2018-04-06

1-(3-Halopropyl)-1H-tetrazoles and their corresponding Fe II spin-crossover complexes have been investigated in a combined experimental and theoretical study. Halogen substitution was found to positively influence the spin transition, shifting the transition temperature about 70 K towards room temperature. Halogens located at the ω position were found to be too far away from the coordinating tetrazole moiety to have an electronic impact on the spin transition. The subtle variation of the steric demand of the ligand in a highly comparable series was found to have a comparatively large impact on the spin-transition behavior, which highlights the sensitivity of the effect to subtle structural changes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Water-Soluble Polyphosphazenes and Their Hydrogels

DTIC Science & Technology

1994-05-18

side groups, such as -OH, -COONa, -NH2, -NHCH3, -SO3", or -C=O, or amphiphilic units such as -OCH2CH20-, etc. High concentrations of hydrophilic side...soluble polymers since it allows a high degree of utilization of molecular design and either extensive or subtle structural manipulation. The third...advantages for development as water-soluble polymers or hydrogels. The backbone is hydrophilic, the chain structure has a high 3 degree of flexibility, and

CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

PubMed

Huynh, Kevin W; Jiang, Jiansen; Abuladze, Natalia; Tsirulnikov, Kirill; Kao, Liyo; Shao, Xuesi; Newman, Debra; Azimov, Rustam; Pushkin, Alexander; Zhou, Z Hong; Kurtz, Ira

2018-03-02

Na + -coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na + -coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.

The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity

PubMed Central

Bolam, David N.; Roberts, Shirley; Proctor, Mark R.; Turkenburg, Johan P.; Dodson, Eleanor J.; Martinez-Fleites, Carlos; Yang, Min; Davis, Benjamin G.; Davies, Gideon J.; Gilbert, Harry J.

2007-01-01

Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI and OleD, glycosylate and inactivate oleandomycin and diverse macrolides including erythromycin, respectively. The structure of these enzyme–ligand complexes, in tandem with kinetic analysis of site-directed variants, provide insight into the interaction of macrolides with their synthetic apparatus. Erythromycin binds to OleD and the 23S RNA of its target ribosome in the same conformation and, although the antibiotic contains a large number of polar groups, its interaction with these macromolecules is primarily through hydrophobic contacts. Erythromycin and oleandomycin, when bound to OleD and OleI, respectively, adopt different conformations, reflecting a subtle effect on sugar positioning by virtue of a single change in the macrolide backbone. The data reported here provide structural insight into the mechanism of resistance to both endogenous and exogenous antibiotics, and will provide a platform for the future redesign of these catalysts for antibiotic remodelling. PMID:17376874

Mechanical Characteristics of SiC Coating Layer in TRISO Fuel Particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

P. Hosemann; J. N. Martos; D. Frazer

2013-11-01

Tristructural isotropic (TRISO) particles are considered as advanced fuel forms for a variety of fission platforms. While these fuel structures have been tested and deployed in reactors, the mechanical properties of these structures as a function of production parameters need to be investigated in order to ensure their reliability during service. Nanoindentation techniques, indentation crack testing, and half sphere crush testing were utilized in order to evaluate the integrity of the SiC coating layer that is meant to prevent fission product release in the coated particle fuel form. The results are complimented by scanning electron microscopy (SEM) of the grainmore » structure that is subject to change as a function of processing parameters and can alter the mechanical properties such as hardness, elastic modulus, fracture toughness and fracture strength. Through utilization of these advanced techniques, subtle differences in mechanical properties that can be important for in-pile fuel performance can be distinguished and optimized in iteration with processing science of coated fuel particle production.« less

Morphological alterations in the prefrontal cortex and the amygdala in unsuccessful psychopaths.

PubMed

Yang, Yaling; Raine, Adrian; Colletti, Patrick; Toga, Arthur W; Narr, Katherine L

2010-08-01

Although deficits in several cortical and subcortical structures have been found in psychopaths, it remains unclear whether the neuropathology differs between subgroups of psychopaths (i.e., unsuccessful and successful). Using both traditional and novel image analyses methods, this study aims to reveal gross and subtle morphological changes in the prefrontal cortex and the amygdala in unsuccessful and successful psychopaths. Volumetric segmentation, cortical pattern matching, and surface-based mesh modeling methods were used to examine prefrontal and amygdala structures in 16 unsuccessful psychopaths, 10 successful psychopaths, and 27 controls. Significant reduced gray matter volume and cortical thickness/surface shape in the middle frontal, orbitofrontal cortex and the amygdala were found in unsuccessful psychopaths but not successful psychopaths, compared with controls. This study provides the first evidence of greater prefrontal and amygdala structural deficits in unsuccessful psychopaths, which may predispose them to poor behavioral control and impaired decision-making, thus making them more prone to convictions. Copyright 2010 APA, all rights reserved

Lineup administrator influences on eyewitness identification decisions.

PubMed

Clark, Steven E; Marshall, Tanya E; Rosenthal, Robert

2009-03-01

The present research examines how a lineup administrator may influence eyewitness identification decisions through different forms of influence, after providing the witness with standard, unbiased instructions. Participant-witnesses viewed a staged crime and were later shown a target-present or target-absent lineup. The lineup administrators either remained silent while the witness examined the lineup, made ostensibly cautionary statements to the witness, or prompted the witness to identify the person in the lineup who seemed most similar to the perpetrator. These two forms of influence, denoted as subtle-influence and similarity-influence conditions, led to different patterns of identification results. Results for the similarity-influence condition were generally consistent with criterion shift and relative judgment models of eyewitness decision making. Results for the subtle-influence condition, however, cannot be explained by alterations in the decision rule. A weighted matching model is outlined to explain results from the subtle-influence condition. Witnesses seemed generally unaware of the attempts by the lineup administrator to influence their decision, although some noted it, and the probative value of suspect identifications was lower for those who did note it. Implications for theory and policy are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

The structures of cytosolic and plastid-located glutamine synthetases from Medicago truncatula reveal a common and dynamic architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torreira, Eva; Seabra, Ana Rita; Marriott, Hazel

The experimental models of dicotyledonous cytoplasmic and plastid-located glutamine synthetases unveil a conserved eukaryotic-type decameric architecture, with subtle structural differences in M. truncatula isoenzymes that account for their distinct herbicide resistance. The first step of nitrogen assimilation in higher plants, the energy-driven incorporation of ammonia into glutamate, is catalyzed by glutamine synthetase. This central process yields the readily metabolizable glutamine, which in turn is at the basis of all subsequent biosynthesis of nitrogenous compounds. The essential role performed by glutamine synthetase makes it a prime target for herbicidal compounds, but also a suitable intervention point for the improvement of cropmore » yields. Although the majority of crop plants are dicotyledonous, little is known about the structural organization of glutamine synthetase in these organisms and about the functional differences between the different isoforms. Here, the structural characterization of two glutamine synthetase isoforms from the model legume Medicago truncatula is reported: the crystallographic structure of cytoplasmic GSII-1a and an electron cryomicroscopy reconstruction of plastid-located GSII-2a. Together, these structural models unveil a decameric organization of dicotyledonous glutamine synthetase, with two pentameric rings weakly connected by inter-ring loops. Moreover, rearrangement of these dynamic loops changes the relative orientation of the rings, suggesting a zipper-like mechanism for their assembly into a decameric enzyme. Finally, the atomic structure of M. truncatula GSII-1a provides important insights into the structural determinants of herbicide resistance in this family of enzymes, opening new avenues for the development of herbicide-resistant plants.« less

Differences in mechanical and structural properties of surface and aerial petioles of the aquatic plant Nymphaea odorata subsp. tuberosa (Nymphaeaceae).

PubMed

Etnier, Shelley A; Villani, Philip J

2007-07-01

Lily pads (Nymphaea odorata) exhibit heterophylly where a single plant may have leaves that are submerged, floating, or above (aerial) the surface of the water. Lily pads are placed in a unique situation because each leaf form is exposed to a distinctly different set of mechanical demands. While surface petioles may be loaded in tension under conditions of wind or waves, aerial petioles are loaded in compression because they must support the weight of the lamina. Using standard techniques, we compared the mechanical and morphological properties of both surface and aerial leaf petioles. Structural stiffness (EI) and the second moment of area (I) were higher in aerial petioles, although we detected no differences in other mechanical values (elastic modulus [E], extension ratio, and breaking strength). Morphologically, aerial petioles had a thicker rind, with increased collenchyma tissue and sclereid cell frequency. Aerial petioles also had a larger cross-sectional area and were more elliptical. Thus, subtle changes in the distribution of materials, rather than differences in their makeup, differentiate petiole forms. We suggest that the growth of aerial petioles may be an adaptive response to shading, allowing aerial leaves to rise above a crowded water surface.

Site-specific incorporation of uranyl carbonate species at the calcite surface

NASA Astrophysics Data System (ADS)

Reeder, Richard J.; Elzinga, Evert J.; Tait, C. Drew; Rector, K. D.; Donohoe, Robert J.; Morris, David E.

2004-12-01

Spatially resolved luminescence spectra from U(VI) co-precipitated at the (101¯4) growth surface of synthetic calcite single crystals confirm heterogeneous incorporation corresponding to the distribution of structurally non-equivalent steps composing the vicinal surfaces of spiral growth hillocks. Spectral structure from U(VI) luminescence at the "-" vicinal regions and featureless, weak luminescence at the "+" vicinal regions are consistent with previously reported observations of enrichment at the former sites during calcite growth. Luminescence spectra differ between the non-equivalent regions of the crystal, with the spectral features from the "-" vicinal region corresponding to those observed in bulk calcite samples. Subtle spectral shifts are observed from U(VI) co-precipitated with microcrystalline calcite synthesized by a different method, and all of the U(VI)-calcite sample spectra differ significantly from that of U(VI) co-precipitated with aragonite. The step-selective incorporation of U(VI) can be explained by a proposed model in which the allowed orientation for adsorption of the dominant calcium uranyl triscarbonate species is controlled by the atomic arrangement at step edges. Differences in the tilt angles of carbonate groups between non-equivalent growth steps favor adsorption of the calcium uranyl triscarbonate species at "-" steps, as observed in experiments.

Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant

NASA Astrophysics Data System (ADS)

Moe, Elin; Rollo, Filipe; Silveira, Célia M.; Sezer, Murat; Hildebrandt, Peter; Todorovic, Smilja

2018-01-01

Endonuclease III is a Fe-S containing bifunctional DNA glycosylase which is involved in the repair of oxidation damaged DNA. Here we employ surface enhanced IR spectroelectrochemistry and electrochemistry to study the enzyme from the highly radiation- and desiccation-resistant bacterium Deinococcus radiodurans (DrEndoIII2). The experiments are designed to shed more light onto specific parameters that are currently proposed to govern damage search and recognition by endonucleases III. We demonstrate that electrostatic interactions required for the redox activation of DrEndoIII2 may result in high electric fields that alter its structural and thermodynamic properties. Analysis of inactive DrEndoIII2 (K132A/D150A double mutant) interacting with undamaged DNA, and the active enzyme interacting with damaged DNA also indicate that the electron transfer is modulated by subtle differences in the protein-DNA complex.

Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation

NASA Astrophysics Data System (ADS)

Carnevale, V.; Raugei, S.

2009-12-01

Lysine acetylation is a post-translational modification, which modulates the affinity of protein-protein and/or protein-DNA complexes. Its crucial role as a switch in signaling pathways highlights the relevance of charged chemical groups in determining the interactions between water and biomolecules. A great effort has been recently devoted to assess the reliability of classical molecular dynamics simulations in describing the solvation properties of charged moieties. In the spirit of these investigations, we performed classical and Car-Parrinello molecular dynamics simulations on lysine and acetylated-lysine in aqueous solution. A comparative analysis between the two computational schemes is presented with a focus on the first solvation shell of the charged groups. An accurate structural analysis unveils subtle, yet statistically significant, differences which are discussed in connection to the significant electronic density charge transfer occurring between the solute and the surrounding water molecules.

Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant.

PubMed

Moe, Elin; Rollo, Filipe; Silveira, Célia M; Sezer, Murat; Hildebrandt, Peter; Todorovic, Smilja

2018-01-05

Endonuclease III is a Fe-S containing bifunctional DNA glycosylase which is involved in the repair of oxidation damaged DNA. Here we employ surface enhanced IR spectroelectrochemistry and electrochemistry to study the enzyme from the highly radiation- and desiccation-resistant bacterium Deinococcus radiodurans (DrEndoIII 2 ). The experiments are designed to shed more light onto specific parameters that are currently proposed to govern damage search and recognition by endonucleases III. We demonstrate that electrostatic interactions required for the redox activation of DrEndoIII 2 may result in high electric fields that alter its structural and thermodynamic properties. Analysis of inactive DrEndoIII 2 (K132A/D150A double mutant) interacting with undamaged DNA, and the active enzyme interacting with damaged DNA also indicate that the electron transfer is modulated by subtle differences in the protein-DNA complex. Copyright © 2017 Elsevier B.V. All rights reserved.

Peroxisome protein import: a complex journey.

PubMed

Baker, Alison; Lanyon-Hogg, Thomas; Warriner, Stuart L

2016-06-15

The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor-cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes. © 2016 The Author(s).

Multiple crossovers and coherent states in a Mott-Peierls insulator

NASA Astrophysics Data System (ADS)

Nájera, O.; Civelli, M.; Dobrosavljević, V.; Rozenberg, M. J.

2018-01-01

We consider the dimer Hubbard model within dynamical mean-field theory to study the interplay and competition between Mott and Peierls physics. We describe the various metal-insulator transition lines of the phase diagram and the breakdown of the different solutions that occur along them. We focus on the specific issue of the debated Mott-Peierls insulator crossover and describe the systematic evolution of the electronic structure across the phase diagram. We found that at low intradimer hopping, the emerging local magnetic moments can unbind above a characteristic singlet temperature T*. Upon increasing the interdimer hopping, subtle changes occur in the electronic structure. Notably, we find Hubbard bands of a mix character with coherent and incoherent excitations. We argue that this state might be relevant for materials such as VO2 and its signatures may be observed in spectroscopic studies, and possibly through pump-probe experiments.

Layered copper hydroxide n-alkylsulfonate salts: synthesis, characterization, and magnetic behaviors in relation to the basal spacing.

PubMed

Park, Seong-Hun; Lee, Cheol Eui

2005-01-27

A series of hybrid inorganic-organic copper(II) hydroxy n-alkylsulfonate with a triangular lattice, Cu(2)(OH)(3)(C(n)H(2)(n)(+1)SO(3)) (n = 6, 8, 10), are prepared by anion exchange, starting from copper hydroxy nitrate Cu(2)(OH)(3)NO(3). These compounds show a layered structure as determined by X-ray diffraction, with interlayer distances of 14.3-34.8 A in alternation with interdigitated bilayer packing. Magnetic properties have been investigated by means of dc and ac measurements. All the compounds show similar metamagnet behaviors, with a Neel temperature of about 11 K. A subtle difference in the ac magnetic susceptibility among the compounds is understood by the existence of hydrogen bonding between the sulfonate headgroup and the hydroxide anion. A detailed molecular structure of the alkyl chains incorporated to the inorganic copper hydroxide layer is also discussed from the FTIR data.

The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition.

PubMed

Jauch, Ralf; Ng, Calista K L; Narasimhan, Kamesh; Kolatkar, Prasanna R

2012-04-01

It has recently been proposed that the sequence preferences of DNA-binding TFs (transcription factors) can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. In the present study we examine the crystal structure of the HMG (high-mobility group) domain of Sox4 [Sry (sex-determining region on the Y chromosome)-related HMG box 4] bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2, we observed subtle conformational differences at the DNA-binding interface. Furthermore, using quantitative electrophoretic mobility-shift assays we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These results suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adaptations lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs.

Strain Phase Diagram of SrTiO3 Thin Films

NASA Astrophysics Data System (ADS)

He, Feizhou; Shapiro, S. M.

2005-03-01

SrTiO3 thin films were used as a model system to study the effects of strain and epitaxial constraint on structural phase transitions of oxide films. The basic phenomena revealed will apply to a variety of important structural transitions including the ferroelectric transition. Highly strained, epitaxial films of SrTiO3 were grown on different substrates. The structural phase transition temperature Tc increases from 105 K in bulk STO to 167 K for films under tensile strain and 330 K for films with compressive strain. The measured temperature-strain phase diagram is qualitatively consistent with theory [1], however the increase in Tc is much larger than predicted in all cases. The symmetry of the phases involved in the transition is different from the corresponding bulk structures largely because of epitaxial constraint, the clamping effect. Thus the shape of the STO unit cell is tetragonal at all temperatures. The possibility exists of a very unique low temperature phase with orthorhombic symmetry (Cmcm) but tetragonal unit cell shape. More generally, we have characterized at least three different manifestations of the clamping effect, showing it is much more subtle than usually recognized. This work is supported through NSF DMR-0239667, DMR-0132918, by the Research Corp, and at BNL by the US DOE DE-AC02-98CH10886. [1] N. A. Pertsev, A. K. Tagantsev and N. Setter, Phys. Rev. B61, R825 (2000).

On the universality of inertial energy in the log layer of turbulent boundary layer and pipe flows

NASA Astrophysics Data System (ADS)

Chung, D.; Marusic, I.; Monty, J. P.; Vallikivi, M.; Smits, A. J.

2015-07-01

Recent experiments in high Reynolds number pipe flow have shown the apparent obfuscation of the behaviour in spectra of streamwise velocity fluctuations (Rosenberg et al. in J Fluid Mech 731:46-63, 2013). These data are further analysed here from the perspective of the behaviour in second-order structure functions, which have been suggested as a more robust diagnostic to assess scaling behaviour. A detailed comparison between pipe flows and boundary layers at friction Reynolds numbers of 5000-20,000 reveals subtle differences. In particular, the slope of the pipe flow structure function decreases with increasing wall distance, departing from the expected slope in a manner that is different to boundary layers. Here, , the slope of the log law in the streamwise turbulence intensity profile at high Reynolds numbers. Nevertheless, the structure functions for both flows recover the slope in the log layer sufficiently close to the wall, provided the Reynolds number is also high enough to remain in the log layer. This universality is further confirmed in very high Reynolds number data from measurements in the neutrally stratified atmospheric surface layer. A simple model that accounts for the `crowding' effect near the pipe axis is proposed in order to interpret the aforementioned differences.

Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans

NASA Astrophysics Data System (ADS)

Satpati, Suresh; Manohar, Kodavati; Acharya, Narottam; Dixit, Anshuman

2017-01-01

Genomic instability in Candida albicans is believed to play a crucial role in fungal pathogenesis. DNA polymerases contribute significantly to stability of any genome. Although Candida Genome database predicts presence of S. cerevisiae DNA polymerase orthologs; functional and structural characterizations of Candida DNA polymerases are still unexplored. DNA polymerase eta (Polη) is unique as it promotes efficient bypass of cyclobutane pyrimidine dimers. Interestingly, C. albicans is heterozygous in carrying two Polη genes and the nucleotide substitutions were found only in the ORFs. As allelic differences often result in functional differences of the encoded proteins, comparative analyses of structural models and molecular dynamic simulations were performed to characterize these orthologs of DNA Polη. Overall structures of both the ORFs remain conserved except subtle differences in the palm and PAD domains. The complementation analysis showed that both the ORFs equally suppressed UV sensitivity of yeast rad30 deletion strain. Our study has predicted two novel molecular interactions, a highly conserved molecular tetrad of salt bridges and a series of π-π interactions spanning from thumb to PAD. This study suggests these ORFs as the homologues of yeast Polη, and due to its heterogeneity in C. albicans they may play a significant role in pathogenicity.

Mesiodistal width of canines: a tool for sex determination.

PubMed

Bakkannavar, Shankar M; Monteiro, Francis N P; Arun, M; Pradeep Kumar, G

2012-01-01

Teeth, in the living as well as the dead, are the most useful objects in the field of forensic investigation. Their ability to survive in situations like mass disasters makes them important tools in victim identification. Though the morphology and structure is similar in both men and women, there are subtle differences. Variation in dental size can give a clue about differences between the sexes. Many authors have measured the crowns of teeth in both men and women and found certain variations. Canines, reported to survive air crash and hurricane disasters, are perhaps the most stable teeth in the oral cavity because of the labiolingual thickness of the crown and the root anchorage in the alveolar process of the jaws. Measurement of mesiodistal width of the mandibular and maxillary canines provides good evidence of sex identification due to dimorphism.

Sensitivity analysis for oblique incidence reflectometry using Monte Carlo simulations.

PubMed

Kamran, Faisal; Andersen, Peter E

2015-08-10

Oblique incidence reflectometry has developed into an effective, noncontact, and noninvasive measurement technology for the quantification of both the reduced scattering and absorption coefficients of a sample. The optical properties are deduced by analyzing only the shape of the reflectance profiles. This article presents a sensitivity analysis of the technique in turbid media. Monte Carlo simulations are used to investigate the technique and its potential to distinguish the small changes between different levels of scattering. We present various regions of the dynamic range of optical properties in which system demands vary to be able to detect subtle changes in the structure of the medium, translated as measured optical properties. Effects of variation in anisotropy are discussed and results presented. Finally, experimental data of milk products with different fat content are considered as examples for comparison.

Correlation between temperature variations of static and dynamic properties in glass-forming liquids

DOE PAGES

Voylov, D. N.; Griffin, P. J.; Mercado, B.; ...

2016-12-29

In this detailed analysis of the static structure factor S(Q) in several glass-forming liquids we show that the temperature variations of the width of the main diffraction peak Q(T ) correlate with the fragility of these liquids. Our observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We also show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, lc 2 /Q, and the size of cooperatively rearranging regions.

Abdominal Pain in the Geriatric Patient.

PubMed

Magidson, Phillip D; Martinez, Joseph P

2016-08-01

With an aging population, emergency department clinicians can expect an increase in geriatric patients presenting with abdominal pain. Compared with younger patients, this patient population is less likely to present with classic symptoms, physical examination findings, and laboratory values of abdominal disease. However, the morbidity and mortality associated with elderly patients presenting with abdominal pathologic conditions are significant. For this reason, the clinician must be familiar with some subtle and not so subtle differences when caring for the geriatric patient with abdominal pain to ensure timely diagnosis and appropriate treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

FTIR spectra and properties of iron borophosphate glasses containing simulated nuclear wastes

NASA Astrophysics Data System (ADS)

Liao, Qilong; Wang, Fu; Chen, Kuiru; Pan, Sheqi; Zhu, Hanzhen; Lu, Mingwei; Qin, Jianfa

2015-07-01

30 wt.% simulated nuclear wastes were successfully immobilized by B2O3-doped iron phosphate base glasses. The structure and thermal stability of the prepared wasteforms were characterized by Fourier transform infrared spectroscopy and differential thermal analysis, respectively. The subtle structural variations attributed to different B2O3 doping modes have been discussed in detail. The results show that the thermal stability and glass forming tendency of the iron borophosphate glass wasteforms are faintly affected by different B2O3 doping modes. The main structural networks of iron borophosphate glass wasteforms are PO43-, P2O74-, [BO4] groups. Furthermore, for the wasteform prepared by using 10B2O3-36Fe2O3-54P2O5 as base glass, the distributions of Fe-O-P bonds, [BO4], PO43- and P2O74- groups are optimal. In general, the dissolution rate (DR) values of the studied iron borophosphate wasteforms are about 10-8 g cm-2 min-1. The obtained conclusions can offer some useful information for the disposal of high-level radioactive wastes using boron contained phosphate glasses.

Effect of viroid infection on the dynamics of phenolic metabolites in the apoplast of tomato

USDA-ARS?s Scientific Manuscript database

Plants are capable of producing a wide array of secondary metabolites which serve many functions, due to their bioactive, redox or structural properties. Subtle changes in the external or internal environment can cause significant changes in the array of secondary metabolites presented in the tissu...

Accountable Game Design: Structuring the Dynamics of Student Learning Interactions

ERIC Educational Resources Information Center

Charoenying, Timothy

2010-01-01

Game-based classroom activity is intended to leverage students' interest and motivation to play, and to provide safe contexts for supporting students' academic learning. However, a basic criticism of many games currently used in classroom settings is that they can fail to meaningfully embody academic content. A more subtle concern is that…

Detection and analysis of diamond fingerprinting feature and its application

NASA Astrophysics Data System (ADS)

Li, Xin; Huang, Guoliang; Li, Qiang; Chen, Shengyi

2011-01-01

Before becoming a jewelry diamonds need to be carved artistically with some special geometric features as the structure of the polyhedron. There are subtle differences in the structure of this polyhedron in each diamond. With the spatial frequency spectrum analysis of diamond surface structure, we can obtain the diamond fingerprint information which represents the "Diamond ID" and has good specificity. Based on the optical Fourier Transform spatial spectrum analysis, the fingerprinting identification of surface structure of diamond in spatial frequency domain was studied in this paper. We constructed both the completely coherent diamond fingerprinting detection system illuminated by laser and the partially coherent diamond fingerprinting detection system illuminated by led, and analyzed the effect of the coherence of light source to the diamond fingerprinting feature. We studied rotation invariance and translation invariance of the diamond fingerprinting and verified the feasibility of real-time and accurate identification of diamond fingerprint. With the profit of this work, we can provide customs, jewelers and consumers with a real-time and reliable diamonds identification instrument, which will curb diamond smuggling, theft and other crimes, and ensure the healthy development of the diamond industry.

Structural and functional characterisation of ferret interleukin-2.

PubMed

Ren, Bin; McKinstry, William J; Pham, Tam; Newman, Janet; Layton, Daniel S; Bean, Andrew G; Chen, Zhenjun; Laurie, Karen L; Borg, Kathryn; Barr, Ian G; Adams, Timothy E

2016-02-01

While the ferret is a valuable animal model for a number of human viral infections, such as influenza, Hendra and Nipah, evaluating the cellular immune response following infection has been hampered by the lack of a number of species-specific immunological reagents. Interleukin 2 (IL-2) is one such key cytokine. Ferret recombinant IL-2 incorporating a C-terminal histidine tag was expressed and purified and the three-dimensional structure solved and refined at 1.89 Å by X-ray crystallography, which represents the highest resolution and first non-human IL-2 structure. While ferret IL-2 displays the classic cytokine fold of the four-helix bundle structure, conformational flexibility was observed at the second helix and its neighbouring region in the bundle, which may result in the disruption of the spatial arrangement of residues involved in receptor binding interactions, implicating subtle differences between ferret and human IL-2 when initiating biological functions. Ferret recombinant IL-2 stimulated the proliferation of ferret lymph node cells and induced the expression of mRNA for IFN-γ and Granzyme A. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases

PubMed Central

2015-01-01

Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies. PMID:24568342

Relative Sizes of Organic Molecules

NASA Technical Reports Server (NTRS)

2000-01-01

This computer graphic depicts the relative complexity of crystallizing large proteins in order to study their structures through x-ray crystallography. Insulin is a vital protein whose structure has several subtle points that scientists are still trying to determine. Large molecules such as insuline are complex with structures that are comparatively difficult to understand. For comparison, a sugar molecule (which many people have grown as hard crystals in science glass) and a water molecule are shown. These images were produced with the Macmolecule program. Photo credit: NASA/Marshall Space Flight Center (MSFC)

Floral heterochrony promotes flexibility of reproductive strategies in the morphologically homogeneous genus Eugenia (Myrtaceae).

PubMed

Vasconcelos, Thais N C; Lucas, Eve J; Faria, Jair E Q; Prenner, Gerhard

2018-01-25

Comparative floral ontogeny represents a valuable tool to understand angiosperm evolution. Such an approach may elucidate subtle changes in development that discretely modify floral architecture and underlie reproductive lability in groups with superficial homogeneous morphology. This study presents a comparative survey of floral development in Eugenia (Myrtaceae), one of the largest genera of angiosperms, and shows how previously undocumented ontogenetic trends help to explain the evolution of its megadiversity in contrast to its apparent flower uniformity. Using scanning electron microscopy, selected steps of the floral ontogeny of a model species (Eugenia punicifolia) are described and compared with 20 further species representing all ten major clades in the Eugenia phylogenetic tree. Additional floral trait data are contrasted for correlation analysis and character reconstructions performed against the Myrtaceae phylogenetic tree. Eugenia flowers show similar organ arrangement patterns: radially symmetrical, (most commonly) tetramerous flowers with variable numbers of stamens and ovules. Despite a similar general organization, heterochrony is evident from size differences between tissues and structures at similar developmental stages. These differences underlie variable levels of investment in protection, subtle modifications to symmetry, herkogamic effects and independent androecium and gynoecium variation, producing a wide spectrum of floral display and contributing to fluctuations in fitness. During Eugenia's bud development, the hypanthium (as defined here) is completely covered by stamen primordia, unusual in other Myrtaceae. This is the likely plesiomorphic state for Myrteae and may have represented a key evolutionary novelty in the tribe. Floral evolution in Eugenia depends on heterochronic patterns rather than changes in complexity to promote flexibility in floral strategies. The successful early establishment of Myrteae, previously mainly linked to the key innovation of fleshy fruit, may also have benefitted from changes in flower structure. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular simulation of structure and diffusion at smectite-water interfaces: Using expanded clay interlayers as model nanopores

DOE PAGES

Greathouse, Jeffery A.; Hart, David; Bowers, Geoffrey M.; ...

2015-07-20

In geologic settings relevant to a number of extraction and potential sequestration processes, nanopores bounded by clay mineral surfaces play a critical role in the transport of aqueous species. Solution structure and dynamics at clay–water interfaces are quite different from their bulk values, and the spatial extent of this disruption remains a topic of current interest. We have used molecular dynamics simulations to investigate the structure and diffusion of aqueous solutions in clay nanopores approximately 6 nm thick, comparing the effect of clay composition with model Na-hectorite and Na-montmorillonite surfaces. In addition to structural properties at the interface, water andmore » ion diffusion coefficients were calculated within each aqueous layer at the interface, as well as in the central bulk-like region of the nanopore. The results show similar solution structure and diffusion properties at each surface, with subtle differences in sodium adsorption complexes and water structure in the first adsorbed layer due to different arrangements of layer hydroxyl groups in the two clay models. Interestingly, the extent of surface disruption on bulk-like solution structure and diffusion extends to only a few water layers. Additionally, a comparison of sodium ion residence times confirms similar behavior of inner-sphere and outer-sphere surface complexes at each clay surface, but ~1% of sodium ions adsorb in ditrigonal cavities on the hectorite surface. Thus, the presence of these anhydrous ions is consistent with highly immobile anhydrous ions seen in previous nuclear magnetic resonance spectroscopic measurements of hectorite pastes.« less

A new approach to the characterization of subtle errors in everyday action: implications for mild cognitive impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania; Sestito, John; Libon, David J

2014-01-01

Mild functional difficulties have been associated with early cognitive decline in older adults and increased risk for conversion to dementia in mild cognitive impairment, but our understanding of this decline has been limited by a dearth of objective methods. This study evaluated the reliability and validity of a new system to code subtle errors on an established performance-based measure of everyday action and described preliminary findings within the context of a theoretical model of action disruption. Here 45 older adults completed the Naturalistic Action Test (NAT) and neuropsychological measures. NAT performance was coded for overt errors, and subtle action difficulties were scored using a novel coding system. An inter-rater reliability coefficient was calculated. Validity of the coding system was assessed using a repeated-measures ANOVA with NAT task (simple versus complex) and error type (overt versus subtle) as within-group factors. Correlation/regression analyses were conducted among overt NAT errors, subtle NAT errors, and neuropsychological variables. The coding of subtle action errors was reliable and valid, and episodic memory breakdown predicted subtle action disruption. Results suggest that the NAT can be useful in objectively assessing subtle functional decline. Treatments targeting episodic memory may be most effective in addressing early functional impairment in older age.

Even subtle cultural differences affect face tuning.

PubMed

Pavlova, Marina A; Heiz, Julie; Sokolov, Alexander N; Fallgatter, Andreas J; Barisnikov, Koviljka

2018-01-01

Culture shapes social cognition in many ways. Yet cultural impact on face tuning remains largely unclear. Here typically developing females and males from the French-speaking part of Switzerland were presented with a set of Arcimboldo-like Face-n-Food images composed of food ingredients and in different degree resembling a face. The outcome had been compared with previous findings obtained in young adults of the South-West Germany. In that study, males exhibit higher thresholds for face tuning on the Face-n-Food task than females. In Swiss participants, no gender differences exist in face tuning. Strikingly, males from the French-speaking part of Switzerland possess higher sensitivity to faces than their German peers, whereas no difference in face tuning occurs between females. The outcome indicates that even relatively subtle cultural differences as well as culture by gender interaction can modulate social cognition. Clarification of the nature of cultural impact on face tuning as well as social cognition at large is of substantial value for understanding a wide range of neuropsychiatric and neurodevelopmental conditions.

A Top-down versus a Bottom-up Hidden-variables Description of the Stern-Gerlach Experiment

NASA Astrophysics Data System (ADS)

Arsenijević, M.; Jeknić-Dugić, J.; Dugić, M.

We employ the Stern-Gerlach experiment to highlight the basics of a minimalist, non-interpretational top-down approach to quantum foundations. Certain benefits of the "quantum structural studies" (QSS) highlightedhere are detected and discussed. While the top-down approach can be described without making any reference to the fundamental structure of a closed system, the hidden variables (HV) theory á la Bohm proves to be more subtle than it is typically regarded.

Evidence for population bottlenecks and subtle genetic structure in the yellow rail

USGS Publications Warehouse

Popper, Kenneth J.; Miller, Leonard F.; Green, Michael; Haig, Susan M.; Mullins, Thomas D.

2012-01-01

The Yellow Rail (Coturnicops noveboracencis) is among the most enigmatic and least studied North American birds. Nesting exclusively in marshes and wetlands, it breeds largely east of the Rocky Mountains in the northern United States and Canada, but there is an isolated population in southern Oregon once believed extirpated. The degree of connectivity of the Oregon population with the main population is unknown. We used mitochondrial DNA sequences (mtDNA) and six microsatellite loci to characterize the Yellow Rail's genetic structure and diversity patterns in six areas. Our mtDNA-based analyses of genetic structure identified significant population differentiation, but pairwise comparison of regions identified no clear geographic trends. In contrast, microsatellites suggested subtle genetic structure differentiating the Oregon population from those in the five regions sampled in the Yellow Rail's main breeding range. The genetic diversity of the Oregon population was also the lowest of the six regions sampled, and Oregon was one of three regions that demonstrated evidence of recent population bottlenecks. Factors that produced population reductions may include loss of wetlands to development and agricultural conversion, drought, and wildfire. At this time, we are unable to determine if the high percentage (50%) of populations having experienced bottlenecks is representative of the Yellow Rail's entire range. Further genetic data from additional breeding populations will be required for this issue to be addressed.

Glioblastoma entities express subtle differences in molecular composition and response to treatment

PubMed Central

Balça-Silva, Joana; Matias, Diana; Do Carmo, Anália; Dubois, Luiz Gustavo; Gonçalves, Ana Cristina; Girão, Henrique; Silva Canedo, Nathalie Henriques; Correia, Ana Helena; De Souza, Jorge Marcondes; Sarmento-Ribeiro, Ana Bela; Lopes, Maria Celeste; Moura-Neto, Vivaldo

2017-01-01

Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines. We evaluated the cell death, cell cycle arrest and cell proliferation, mainly through PKC expression, by flow cytometry and western blot analysis and, ultimately, cell migration capability and F-actin filament disorganization by fluorescence microscopy. We demonstrated that the constitutive activation of p-PKC seems to be one of the main metabolic implicated on GBM malignancy. Despite of its higher resistance, possibly due to the overexpression of P-glycoprotein and stem-like cell markers, GBM11 cells presented a subtle different chemotherapeutic response compared to U87 and U118 cells. The GBM11, U87, U118 cell lines show subtle molecular differences, which clearly indicate the characterization of GBM heterogeneity, one of the main reasons for tumor resistance. The adding of cellular heterogeneity in molecular behaviour constitutes a step closer in the understanding of resistant molecular mechanisms in GBM, and can circumvents the eventual impaired therapy. PMID:28714013

Structural Characterization of Missense Mutations Using High Resolution Mass Spectrometry: A Case Study of the Parkinson's-Related Protein, DJ-1

NASA Astrophysics Data System (ADS)

Ben-Nissan, Gili; Chotiner, Almog; Tarnavsky, Mark; Sharon, Michal

2016-06-01

Missense mutations that lead to the expression of mutant proteins carrying single amino acid substitutions are the cause of numerous diseases. Unlike gene lesions, insertions, deletions, nonsense mutations, or modified RNA splicing, which affect the length of a polypeptide, or determine whether a polypeptide is translated at all, missense mutations exert more subtle effects on protein structure, which are often difficult to evaluate. Here, we took advantage of the spectral resolution afforded by the EMR Orbitrap platform, to generate a mass spectrometry-based approach relying on simultaneous measurements of the wild-type protein and the missense variants. This approach not only considerably shortens the analysis time due to the concurrent acquisition but, more importantly, enables direct comparisons between the wild-type protein and the variants, allowing identification of even subtle structural changes. We demonstrate our approach using the Parkinson's-associated protein, DJ-1. Together with the wild-type protein, we examined two missense mutants, DJ-1A104T and DJ-1D149A, which lead to early-onset familial Parkinson's disease. Gas-phase, thermal, and chemical stability assays indicate clear alterations in the conformational stability of the two mutants: the structural stability of DJ-1D149A is reduced, whereas that of DJ-1A104T is enhanced. Overall, we anticipate that the methodology presented here will be applicable to numerous other missense mutants, promoting the structural investigations of multiple variants of the same protein.

Fractal based modelling and analysis of electromyography (EMG) to identify subtle actions.

PubMed

Arjunan, Sridhar P; Kumar, Dinesh K

2007-01-01

The paper reports the use of fractal theory and fractal dimension to study the non-linear properties of surface electromyogram (sEMG) and to use these properties to classify subtle hand actions. The paper reports identifying a new feature of the fractal dimension, the bias that has been found to be useful in modelling the muscle activity and of sEMG. Experimental results demonstrate that the feature set consisting of bias values and fractal dimension of the recordings is suitable for classification of sEMG against the different hand gestures. The scatter plots demonstrate the presence of simple relationships of these features against the four hand gestures. The results indicate that there is small inter-experimental variation but large inter-subject variation. This may be due to differences in the size and shape of muscles for different subjects. The possible applications of this research include use in developing prosthetic hands, controlling machines and computers.

Why are the seed cones of conifers so diverse at pollination?

PubMed

Losada, Juan M; Leslie, Andrew B

2018-06-08

Form and function relationships in plant reproductive structures have long fascinated biologists. Although the intricate associations between specific pollinators and reproductive morphology have been widely explored among animal-pollinated plants, the evolutionary processes underlying the diverse morphologies of wind-pollinated plants remain less well understood. Here we study how this diversity may have arisen by focusing on two conifer species in the pine family that have divergent reproductive cone morphologies at pollination. Standard histology methods, artificial wind pollination assays and phylogenetic analyses were used in this study. A detailed study of cone ontogeny in these species reveals that variation in the rate at which their cone scales mature means that pollination occurs at different stages in their development, and thus in association with different specific morphologies. Pollination experiments nevertheless indicate that both species effectively capture pollen. In wind-pollinated plants, morphological diversity may result from simple variation in development among lineages rather than selective pressures for any major differences in function or performance. This work also illustrates the broader importance of developmental context in understanding plant form and function relationships; because plant reproductive structures perform many different functions over their lifetime, subtle differences in development may dramatically alter the specific morphologies that they use to meet these demands.

Exploring sex differences in autistic traits: A factor analytic study of adults with autism.

PubMed

Grove, Rachel; Hoekstra, Rosa A; Wierda, Marlies; Begeer, Sander

2017-08-01

Research has highlighted potential differences in the phenotypic and clinical presentation of autism spectrum conditions across sex. Furthermore, the measures utilised to evaluate autism spectrum conditions may be biased towards the male autism phenotype. It is important to determine whether these instruments measure the autism phenotype consistently in autistic men and women. This study evaluated the factor structure of the Autism Spectrum Quotient Short Form in a large sample of autistic adults. It also systematically explored specific sex differences at the item level, to determine whether the scale assesses the autism phenotype equivalently across males and females. Factor analyses were conducted among 265 males and 285 females. A two-factor structure consisting of a social behaviour and numbers and patterns factor was consistent across groups, indicating that the latent autism phenotype is similar among both autistic men and women. Subtle differences were observed on two social behaviour item thresholds of the Autism Spectrum Quotient Short Form, with women reporting scores more in line with the scores expected in autism on these items than men. However, these differences were not substantial. This study showed that the Autism Spectrum Quotient Short Form detects autistic traits equivalently in males and females and is not biased towards the male autism phenotype.

Compressive Force Spectroscopy: From Living Cells to Single Proteins.

PubMed

Wang, Jiabin; Liu, Meijun; Shen, Yi; Sun, Jielin; Shao, Zhifeng; Czajkowsky, Daniel Mark

2018-03-23

One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these "tensile" force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.

Multi-methodological investigation of the variability of the microstructure of HPMC hard capsules.

PubMed

Faulhammer, E; Kovalcik, A; Wahl, V; Markl, D; Stelzer, F; Lawrence, S; Khinast, J G; Paudel, A

2016-09-25

The objective of this study was to analyze differences in the subtle microstructure of three different grades of HMPC hard capsule shells using mechanical, spectroscopic, microscopic and tomographic approaches. Dynamic mechanical analysis (DMA), thermogravimetric analysis (TGA), vibrational spectroscopic, X-Ray scattering techniques as well as environmental scanning electron microscopy (ESEM) and optical coherence tomography (OCT) were used. Two HPMC capsules manufactured via chemical gelling, one capsule shell manufactured via thermal gelling and one thermally gelled transparent capsule were included. Characteristic micro-structural alterations (associated manufacturing processes) such as mechanical and physical properties relevant to capsule performance and processability were thoroughly elucidated with the integration of data obtained from multi-methodological investigations. The physico-chemical and physico-mechanical data obtained from a gamut of techniques implied that thermally gelled HPMC hard capsule shells could offer an advantage in terms of machinability during capsule filling, owing to their superior micro- and macroscopic structure as well as specifically the mechanical stability under dry or humid conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

A research for Class II defect Bored Pile’s Accept Criteria: A case of Penang Second Marine bridge

NASA Astrophysics Data System (ADS)

Huang, Kang

2018-03-01

The aim of this preliminary research is to study the accept criteria of class II bored pile with subtle defect. According to a detailed comparison of the existed different standards, Chinese ones are more applicable especially for the large diameter bored piles. Through the concrete coring at pile No P25-03 of this case and the comparison to the actual calculation, the Class II pile’s defects were very minor. Comparison was also made for the effects on pile structural capacities before and after repair of the defects. the feasible repair proposal may bring forward to more defects to the piles. The Class II piles don’t need any further repairation when piles have typical of similar character and sonic logging test result with P25-03‘s one. For other Class II piles with some differences in characters, verification is needed through further concrete coring on the pile. The recommendation of this research could be adopted for the similar huge marine structures which installed large diameter bored piles.

Interfacial Coupling-Induced Ferromagnetic Insulator Phase in Manganite Film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bangmin; Wu, Lijun; Yin, Wei-Guo

Interfaces with subtle difference in atomic and electronic structures in perovskite ABO3 heterostructures often yield intriguingly different properties, yet their exact roles remain elusive. Here, we report an integrated study of unusual transport, magnetic, and structural properties of Pr0.67Sr0.33MnO3 (PSMO) film on SrTiO3 (STO) substrate. The variations in out-of-plane lattice constant and BO6 octahedral rotation across the PSMO/STO interface strongly depend on the thickness of PSMO films. In the 12-nm film, a new interface-sensitive ferromagnetic polaronic insulator (FI’) phase is formed during the cubic-to-tetragonal phase transition of STO, apparently due to enhanced electron-phonon interaction and atomic disorder in the film.more » The transport properties of the FI’ phase in the 30-nm film are masked because of the reduced interfacial effect and smaller interface-to-volume ratio. This work demonstrates how thickness-dependent interfacial coupling leads to formation of the theoretically predicted novel ferromagnetic-polaronic insulator in systems, as illustrated in a new phase diagram, that are otherwise ferromagnetic metals (FM) in bulk form.« less

Signatures of polygenic adaptation associated with climate across the range of a threatened fish species with high genetic connectivity.

PubMed

Harrisson, Katherine A; Amish, Stephen J; Pavlova, Alexandra; Narum, Shawn R; Telonis-Scott, Marina; Rourke, Meaghan L; Lyon, Jarod; Tonkin, Zeb; Gilligan, Dean M; Ingram, Brett A; Lintermans, Mark; Gan, Han Ming; Austin, Christopher M; Luikart, Gordon; Sunnucks, Paul

2017-11-01

Adaptive differences across species' ranges can have important implications for population persistence and conservation management decisions. Despite advances in genomic technologies, detecting adaptive variation in natural populations remains challenging. Key challenges in gene-environment association studies involve distinguishing the effects of drift from those of selection and identifying subtle signatures of polygenic adaptation. We used paired-end restriction site-associated DNA sequencing data (6,605 biallelic single nucleotide polymorphisms; SNPs) to examine population structure and test for signatures of adaptation across the geographic range of an iconic Australian endemic freshwater fish species, the Murray cod Maccullochella peelii. Two univariate gene-association methods identified 61 genomic regions associated with climate variation. We also tested for subtle signatures of polygenic adaptation using a multivariate method (redundancy analysis; RDA). The RDA analysis suggested that climate (temperature- and precipitation-related variables) and geography had similar magnitudes of effect in shaping the distribution of SNP genotypes across the sampled range of Murray cod. Although there was poor agreement among the candidate SNPs identified by the univariate methods, the top 5% of SNPs contributing to significant RDA axes included 67% of the SNPs identified by univariate methods. We discuss the potential implications of our findings for the management of Murray cod and other species generally, particularly in relation to informing conservation actions such as translocations to improve evolutionary resilience of natural populations. Our results highlight the value of using a combination of different approaches, including polygenic methods, when testing for signatures of adaptation in landscape genomic studies. © 2017 John Wiley & Sons Ltd.

Lymphocyte signaling : beyond knockouts

PubMed Central

Saveliev, Alexander; Tybulewicz, Victor L. J.

2016-01-01

The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Whereas this gene ‘knockout’ approach is often informative, in many cases the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to ‘knockin’ subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully designed based on structural and biophysical data. PMID:19295633

X-ray structure and inhibition of 3C-like protease from porcine epidemic diarrhea virus

DOE PAGES

St. John, Sarah E.; Anson, Brandon J.; Mesecar, Andrew D.

2016-05-13

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL pro) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 angstrom X-ray structure of 3CL pro from PEDV. Analysis of the PEDV 3CL pro structure and comparison to other coronaviral 3CL pro's from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL pro's are conserved, with the exception of amore » loop that comprises the protease S-2 pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL pro, (R)-16, to have inhibitor activity against PEDV 3CL pro, despite that SARS-3CL pro and PEDV 3CL pro share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL pro are conserved in PEDV-3CL pro; however, the sequence variation and positional difference in the loop forming the S-2 pocket may account for large observed difference in IC 50 values. In conclusion, this work advances our understanding of the subtle, but important, differences in coronaviral 3CL pro architecture and contributes to the broader structural knowledge of coronaviral 3CL pro's.« less

X-ray structure and inhibition of 3C-like protease from porcine epidemic diarrhea virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

St. John, Sarah E.; Anson, Brandon J.; Mesecar, Andrew D.

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL pro) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 angstrom X-ray structure of 3CL pro from PEDV. Analysis of the PEDV 3CL pro structure and comparison to other coronaviral 3CL pro's from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL pro's are conserved, with the exception of amore » loop that comprises the protease S-2 pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL pro, (R)-16, to have inhibitor activity against PEDV 3CL pro, despite that SARS-3CL pro and PEDV 3CL pro share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL pro are conserved in PEDV-3CL pro; however, the sequence variation and positional difference in the loop forming the S-2 pocket may account for large observed difference in IC 50 values. In conclusion, this work advances our understanding of the subtle, but important, differences in coronaviral 3CL pro architecture and contributes to the broader structural knowledge of coronaviral 3CL pro's.« less

Structures in general relativity

NASA Astrophysics Data System (ADS)

Tieu, Steven

Structures within general relativity are examined. The differences between man-made structures and those predicted by the Einstein differential equations are very subtle. Exotic structures such as the Godel Universe and the Gott cosmic string are examined with emphasis on closed time-like curves. Newtonian models are seen to also have an exotic aspect in that a vast halo consisting of unknown matter dominates the galaxy. We introduce a model for galaxies based on a general relativity framework with the goal of excluding such artifacts from the system while describing the flat-rotation curves. Structures within this model were speculated to be exotic but after close scrutiny, their nature is shown to be benign. Numerical approaches are applied to model four galaxies: The Milky Way, NGC 3031, NGC 3198 and NGC 7331. Density and mass are deduced from these models and compared to the Newtonian models. Within the visible/HI region, there is 30% reduction in total mass. Extending the model to 10 times beyond the HI region using various fall-off scenerios, it is shown that there is only modest increase of the accumulated mass. In comparison to the Newtonian approach to galactic dynamics, the massive halos are not required to account for the flat velocity profiles.

Effects of Hurricane Katrina on the fish fauna of the Pascagoula River Drainage

Treesearch

J. Schaefer; P. Mickle; J. Spaeth; B.R. Kreiser; S.B. Adams; W. Matamoros; B. Zuber; P. Vigueira

2006-01-01

Large tropical storms can have dramatic effects on coastal, estuarine and terrestrial ecosystems. However, it is not as well understood how these types of disturbances might impact freshwater communities further inland. Storm surges can change critical water quality parameters for kilometers upstream, potentially causing subtle shifts in community structure or more...

Using Molecular Modeling to Understand Some of the More Subtle Aspects of Aromaticity and Antiaromaticity

ERIC Educational Resources Information Center

Box, Vernon G. S.

2011-01-01

pi-Electron delocalization exerts one of the most significant structure or energy influences in organic chemistry. Apart from determining the shapes of alkenes and alkynes, the planarity of aromatic molecules is a hallmark of pi-electron delocalization. Huckel's rules for aromaticity are easily applied in the teaching of undergraduates, but…

Conservation of forest birds: evidence of a shifting baseline in community structure

Treesearch

Chadwick D. Rittenhouse; Anna M. Pidgeon; Thomas P. Albright; Patrick D. Culbert; Murray K. Clayton; Curtis H. Flather; Chengquan Huang; Jeffrey G. Masek; Susan I. Stewart; Volker C. Radeloff

2010-01-01

Quantifying changes in forest bird diversity is an essential task for developing effective conservation actions. When subtle changes in diversity accumulate over time, annual comparisons may offer an incomplete perspective of changes in diversity. In this case, progressive change, the comparison of changes in diversity from a baseline condition, may offer greater...

Subcontinental impacts of an invasive tree disease on forest structure and dynamics

Treesearch

Jeffrey R. Garnas; Matthew P. Ayres; Andrew M. Liebhold; Celia. Evans

2011-01-01

Introduced pests and pathogens are a major source of disturbance to ecosystems world-wide. The famous examples have produced dramatic reductions in host abundance, including virtual extirpation, but most introductions have more subtle impacts that are hard to quantify but are potentially at least as important due to the pathogens' effects on host reproduction,...

Identity Matters: The Centrality of "Conferred Identity" as Symbolic Power and Social Capital in Higher Education Mobility

ERIC Educational Resources Information Center

Holt, Brenda

2012-01-01

Although any "choice" young people make about higher education incorporates a subtle interplay of individual agency, circumstance and social structure, the centrality of identity in such life choices for rural young people cannot be underestimated. Since mobility is an ontological absolute for most rural young people accessing…

Becoming Legible: Helping Students Navigate Promotional Genres of Self-Narration

ERIC Educational Resources Information Center

Vander Zee, Anton

2017-01-01

The five-paragraph essay is a hard genre to love. Its inverted-triangle intro has enlightened us with too many "dawns" of some monolithic "man." It reduces arguments, which tend to be rather subtle creatures, to the confines of a single-sentence thesis. It confects arguments in bland triplicate structure, as if any claim could…

Quantitative Analysis of Cell Migration Using Optical Flow

PubMed Central

Boric, Katica; Orio, Patricio; Viéville, Thierry; Whitlock, Kathleen

2013-01-01

Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration as a population, and use it here to characterize in detail the subtle defects in cell migration caused by ethanol exposure during early development. The challenge was to quantify changes in the in vivo migration of all Sox10:EGFP expressing cells in the visual field of time-lapse movies. To perform this analysis we used an Optical Flow algorithm for motion detection and combined the analysis with a fit to an affine transformation. Through this analysis we detected and quantified significant differences in the cell migrations of Sox10:EGFP positive cranial neural crest populations in ethanol treated versus untreated embryos. Specifically, treatment affected migration by increasing the left-right asymmetry of the migrating cells and by altering the direction of cell movements. Thus, by applying this novel computational analysis, we were able to quantify the movements of populations of cells, allowing us to detect subtle changes in cell behaviors. Because cranial neural crest cells contribute to the formation of the frontal mass these subtle differences may underlie commonly observed facial asymmetries in normal human populations. PMID:23936049

An intramolecular charge transfer process based fluorescent probe for monitoring subtle pH fluctuation in living cells.

PubMed

Sun, Mingtai; Du, Libo; Yu, Huan; Zhang, Kui; Liu, Yang; Wang, Suhua

2017-01-01

It is crucial to monitor intracellular pH values and their fluctuation since the organelles of cells have different pH distribution. Herein we construct a new small molecule fluorescent probe HBT-O for monitoring the subtle pH values within the scope of neutral to acid in living cells. The probe exhibited good water solubility, a marked turquoise to olivine emission color change in response to pH, and tremendous fluorescence hypochromatic shift of ∼50nm (1718cm -1 ) as well as the increased fluorescence intensity when the pH value changed from neutral to acid. Thus, the probe HBT-O can distinguish the subtle changes in the range of normal pH values from neutral to acid with significant fluorescence changes. These properties can be attributed to the intramolecular charge transfer (ICT) process of the probe upon protonation in buffer solutions at varied pH values. Moreover, the probe was reversible and nearly non-toxic for living cells. Then the probe was successfully used to detect pH fluctuation in living cells by exhibiting different fluorescence colors and intensity. These findings demonstrate that the probe will find useful applications in biology and biomedical research. Copyright © 2016 Elsevier B.V. All rights reserved.

Fractal Interrelationships in Field and Seismic Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, T.H.; Dominic, Jovita; Halverson, Joel

1997-10-01

Size scaling interrelationships are evaluated in this study using a fractal model. Fractal models of several geologic variables are examined and include fracture patterns, reflection travel times, structural relief, drainage, topographic relief and active fault patterns. The fractal properties of structural relief inferred from seismic data and structural cross sections provide a quantitative means to characterize and compare complex structural patterns. Studies were conducted using seismic data from the Granny Creek oil field in the Appalachian Plateau. Previous studies of the field reveal that subtle detached structures present on the limb of a larger structure are associated with enhanced productionmore » from the field. Vertical increases of fractal dimension across the zone of detachment provide a measure of the extent to which detachment has occurred. The increases of fractal dimension are greatest in the more productive areas of the field. A result with equally important ramifications is that fracture systems do not appear to be intrinsically fractal as is often suggested in the literature. While examples of nearly identical patterns can be found at different scales supporting the idea of self-similarity, these examples are often taken from different areas and from different lithologies. Examination of fracture systems at different scales in the Valley and Ridge Province suggest that their distribution become increasingly sparse with scale reduction, and therefore are dissimilar or non-fractal. Box counting data in all cases failed to yield a fractal regime. The results obtained from this analysis bring into question the general applicability of reservoir simulations employing fractal models of fracture distribution. The same conclusions were obtained from the analysis of 1D fracture patterns such as those that might appear in a horizontal well.« less

Structures of MART-1 26/27-35Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borbulevych, Oleg Y; Insaidoo, Francis K; Baxter, Tiffany K

2008-09-17

Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning aminomore » acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26-35 decamer, although only the 27-35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26-35 and 27-35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-1{sub 26/27-35}-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27-35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone.« less

Structures of MART-126/27–35 Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition

PubMed Central

Borbulevych, Oleg Y.; Insaidoo, Francis K.; Baxter, Tiffany K.; Powell, Daniel J.; Johnson, Laura A.; Restifo, Nicholas P.; Baker, Brian M.

2007-01-01

Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning amino acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26–35 decamer, although only the 27–35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26–35 and 27–35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-126/27–35-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27–35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone. PMID:17719062

Diseases

Treesearch

Thomas E. Hinds

1985-01-01

Although many diseases attack aspen, relatively few kill or seriously injure living trees. The common leaf diseases, in general, are widely distributed throughout the range of aspen, whereas there are subtle differences in distribution between the important decay fungi, and apparently entirely different areas of distribution of major cankercausing organisms. However,...

Early abnormalities of cardiovascular structure and function in middle-aged Korean adults with prehypertension: The Korean Genome Epidemiology study.

PubMed

Kim, Seong Hwan; Cho, Goo-Yeong; Baik, Inkyung; Lim, Sang Yup; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Park, Juri; Kim, Jinyoung; Shin, Chol

2011-02-01

Prehypertension is associated with increased cardiovascular morbidity and mortality. However, there are few population-based studies on the changes of cardiovascular structure and function that characterize prehypertension. The aim of this study was to assess whether prehypertension is associated with abnormalities of cardiovascular structure and function in the general Korean population. We analyzed the cross-sectional relationships between prehypertension and cardiovascular structure and function in a sample from the Korean Genome Epidemiology Study. A total of 1,671 individuals (54.5% women; mean age: 53 ± 6 years) without hypertension and diabetes mellitus were enrolled. Cardiovascular structure and function were assessed by conventional echocardiography, tissue Doppler imaging (TDI), carotid ultrasonography, and pulse wave velocity (PWV). The left ventricular (LV) mass index was significantly higher in subjects with prehypertension than in those with normotension (41 ± 8 g/m²·⁷ vs. 38 ± 7 g/m²·⁷, P < 0.001). LV diastolic parameters, such as the E/A ratio, TDI E(a) velocity, and E/E(a) ratio, were also impaired in subjects with prehypertension (all P < 0.001). Compared with normotension, prehypertension was characterized by a significantly higher common carotid artery intima-media thickness and a higher brachial-ankle PWV (all P < 0.001). These abnormalities of cardiovascular structure and function remained significant after adjustment for covariates. In this population-based cohort, we found that subtle alterations in cardiovascular structure and function were already present at the prehypertensive stage. Whether such subtle alterations convey an increased risk of cardiovascular events and whether the changes are reversible with treatment warrant further study.

Consensus and stratification in the affective meaning of human sociality

PubMed Central

Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

2014-01-01

We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification. PMID:24843121

Age-related differences in responses to thoughts of one's own death: mortality salience and judgments of moral transgressions.

PubMed

Maxfield, Molly; Pyszczynski, Tom; Kluck, Benjamin; Cox, Cathy R; Greenberg, Jeff; Solomon, Sheldon; Weise, David

2007-06-01

Two experiments explored age differences in response to reminders of death. Terror management research has shown that death reminders lead to increased adherence to and defense of one's cultural worldview. In Study 1, the effect of mortality salience (MS) on evaluations of moral transgressions made by younger and older adults was compared. Whereas younger adults showed the typical pattern of harsher judgments in response to MS, older adults did not. Study 2 compared younger and older adults' responses to both the typical MS induction and a more subtle death reminder. Whereas younger adults responded to both MS inductions with harsher evaluations, older adults made significantly less harsh evaluations after the subtle MS induction. Explanations for this developmental shift in responses to reminders of death are discussed. ((c) 2007 APA, all rights reserved).

Replacement Condition Detection of Railway Point Machines Using an Electric Current Sensor.

PubMed

Sa, Jaewon; Choi, Younchang; Chung, Yongwha; Kim, Hee-Young; Park, Daihee; Yoon, Sukhan

2017-01-29

Detecting replacement conditions of railway point machines is important to simultaneously satisfy the budget-limit and train-safety requirements. In this study, we consider classification of the subtle differences in the aging effect-using electric current shape analysis-for the purpose of replacement condition detection of railway point machines. After analyzing the shapes of after-replacement data and then labeling the shapes of each before-replacement data, we can derive the criteria that can handle the subtle differences between "does-not-need-to-be-replaced" and "needs-to-be-replaced" shapes. On the basis of the experimental results with in-field replacement data, we confirmed that the proposed method could detect the replacement conditions with acceptable accuracy, as well as provide visual interpretability of the criteria used for the time-series classification.

Replacement Condition Detection of Railway Point Machines Using an Electric Current Sensor

PubMed Central

Sa, Jaewon; Choi, Younchang; Chung, Yongwha; Kim, Hee-Young; Park, Daihee; Yoon, Sukhan

2017-01-01

Detecting replacement conditions of railway point machines is important to simultaneously satisfy the budget-limit and train-safety requirements. In this study, we consider classification of the subtle differences in the aging effect—using electric current shape analysis—for the purpose of replacement condition detection of railway point machines. After analyzing the shapes of after-replacement data and then labeling the shapes of each before-replacement data, we can derive the criteria that can handle the subtle differences between “does-not-need-to-be-replaced” and “needs-to-be-replaced” shapes. On the basis of the experimental results with in-field replacement data, we confirmed that the proposed method could detect the replacement conditions with acceptable accuracy, as well as provide visual interpretability of the criteria used for the time-series classification. PMID:28146057

Diversity of Secondary Structure in Catalytic Peptides with β-Turn-Biased Sequences

PubMed Central

2016-01-01

X-ray crystallography has been applied to the structural analysis of a series of tetrapeptides that were previously assessed for catalytic activity in an atroposelective bromination reaction. Common to the series is a central Pro-Xaa sequence, where Pro is either l- or d-proline, which was chosen to favor nucleation of canonical β-turn secondary structures. Crystallographic analysis of 35 different peptide sequences revealed a range of conformational states. The observed differences appear not only in cases where the Pro-Xaa loop-region is altered, but also when seemingly subtle alterations to the flanking residues are introduced. In many instances, distinct conformers of the same sequence were observed, either as symmetry-independent molecules within the same unit cell or as polymorphs. Computational studies using DFT provided additional insight into the analysis of solid-state structural features. Select X-ray crystal structures were compared to the corresponding solution structures derived from measured proton chemical shifts, 3J-values, and 1H–1H-NOESY contacts. These findings imply that the conformational space available to simple peptide-based catalysts is more diverse than precedent might suggest. The direct observation of multiple ground state conformations for peptides of this family, as well as the dynamic processes associated with conformational equilibria, underscore not only the challenge of designing peptide-based catalysts, but also the difficulty in predicting their accessible transition states. These findings implicate the advantages of low-barrier interconversions between conformations of peptide-based catalysts for multistep, enantioselective reactions. PMID:28029251

Fgfr3 regulates development of the caudal telencephalon.

PubMed

Moldrich, Randal X; Mezzera, Cecilia; Holmes, William M; Goda, Sailaja; Brookfield, Sam J; Rankin, Alastair J; Barr, Emily; Kurniawan, Nyoman; Dewar, Deborah; Richards, Linda J; López-Bendito, Guillermina; Iwata, Tomoko

2011-06-01

The fibroblast growth factor receptor 3 (Fgfr3) is expressed in a rostral(low) to caudal(high) gradient in the developing cerebral cortex. Therefore, we hypothesized that Fgfr3 contributes to the correct morphology and connectivity of the caudal cortex. Overall, the forebrain structures appeared normal in Fgfr3(-/-) mice. However, cortical and hippocampal volumes were reduced by 26.7% and 16.3%, respectively. Hypoplasia was particularly evident in the caudo-ventral region of the telencephalon where proliferation was mildly decreased at embryonic day 18.5. Dysplasia of GABAergic neurons in the amygdala and piriform cortex was seen following GAD67 immunohistochemistry. Dye-tracing studies and diffusion magnetic resonance imaging and tractography detected a subtle thalamocortical tract deficit, and significant decreases in the stria terminalis and lateral arms of the anterior commissure. These results indicate the subtle role of Fgfr3 in formation of caudal regions of the telencephalon affecting some brain projections. Copyright © 2011 Wiley-Liss, Inc.

Motion magnification for endoscopic surgery

NASA Astrophysics Data System (ADS)

McLeod, A. Jonathan; Baxter, John S. H.; de Ribaupierre, Sandrine; Peters, Terry M.

2014-03-01

Endoscopic and laparoscopic surgeries are used for many minimally invasive procedures but limit the visual and haptic feedback available to the surgeon. This can make vessel sparing procedures particularly challenging to perform. Previous approaches have focused on hardware intensive intraoperative imaging or augmented reality systems that are difficult to integrate into the operating room. This paper presents a simple approach in which motion is visually enhanced in the endoscopic video to reveal pulsating arteries. This is accomplished by amplifying subtle, periodic changes in intensity coinciding with the patient's pulse. This method is then applied to two procedures to illustrate its potential. The first, endoscopic third ventriculostomy, is a neurosurgical procedure where the floor of the third ventricle must be fenestrated without injury to the basilar artery. The second, nerve-sparing robotic prostatectomy, involves removing the prostate while limiting damage to the neurovascular bundles. In both procedures, motion magnification can enhance subtle pulsation in these structures to aid in identifying and avoiding them.

Crystal structure of a chimaeric bacterial glutamate dehydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliveira, Tânia; Sharkey, Michael A.; Engel, Paul C.

2016-05-23

Glutamate dehydrogenases (EC 1.4.1.2–4) catalyse the oxidative deamination of L-glutamate to α-ketoglutarate using NAD(P) +as a cofactor. The bacterial enzymes are hexameric, arranged with 32 symmetry, and each polypeptide consists of an N-terminal substrate-binding segment (domain I) followed by a C-terminal cofactor-binding segment (domain II). The catalytic reaction takes place in the cleft formed at the junction of the two domains. Distinct signature sequences in the nucleotide-binding domain have been linked to the binding of NAD +versusNADP +, but they are not unambiguous predictors of cofactor preference. In the absence of substrate, the two domains move apart as rigid bodies,more » as shown by the apo structure of glutamate dehydrogenase fromClostridium symbiosum. Here, the crystal structure of a chimaeric clostridial/Escherichia colienzyme has been determined in the apo state. The enzyme is fully functional and reveals possible determinants of interdomain flexibility at a hinge region following the pivot helix. The enzyme retains the preference for NADP +cofactor from the parentE. colidomain II, although there are subtle differences in catalytic activity.« less

Energetic and Informative Interaction of Microwaves with Neurons and Enzymes

NASA Astrophysics Data System (ADS)

Maharramov, A. A.; Babazade, S. N.; Yusifov, E. Yu.; Gajiyev, A. M.

2007-04-01

Besides Purkinje Cells (PC) in cat cerebellum, experiments on Microwave-Living System interaction have been performed on some antioxidant enzymes - Super oxide dismutase (SOD), Catalase (C) and Glutathione peroxidase (GP) in the eye structures (pigment epithelium and neuronal structure - retina) in frogs, and on Glucose-6-Phosphatedehydrogenase (GPD) and Pyruvate-kinase (PK) in different organs - cerebellum, hypothalamus, liver and erythrocytes - of wistar albino rats. Exposure parameters of Microwaves of decimetre range (DRM) - total exposure, λ=65 cm, duration of exposition 10-20 minutes. According to the data obtained it may be concluded that, PC increasing their impulse activity irregularity, may react to the energetic (thermal) component of DRM action, whereas the result of informative (subtle) interaction between DRM and PC leads to the increase of regularity in electrophysiological activity of the latter. In the case of enzymes, in identification of the character of interactions, the type of the enzymes, the structure where an enzyme activity is studied and the physiological conditions related to such a factor as hunger, for example, take places. In this paper the effects of DRM on PC, G6PD and PK have been presented.

Constituent order and semantic parallelism in online comprehension: eye-tracking evidence from German.

PubMed

Knoeferle, Pia; Crocker, Matthew W

2009-12-01

Reading times for the second conjunct of and-coordinated clauses are faster when the second conjunct parallels the first conjunct in its syntactic or semantic (animacy) structure than when its structure differs (Frazier, Munn, & Clifton, 2000; Frazier, Taft, Roeper, & Clifton, 1984). What remains unclear, however, is the time course of parallelism effects, their scope, and the kinds of linguistic information to which they are sensitive. Findings from the first two eye-tracking experiments revealed incremental constituent order parallelism across the board-both during structural disambiguation (Experiment 1) and in sentences with unambiguously case-marked constituent order (Experiment 2), as well as for both marked and unmarked constituent orders (Experiments 1 and 2). Findings from Experiment 3 revealed effects of both constituent order and subtle semantic (noun phrase similarity) parallelism. Together our findings provide evidence for an across-the-board account of parallelism for processing and-coordinated clauses, in which both constituent order and semantic aspects of representations contribute towards incremental parallelism effects. We discuss our findings in the context of existing findings on parallelism and priming, as well as mechanisms of sentence processing.

Spatio-Temporal Regularization for Longitudinal Registration to Subject-Specific 3d Template

PubMed Central

Guizard, Nicolas; Fonov, Vladimir S.; García-Lorenzo, Daniel; Nakamura, Kunio; Aubert-Broche, Bérengère; Collins, D. Louis

2015-01-01

Neurodegenerative diseases such as Alzheimer's disease present subtle anatomical brain changes before the appearance of clinical symptoms. Manual structure segmentation is long and tedious and although automatic methods exist, they are often performed in a cross-sectional manner where each time-point is analyzed independently. With such analysis methods, bias, error and longitudinal noise may be introduced. Noise due to MR scanners and other physiological effects may also introduce variability in the measurement. We propose to use 4D non-linear registration with spatio-temporal regularization to correct for potential longitudinal inconsistencies in the context of structure segmentation. The major contribution of this article is the use of individual template creation with spatio-temporal regularization of the deformation fields for each subject. We validate our method with different sets of real MRI data, compare it to available longitudinal methods such as FreeSurfer, SPM12, QUARC, TBM, and KNBSI, and demonstrate that spatially local temporal regularization yields more consistent rates of change of global structures resulting in better statistical power to detect significant changes over time and between populations. PMID:26301716

Structural Evolution of Differential Amino Acid Effector Regulation in Plant Chorismate Mutases*

PubMed Central

Westfall, Corey S.; Xu, Ang; Jez, Joseph M.

2014-01-01

Chorismate mutase converts chorismate into prephenate for aromatic amino acid biosynthesis. To understand the molecular basis of allosteric regulation in the plant chorismate mutases, we analyzed the three Arabidopsis thaliana chorismate mutase isoforms (AtCM1–3) and determined the x-ray crystal structures of AtCM1 in complex with phenylalanine and tyrosine. Functional analyses show a wider range of effector control in the Arabidopsis chorismate mutases than previously reported. AtCM1 is activated by tryptophan with phenylalanine and tyrosine acting as negative effectors; however, tryptophan, cysteine, and histidine activate AtCM3. AtCM2 is a nonallosteric form. The crystal structure of AtCM1 in complex with tyrosine and phenylalanine identifies differences in the effector sites of the allosterically regulated yeast enzyme and the other two Arabidopsis isoforms. Site-directed mutagenesis of residues in the effector site reveals key features leading to differential effector regulation in these enzymes. In AtCM1, mutations of Gly-213 abolish allosteric regulation, as observed in AtCM2. A second effector site position, Gly-149 in AtCM1 and Asp-132 in AtCM3, controls amino acid effector specificity in AtCM1 and AtCM3. Comparisons of chorismate mutases from multiple plants suggest that subtle differences in the effector site are conserved in different lineages and may lead to specialized regulation of this branch point enzyme. PMID:25160622

The NMR contribution to protein-protein networking in Fe-S protein maturation.

PubMed

Banci, Lucia; Camponeschi, Francesca; Ciofi-Baffoni, Simone; Piccioli, Mario

2018-03-22

Iron-sulfur proteins were among the first class of metalloproteins that were actively studied using NMR spectroscopy tailored to paramagnetic systems. The hyperfine shifts, their temperature dependencies and the relaxation rates of nuclei of cluster-bound residues are an efficient fingerprint of the nature and the oxidation state of the Fe-S cluster. NMR significantly contributed to the analysis of the magnetic coupling patterns and to the understanding of the electronic structure occurring in [2Fe-2S], [3Fe-4S] and [4Fe-4S] clusters bound to proteins. After the first NMR structure of a paramagnetic protein was obtained for the reduced E. halophila HiPIP I, many NMR structures were determined for several Fe-S proteins in different oxidation states. It was found that differences in chemical shifts, in patterns of unobserved residues, in internal mobility and in thermodynamic stability are suitable data to map subtle changes between the two different oxidation states of the protein. Recently, the interaction networks responsible for maturing human mitochondrial and cytosolic Fe-S proteins have been largely characterized by combining solution NMR standard experiments with those tailored to paramagnetic systems. We show here the contribution of solution NMR in providing a detailed molecular view of "Fe-S interactomics". This contribution was particularly effective when protein-protein interactions are weak and transient, and thus difficult to be characterized at high resolution with other methodologies.

The Breast Health Intervention Evaluation Study

DTIC Science & Technology

2001-08-01

content due to its subtle almost subliminal impact even though this issue did not surface in the various pre-tests during video development. A third...A. (1990). Involuntary attention and physiological arousal evoked by structural features and emotional content in TV commercials. Communication...Human communication research, 13, 399-420. Pezdek, K., and Stevens, E. (1984). Children=s memory for auditory and visual information on television

Four Year-Olds Use Norm-Based Coding for Face Identity

ERIC Educational Resources Information Center

Jeffery, Linda; Read, Ainsley; Rhodes, Gillian

2013-01-01

Norm-based coding, in which faces are coded as deviations from an average face, is an efficient way of coding visual patterns that share a common structure and must be distinguished by subtle variations that define individuals. Adults and school-aged children use norm-based coding for face identity but it is not yet known if pre-school aged…

Social Function and Communication in Optimal Outcome Children and Adolescents with an Autism History on Structured Test Measures

ERIC Educational Resources Information Center

Orinstein, Alyssa J.; Suh, Joyce; Porter, Kaitlyn; De Yoe, Kaitlin A.; Tyson, Katherine E.; Troyb, Eva; Barton, Marianne L.; Eigsti, Inge-Marie; Stevens, Michael C.; Fein, Deborah A.

2015-01-01

Youth who lose their ASD diagnosis may have subtle social and communication difficulties. We examined social and communication functioning in 44 high-functioning autism (HFA), 34 optimal outcome (OO) and 34 typically developing (TD) youth. Results indicated that OO participants had no autism communication symptoms, no pragmatic language deficits,…

Digital Breast Tomosynthesis: Observer Performance of Clustered Microcalcification Detection on Breast Phantom Images Acquired with an Experimental System Using Variable Scan Angles, Angular Increments, and Number of Projection Views

PubMed Central

Goodsitt, Mitchell M.; Helvie, Mark A.; Zelakiewicz, Scott; Schmitz, Andrea; Noroozian, Mitra; Paramagul, Chintana; Roubidoux, Marilyn A.; Nees, Alexis V.; Neal, Colleen H.; Carson, Paul; Lu, Yao; Hadjiiski, Lubomir; Wei, Jun

2014-01-01

Purpose To investigate the dependence of microcalcification cluster detectability on tomographic scan angle, angular increment, and number of projection views acquired at digital breast tomosynthesis (DBTdigital breast tomosynthesis). Materials and Methods A prototype DBTdigital breast tomosynthesis system operated in step-and-shoot mode was used to image breast phantoms. Four 5-cm-thick phantoms embedded with 81 simulated microcalcification clusters of three speck sizes (subtle, medium, and obvious) were imaged by using a rhodium target and rhodium filter with 29 kV, 50 mAs, and seven acquisition protocols. Fixed angular increments were used in four protocols (denoted as scan angle, angular increment, and number of projection views, respectively: 16°, 1°, and 17; 24°, 3°, and nine; 30°, 3°, and 11; and 60°, 3°, and 21), and variable increments were used in three (40°, variable, and 13; 40°, variable, and 15; and 60°, variable, and 21). The reconstructed DBTdigital breast tomosynthesis images were interpreted by six radiologists who located the microcalcification clusters and rated their conspicuity. Results The mean sensitivity for detection of subtle clusters ranged from 80% (22.5 of 28) to 96% (26.8 of 28) for the seven DBTdigital breast tomosynthesis protocols; the highest sensitivity was achieved with the 16°, 1°, and 17 protocol (96%), but the difference was significant only for the 60°, 3°, and 21 protocol (80%, P < .002) and did not reach significance for the other five protocols (P = .01–.15). The mean sensitivity for detection of medium and obvious clusters ranged from 97% (28.2 of 29) to 100% (24 of 24), but the differences fell short of significance (P = .08 to >.99). The conspicuity of subtle and medium clusters with the 16°, 1°, and 17 protocol was rated higher than those with other protocols; the differences were significant for subtle clusters with the 24°, 3°, and nine protocol and for medium clusters with 24°, 3°, and nine; 30°, 3°, and 11; 60°, 3° and 21; and 60°, variable, and 21 protocols (P < .002). Conclusion With imaging that did not include x-ray source motion or patient motion during acquisition of the projection views, narrow-angle DBTdigital breast tomosynthesis provided higher sensitivity and conspicuity than wide-angle DBTdigital breast tomosynthesis for subtle microcalcification clusters. © RSNA, 2014 PMID:25007048

Size Matters: Cerebral Volume Influences Sex Differences in Neuroanatomy

PubMed Central

Towler, Stephen; Welcome, Suzanne; Halderman, Laura K.; Otto, Ron; Eckert, Mark A.; Chiarello, Christine

2008-01-01

Biological and behavioral differences between the sexes range from obvious to subtle or nonexistent. Neuroanatomical differences are particularly controversial, perhaps due to the implication that they might account for behavioral differences. In this sample of 200 men and women, large effect sizes (Cohen's d > 0.8) were found for sex differences in total cerebral gray and white matter, cerebellum, and gray matter proportion (women had a higher proportion of gray matter). The only one of these sex differences that survived adjustment for the effect of cerebral volume was gray matter proportion. Individual differences in cerebral volume accounted for 21% of the difference in gray matter proportion, while sex accounted for an additional 4%. The relative size of the corpus callosum was 5% larger in women, but this difference was completely explained by a negative relationship between relative callosal size and cerebral volume. In agreement with Jancke et al., individuals with higher cerebral volume tended to have smaller corpora callosa. There were few sex differences in the size of structures in Broca's and Wernicke's area. We conclude that individual differences in brain volume, in both men and women, account for apparent sex differences in relative size. PMID:18440950

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE PAGES

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael; ...

2016-01-29

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

A Table! (At the Table).

ERIC Educational Resources Information Center

Terry, Robert M.

A review of French dining habits and table manners outlines: elements of the place setting, courtesies used at the table, serving conventions, restaurant tipping, the size and content of the different meals of the day, subtle differences in common foods, restaurant types, menu types, general wine and cheese choices, waiter-client communication,…

Trust versus Manipulation

ERIC Educational Resources Information Center

Lewis, Anne C.

2005-01-01

This article discusses the issue of trust in the education system. What is different about the issue of trust in the education system is the assault upon it, sometimes overt but most often subtle. There is a difference between strong criticism and willful manipulation. The nation's schools are responding to the former--perhaps too slowly for…

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

PubMed Central

Mitchelson, Keith Richard; Qin, Wen-Yan

2015-01-01

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development. PMID:26322174

[Visual and motor functions in schizophrenic patients].

PubMed

Del Vecchio, S; Gargiulo, P A

1992-12-01

In the present work, visual and motor functions have been explored in 26 chronic schizophrenic patients, and 7 acute schizophrenic patients, compared with 26 normal controls, by means of the Bender-Gestalt Test. Parameters under consideration were: Form distortion, rotation, integration, perseveration, use of space, subtle motricity, score (global parameter), and time employed. As regards distortion and rotation there have been highly significant differences between chronic patients and control group. Among acute patients, it was observed that perseveration was also highly significant. Conversely, integration and use of space did not differ significantly among the three groups involved. The global score, resulting from all the above mentioned parameters showed important differences between both patient groups on the one hand, and control group on the other hand. Taking into account that patients were being administered neuroleptic drugs, it can safely be said, however, that the Bender-Gestalt Test allows to recognize alteration in perceptual closure consistent with a loss of the objective structure of perceived phenomena, in both chronic and acute patients.

Gray matter structural compromise is equally distributed in left and right temporal lobe epilepsy.

PubMed

Liu, Min; Bernhardt, Boris C; Bernasconi, Andrea; Bernasconi, Neda

2016-02-01

In drug-resistant temporal lobe epilepsy (TLE), MRI studies have shown consistent mesiotemporal and neocortical structural alterations when comparing patients to healthy controls. It remains, however, relatively unclear whether the side of seizure focus differentially impacts the degree of structural damage. This work performed a comprehensive surface-based analysis of mesiotemporal and neocortical morphology on preoperative 1.5 T MRI in 25/35 LTLE/RTLE patients that achieved seizure freedom after surgery (i.e., Engel-I outcome; 7 ± 2 years follow-up), an imaging-independent confirmation of focus lateralization. Compared to 46 age- and sex-matched controls, both TLE groups displayed marked ipsilateral atrophy in mesiotemporal regions, while cortical thinning was bilateral. Direct contrasts between LTLE and RTLE did not reveal significant differences. Bootstrap simulations indicated low reproducibility of observing a between-cohort difference; power analysis revealed that more than 110 patients would be necessary to detect subtle differences. No difference between LTLE and RTLE was confirmed when using voxel-based morphometry, an independent proxy of gray matter volume. Similar results were obtained analyzing a separate 3 T dataset (15/15 LTLE/RTLE patients; Engel-I after 4 ± 2 years follow-up; 42 controls). Our results strongly support equivalent gray matter compromise in left and right TLE. The morphological profile of seizure-free patients, presenting with ipsilateral mesiotemporal and bilateral cortical atrophy, motivates the development of neuromarkers of outcome that consider both mesiotemporal and neocortical structures. Hum Brain Mapp 37:515-524, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Exploring glycogen biosynthesis through Monte Carlo simulation.

PubMed

Zhang, Peng; Nada, Sharif S; Tan, Xinle; Deng, Bin; Sullivan, Mitchell A; Gilbert, Robert G

2018-05-08

Glycogen, a complex branched polymer of glucose (average chain length ~10 monomer units), is the blood-sugar reservoir in humans and other animals. Certain aspects of its molecular structure relevant to its biological functions are currently unamenable to experimental exploration. Knowledge of these is needed to develop future models for quantitative data-fitting to obtain mechanistic understanding of the biosynthetic processes that give rise to glycogen structure. Monte Carlo simulations of the biosynthesis of this structure with realistic macromolecular parameters reveal how chain growth and stoppage (the latter assumed to be through both the action of glycogen branching enzyme and other degradative enzymes, and by hindrance) control structural features. The simulated chain-length, pair-distance and radial density distributions agree semi-quantitatively with the limited available data. The simulations indicate that a steady state in molecular structure and size is rapidly obtained, that molecular density reaches a maximum near the center of the particle (not at the periphery, as is the case with dendrimers), and that particle size is controlled by both enzyme activity and hindrance. This knowledge will aid in the understanding of diabetes (loss of blood-sugar control), which has been found to involve subtle differences in glycogen molecular structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Gently does it: Humans outperform a software classifier in recognizing subtle, nonstereotypical facial expressions.

PubMed

Yitzhak, Neta; Giladi, Nir; Gurevich, Tanya; Messinger, Daniel S; Prince, Emily B; Martin, Katherine; Aviezer, Hillel

2017-12-01

According to dominant theories of affect, humans innately and universally express a set of emotions using specific configurations of prototypical facial activity. Accordingly, thousands of studies have tested emotion recognition using sets of highly intense and stereotypical facial expressions, yet their incidence in real life is virtually unknown. In fact, a commonplace experience is that emotions are expressed in subtle and nonprototypical forms. Such facial expressions are at the focus of the current study. In Experiment 1, we present the development and validation of a novel stimulus set consisting of dynamic and subtle emotional facial displays conveyed without constraining expressers to using prototypical configurations. Although these subtle expressions were more challenging to recognize than prototypical dynamic expressions, they were still well recognized by human raters, and perhaps most importantly, they were rated as more ecological and naturalistic than the prototypical expressions. In Experiment 2, we examined the characteristics of subtle versus prototypical expressions by subjecting them to a software classifier, which used prototypical basic emotion criteria. Although the software was highly successful at classifying prototypical expressions, it performed very poorly at classifying the subtle expressions. Further validation was obtained from human expert face coders: Subtle stimuli did not contain many of the key facial movements present in prototypical expressions. Together, these findings suggest that emotions may be successfully conveyed to human viewers using subtle nonprototypical expressions. Although classic prototypical facial expressions are well recognized, they appear less naturalistic and may not capture the richness of everyday emotional communication. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Unsupervised data mining in nanoscale x-ray spectro-microscopic study of NdFeB magnet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Xiaoyue; Yang, Feifei; Antono, Erin

Novel developments in X-ray based spectro-microscopic characterization techniques have increased the rate of acquisition of spatially resolved spectroscopic data by several orders of magnitude over what was possible a few years ago. This accelerated data acquisition, with high spatial resolution at nanoscale and sensitivity to subtle differences in chemistry and atomic structure, provides a unique opportunity to investigate hierarchically complex and structurally heterogeneous systems found in functional devices and materials systems. However, handling and analyzing the large volume data generated poses significant challenges. Here we apply an unsupervised data-mining algorithm known as DBSCAN to study a rare-earth element based permanentmore » magnet material, Nd 2Fe 14B. We are able to reduce a large spectro-microscopic dataset of over 300,000 spectra to 3, preserving much of the underlying information. Scientists can easily and quickly analyze in detail three characteristic spectra. Our approach can rapidly provide a concise representation of a large and complex dataset to materials scientists and chemists. For instance, it shows that the surface of common Nd 2Fe 14B magnet is chemically and structurally very different from the bulk, suggesting a possible surface alteration effect possibly due to the corrosion, which could affect the material’s overall properties.« less

Combined strong anion-exchange HPLC and PAGE approach for the purification of heparan sulphate oligosaccharides.

PubMed

Vivès, R R; Goodger, S; Pye, D A

2001-02-15

Heparan sulphates are highly sulphated linear polysaccharides involved in many cellular functions. Their biological properties stem from their ability to interact with a wide range of proteins. An increasing number of studies, using heparan sulphate-derived oligosaccharides, suggest that specific structural features within the polysaccharide are responsible for ligand recognition and regulation. In the present study, we show that strong anion-exchange HPLC alone, a commonly used technique for purification of heparan sulphate-derived oligosaccharides, may not permit the isolation of highly pure heparan sulphate oligosaccharide species. This was determined by PAGE analysis of hexa-, octa- and decasaccharide samples deemed to be pure by strong anion-exchange HPLC. In addition, subtle differences in the positioning of sulphate groups within heparan sulphate hexasaccharides were impossible to detect by strong anion-exchange HPLC. PAGE analysis on the other hand afforded excellent resolution of these structural isomers. The precise positioning of specific sulphate groups has been implicated in determining the specificity of heparan sulphate interactions and biological activities; hence, the purification of oligosaccharide species that differ in this way becomes an important issue. In this study, we have used strong anion-exchange HPLC and PAGE techniques to allow production of the homogeneous heparan sulphate oligosaccharide species that will be required for the detailed study of structure/activity relationships.

Br...Br and van der Waals interactions along a homologous series: crystal packing of 1,2-dibromo-4,5-dialkoxybenzenes.

PubMed

Suarez, Sebastián A; Muller, Federico; Gutiérrez Suburu, Matías E; Fonrouge, Ana; Baggio, Ricardo F; Cukiernik, Fabio D

2016-10-01

The crystalline structures of four homologues of the 1,2-dibromo-4,5-dialkoxybenzene series [Br 2 C 6 H 2 (OC n H 2n + 1 ) 2 for n = 2, 12, 14 and 18] have been solved by means of single-crystal crystallography. Comparison along the series, including the previously reported n = 10 and n = 16 derivatives, shows a clear metric trend (b and c essentially fixed along the series and a growing linearly with n), in spite of some subtle differences in space groups and/or packing modes. A uniform packing pattern for the aliphatic chains has been found for the n = 12 to 18 homologues, which slightly differs from that of the n = 10 derivative. The crystalline structures of all the higher homologues (n = 10-18) seem to arise from van der Waals interchain interactions and, to a lesser extent, type II Br...Br interactions. The dominant role of interchain interactions provides direct structural support for the usual interpretation of melting point trends like that found along this series. Atoms in Molecules (AIM) analysis allows a comparison of the relative magnitude of the interchain and Br...Br interactions, an analysis validated by the measured melting enthalpies.

Unsupervised data mining in nanoscale x-ray spectro-microscopic study of NdFeB magnet

DOE PAGES

Duan, Xiaoyue; Yang, Feifei; Antono, Erin; ...

2016-09-29

Novel developments in X-ray based spectro-microscopic characterization techniques have increased the rate of acquisition of spatially resolved spectroscopic data by several orders of magnitude over what was possible a few years ago. This accelerated data acquisition, with high spatial resolution at nanoscale and sensitivity to subtle differences in chemistry and atomic structure, provides a unique opportunity to investigate hierarchically complex and structurally heterogeneous systems found in functional devices and materials systems. However, handling and analyzing the large volume data generated poses significant challenges. Here we apply an unsupervised data-mining algorithm known as DBSCAN to study a rare-earth element based permanentmore » magnet material, Nd 2Fe 14B. We are able to reduce a large spectro-microscopic dataset of over 300,000 spectra to 3, preserving much of the underlying information. Scientists can easily and quickly analyze in detail three characteristic spectra. Our approach can rapidly provide a concise representation of a large and complex dataset to materials scientists and chemists. For instance, it shows that the surface of common Nd 2Fe 14B magnet is chemically and structurally very different from the bulk, suggesting a possible surface alteration effect possibly due to the corrosion, which could affect the material’s overall properties.« less

Spatial phenotypic and genetic structure of threespine stickleback (Gasterosteus aculeatus) in a heterogeneous natural system, Lake Mývatn, Iceland.

PubMed

Millet, Antoine; Kristjánsson, Bjarni K; Einarsson, Arni; Räsänen, Katja

2013-09-01

Eco-evolutionary responses of natural populations to spatial environmental variation strongly depend on the relative strength of environmental differences/natural selection and dispersal/gene flow. In absence of geographic barriers, as often is the case in lake ecosystems, gene flow is expected to constrain adaptive divergence between environments - favoring phenotypic plasticity or high trait variability. However, if divergent natural selection is sufficiently strong, adaptive divergence can occur in face of gene flow. The extent of divergence is most often studied between two contrasting environments, whereas potential for multimodal divergence is little explored. We investigated phenotypic (body size, defensive structures, and feeding morphology) and genetic (microsatellites) structure in threespine stickleback (Gasterosteus aculeatus) across five habitat types and two basins (North and South) within the geologically young and highly heterogeneous Lake Mývatn, North East Iceland. We found that (1) North basin stickleback were, on average, larger and had relatively longer spines than South basin stickleback, whereas (2) feeding morphology (gill raker number and gill raker gap width) differed among three of five habitat types, and (3) there was only subtle genetic differentiation across the lake. Overall, our results indicate predator and prey mediated phenotypic divergence across multiple habitats in the lake, in face of gene flow.

Spatial phenotypic and genetic structure of threespine stickleback (Gasterosteus aculeatus) in a heterogeneous natural system, Lake Mývatn, Iceland

PubMed Central

Millet, Antoine; Kristjánsson, Bjarni K; Einarsson, Árni; Räsänen, Katja

2013-01-01

Eco-evolutionary responses of natural populations to spatial environmental variation strongly depend on the relative strength of environmental differences/natural selection and dispersal/gene flow. In absence of geographic barriers, as often is the case in lake ecosystems, gene flow is expected to constrain adaptive divergence between environments – favoring phenotypic plasticity or high trait variability. However, if divergent natural selection is sufficiently strong, adaptive divergence can occur in face of gene flow. The extent of divergence is most often studied between two contrasting environments, whereas potential for multimodal divergence is little explored. We investigated phenotypic (body size, defensive structures, and feeding morphology) and genetic (microsatellites) structure in threespine stickleback (Gasterosteus aculeatus) across five habitat types and two basins (North and South) within the geologically young and highly heterogeneous Lake Mývatn, North East Iceland. We found that (1) North basin stickleback were, on average, larger and had relatively longer spines than South basin stickleback, whereas (2) feeding morphology (gill raker number and gill raker gap width) differed among three of five habitat types, and (3) there was only subtle genetic differentiation across the lake. Overall, our results indicate predator and prey mediated phenotypic divergence across multiple habitats in the lake, in face of gene flow. PMID:24223263

Aversive Disablism: Subtle Prejudice toward Disabled People

ERIC Educational Resources Information Center

Deal, Mark

2007-01-01

Blatant forms of prejudice towards disabled people appear to be disappearing in the UK. However, subtle forms of prejudice remain and may be highly damaging to the achievement of the vision of disabled people being "respected and included as equal members of society". In order to assist placing subtle forms of prejudice within a…

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Localized Surface Plasmon Resonance in Au Nanoparticles Embedded dc Sputtered ZnO Thin Films.

PubMed

Patra, Anuradha; Balasubrahmaniyam, M; Lahal, Ranjit; Malar, P; Osipowicz, T; Manivannan, A; Kasiviswanathan, S

2015-02-01

The plasmonic behavior of metallic nanoparticles is explicitly dependent on their shape, size and the surrounding dielectric space. This study encompasses the influence of ZnO matrix, morphology of Au nanoparticles (AuNPs) and their organization on the optical behavior of ZnO/AuNPs-ZnO/ZnO/GP structures (GP: glass plate). These structures have been grown by a multiple-step physical process, which includes dc sputtering, thermal evaporation and thermal annealing. Different analytical techniques such as scanning electron microscopy, glancing angle X-ray diffraction, Rutherford backscattering spectrometry and optical absorption have been used to study the structures. In-situ rapid thermal treatment during dc sputtering of ZnO film has been found to induce subtle changes in the morphology of AuNPs, thereby altering the profile of the plasmon band in the absorption spectra. The results have been contrasted with a recent study on the spectral response of dc magnetron sputtered ZnO films embedded with AuNPs. Initial simulation results indicate that AuNPs-ZnO/Au/GP structure reflects/absorbs UV and infrared radiations, and therefore can serve as window coatings.

The subtle role of climate change on population genetic structure in Canada lynx.

PubMed

Row, Jeffrey R; Wilson, Paul J; Gomez, Celine; Koen, Erin L; Bowman, Jeff; Thornton, Daniel; Murray, Dennis L

2014-07-01

Anthropogenically driven climatic change is expected to reshape global patterns of species distribution and abundance. Given recent links between genetic variation and environmental patterns, climate change may similarly impact genetic population structure, but we lack information on the spatial and mechanistic underpinnings of genetic-climate associations. Here, we show that current genetic variability of Canada lynx (Lynx canadensis) is strongly correlated with a winter climate gradient (i.e. increasing snow depth and winter precipitation from west-to-east) across the Pacific-North American (PNO) to North Atlantic Oscillation (NAO) climatic systems. This relationship was stronger than isolation by distance and not explained by landscape variables or changes in abundance. Thus, these patterns suggest that individuals restricted dispersal across the climate boundary, likely in the absence of changes in habitat quality. We propose habitat imprinting on snow conditions as one possible explanation for this unusual phenomenon. Coupling historical climate data with future projections, we also found increasingly diverging snow conditions between the two climate systems. Based on genetic simulations using projected climate data (2041-2070), we predicted that this divergence could lead to a threefold increase in genetic differentiation, potentially leading to isolated east-west populations of lynx in North America. Our results imply that subtle genetic structure can be governed by current climate and that substantive genetic differentiation and related ecological divergence may arise from changing climate patterns. © 2014 John Wiley & Sons Ltd.

Oriental approaches to masculine and feminine subtle energy principles.

PubMed

Telles, Shirley

2005-04-01

According to ancient Indian and Chinese texts the subtle energy (prana or chi) flows through several thousand anatomically indistinguishable channels or meridians (nadis). Three channels are especially important (ida, pingala, and sushumna). The ida and pingala channels correlate with left and right uninostril breathing, respectively. Like yin and yang, they are considered to represent the masculine and feminine principles present in all creation irrespective of sex. From this perspective these principles are assumed to be present simultaneously in persons of both sexes. This suggests that any sex-specific effects of uninostril breathing may be associated with sex-based physiological differences, not with 'masculine' and 'feminine' attributes of the channels (and the corresponding nostrils).

Geo-Engineering through Internet Informatics (GEMINI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watney, W. Lynn; Doveton, John H.; Victorine, John R.

GEMINI will resolve reservoir parameters that control well performance; characterize subtle reservoir properties important in understanding and modeling hydrocarbon pore volume and fluid flow; expedite recognition of bypassed, subtle, and complex oil and gas reservoirs at regional and local scale; differentiate commingled reservoirs; build integrated geologic and engineering model based on real-time, iterate solutions to evaluate reservoir management options for improved recovery; provide practical tools to assist the geoscientist, engineer, and petroleum operator in making their tasks more efficient and effective; enable evaluations to be made at different scales, ranging from individual well, through lease, field, to play and regionmore » (scalable information infrastructure); and provide training and technology transfer to evaluate capabilities of the client.« less

Detecting subtle hydrochemical anomalies with multivariate statistics: an example from homogeneous groundwaters in the Great Artesian Basin, Australia

NASA Astrophysics Data System (ADS)

O'Shea, Bethany; Jankowski, Jerzy

2006-12-01

The major ion composition of Great Artesian Basin groundwater in the lower Namoi River valley is relatively homogeneous in chemical composition. Traditional graphical techniques have been combined with multivariate statistical methods to determine whether subtle differences in the chemical composition of these waters can be delineated. Hierarchical cluster analysis and principal components analysis were successful in delineating minor variations within the groundwaters of the study area that were not visually identified in the graphical techniques applied. Hydrochemical interpretation allowed geochemical processes to be identified in each statistically defined water type and illustrated how these groundwaters differ from one another. Three main geochemical processes were identified in the groundwaters: ion exchange, precipitation, and mixing between waters from different sources. Both statistical methods delineated an anomalous sample suspected of being influenced by magmatic CO2 input. The use of statistical methods to complement traditional graphical techniques for waters appearing homogeneous is emphasized for all investigations of this type. Copyright

Detail on Dione False color

NASA Image and Video Library

2006-01-27

The leading hemisphere of Dione displays subtle variations in color across its surface in this false color view. To create this view, ultraviolet, green and infrared images were combined into a single black and white picture that isolates and maps regional color differences. This "color map" was then superposed over a clear-filter image. The origin of the color differences is not yet understood, but may be caused by subtle differences in the surface composition or the sizes of grains making up the icy soil. Terrain visible here is on the moon's leading hemisphere. North on Dione (1,126 kilometers, or 700 miles across) is up and rotated 17 degrees to the right. All images were acquired with the Cassini spacecraft narrow-angle camera on Dec. 24, 2005 at a distance of approximately 597,000 kilometers (371,000 miles) from Dione and at a Sun-Dione-spacecraft, or phase, angle of 21 degrees. Image scale is 4 kilometers (2 miles) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA07688

Mapping the structure of animal behavior

NASA Astrophysics Data System (ADS)

Berman, Gordon; Choi, Daniel; Bialek, William; Shaevitz, Joshua

2014-03-01

Most animals possess the ability to actuate a vast diversity of movements, ostensibly constrained only by morphology and physics. In practice, however, a frequent assumption in behavioral science is that most of an animal's activities can be described in terms of a small set of stereotyped motifs. Here we introduce a method for mapping the behavioral space of organisms, relying only upon the underlying structure of postural movement data to organize and classify behaviors. Applying our method to movies of size closely-related species of freely-behaving fruit flies, we find a wide variety of non-stereotyped and stereo-typed behaviors, spanning a wide range of time scales. We observe subtle behavioral differences between these species, identifying the some of the effects of phylogenic history on behavior. Moreover, we find that the transitions between the observed behaviors display a hierarchical syntax, with similar behaviors likely to transition between each other, but with a long time scale of memory. These results suggest potential mechanisms for the evolution of behavior and for the neural control of movements.

Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.

PubMed

Metzger, Vincent T; Eun, Changsun; Kekenes-Huskey, Peter M; Huber, Gary; McCammon, J Andrew

2014-11-18

We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.

Electronic structure of Fe- vs. Ru-based dye molecules

NASA Astrophysics Data System (ADS)

Johnson, Phillip S.; Cook, Peter L.; Zegkinoglou, Ioannis; García-Lastra, J. M.; Rubio, Angel; Ruther, Rose E.; Hamers, Robert J.; Himpsel, F. J.

2013-01-01

In order to explore whether Ru can be replaced by inexpensive Fe in dye molecules for solar cells, the differences in the electronic structure of Fe- and Ru-based dyes are investigated by X-ray absorption spectroscopy and first-principles calculations. Molecules with the metal in a sixfold, octahedral N cage, such as tris(bipyridines) and tris(phenanthrolines), exhibit a systematic downward shift of the N 1s-to-π* transition when Ru is replaced by Fe. This shift is explained by an extra transfer of negative charge from the metal to the N ligands in the case of Fe, which reduces the binding energy of the N 1s core level. The C 1s-to-π* transitions show the opposite trend, with an increase in the transition energy when replacing Ru by Fe. Molecules with the metal in a fourfold, planar N cage (porphyrins) exhibit a more complex behavior due to a subtle competition between the crystal field, axial ligands, and the 2+ vs. 3+ oxidation states.

[Recurrent Corneal Erosions in Epithelial Corneal Dystrophies].

PubMed

Geerling, Gerd; Lisch, Walter; Finis, David

2018-06-01

The corneal epithelium is the most important structure of the ocular optical system. Recurrent corneal erosions can result from inflammation, trauma, degeneration and dystrophies. Epithelial basement membrane dystrophy (EBMD), epithelial recurrent erosion dystrophy (ERED) and Francheschetti and Meesmann's epithelial corneal dystrophy (MECD) can all - besides other signs and symptoms - result in more or less frequent corneal erosions. The pathomechanisms involved however are different. In EBMD, corneal erosions are facultative and clinical signs are often subtle. Aberrant basement membrane structures are associated with thinning of the epithelium and can be clinically identified as maps or fingerprints. In ERED, recurrent corneal erosions are - predominantly in the first decades of life - always present. A defect in the COL17A1 gene results in a dysfunctional hemidesmosome. In MECD, punctate corneal erosions are less frequent and result from intraepithelial microcysts which open spontaneously onto the ocular surface. Usually lubricants, therapeutic contact lenses and sometimes epithelial debridement and phototherapeutic keratectomy are the mainstay for treating corneal erosions in these three dystrophies. Georg Thieme Verlag KG Stuttgart · New York.

Host population genetic structure and zooxanthellae diversity of two reef-building coral species along the Florida Reef Tract and wider Caribbean

NASA Astrophysics Data System (ADS)

Baums, I. B.; Johnson, M. E.; Devlin-Durante, M. K.; Miller, M. W.

2010-12-01

In preparation for a large-scale coral restoration project, we surveyed host population genetic structure and symbiont diversity of two reef-building corals in four reef zones along the Florida reef tract (FRT). There was no evidence for coral population subdivision along the FRT in Acropora cervicornis or Montastraea faveolata based on microsatellite markers. However, in A. cervicornis, significant genetic differentiation was apparent when extending the analysis to broader scales (Caribbean). Clade diversity of the zooxanthellae differed along the FRT. A. cervicornis harbored mostly clade A with clade D zooxanthellae being prominent in colonies growing inshore and in the mid-channel zones that experience greater temperature fluctuations and receive significant nutrient and sediment input. M. faveolata harbored a more diverse array of symbionts, and variation in symbiont diversity among four habitat zones was more subtle but still significant. Implications of these results are discussed for ongoing restoration and conservation work.

Coupling of active motion and advection shapes intracellular cargo transport.

PubMed

Khuc Trong, Philipp; Guck, Jochen; Goldstein, Raymond E

2012-07-13

Intracellular cargo transport can arise from passive diffusion, active motor-driven transport along cytoskeletal filament networks, and passive advection by fluid flows entrained by such cargo-motor motion. Active and advective transport are thus intrinsically coupled as related, yet different representations of the same underlying network structure. A reaction-advection-diffusion system is used here to show that this coupling affects the transport and localization of a passive tracer in a confined geometry. For sufficiently low diffusion, cargo localization to a target zone is optimized either by low reaction kinetics and decoupling of bound and unbound states, or by a mostly disordered cytoskeletal network with only weak directional bias. These generic results may help to rationalize subtle features of cytoskeletal networks, for example as observed for microtubules in fly oocytes.

Enhancement of infectious disease vaccines through TLR9-dependent recognition of CpG DNA.

PubMed

McCluskie, M J; Krieg, A M

2006-01-01

The adaptive immune system-with its remarkable ability to generate antigen-specific antibodies and T lymphocytes against pathogens never before "seen" by an organism-is one of the marvels of evolution. However, to generate these responses, the adaptive immune system requires activation by the innate immune system. Toll-like receptors (TLRs) are perhaps the best-understood family of innate immune receptors for detecting infections and stimulating adaptive immune responses. TLR9 appears to have evolved to recognize infections by a subtle structural difference between eukaryotic and prokaryotic/viral DNA; only the former frequently methylates CpG dinucleotides. Used as vaccine adjuvants, synthetic oligodeoxynucleotide (ODN) ligands for TLR9--CpG ODN--greatly enhance the speed and strength of the immune responses to vaccination.

A fabrication guide for planar silicon quantum dot heterostructures

NASA Astrophysics Data System (ADS)

Spruijtenburg, Paul C.; Amitonov, Sergey V.; van der Wiel, Wilfred G.; Zwanenburg, Floris A.

2018-04-01

We describe important considerations to create top-down fabricated planar quantum dots in silicon, often not discussed in detail in literature. The subtle interplay between intrinsic material properties, interfaces and fabrication processes plays a crucial role in the formation of electrostatically defined quantum dots. Processes such as oxidation, physical vapor deposition and atomic-layer deposition must be tailored in order to prevent unwanted side effects such as defects, disorder and dewetting. In two directly related manuscripts written in parallel we use techniques described in this work to create depletion-mode quantum dots in intrinsic silicon, and low-disorder silicon quantum dots defined with palladium gates. While we discuss three different planar gate structures, the general principles also apply to 0D and 1D systems, such as self-assembled islands and nanowires.

Consistency condition for inflation from (broken) conformal symmetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schalm, Koenraad; Aalst, Ted van der; Shiu, Gary, E-mail: kschalm@lorentz.leidenuniv.nl, E-mail: shiu@physics.wisc.edu, E-mail: vdaalst@lorentz.leidenuniv.nl

2013-03-01

We investigate the symmetry constraints on the bispectrum, i.e. the three-point correlation function of primordial density fluctuations, in slow-roll inflation. It follows from the defining property of slow-roll inflation that primordial correlation functions inherit most of their structure from weakly broken de Sitter symmetries. Using holographic techniques borrowed from the AdS/CFT correspondence, the symmetry constraints on the bispectrum can be mapped to a set of stress-tensor Ward identities in a weakly broken 2+1-dimensional Euclidean CFT. We construct the consistency condition from these Ward identities using conformal perturbation theory. This requires a second order Ward identity and the use of themore » evolution equation. Our result also illustrates a subtle difference between conformal perturbation theory and the slow-roll expansion.« less

Impacts of exploratory drilling for oil and gas on the benthic environment of Georges Bank

USGS Publications Warehouse

Neff, J. M.; Bothner, Michael H.; Maciolek, N. J.; Grassle, J. F.

1989-01-01

Cluster analysis revealed a strong relationship between community structure and both sediment type and water depth. Little seasonal variation was detected, but some interannual differences were revealed by cluster analysis and correspondence analysis. The replicates from a station always resembled each other more than they resembled any replicates from other stations. In addition, the combined replicates from a station always clustered with samples from that station taken on other cruises. This excellent replication and uniformity of the benthic infaunal community at a station over time made it possible to detect very subtle changes in community parameters that might be related to discharges of drilling fluid and drill cuttings. Nevertheless, no changes were detected in benthic communities of Georges Bank that could be attributed to drilling activities.

Social function and communication in optimal outcome children and adolescents with an autism history on structured test measures

PubMed Central

Orinstein, A.; Suh, J.; Porter, K.; de Yoe, K.A; Tyson, K.; Troyb, E.; Barton, M.; Eigsti, I.M.; Stevens, M.C.; Fein, D. A.

2015-01-01

Youth who lose their ASD diagnosis may have subtle social and communication difficulties. We examined social and communication functioning in 44 high-functioning autism (HFA), 34 optimal outcome (OO) and 34 typically developing (TD) youth. Results indicated that OO participants had no autism communication symptoms, no pragmatic language deficits, and were judged as likable as TD peers. Some group differences were found: OO youth had less insight into social relationships and poorer friendship descriptions than TD youth. OO participants had attention, self-control, and immaturity difficulties that may impact social abilities. However, OO participants were most engaged, friendliest, warmest, and most approachable. Overall, OO participants had no social and communicative impairments, although some exhibited mild social difficulties that often accompany attentional problems. PMID:25758821

Modeling 15N NMR chemical shift changes in protein backbone with pressure

NASA Astrophysics Data System (ADS)

La Penna, Giovanni; Mori, Yoshiharu; Kitahara, Ryo; Akasaka, Kazuyuki; Okamoto, Yuko

2016-08-01

Nitrogen chemical shift is a useful parameter for determining the backbone three-dimensional structure of proteins. Empirical models for fast calculation of N chemical shift are improving their reliability, but there are subtle effects that cannot be easily interpreted. Among these, the effects of slight changes in hydrogen bonds, both intramolecular and with water molecules in the solvent, are particularly difficult to predict. On the other hand, these hydrogen bonds are sensitive to changes in protein environment. In this work, the change of N chemical shift with pressure for backbone segments in the protein ubiquitin is correlated with the change in the population of hydrogen bonds involving the backbone amide group. The different extent of interaction of protein backbone with the water molecules in the solvent is put in evidence.

Resource Scarcity and Prescriptive Attitudes Generate Subtle, Intergenerational Older-Worker Exclusion

PubMed Central

North, Michael S.; Fiske, Susan T.

2016-01-01

Prior work describes specific, prescriptive resource tensions between generations, comprising active Succession, passive Consumption, and symbolic Identity (SCI; North & Fiske, 2013a, 2013b). The current paper focuses on how these domains potentially drive intergenerational exclusion in work-related networking and training spheres. Studies 1a–1c—each focusing on a different SCI domain—manipulated perceived resource availability between generations, then introduced a professional networking opportunity. Across studies, scarcity reduced the likelihood of young participants’ networking engagement with older workers who violated SCI resource expectations. Study 2 impelled participants to allocate scarce training resources among three similarly qualified but different-aged employees (younger, middle-aged, and older). Older workers received the lowest such investment, particularly among younger participants—an effect driven by Succession beliefs, per mediation analyses. Overall, the findings emphasize resource tensions in driving older workers’ subtle exclusion by younger generations; minimizing such tensions will be critical for aging, increasingly intergenerational workplaces. PMID:27499555

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.

PubMed

Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; Dive, Vincent; Sturrock, Edward D; Isaac, R Elwyn; Acharya, K Ravi

2010-07-16

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE. 2010 Elsevier Ltd. All rights reserved.

Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

PubMed

Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

2017-06-21

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

Structural styles of the paradox basin: Something to consider in a basin dominated by stratigraphic traps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevenson, G.M.

1993-08-01

The Paradox basin has produced a considerable amount of oil and gas from Pennsylvanian and Mississippian reservoirs. Most of the production has been from stratigraphic traps associated with subtle rejuvenated basement structures. Only the Blanding sub-basin and west flank of the salt anticlines (Lisbon Valley to Salt Wash fields) have been explored in sufficient quantity to classify as the mature parts of the basin, and even in these areas, new fields are currently being discovered. The majority of the basin still remains an exploration frontier. Certainly, structural and stratigraphic conditions analogous to those in the proven areas exist in muchmore » of these underexplored parts of the Paradox basin, but the potential for new and different types of hydrocarbon traps should not be overlooked. Structural styles present in the Paradox basin range from high-angle reverse, to normal, to inverted, which records different periods of crustal shortening and extension. To provide a full appreciation of the variety and complexities of structural styles in the Paradox basin and their influence on the orientation and distribution of different stratigraphic mechanisms, comparisons are made in the following areas: the Uncompahgre frontal fault zone, salt anticlines, Cane Creek anticline, Nequoia arch, Blanding basin, and Hogback monocline. To demonstrate the episodic nature of tectonism throughout the entire Phanerozoic Era, potential and proven hydrocarbon trapping styles are illustrated in strata ranging from Devonian to Late Pennsylvanian age. In particular, the Pennsylvanian Paradox evaporites and equivalent shelf carbonates and siliciclastics provide an excellent example of chronostratigraphic and glacioeustatic relationships. Due to the proven prolific nature of these Pennsylvanian reservoirs, the interrelationships of structure to stratigraphy in the Blanding basin and along the Cane Creek anticline will be emphasized.« less

Prenatal cocaine effects on brain structure in early infancy.

PubMed

Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

2014-11-01

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. Copyright © 2014 Elsevier Inc. All rights reserved.

Tunable alumina 2D photonic-crystal structures via biomineralization of peacock tail feathers

NASA Astrophysics Data System (ADS)

Jiang, Yonggang; Wang, Rui; Feng, Lin; Li, Jian; An, Zhonglie; Zhang, Deyuan

2018-04-01

Peacock tail feathers with subtle periodic nanostructures exhibit diverse striking brilliancy, which can be applied as natural templates to fabricate artificial photonic crystals (PhCs) via a biomineralization method. Alumina photonic-crystal structures are successfully synthesized via an immersion and two-step calcination process. The lattice constants of the artificial PhCs are greatly reduced compared to their natural matrices. The lattice constants are tunable by modifying the final annealing conditions in the biomineralization process. The reflection spectra of the alumina photonic-crystal structures are measured, which is related to their material and structural parameters. This work suggests a facile fabrication process to construct alumina PhCs with a high-temperature resistance.

Gender effects in alcohol dependence: an fMRI pilot study examining affective processing.

PubMed

Padula, Claudia B; Anthenelli, Robert M; Eliassen, James C; Nelson, Erik; Lisdahl, Krista M

2015-02-01

Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Fearful Condition-The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition-AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. Copyright © 2015 by the Research Society on Alcoholism.

Gender Effects in Alcohol Dependence: An fMRI Pilot Study Examining Affective Processing

PubMed Central

Padula, Claudia B.; Anthenelli, Robert M.; Eliassen, James C.; Nelson, Erik; Lisdahl, Krista M.

2017-01-01

Background Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Methods Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Results Fearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Conclusions Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. PMID:25684049

Asymmetry in auditory and spatial attention span in normal elderly genetically at risk for Alzheimer's disease.

PubMed

Jacobson, Mark W; Delis, Dean C; Bondi, Mark W; Salmon, David P

2005-02-01

Some studies of elderly individuals with the ApoE-e4 genotype noted subtle deficits on tests of attention such as the WAIS-R Digit Span subtest, but these findings have not been consistently reported. One possible explanation for the inconsistent results could be the presence of subgroups of e4+ individuals with asymmetric cognitive profiles (i.e., significant discrepancies between verbal and visuospatial skills). Comparing genotype groups with individual, modality-specific tests might obscure subtle differences between verbal and visuospatial attention in these asymmetric subgroups. In this study, we administered the WAIS-R Digit Span and WMS-R Visual Memory Span subtests to 21 nondemented elderly e4+ individuals and 21 elderly e4- individuals matched on age, education, and overall cognitive ability. We hypothesized that a) the e4+ group would show a higher incidence of asymmetric cognitive profiles when comparing Digit Span/Visual Memory Span performance relative to the e4- group; and (b) an analysis of individual test performance would fail to reveal differences between the two subject groups. Although the groups' performances were comparable on the individual attention span tests, the e4+ group showed a significantly larger discrepancy between digit span and spatial span scores compared to the e4- group. These findings suggest that contrast measures of modality-specific attentional skills may be more sensitive to subtle group differences in at-risk groups, even when the groups do not differ on individual comparisons of standardized test means. The increased discrepancy between verbal and visuospatial attention may reflect the presence of "subgroups" within the ApoE-e4 group that are qualitatively similar to asymmetric subgroups commonly associated with the earliest stages of AD.

Schoolyard Geology as a Bridge between Urban Thinkers and the Natural World

ERIC Educational Resources Information Center

d'Alessio, Matthew A.

2012-01-01

Students who have a strong urban place-identity may perceive the natural world differently from many geoscience instructors. These urban thinkers have less experience in the natural world and are more comfortable in built environments. They may have subtle differences in cognitive and spatial skill development, interest level in the natural…

Impacts of invasive plants on songbirds: Using song structure as an indicator of habitat quality

Treesearch

Yvette Ortega

2007-01-01

Invasive species can alter habitat quality over broad scales, so they pose a severe threat to songbird populations. Through our long-term research program supported by BEMRP, we have found that changes in habitat quality induced by exotic plants like spotted knapweed can lead to subtle yet profound changes in songbird populations. For example, in knapweed-invaded...

Putting time into proof outlines

NASA Technical Reports Server (NTRS)

Schneider, Fred B.; Bloom, Bard; Marzullo, Keith

1993-01-01

A logic for reasoning about timing properties of concurrent programs is presented. The logic is based on Hoare-style proof outlines and can handle maximal parallelism as well as certain resource-constrained execution environments. The correctness proof for a mutual exclusion protocol that uses execution timings in a subtle way illustrates the logic in action. A soundness proof using structural operational semantics is outlined in the appendix.

Structure of the Stern layer in Phospholipid Systems

NASA Astrophysics Data System (ADS)

Vangaveti, Sweta; Travesset, Alex

2011-03-01

The structure of the Stern layer in Phospholipid Systems results from a subtle competition of salt concentration, ionic valence, specific ionic-phospolipid interactions and pH. It becomes very challenging to develop a rigorous theory that encompasses all these effects, yet its understanding is extremely relevant for both model and biological systems, as the structure of the Stern layer determines the interactions of phospholipids with proteins or electrostatic phase separation (rafts). In this talk we will present our theoretical model for the Stern Layer and discuss how all these effects are included. Particularly emphasis is made to Phosphoinositides and Phosphatidic acid. This work is supported by grant NSF DMR-0748475.

Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity

PubMed Central

Erceg, Jelena; Saunders, Timothy E.; Girardot, Charles; Devos, Damien P.; Hufnagel, Lars; Furlong, Eileen E. M.

2014-01-01

Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood. PMID:24391522

MCD spectroscopy of hexanuclear Mn(III) salicylaldoxime single-molecule magnets.

PubMed

Bradley, Justin M; Thomson, Andrew J; Inglis, Ross; Milios, Constantinos J; Brechin, Euan K; Piligkos, Stergios

2010-11-07

The hexanuclear cages [Mn(6)O(2)(R-sao)(6)L(2)(EtOH)(x)(H(2)O)(y)] "Mn(6)" behave as single-molecule magnets (SMMs) below a characteristic blocking temperature. As with [Mn(12)O(12)(O(2)CR)(16)(H(2)O)(4)] "Mn(12)" the electronic absorption spectra are rather featureless, yielding little information on the electronic structure of the magnetic ions. Low temperature Magnetic Circular Dichroism (MCD) spectra afford greater resolution of the optical transitions and also probe the magnetic properties of the system. Both the ground state spin and blocking temperature of the Mn(6) cages are determined by subtle structural perturbations of a generic Mn(6)O(2) core. Absorbance and MCD spectra are reported for [Mn(6)O(2)(Et-sao)(6){O(2)CPh(Me)(2)}(2)(EtOH)(6)] (1), [Mn(6)O(2)(Et-sao)(6){O(2)CPh}(2)(EtOH)(4)(H(2)O)(2)] (2), [Mn(6)O(2)(sao)(6){O(2)CPh}(2)(EtOH)(4)]·EtOH (3) and the trinuclear precursor [Mn(3)O(Et-sao)(3)(MeOH)(3)](ClO(4)) (4) cast into polymer film. SMM behaviour has previously been observed using magnetic susceptibility measurements on powder and single-crystal samples. The ligand field environment of the magnetic ions is assumed to be similar in (1) and (2) and their different blocking temperatures are attributed to the magnitude of the effective exchange constant. The MCD spectra of (1) and (2), in which the ground state spin S = 12, show that the ligand field environments of the Mn ions are almost identical and that magnetic hysteresis persists for isolated molecules when crystal packing forces are removed. The subtle structural differences between (1) and (2) are manifested in the field dependence of the MCD response at different wavelengths that reflect changes in band polarisation. The MCD spectrum of (3) contains features not apparent in those of (1) and (2). These are attributed to 5-coordinate Mn(iii), which is unique to (3) among the compounds studied. (3) has ground state spin S = 4, a lower blocking temperature and consequently no observable hysteresis in the MCD down to 1.7 K. Comparison of the MCD spectra of (1)-(3) to that of (4) confirms the integrity of the Mn(6)O(2) core when these materials are cast into polymer film.

Mechanical Properties of Plant Cell Walls Probed by Relaxation Spectra1[W][OA

PubMed Central

Hansen, Steen Laugesen; Ray, Peter Martin; Karlsson, Anders Ola; Jørgensen, Bodil; Borkhardt, Bernhard; Petersen, Bent Larsen; Ulvskov, Peter

2011-01-01

Transformants and mutants with altered cell wall composition are expected to display a biomechanical phenotype due to the structural role of the cell wall. It is often quite difficult, however, to distinguish the mechanical behavior of a mutant's or transformant's cell walls from that of the wild type. This may be due to the plant’s ability to compensate for the wall modification or because the biophysical method that is often employed, determination of simple elastic modulus and breakstrength, lacks the resolving power necessary for detecting subtle mechanical phenotypes. Here, we apply a method, determination of relaxation spectra, which probes, and can separate, the viscoelastic properties of different cell wall components (i.e. those properties that depend on the elastic behavior of load-bearing wall polymers combined with viscous interactions between them). A computer program, BayesRelax, that deduces relaxation spectra from appropriate rheological measurements is presented and made accessible through a Web interface. BayesRelax models the cell wall as a continuum of relaxing elements, and the ability of the method to resolve small differences in cell wall mechanical properties is demonstrated using tuber tissue from wild-type and transgenic potatoes (Solanum tuberosum) that differ in rhamnogalacturonan I side chain structure. PMID:21075961

New Insights into the In Silico Prediction of HIV Protease Resistance to Nelfinavir

PubMed Central

Antunes, Dinler A.; Rigo, Maurício M.; Sinigaglia, Marialva; de Medeiros, Rúbia M.; Junqueira, Dennis M.; Almeida, Sabrina E. M.; Vieira, Gustavo F.

2014-01-01

The Human Immunodeficiency Virus type 1 protease enzyme (HIV-1 PR) is one of the most important targets of antiretroviral therapy used in the treatment of AIDS patients. The success of protease-inhibitors (PIs), however, is often limited by the emergence of protease mutations that can confer resistance to a specific drug, or even to multiple PIs. In the present study, we used bioinformatics tools to evaluate the impact of the unusual mutations D30V and V32E over the dynamics of the PR-Nelfinavir complex, considering that codons involved in these mutations were previously related to major drug resistance to Nelfinavir. Both studied mutations presented structural features that indicate resistance to Nelfinavir, each one with a different impact over the interaction with the drug. The D30V mutation triggered a subtle change in the PR structure, which was also observed for the well-known Nelfinavir resistance mutation D30N, while the V32E exchange presented a much more dramatic impact over the PR flap dynamics. Moreover, our in silico approach was also able to describe different binding modes of the drug when bound to different proteases, identifying specific features of HIV-1 subtype B and subtype C proteases. PMID:24498124

Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism*

PubMed Central

Cameron, Elizabeth A.; Maynard, Mallory A.; Smith, Christopher J.; Smith, Thomas J.; Koropatkin, Nicole M.; Martens, Eric C.

2012-01-01

Human colonic bacteria are necessary for the digestion of many dietary polysaccharides. The intestinal symbiont Bacteroides thetaiotaomicron uses five outer membrane proteins to bind and degrade starch. Here, we report the x-ray crystallographic structures of SusE and SusF, two outer membrane proteins composed of tandem starch specific carbohydrate-binding modules (CBMs) with no enzymatic activity. Examination of the two CBMs in SusE and three CBMs in SusF reveals subtle differences in the way each binds starch and is reflected in their Kd values for both high molecular weight starch and small maltooligosaccharides. Thus, each site seems to have a unique starch preference that may enable these proteins to interact with different regions of starch or its breakdown products. Proteins similar to SusE and SusF are encoded in many other polysaccharide utilization loci that are possessed by human gut bacteria in the phylum Bacteroidetes. Thus, these proteins are likely to play an important role in carbohydrate metabolism in these abundant symbiotic species. Understanding structural changes that diversify and adapt related proteins in the human gut microbial community will be critical to understanding the detailed mechanistic roles that they perform in the complex digestive ecosystem. PMID:22910908

Structure of hydrophobic hydration of benzene and hexafluorobenzene from first principles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allesch, M; Schwegler, E; Galli, G

We report on the aqueous hydration of benzene and hexafluorobenzene, as obtained by carrying out extensive (>100 ps) first principles molecular dynamics simulations. Our results show that benzene and hexafluorobenzene do not behave as ordinary hydrophobic solutes, but rather present two distinct regions, one equatorial and the other axial, that exhibit different solvation properties. While in both cases the equatorial regions behave as typical hydrophobic solutes, the solvation properties of the axial regions depend strongly on the nature of the {pi}-water interaction. In particular, {pi}-hydrogen and {pi}-lone pair interactions are found to dominate in benzene and hexafluorobenzene, respectively, which leadsmore » to substantially different orientations of water near the two solutes. We present atomic and electronic structure results (in terms of Maximally Localized Wannier Functions) providing a microscopic description of benzene- and hexafluorobenzene-water interfaces, as well as a comparative study of the two solutes. Our results point at the importance of an accurate description of interfacial water in order to characterize hydration properties of apolar molecules, as these are strongly influenced by subtle charge rearrangements and dipole moment redistributions in interfacial regions.« less

Comparison of alternative approaches for analysing multi-level RNA-seq data

PubMed Central

Mohorianu, Irina; Bretman, Amanda; Smith, Damian T.; Fowler, Emily K.; Dalmay, Tamas

2017-01-01

RNA sequencing (RNA-seq) is widely used for RNA quantification in the environmental, biological and medical sciences. It enables the description of genome-wide patterns of expression and the identification of regulatory interactions and networks. The aim of RNA-seq data analyses is to achieve rigorous quantification of genes/transcripts to allow a reliable prediction of differential expression (DE), despite variation in levels of noise and inherent biases in sequencing data. This can be especially challenging for datasets in which gene expression differences are subtle, as in the behavioural transcriptomics test dataset from D. melanogaster that we used here. We investigated the power of existing approaches for quality checking mRNA-seq data and explored additional, quantitative quality checks. To accommodate nested, multi-level experimental designs, we incorporated sample layout into our analyses. We employed a subsampling without replacement-based normalization and an identification of DE that accounted for the hierarchy and amplitude of effect sizes within samples, then evaluated the resulting differential expression call in comparison to existing approaches. In a final step to test for broader applicability, we applied our approaches to a published set of H. sapiens mRNA-seq samples, The dataset-tailored methods improved sample comparability and delivered a robust prediction of subtle gene expression changes. The proposed approaches have the potential to improve key steps in the analysis of RNA-seq data by incorporating the structure and characteristics of biological experiments. PMID:28792517

Preservation potential of subtle glacial landforms based on detailed mapping of recently exposed proglacial areas: application of unmanned aerial vehicle (UAV) and structure-from-motion (SfM)

NASA Astrophysics Data System (ADS)

Ewertowski, Marek; Evans, David; Roberts, David; Tomczyk, Aleksandra; Ewertowski, Wojciech

2016-04-01

Ongoing glacier retreat results in the continuous exposure of proglacial areas. Such areas contain invaluable information about glacial process-form relationships manifest in specific landform assemblages. However, preservation potential of freshly exposed glacial landforms is very low, as proglacial terrains are one of the most dynamic parts of the landscape. Therefore, rapid mapping and geomorphological characterisation of such areas is important from a glaciological and geomorphological point of view for proper understanding and reconstruction of glacier-landform dynamics and chronology of glacial events. Annual patterns of recession and relatively small areas exposed every year, mean that the performing of regular aerial or satellite survey is expensive and therefore impractical. Recent advances in technology enables the development of low-cost alternatives for traditional aerial surveys. Small unmanned aerial vehicles (UAV) can be used to acquire high-resolution (several cm) low-altitude photographs. The UAV-based photographs can be subsequently processed through the structure-from-motion process to generate detailed orthophotomaps and digital elevation models. In this study we present case studies from the forelands of various glaciers on Iceland and Svalbard representing different types of proglacial landscapes: Fláajökull (annual push moraines); Hofellsjökul (bedrock bedforms and push moraines); Fjallsjökull (marginal drainage network); Rieperbreen (crevasse squeeze ridges and longitudinal debris stripes); Ayerbreen (transverse debris ridges); Foxfonna (longitudinal debris stripes);Hørbyebreen (geometric ridge network); Nordenskiöldbreen (fluted till surface); Ebbabreen (controlled moraine complex). UAV campaigns were conducted using a low-cost quadcopter platform. Resultant orthophotos and DEMs enabled mapping and assessment of recent glacial landscape development in different types of glacial landsystems. Results of our study indicate that preservation potential of geometric ridge networks and debris stripes produced by polythermal glaciers on Svalbard is very low (< 5 years), whereas subtle landforms indicative for temperate conditions: annual push moraines (Iceland)and flutings (Iceland and Svalbard) - can survive decades without being seriously modified.

Frustration in Biomolecules

PubMed Central

Ferreiro, Diego U.; Komives, Elizabeth A.; Wolynes, Peter G.

2014-01-01

Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their own structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellular functions. In large computational systems with a finite interaction-codes, the appearance of conflicting goals is inevitable. Simple conflicting forces can lead to quite complex structures and behaviors, leading to the concept of frustration in condensed matter. We present here some basic ideas about frustration in biomolecules and how the frustration concept leads to a better appreciation of many aspects of the architecture of biomolecules, and how biomolecular structure connects to function. These ideas are simultaneously both seductively simple and perilously subtle to grasp completely. The energy landscape theory of protein folding provides a framework for quantifying frustration in large systems and has been implemented at many levels of description. We first review the notion of frustration from the areas of abstract logic and its uses in simple condensed matter systems. We discuss then how the frustration concept applies specifically to heteropolymers, testing folding landscape theory in computer simulations of protein models and in experimentally accessible systems. Studying the aspects of frustration averaged over many proteins provides ways to infer energy functions useful for reliable structure prediction. We discuss how frustration affects folding mechanisms. We review here how a large part of the biological functions of proteins are related to subtle local physical frustration effects and how frustration influences the appearance of metastable states, the nature of binding processes, catalysis and allosteric transitions. We hope to illustrate how Frustration is a fundamental concept in relating function to structural biology. PMID:25225856

Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

PubMed

Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

2015-03-13

As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

Age-related reduction in microcolumnar structure correlates with cognitive decline in ventral but not dorsal area 46 of the rhesus monkey.

PubMed

Cruz, L; Roe, D L; Urbanc, B; Inglis, A; Stanley, H E; Rosene, D L

2009-02-18

The age-related decline in cognitive function that is observed in normal aging monkeys and humans occurs without significant loss of cortical neurons. This suggests that cognitive impairment results from subtle, sub-lethal changes in the cortex. Recently, changes in the structural coherence in mini- or microcolumns without loss of neurons have been linked to loss of function. Here we use a density map method to quantify microcolumnar structure in both banks of the sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal) behaviorally tested female rhesus monkeys from 6 to 33 years of age. While total neuronal density does not change with age in either of these banks, there is a significant age-related reduction in the strength of microcolumns in both regions on the order of 40%. This likely reflects a subtle but definite loss of organization in the structure of the cortical microcolumn. The reduction in strength in ventral area 46 correlates with cognitive impairments in learning and memory while the reduction in dorsal area 46 does not. This result is congruent with published data attributing cognitive functions to ventral area 46 that are similar to our particular cognitive battery which does not optimally tap cognitive functions attributed to dorsal area 46. While the exact mechanisms underlying this loss of microcolumnar organization remain to be determined, it is plausible that they reflect age-related alterations in dendritic and/or axonal organization which alter connectivity and may contribute to age-related declines in cognitive performance.

Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

NASA Astrophysics Data System (ADS)

Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

2006-07-01

Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

Europa Global Views in Natural and Enhanced Colors

NASA Image and Video Library

1998-05-08

This color composite view combines violet, green, and infrared images of Jupiter intriguing moon, Europa, for a view of the moon in natural color left and in enhanced color designed to bring out subtle color differences in the surface right.

Apparatus and method for spectroscopic analysis of scattering media

DOEpatents

Strobl, Karlheinz; Bigio, Irving J.; Loree, Thomas R.

1994-01-01

Apparatus and method for spectroscopic analysis of scattering media. Subtle differences in materials have been found to be detectable from plots of intensity as a function of wavelength of collected emitted and scattered light versus wavelength of excitation light.

See no evil: color blindness and perceptions of subtle racial discrimination in the workplace.

PubMed

Offermann, Lynn R; Basford, Tessa E; Graebner, Raluca; Jaffer, Salman; De Graaf, Sumona Basu; Kaminsky, Samuel E

2014-10-01

Workplace discrimination has grown more ambiguous, with interracial interactions often perceived differently by different people. The present study adds to the literature by examining a key individual difference variable in the perception of discrimination at work, namely individual color-blind attitudes. We examined relationships between 3 dimensions of color-blind attitudes (Racial Privilege, Institutional Discrimination, and Blatant Racial Issues) and perceptions of racial microaggressions in the workplace as enacted by a White supervisor toward a Black employee (i.e., discriminatory actions ranging from subtle to overt). Findings showed that observer views on institutional discrimination fully mediated, and blatant racial issues partially mediated, the relationships between racial group membership and the perception of workplace microaggressions. Non-Hispanic Whites endorsed color blindness as institutional discrimination and blatant racial issues significantly more than members of racioethnic minority groups, and higher levels of color-blind worldviews were associated with lower likelihoods of perceiving microaggressions. Views on racial privilege did not differ significantly between members of different racial groups or affect microaggression perceptions. Implications for organizations concerned about promoting more inclusive workplaces are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies?

PubMed

Batcheller, April; Cardozo, Eden; Maguire, Marcy; DeCherney, Alan H; Segars, James H

2011-12-01

To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. A PubMed computer search was performed to identify relevant articles. Research institution. Not applicable. None. Not applicable. Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. Published by Elsevier Inc.

Attention deficit hyperactivity disorder, combined type, dysthymic disorder and anxiety disorders: differential patterns of neurodevelopmental deficits.

PubMed

Vance, Alasdair; Arduca, Yolanda; Sanders, Michelle; Karamitsios, Mary; Hall, Nicole; Hetrick, Sarah

2006-08-30

The associations between neurodevelopmental deficits (NDD) and (1) attention deficit hyperactivity disorder, combined type (ADHD-CT) and (2) internalising disorders have been replicated. To date, the specific association between standardized NDD and carefully defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone has not been systematically investigated in children of primary school age. A cross-sectional study of NDD in 99 six- to 12-year-old children with categorically and dimensionally defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone and 20 age-matched healthy children was undertaken. The ADHD-CT and dysthymic disorder groups had increased total neurological subtle signs, compared to the anxiety disorders group, which, in turn, had increased total neurological subtle signs compared with the healthy children. Interestingly, the dysthymic disorder children had increased conjugate eye gaze difficulties compared with the other three groups. The differences remained after controlling for full scale IQ. These findings suggest a neurobiological underpinning of dysthymic disorder, while confirming that of ADHD-CT in primary school age children. Future studies will explore whether the above more specific neurological subtle signs are developmental phase specific or independent associations.

Potential of airborne LiDAR data analysis to detect subtle landforms of slope failure: Portainé, Central Pyrenees

NASA Astrophysics Data System (ADS)

Ortuño, María; Guinau, Marta; Calvet, Jaume; Furdada, Glòria; Bordonau, Jaume; Ruiz, Antonio; Camafort, Miquel

2017-10-01

Slope failures have been traditionally detected by field inspection and aerial-photo interpretation. These approaches are generally insufficient to identify subtle landforms, especially those generated during the early stages of failures, and particularly where the site is located in forested and remote terrains. We present the identification and characterization of several large and medium size slope failures previously undetected within the Orri massif, Central Pyrenees. Around 130 scarps were interpreted as being part of Rock Slope Failures (RSFs), while other smaller and more superficial failures were interpreted as complex movements combining colluvium slow flow/slope creep and RSFs. Except for one of them, these slope failures had not been previously detected, albeit they extend across a 15% of the studied region. The failures were identified through the analysis of a high-resolution (1 m) LIDAR-derived bare earth Digital Elevation Model (DEM). Most of the scarps are undetectable either by fieldwork, photo interpretation or 5 m resolution topography analysis owing to their small heights (0.5 to 2 m) and their location within forest areas. In many cases, these landforms are not evident in the field due to the presence of other minor irregularities in the slope and the lack of open views due to the forest. 2D and 3D visualization of hillshade maps with different sun azimuths provided an overall picture of the scarp assemblage and permitted a more complete analysis of the geometry of the scarps with respect to the slope and the structural fabric. The sharpness of some of the landforms suggests ongoing activity, which should be explored in future detailed studies in order to assess potential hazards affecting the Portainé ski resort. Our results reveal that close analysis of the 1 m LIDAR-derived DEM can significantly help to detect early-stage slope deformations in high mountain regions, and that expert judgment of the DEM is essential when dealing with subtle landforms. The incorporation of this approach in regional mapping represents a great advance in completing the catalogue of slope failures and will eventually contribute to a better understanding of the spatial factors controlling them.

Gravitational and magnetic field variations synergize to cause subtle variations in the global transcriptional state of Arabidopsis in vitro callus cultures

PubMed Central

2012-01-01

Background Biological systems respond to changes in both the Earth's magnetic and gravitational fields, but as experiments in space are expensive and infrequent, Earth-based simulation techniques are required. A high gradient magnetic field can be used to levitate biological material, thereby simulating microgravity and can also create environments with a reduced or an enhanced level of gravity (g), although special attention should be paid to the possible effects of the magnetic field (B) itself. Results Using diamagnetic levitation, we exposed Arabidopsis thaliana in vitro callus cultures to five environments with different levels of effective gravity and magnetic field strengths. The environments included levitation, i.e. simulated μg* (close to 0 g* at B = 10.1 T), intermediate g* (0.1 g* at B = 14.7 T) and enhanced gravity levels (1.9 g* at B = 14.7 T and 2 g* at B = 10.1 T) plus an internal 1 g* control (B = 16.5 T). The asterisk denotes the presence of the background magnetic field, as opposed to the effective gravity environments in the absence of an applied magnetic field, created using a Random Position Machine (simulated μg) and a Large Diameter Centrifuge (2 g). Microarray analysis indicates that changes in the overall gene expression of cultured cells exposed to these unusual environments barely reach significance using an FDR algorithm. However, it was found that gravitational and magnetic fields produce synergistic variations in the steady state of the transcriptional profile of plants. Transcriptomic results confirm that high gradient magnetic fields (i.e. to create μg* and 2 g* conditions) have a significant effect, mainly on structural, abiotic stress genes and secondary metabolism genes, but these subtle gravitational effects are only observable using clustering methodologies. Conclusions A detailed microarray dataset analysis, based on clustering of similarly expressed genes (GEDI software), can detect underlying global-scale responses, which cannot be detected by means of individual gene expression techniques using raw or corrected p values (FDR). A subtle, but consistent, genome-scale response to hypogravity environments was found, which was opposite to the response in a hypergravity environment. PMID:22435851

Applications of nuclear magnetic resonance spectroscopy for the understanding of enantiomer separation mechanisms in capillary electrophoresis.

PubMed

Salgado, Antonio; Chankvetadze, Bezhan

2016-10-07

This review deals with the applications of nuclear magnetic resonance (NMR) spectroscopy to understand the mechanisms of chiral separation in capillary electrophoresis (CE). It is accepted that changes observed in the separation process, including the reversal of enantiomer migration order (EMO), can be caused by subtle modifications in the molecular recognition mechanisms between enantiomer and chiral selector. These modifications may imply minor structural differences in those selector-selectand complexes that arise from the above mentioned interactions. Therefore, it is mandatory to understand the fine intermolecular interactions between analytes and chiral selectors. In other words, it is necessary to know in detail the structures of the complexes formed by the enantiomer (selectand) and the selector. Any differences in the structures of these complexes arising from either enantiomer should be detected, so that enantiomeric bias in the separation process could be explained. As to the nature of these interactions, those have been extensively reviewed, and it is not intended to be discussed here. These interactions contemplate ionic, ion-dipole and dipole-dipole interactions, hydrogen bonding, van der Waals forces, π-π stacking, steric and hydrophobic interactions. The main subject of this review is to describe how NMR spectroscopy helps to gain insight into the non-covalent intermolecular interactions between selector and selectand that lead to enantiomer separation by CE. Examples in which diastereomeric species are created by covalent (irreversible) derivatization will not be considered here. This review is structured upon the different structural classes of chiral selectors employed in CE, in which NMR spectroscopy has made substantial contributions to rationalize the observed enantioseparations. Cases in which other techniques complement NMR spectroscopic data are also mentioned. Copyright © 2016 Elsevier B.V. All rights reserved.

Nuanced Understandings of Privatization in Local Authorities' Services to Schools

ERIC Educational Resources Information Center

Boyask, Ruth

2015-01-01

This article draws upon findings from the New Relations between Local Authorities (LAs) and Schools project to identify ideological and value-based differences between the models of service to schools adopted within four case study LAs. While each of the LAs has developed a privatized model of service, there are subtle differences between the…

A note on contagion indices for landscape analysis

Treesearch

Kurt H. Riitters; Robert V. O' Neill; James D. Wickham; K. Bruce Jones

1996-01-01

The landscape contagion index measures the degree of clumping of attributes on raster maps. The index is computed from the frequencies by which different pairs of attributes occur as adjacent pixels on a map. Because there are subtle differences in the way the attribute adjacencies may be tabulated, the standard index formula may not always apply, and published index...

The Impact of Gender, Perceived Female Isolation and Beliefs in Traditional Roles for Women on Job Satisfaction.

ERIC Educational Resources Information Center

Barclay, Lizabeth A.; And Others

Past research has detailed conflicting results in investigations of sex differences and job satisfaction. To explain sex differences and job satisfaction within the framework of subtle treatment discrimination (a situation variable) and beliefs about roles for women (a person variable), 1578 employees of a large corporation completed demographic…

Coupling XRD, EXAFS, and 13C NMR to study the effect of the carbon stoichiometry on the local structure of UC(1±x).

PubMed

Carvajal Nuñez, U; Martel, L; Prieur, D; Lopez Honorato, E; Eloirdi, R; Farnan, I; Vitova, T; Somers, J

2013-10-07

A series of uranium carbide samples, prepared by arc melting with a C/U ratio ranging from 0.96 to 1.04, has been studied by X-ray diffraction (XRD), (13)C nuclear magnetic resonance (NMR), and extended X-ray absorption fine structure (EXAFS). XRD determines phase uniqueness and the increase of the lattice parameter versus the carbon content. In contrast, (13)C NMR detects the different carbon environments in the lattice and in this study, clearly identifies the presence of discrete peaks for carbon in the octahedral lattice site in UC and an additional peak associated with excess carbon in hyperstoichiometric samples. Two peaks associated with different levels of carbon deficiency are detected for all hypostoichiometric compositions. More than one carbon environment is always detected by (13)C NMR. This exemplifies the difficulty in obtaining a perfect stoichiometric uranium monocarbide UC(1.00). The (13)C MAS spectra of uranium carbides exhibit the effects resulting from the carbon content on both the broadening of the peaks and on the Knight shift. An abrupt spectral change occurs between hypo- and hyperstoichiometric samples. The results obtained by EXAFS highlight subtle differences between the different stoichiometries, and in the hyperstoichiometric samples, the EXAFS results are consistent with the excess carbon atoms being in the tetrahedral interstitial position.

Macromolecular Crystal Quality

NASA Technical Reports Server (NTRS)

Snell, Edward H.; Borgstahl, Gloria E. O.; Bellamy, Henry D.; Curreri, Peter A. (Technical Monitor)

2001-01-01

There are many ways of judging a good crystal. Which we use depends on the qualities we seek. For gemstones size, clarity and impurity levels (color) are paramount. For the semiconductor industry purity is probably the most important quality. For the structural crystallographer the primary desideratum is the somewhat more subtle concept of internal order. In this chapter we discuss the effect of internal order (or the lack of it) on the crystal's diffraction properties.

BcL-xL Conformational Changes upon Fragment Binding Revealed by NMR

PubMed Central

Aguirre, Clémentine; ten Brink, Tim; Walker, Olivier; Guillière, Florence; Davesne, Dany; Krimm, Isabelle

2013-01-01

Protein-protein interactions represent difficult but increasingly important targets for the design of therapeutic compounds able to interfere with biological processes. Recently, fragment-based strategies have been proposed as attractive approaches for the elaboration of protein-protein surface inhibitors from fragment-like molecules. One major challenge in targeting protein-protein interactions is related to the structural adaptation of the protein surface upon molecular recognition. Methods capable of identifying subtle conformational changes of proteins upon fragment binding are therefore required at the early steps of the drug design process. In this report we present a fast NMR method able to probe subtle conformational changes upon fragment binding. The approach relies on the comparison of experimental fragment-induced Chemical Shift Perturbation (CSP) of amine protons to CSP simulated for a set of docked fragment poses, considering the ring-current effect from fragment binding. We illustrate the method by the retrospective analysis of the complex between the anti-apoptotic Bcl-xL protein and the fragment 4′-fluoro-[1,1′-biphenyl]-4-carboxylic acid that was previously shown to bind one of the Bcl-xL hot spots. The CSP-based approach shows that the protein undergoes a subtle conformational rearrangement upon interaction, for residues located in helices 2, 3 and the very beginning of 5. Our observations are corroborated by residual dipolar coupling measurements performed on the free and fragment-bound forms of the Bcl-xL protein. These NMR-based results are in total agreement with previous molecular dynamic calculations that evidenced a high flexibility of Bcl-xL around the binding site. Here we show that CSP of protein amine protons are useful and reliable structural probes. Therefore, we propose to use CSP simulation to assess protein conformational changes upon ligand binding in the fragment-based drug design approach. PMID:23717610

Study of the incidence and nature of "very subtle epidermal melasma" in relation to intense pulsed light treatment.

PubMed

Negishi, Kei; Kushikata, Nobuharu; Tezuka, Yukiko; Takeuchi, Kaori; Miyamoto, Eiko; Wakamatsu, Shingo

2004-06-01

Skin rejuvenation with intense pulsed light (IPL) is effective for clearing epidermal pigment disorders. Complications are mild and limited to epidermal burns caused by excessive settings. Some patients, however, experience IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin. These patients seem to have very subtle epidermal melasma not visible to the naked eye. Ultraviolet photography has been useful in identifying these patients and preventing complications. The study investigated the incidence of very subtle melasma in patients using UV photography, and assessed this tool in identifying high-risk patients. 223 Japanese women, 30-69 years old, participated in the study. Very subtle melasma invisible to the naked eye under normal light was diagnosed by UV photography by two physicians, and any relationship among the disease incidence, age, and regular sunscreen use was examined. Sixty-three cases of very subtle melasma (28.3%) were identified among the 223 subjects, with a significantly lower incidence in sunscreen users. Patients diagnosed with subtle epidermal melasma and treated with mild IPL parameters did not suffer induced secondary hyperpigmentaion. To help avoid complications after treatment, IPL users should be aware of the age and sunscreen-related incidence of this phenomenon in Asian patients.

Hierarchical structure of the Sicilian goats revealed by Bayesian analyses of microsatellite information.

PubMed

Siwek, M; Finocchiaro, R; Curik, I; Portolano, B

2011-02-01

Genetic structure and relationship amongst the main goat populations in Sicily (Girgentana, Derivata di Siria, Maltese and Messinese) were analysed using information from 19 microsatellite markers genotyped on 173 individuals. A posterior Bayesian approach implemented in the program STRUCTURE revealed a hierarchical structure with two clusters at the first level (Girgentana vs. Messinese, Derivata di Siria and Maltese), explaining 4.8% of variation (amovaФ(ST) estimate). Seven clusters nested within these first two clusters (further differentiations of Girgentana, Derivata di Siria and Maltese), explaining 8.5% of variation (amovaФ(SC) estimate). The analyses and methods applied in this study indicate their power to detect subtle population structure. © 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.

Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors*

PubMed Central

Nascimento, Andrey F. Z.; Trindade, Daniel M.; Tonoli, Celisa C. C.; de Giuseppe, Priscila O.; Assis, Leandro H. P.; Honorato, Rodrigo V.; de Oliveira, Paulo S. L.; Mahajan, Pravin; Burgess-Brown, Nicola A.; von Delft, Frank; Larson, Roy E.; Murakami, Mario T.

2013-01-01

Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here, we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors. PMID:24097982

The Corporate View. A Multicultural Workforce Can Be a Competitive Advantage.

ERIC Educational Resources Information Center

Wilcox, John

1991-01-01

Work force diversity programs are designed to protect the company's return on investment by bringing to the surface the subtle discomforts, fears, and biases most people experience when they find themselves working with people who are different from themselves. (Author)

A diagnosis of discrimination. Women physicians and the glass ceiling.

PubMed

Sebastian, C

1994-01-01

Author Christy Sebastian writes about some of the limits facing women physicians, from the glass ceiling on down. She relates the limits faced by women physicians to the gender differences--both subtle and blatant--evident in society as a whole.

Modeling {sup 15}N NMR chemical shift changes in protein backbone with pressure

DOE Office of Scientific and Technical Information (OSTI.GOV)

La Penna, Giovanni, E-mail: glapenna@iccom.cnr.it; Mori, Yoshiharu, E-mail: ymori@ims.ac.jp; Kitahara, Ryo, E-mail: ryo@ph.ritsumei.ac.jp

2016-08-28

Nitrogen chemical shift is a useful parameter for determining the backbone three-dimensional structure of proteins. Empirical models for fast calculation of N chemical shift are improving their reliability, but there are subtle effects that cannot be easily interpreted. Among these, the effects of slight changes in hydrogen bonds, both intramolecular and with water molecules in the solvent, are particularly difficult to predict. On the other hand, these hydrogen bonds are sensitive to changes in protein environment. In this work, the change of N chemical shift with pressure for backbone segments in the protein ubiquitin is correlated with the change inmore » the population of hydrogen bonds involving the backbone amide group. The different extent of interaction of protein backbone with the water molecules in the solvent is put in evidence.« less

A cosmic question in NGC 4696

NASA Image and Video Library

2017-12-08

This picture, taken by Hubble’s Advanced Camera for Surveys, shows NGC 4696, the largest galaxy in the Centaurus Cluster. (To see a video of NGC 4696 go here: www.flickr.com/photos/gsfc/4888176841/) The huge dust lane, around 30 000 light-years across, that sweeps across the face of the galaxy makes NGC 4696 look different from most other elliptical galaxies. Viewed at certain wavelengths, strange thin filaments of ionised hydrogen are visible within it. In this picture, these structures are visible as a subtle marbling effect across the galaxy’s bright centre. Credit: ESA/Hubble and NASA NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe. Follow us on Twitter Join us on Facebook

Predictability of weather and climate in a coupled ocean-atmosphere model: A dynamical systems approach. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Nese, Jon M.

1989-01-01

A dynamical systems approach is used to quantify the instantaneous and time-averaged predictability of a low-order moist general circulation model. Specifically, the effects on predictability of incorporating an active ocean circulation, implementing annual solar forcing, and asynchronously coupling the ocean and atmosphere are evaluated. The predictability and structure of the model attractors is compared using the Lyapunov exponents, the local divergence rates, and the correlation, fractal, and Lyapunov dimensions. The Lyapunov exponents measure the average rate of growth of small perturbations on an attractor, while the local divergence rates quantify phase-spatial variations of predictability. These local rates are exploited to efficiently identify and distinguish subtle differences in predictability among attractors. In addition, the predictability of monthly averaged and yearly averaged states is investigated by using attractor reconstruction techniques.

pH-Responsive Mesoporous Silica and Carbon Nanoparticles for Drug Delivery

PubMed Central

Gisbert-Garzarán, Miguel; Manzano, Miguel; Vallet-Regí, María

2017-01-01

The application of nanotechnology to medicine constitutes a major field of research nowadays. In particular, the use of mesoporous silica and carbon nanoparticles has attracted the attention of numerous researchers due to their unique properties, especially when applied to cancer treatment. Many strategies based on stimuli-responsive nanocarriers have been developed to control the drug release and avoid premature release. Here, we focus on the use of the subtle changes of pH between healthy and diseased areas along the body to trigger the release of the cargo. In this review, different approximations of pH-responsive systems are considered: those based on the use of the host-guest interactions between the nanocarriers and the drugs, those based on the hydrolysis of acid-labile bonds and those based on supramolecular structures acting as pore capping agents. PMID:28952481

Therapeutic index of gramicidin S is strongly modulated by D-phenylalanine analogues at the beta-turn.

PubMed

Solanas, Concepción; de la Torre, Beatriz G; Fernández-Reyes, María; Santiveri, Clara M; Jiménez, M Angeles; Rivas, Luis; Jiménez, Ana I; Andreu, David; Cativiela, Carlos

2009-02-12

Analogues of the cationic antimicrobial peptide gramicidin S (GS), cyclo(Val-Orn-Leu-D-Phe-Pro)2, with d-Phe residues replaced by different (restricted mobility, mostly) surrogates have been synthesized and used in SAR studies against several pathogenic bacteria. While all D-Phe substitutions are shown by NMR to preserve the overall beta-sheet conformation, they entail subtle structural alterations that lead to significant modifications in biological activity. In particular, the analogue incorporating D-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) shows a modest but significant increase in therapeutic index, mostly due to a sharp decrease in hemolytic effect. The fact that NMR data show a shortened distance between the D-Tic aromatic ring and the Orn delta-amino group may help explain the improved antibiotic profile of this analogue.

Therapeutic index of gramicidin S is strongly modulated by d-phenylalanine analogues at the β-turn

PubMed Central

Solanas, Concepción; de la Torre, Beatriz G.; Fernández-Reyes, María; Santiveri, Clara M.; Jiménez, M. Ángeles; Rivas, Luis; Jiménez, Ana I.; Andreu, David; Cativiela, Carlos

2009-01-01

Analogues of the cationic antimicrobial peptide gramicidin S (GS), cyclo(Val-Orn-Leu-d-Phe-Pro)2, with d-Phe residues replaced by different (restricted mobility, mostly) surrogates have been synthesized and used in SAR studies against several pathogenic bacteria. While all d-Phe substitutions are shown by NMR to preserve the overall β-sheet conformation, they entail subtle structural alterations that lead to significant modifications in biological activity. In particular, the analogue incorporating d-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) shows a modest but significant increase in therapeutic index, mostly due to a sharp decrease in hemolytic effect. The fact that NMR data show a shortened distance between the d-Tic aromatic ring and the Orn δ-amino group may help explain the improved antibiotic profile of this analogue. PMID:19132829

Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

PubMed Central

Lee, Rachel S.; House, Colin M.; Cristiano, Briony E.; Hannan, Ross D.; Pearson, Richard B.; Hannan, Katherine M.

2011-01-01

The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ. PMID:21869924

Time-dependent photon heat transport through a mesoscopic Josephson device

NASA Astrophysics Data System (ADS)

Lu, Wen-Ting; Zhao, Hong-Kang

2017-02-01

The time-oscillating photon heat current through a dc voltage biased mesoscopic Josephson Junction (MJJ) has been investigated by employing the nonequilibrium Green's function approach. The Landauer-like formula of photon heat current has been derived in both of the Fourier space and its time-oscillating versions, where Coulomb interaction, self inductance, and magnetic flux take effective roles. Nonlinear behaviors are exhibited in the photon heat current due to the quantum nature of MJJ and applied external dc voltage. The magnitude of heat current decreases with increasing the external bias voltage, and subtle oscillation structures appear as the superposition of different photon heat branches. The overall period of heat current with respect to time is not affected by Coulomb interaction, however, the magnitude and phase of it vary considerably by changing the Coulomb interaction.

AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN.

PubMed

te Riet, Joost; Reinieren-Beeren, Inge; Figdor, Carl G; Cambi, Alessandra

2015-11-01

The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), because a detailed characterization at the structural level is lacking. DC-SIGN recognizes specific Candida-associated molecular patterns, that is, mannan structures present in the cell wall of Candida. The molecular recognition mechanism is however poorly understood. We postulated that small differences in mannan-branching may result in considerable differences in the binding affinity. Here, we exploit atomic force microscope-based dynamic force spectroscopy with single Candida cells to gain better insight in the carbohydrate recognition capacity of DC-SIGN. We demonstrate that slight differences in the N-mannan structure of Candida, that is, the absence or presence of a phosphomannan side chain, results in differences in the recognition by DC-SIGN as follows: (i) it contributes to the compliance of the outer cell wall of Candida, and (ii) its presence results in a higher binding energy of 1.6 kB T. The single-bond affinity of tetrameric DC-SIGN for wild-type C. albicans is ~10.7 kB T and a dissociation constant kD of 23 μM, which is relatively strong compared with other carbohydrate-protein interactions described in the literature. In conclusion, this study shows that DC-SIGN specifically recognizes mannan patterns on C. albicans with high affinity. Knowledge on the binding pocket of DC-SIGN and its pathogenic ligands will lead to a better understanding of how fungal-associated carbohydrate structures are recognized by receptors of the immune system and can ultimately contribute to the development of new anti-fungal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

Atypical face shape and genomic structural variants in epilepsy

PubMed Central

Chinthapalli, Krishna; Bartolini, Emanuele; Novy, Jan; Suttie, Michael; Marini, Carla; Falchi, Melania; Fox, Zoe; Clayton, Lisa M. S.; Sander, Josemir W.; Guerrini, Renzo; Depondt, Chantal; Hennekam, Raoul; Hammond, Peter

2012-01-01

Many pathogenic structural variants of the human genome are known to cause facial dysmorphism. During the past decade, pathogenic structural variants have also been found to be an important class of genetic risk factor for epilepsy. In other fields, face shape has been assessed objectively using 3D stereophotogrammetry and dense surface models. We hypothesized that computer-based analysis of 3D face images would detect subtle facial abnormality in people with epilepsy who carry pathogenic structural variants as determined by chromosome microarray. In 118 children and adults attending three European epilepsy clinics, we used an objective measure called Face Shape Difference to show that those with pathogenic structural variants have a significantly more atypical face shape than those without such variants. This is true when analysing the whole face, or the periorbital region or the perinasal region alone. We then tested the predictive accuracy of our measure in a second group of 63 patients. Using a minimum threshold to detect face shape abnormalities with pathogenic structural variants, we found high sensitivity (4/5, 80% for whole face; 3/5, 60% for periorbital and perinasal regions) and specificity (45/58, 78% for whole face and perinasal regions; 40/58, 69% for periorbital region). We show that the results do not seem to be affected by facial injury, facial expression, intellectual disability, drug history or demographic differences. Finally, we use bioinformatics tools to explore relationships between facial shape and gene expression within the developing forebrain. Stereophotogrammetry and dense surface models are powerful, objective, non-contact methods of detecting relevant face shape abnormalities. We demonstrate that they are useful in identifying atypical face shape in adults or children with structural variants, and they may give insights into the molecular genetics of facial development. PMID:22975390

Asymmetry of the Brain: Development and Implications.

PubMed

Duboc, Véronique; Dufourcq, Pascale; Blader, Patrick; Roussigné, Myriam

2015-01-01

Although the left and right hemispheres of our brains develop with a high degree of symmetry at both the anatomical and functional levels, it has become clear that subtle structural differences exist between the two sides and that each is dominant in processing specific cognitive tasks. As the result of evolutionary conservation or convergence, lateralization of the brain is found in both vertebrates and invertebrates, suggesting that it provides significant fitness for animal life. This widespread feature of hemispheric specialization has allowed the emergence of model systems to study its development and, in some cases, to link anatomical asymmetries to brain function and behavior. Here, we present some of what is known about brain asymmetry in humans and model organisms as well as what is known about the impact of environmental and genetic factors on brain asymmetry development. We specifically highlight the progress made in understanding the development of epithalamic asymmetries in zebrafish and how this model provides an exciting opportunity to address brain asymmetry at different levels of complexity.

Protecting group and switchable pore-discriminating adsorption properties of a hydrophilic-hydrophobic metal-organic framework.

PubMed

Mohideen, M Infas H; Xiao, Bo; Wheatley, Paul S; McKinlay, Alistair C; Li, Yang; Slawin, Alexandra M Z; Aldous, David W; Cessford, Naomi F; Düren, Tina; Zhao, Xuebo; Gill, Rachel; Thomas, K Mark; Griffin, John M; Ashbrook, Sharon E; Morris, Russell E

2011-04-01

Formed by linking metals or metal clusters through organic linkers, metal-organic frameworks are a class of solids with structural and chemical properties that mark them out as candidates for many emerging gas storage, separation, catalysis and biomedical applications. Important features of these materials include their high porosity and their flexibility in response to chemical or physical stimuli. Here, a copper-based metal-organic framework has been prepared in which the starting linker (benzene-1,3,5-tricarboxylic acid) undergoes selective monoesterification during synthesis to produce a solid with two different channel systems, lined by hydrophilic and hydrophobic surfaces, respectively. The material reacts differently to gases or vapours of dissimilar chemistry, some stimulating subtle framework flexibility or showing kinetic adsorption effects. Adsorption can be switched between the two channels by judicious choice of the conditions. The monoesterified linker is recoverable in quantitative yield, demonstrating possible uses of metal-organic frameworks in molecular synthetic chemistry as 'protecting groups' to accomplish selective transformations that are difficult using standard chemistry techniques.

AN OVERVIEW OF COMPUTATIONAL LIFE SCIENCE DATABASES & EXCHANGE FORMATS OF RELEVANCE TO CHEMICAL BIOLOGY RESEARCH

PubMed Central

Hall, Aaron Smalter; Shan, Yunfeng; Lushington, Gerald; Visvanathan, Mahesh

2016-01-01

Databases and exchange formats describing biological entities such as chemicals and proteins, along with their relationships, are a critical component of research in life sciences disciplines, including chemical biology wherein small information about small molecule properties converges with cellular and molecular biology. Databases for storing biological entities are growing not only in size, but also in type, with many similarities between them and often subtle differences. The data formats available to describe and exchange these entities are numerous as well. In general, each format is optimized for a particular purpose or database, and hence some understanding of these formats is required when choosing one for research purposes. This paper reviews a selection of different databases and data formats with the goal of summarizing their purposes, features, and limitations. Databases are reviewed under the categories of 1) protein interactions, 2) metabolic pathways, 3) chemical interactions, and 4) drug discovery. Representation formats will be discussed according to those describing chemical structures, and those describing genomic/proteomic entities. PMID:22934944

Corneal polarimetry after LASIK refractive surgery

NASA Astrophysics Data System (ADS)

Bueno, Juan M.; Berrio, Esther; Artal, Pablo

2006-01-01

Imaging polarimetry provides spatially resolved information on the polarization properties of a system. In the case of the living human eye, polarization could be related to the corneal biomechanical properties, which vary from the normal state as a result of surgery or pathologies. We have used an aberro-polariscope, which we recently developed, to determine and to compare the spatially resolved maps of polarization parameters across the pupil between normal healthy and post-LASIK eyes. The depolarization distribution is not uniform across the pupil, with post-surgery eyes presenting larger levels of depolarization. While retardation increases along the radius in normal eyes, this pattern becomes irregular after LASIK refractive surgery. The maps of slow axis also differ in normal and post-surgery eyes, with a larger disorder in post-LASIK eyes. Since these changes in polarization indicate subtle structural modifications of the cornea, this approach can be useful in a clinical environment to follow the biomechanical and optical changes of the cornea after refractive surgery or for the early diagnosis of different corneal pathologies.

Multispectral image enhancement for H&E stained pathological tissue specimens

NASA Astrophysics Data System (ADS)

Bautista, Pinky A.; Abe, Tokiya; Yamaguchi, Masahiro; Ohyama, Nagaaki; Yagi, Yukako

2008-03-01

The presence of a liver disease such as cirrhosis can be determined by examining the proliferation of collagen fiber from a tissue slide stained with special stain such as the Masson's trichrome(MT) stain. Collagen fiber and smooth muscle, which are both stained the same in an H&E stained slide, are stained blue and pink respectively in an MT-stained slide. In this paper we show that with multispectral imaging the difference between collagen fiber and smooth muscle can be visualized even from an H&E stained image. In the method M KL bases are derived using the spectral data of those H&E stained tissue components which can be easily differentiated from each other, i.e. nucleus, cytoplasm, red blood cells, etc. and based on the spectral residual error of fiber weighting factors are determined to enhance spectral features at certain wavelengths. Results of our experiment demonstrate the capability of multispectral imaging and its advantage compared to the conventional RGB imaging systems to delineate tissue structures with subtle colorimetric difference.

An overview of computational life science databases & exchange formats of relevance to chemical biology research.

PubMed

Smalter Hall, Aaron; Shan, Yunfeng; Lushington, Gerald; Visvanathan, Mahesh

2013-03-01

Databases and exchange formats describing biological entities such as chemicals and proteins, along with their relationships, are a critical component of research in life sciences disciplines, including chemical biology wherein small information about small molecule properties converges with cellular and molecular biology. Databases for storing biological entities are growing not only in size, but also in type, with many similarities between them and often subtle differences. The data formats available to describe and exchange these entities are numerous as well. In general, each format is optimized for a particular purpose or database, and hence some understanding of these formats is required when choosing one for research purposes. This paper reviews a selection of different databases and data formats with the goal of summarizing their purposes, features, and limitations. Databases are reviewed under the categories of 1) protein interactions, 2) metabolic pathways, 3) chemical interactions, and 4) drug discovery. Representation formats will be discussed according to those describing chemical structures, and those describing genomic/proteomic entities.

When cheating would make you a cheater: implicating the self prevents unethical behavior.

PubMed

Bryan, Christopher J; Adams, Gabrielle S; Monin, Benoît

2013-11-01

In 3 experiments using 2 different paradigms, people were less likely to cheat for personal gain when a subtle change in phrasing framed such behavior as diagnostic of an undesirable identity. Participants were given the opportunity to claim money they were not entitled to at the experimenters' expense; instructions referred to cheating with either language that was designed to highlight the implications of cheating for the actor's identity (e.g., "Please don't be a cheater") or language that focused on the action (e.g., "Please don't cheat"). Participants in the "cheating" condition claimed significantly more money than did participants in the "cheater" condition, who showed no evidence of having cheated at all. This difference occurred both in a face-to-face interaction (Experiment 1) and in a private online setting (Experiments 2 and 3). These results demonstrate the power of a subtle linguistic difference to prevent even private unethical behavior by invoking people's desire to maintain a self-image as good and honest. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major.

PubMed

Vidal, Antonio E; Harkiolaki, Maria; Gallego, Claribel; Castillo-Acosta, Victor M; Ruiz-Pérez, Luis M; Wilson, Keith; González-Pacanowska, Dolores

2007-11-02

Apurinic/apyrimidinic endonucleases initiate the repair of abasic sites produced either spontaneously, from attack of bases by reactive oxygen species or as intermediates during base excision repair. The catalytic properties and crystal structure of Leishmania major apurinic/apyrimidinic endonuclease are described and compared with those of human APE1 and bacterial exonuclease III. The purified enzyme is shown to possess apurinic/apyrimidinic endonuclease activity of the same order as eukaryotic and prokaryotic counterparts and an equally robust 3'-phosphodiesterase activity. Consistent with this, expression of the L. major endonuclease confers resistance to both methyl methane sulphonate and H2O2 in Escherichia coli repair-deficient mutants while expression of the human homologue only reverts methyl methane sulphonate sensitivity. Structural analyses and modelling of the enzyme-DNA complex demonstrates a high degree of conservation to previously characterized homologues, although subtle differences in the active site geometry might account for the high 3'-phosphodiesterase activity. Our results confirm that the L. major's enzyme is a key element in mediating repair of apurinic/apyrimidinic sites and 3'-blocked termini and therefore must play an important role in the survival of kinetoplastid parasites after exposure to the highly oxidative environment within the host macrophage.

Changes in microbial communities along redox gradients in polygonized Arctic wet tundra soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipson, David A.; Raab, Theodore K.; Parker, Melanie

2015-08-01

Summary This study investigated how microbial community structure and diversity varied with depth and topography in ice wedge polygons of wet tundra of the Arctic Coastal Plain in northern Alaska and what soil variables explain these patterns. We observed strong changes in community structure and diversity with depth, and more subtle changes between areas of high and low topography, with the largest differences apparent near the soil surface. These patterns are most strongly correlated with redox gradients (measured using the ratio of reduced Fe to total Fe in acid extracts as a proxy): conditions grew more reducing with depth andmore » were most oxidized in shallow regions of polygon rims. Organic matter and pH also changed with depth and topography but were less effective predictors of the microbial community structure and relative abundance of specific taxa. Of all other measured variables, lactic acid concentration was the best, in combination with redox, for describing the microbial community. We conclude that redox conditions are the dominant force in shaping microbial communities in this landscape. Oxygen and other electron acceptors allowed for the greatest diversity of microbes: at depth the community was reduced to a simpler core of anaerobes,« less

Joint inversion of seismic and gravity data for imaging seismic velocity structure of the crust and upper mantle beneath Utah, United States

NASA Astrophysics Data System (ADS)

Syracuse, E. M.; Zhang, H.; Maceira, M.

2017-10-01

We present a method for using any combination of body wave arrival time measurements, surface wave dispersion observations, and gravity data to simultaneously invert for three-dimensional P- and S-wave velocity models. The simultaneous use of disparate data types takes advantage of the differing sensitivities of each data type, resulting in a comprehensive and higher resolution three-dimensional geophysical model. In a case study for Utah, we combine body wave first arrivals mainly from the USArray Transportable Array, Rayleigh wave group and phase velocity dispersion data, and Bouguer gravity anomalies to invert for crustal and upper mantle structure of the region. Results show clear delineations, visible in both P- and S-wave velocities, between the three main tectonic provinces in the region. Without the inclusion of the surface wave and gravity constraints, these delineations are less clear, particularly for S-wave velocities. Indeed, checkerboard tests confirm that the inclusion of the additional datasets dramatically improves S-wave velocity recovery, with more subtle improvements to P-wave velocity recovery, demonstrating the strength of the method in successfully recovering seismic velocity structure from multiple types of constraints.

Model for interevent times with long tails and multifractality in human communications: An application to financial trading

NASA Astrophysics Data System (ADS)

Perelló, Josep; Masoliver, Jaume; Kasprzak, Andrzej; Kutner, Ryszard

2008-09-01

Social, technological, and economic time series are divided by events which are usually assumed to be random, albeit with some hierarchical structure. It is well known that the interevent statistics observed in these contexts differs from the Poissonian profile by being long-tailed distributed with resting and active periods interwoven. Understanding mechanisms generating consistent statistics has therefore become a central issue. The approach we present is taken from the continuous-time random-walk formalism and represents an analytical alternative to models of nontrivial priority that have been recently proposed. Our analysis also goes one step further by looking at the multifractal structure of the interevent times of human decisions. We here analyze the intertransaction time intervals of several financial markets. We observe that empirical data describe a subtle multifractal behavior. Our model explains this structure by taking the pausing-time density in the form of a superstatistics where the integral kernel quantifies the heterogeneous nature of the executed tasks. A stretched exponential kernel provides a multifractal profile valid for a certain limited range. A suggested heuristic analytical profile is capable of covering a broader region.

Structure and Regulation of AMPK.

PubMed

Kurumbail, Ravi G; Calabrese, Matthew F

AMP-activated protein kinase is a family of heterotrimeric serine/threonine protein kinases that come in twelve different flavors. They serve an essential function in all eukaryotes of conserving cellular energy levels. AMPK complexes are regulated by changes in cellular AMP:ATP or ADP:ATP ratios and by a number of neutraceuticals and some of the widely-used diabetes medications such as metformin and thiazolinonediones. Moreover, biochemical activities of AMPK are tightly regulated by phosphorylation or dephosphorylation by upstream kinases and phosphatases respectively. Efforts are underway in many pharmaceutical companies to discover direct AMPK activators for the treatment of cardiovascular and metabolic diseases such as diabetes, non-alcoholic steatohepatitis (NASH) and diabetic nephropathy. Many advances have been made in the AMPK structural biology arena over the last few years that are beginning to provide detailed molecular insights into the overall topology of these fascinating enzymes and how binding of small molecules elicit subtle conformational changes leading to their activation and protection from dephosphorylation. In the brief review below on AMPK structure and function, we have focused on the recent crystallographic results especially on specific molecular interactions of direct synthetic AMPK activators which lead to biased activation of a sub-family of AMPK isoforms.

Use of optical coherence tomography in delineating airways microstructure: comparison of OCT images to histopathological sections

NASA Astrophysics Data System (ADS)

Yang, Ying; Whiteman, Suzanne; Gey van Pittius, Daniel; He, Yonghong; Wang, Ruikang K.; Spiteri, Monica A.

2004-04-01

An ideal diagnostic system for the human airways should be able to detect and define early development of premalignant pathological lesions, to facilitate optimal curative treatment and prevent irreversible and/or invasive lung disease. There is great need for exploration of safe, repeatable imaging techniques which can run at real-time and with high spatial resolution. In this study, optical coherence tomography (OCT) was utilized to acquire cross-sectional images of upper and lower airways using fresh pig lung resections as a model system. Obtained OCT images were compared with parallel tissue characterization by conventional histological analysis. Our objective was to determine whether OCT differentiates the composite structural layers and inherent anatomical variations along different airway locations. The data show that OCT can clearly display the multilayered structure of the airways. The subtle architectural differences in three separate anatomical locations including trachea, main bronchus and tertiary bronchus were clearly delineated. Images of the appropriate anatomical profiles, with depth of up to 2 mm and 10 µm spatial resolution were obtained by our current OCT system, which was sufficient for recognition of the epithelium, subepithelial tissues and cartilage. In addition, the relative thickness of individual structural components was accurately reflected and comparable to histological sections. These data support OCT as a highly feasible, optical biopsy tool, which merits further exploration for early diagnosis of human airway epithelial pathology.

On the Sequence-Directed Nature of Human Gene Mutation: The Role of Genomic Architecture and the Local DNA Sequence Environment in Mediating Gene Mutations Underlying Human Inherited Disease

PubMed Central

Cooper, David N.; Bacolla, Albino; Férec, Claude; Vasquez, Karen M.; Kehrer-Sawatzki, Hildegard; Chen, Jian-Min

2011-01-01

Different types of human gene mutation may vary in size, from structural variants (SVs) to single base-pair substitutions, but what they all have in common is that their nature, size and location are often determined either by specific characteristics of the local DNA sequence environment or by higher-order features of the genomic architecture. The human genome is now recognized to contain ‘pervasive architectural flaws’ in that certain DNA sequences are inherently mutation-prone by virtue of their base composition, sequence repetitivity and/or epigenetic modification. Here we explore how the nature, location and frequency of different types of mutation causing inherited disease are shaped in large part, and often in remarkably predictable ways, by the local DNA sequence environment. The mutability of a given gene or genomic region may also be influenced indirectly by a variety of non-canonical (non-B) secondary structures whose formation is facilitated by the underlying DNA sequence. Since these non-B DNA structures can interfere with subsequent DNA replication and repair, and may serve to increase mutation frequencies in generalized fashion (i.e. both in the context of subtle mutations and SVs), they have the potential to serve as a unifying concept in studies of mutational mechanisms underlying human inherited disease. PMID:21853507

Modulation of surface structure and catalytic properties of cerium oxide nanoparticles by thermal and microwave synthesis techniques

NASA Astrophysics Data System (ADS)

He, Jian; Zhou, Lan; Liu, Jie; Yang, Lu; Zou, Ling; Xiang, Junyu; Dong, Shiwu; Yang, Xiaochao

2017-04-01

Cerium oxide nanoparticles (CNPs) have been intensively explored for biomedical applications in recent few years due to the versatile enzyme mimetic activities of the nanoparticles. However, the control of CNPs quality through the optimization of synthesis conditions remains largely unexplored as most of the previous studies only focus on utilizing the catalytic activities of the nanoparticles. In the present study, CNPs with size about 5 nm were synthesized by thermal decomposition method using traditional convective heating and recently developed microwave irradiation as heating source. The quality of CNPs synthesized by the two heating manner was evaluated. The CNPs synthesized by convective heating were slightly smaller than that synthesized by microwave irradiation heating. The cores of the CNPs synthesized by the two heating manner have similar crystal structure. While the surface subtle structures of the CNPs synthesized by two heating manner were different. The CNPs synthesized by microwave irradiation have more surface reactive hot spot than that synthesized by convective heating as the nanoparticles responded more actively to the redox environment variation. This difference resulted in the higher superoxide dismutase (SOD) mimetic activity of CNPs synthesized by microwave irradiation heating than that of the convective heating. Preliminary experiments indicated that the CNPs synthesized by microwave irradiation heating could better protect cells from oxidative stress due to the higher SOD mimetic activity of the nanoparticles.

Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury.

PubMed

Delouche, Aurélie; Attyé, Arnaud; Heck, Olivier; Grand, Sylvie; Kastler, Adrian; Lamalle, Laurent; Renard, Felix; Krainik, Alexandre

2016-01-01

Mild traumatic brain injury (mTBI) is a leading cause of disability in adults, many of whom report a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion syndrome, that persist after the injury. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of fractional anisotropy or mean diffusivity, have enhanced our knowledge on the different stages of mTBI pathophysiology. Other diffusion imaging-derived techniques, including diffusion kurtosis imaging with multi-shell diffusion and high-order tractography models, have recently demonstrated their usefulness in mTBI. Our review starts by briefly outlining the physical basis of diffusion tensor imaging including the pitfalls for use in brain trauma, before discussing findings from diagnostic trials testing its usefulness in assessing brain structural changes in patients with mTBI. Use of different post-processing techniques for the diffusion imaging data, identified the corpus callosum as the most frequently injured structure in mTBI, particularly at sub-acute and chronic stages, and a crucial location for evaluating functional outcome. However, structural changes appear too subtle for identification using traditional diffusion biomarkers, thus disallowing expansion of these techniques into clinical practice. In this regard, more advanced diffusion techniques are promising in the assessment of this complex disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structure-based design of Aurora A & B inhibitors

NASA Astrophysics Data System (ADS)

Poulsen, Anders; William, Anthony; Lee, Angeline; Blanchard, Stéphanie; Teo, Eeling; Deng, Weiping; Tu, Noah; Tan, Evelyn; Sun, Eric; Goh, Kay Lin; Ong, Wai Chung; Ng, Chee Pang; Goh, Kee Chuan; Bonday, Zahid

2008-12-01

The Aurora family of serine/threonine kinases are mitotic regulators involved in centrosome duplication, formation of the bipolar mitotic spindle and the alignment of the chromosomes along the spindle. These proteins are frequently overexpressed in tumor cells as compared to normal cells and are therefore potential therapeutic oncology targets. An Aurora A high throughput screen revealed a promising sub-micromolar indazole-benzimidazole lead. Modification of the benzimidazole portion of the lead to a C2 linker with a phenyl ring was proposed to achieve novelty. Docking revealed that a conjugated linker was optimal and the resulting compounds were equipotent with the lead. Further structure-guided optimization of substituents on the 5 & 6 position of the indazole led to single digit nanomolar potency. The homology between the Aurora A & Aurora B kinase domains is 71% but their binding sites only differ at residues 212 & 217 (Aurora A numbering). However interactions with only the latter residue may be used for obtaining selectivity. An analysis of published Aurora A and Aurora B X-ray structures reveals subtle differences in the shape of the binding sites. This was exploited by introduction of appropriately sized substituents in the 4 & 6 position of the indazole leading to Aurora B selective inhibitors. Finally we calculate the conformational energy penalty of the putative bioactive conformation of our inhibitors and show that this property correlates well with the Aurora A binding affinity.

Local self-uniformity in photonic networks.

PubMed

Sellers, Steven R; Man, Weining; Sahba, Shervin; Florescu, Marian

2017-02-17

The interaction of a material with light is intimately related to its wavelength-scale structure. Simple connections between structure and optical response empower us with essential intuition to engineer complex optical functionalities. Here we develop local self-uniformity (LSU) as a measure of a random network's internal structural similarity, ranking networks on a continuous scale from crystalline, through glassy intermediate states, to chaotic configurations. We demonstrate that complete photonic bandgap structures possess substantial LSU and validate LSU's importance in gap formation through design of amorphous gyroid structures. Amorphous gyroid samples are fabricated via three-dimensional ceramic printing and the bandgaps experimentally verified. We explore also the wing-scale structuring in the butterfly Pseudolycaena marsyas and show that it possesses substantial amorphous gyroid character, demonstrating the subtle order achieved by evolutionary optimization and the possibility of an amorphous gyroid's self-assembly.

Structures of Rotavirus Reassortants Demonstrate Correlation of Altered Conformation of the VP4 Spike and Expression of Unexpected VP4-Associated Phenotypes

PubMed Central

Pesavento, Joseph B.; Billingsley, Angela M.; Roberts, Ed J.; Ramig, Robert F.; Prasad, B. V. Venkataram

2003-01-01

Numerous prior studies have indicated that viable rotavirus reassortants containing structural proteins of heterologous parental origin may express unexpected phenotypes, such as changes in infectivity and immunogenicity. To provide a structural basis for alterations in phenotypic expression, a three-dimensional structural analysis of these reassortants was conducted. The structures of the reassortants show that while VP4 generally maintains the parental structure when moved to a heterologous protein background, in certain reassortants, there are subtle alterations in the conformation of VP4. The alterations in VP4 conformation correlated with expression of unexpected VP4-associated phenotypes. Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4. PMID:12584352

Local self-uniformity in photonic networks

NASA Astrophysics Data System (ADS)

Sellers, Steven R.; Man, Weining; Sahba, Shervin; Florescu, Marian

2017-02-01

The interaction of a material with light is intimately related to its wavelength-scale structure. Simple connections between structure and optical response empower us with essential intuition to engineer complex optical functionalities. Here we develop local self-uniformity (LSU) as a measure of a random network's internal structural similarity, ranking networks on a continuous scale from crystalline, through glassy intermediate states, to chaotic configurations. We demonstrate that complete photonic bandgap structures possess substantial LSU and validate LSU's importance in gap formation through design of amorphous gyroid structures. Amorphous gyroid samples are fabricated via three-dimensional ceramic printing and the bandgaps experimentally verified. We explore also the wing-scale structuring in the butterfly Pseudolycaena marsyas and show that it possesses substantial amorphous gyroid character, demonstrating the subtle order achieved by evolutionary optimization and the possibility of an amorphous gyroid's self-assembly.

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

PubMed Central

Holmes, Holly E.; Powell, Nick M.; Ma, Da; Ismail, Ozama; Harrison, Ian F.; Wells, Jack A.; Colgan, Niall; O'Callaghan, James M.; Johnson, Ross A.; Murray, Tracey K.; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M. Jorge; Modat, Marc; O'Neill, Michael J.; Collins, Emily C.; Fisher, Elizabeth M. C.; Ourselin, Sébastien; Lythgoe, Mark F.

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. PMID:28408879

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

PubMed

Holmes, Holly E; Powell, Nick M; Ma, Da; Ismail, Ozama; Harrison, Ian F; Wells, Jack A; Colgan, Niall; O'Callaghan, James M; Johnson, Ross A; Murray, Tracey K; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M Jorge; Modat, Marc; O'Neill, Michael J; Collins, Emily C; Fisher, Elizabeth M C; Ourselin, Sébastien; Lythgoe, Mark F

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

Solution structure of the chick TGFbeta type II receptor ligand-binding domain.

PubMed

Marlow, Michael S; Brown, Christopher B; Barnett, Joey V; Krezel, Andrzej M

2003-02-28

The transforming growth factor beta (TGFbeta) signaling pathway influences cell proliferation, immune responses, and extracellular matrix reorganization throughout the vertebrate life cycle. The signaling cascade is initiated by ligand-binding to its cognate type II receptor. Here, we present the structure of the chick type II TGFbeta receptor determined by solution NMR methods. Distance and angular constraints were derived from 15N and 13C edited NMR experiments. Torsion angle dynamics was used throughout the structure calculations and refinement. The 20 final structures were energy minimized using the generalized Born solvent model. For these 20 structures, the average backbone root-mean-square distance from the average structure is below 0.6A. The overall fold of this 109-residue domain is conserved within the superfamily of these receptors. Chick receptors fully recognize and respond to human TGFbeta ligands despite only 60% identity at the sequence level. Comparison with the human TGFbeta receptor determined by X-ray crystallography reveals different conformations in several regions. Sequence divergence and crystal packing interactions under low pH conditions are likely causes. This solution structure identifies regions were structural changes, however subtle, may occur upon ligand-binding. We also identified two very well conserved molecular surfaces. One was found to bind ligand in the crystallized human TGFbeta3:TGFbeta type II receptor complex. The other, newly identified area can be the interaction site with type I and/or type III receptors of the TGFbeta signaling complex.

Fractal dimension brain morphometry: a novel approach to quantify white matter in traumatic brain injury.

PubMed

Rajagopalan, Venkateswaran; Das, Abhijit; Zhang, Luduan; Hillary, Frank; Wylie, Glenn R; Yue, Guang H

2018-06-16

Traumatic brain injury (TBI) is the main cause of disability in people younger than 35 in the United States. The mechanisms of TBI are complex resulting in both focal and diffuse brain damage. Fractal dimension (FD) is a measure that can characterize morphometric complexity and variability of brain structure especially white matter (WM) structure and may provide novel insights into the injuries evident following TBI. FD-based brain morphometry may provide information on WM structural changes after TBI that is more sensitive to subtle structural changes post injury compared to conventional MRI measurements. Anatomical and diffusion tensor imaging (DTI) data were obtained using a 3 T MRI scanner in subjects with moderate to severe TBI and in healthy controls (HC). Whole brain WM volume, grey matter volume, cortical thickness, cortical area, FD and DTI metrics were evaluated globally and for the left and right hemispheres separately. A neuropsychological test battery sensitive to cognitive impairment associated with traumatic brain injury was performed. TBI group showed lower structural complexity (FD) bilaterally (p < 0.05). No significant difference in either grey matter volume, cortical thickness or cortical area was observed in any of the brain regions between TBI and healthy controls. No significant differences in whole brain WM volume or DTI metrics between TBI and HC groups were observed. Behavioral data analysis revealed that WM FD accounted for a significant amount of variance in executive functioning and processing speed beyond demographic and DTI variables. FD therefore, may serve as a sensitive marker of injury and may play a role in outcome prediction in TBI.

Biophysical Characterisation of Neuroglobin of the Icefish, a Natural Knockout for Hemoglobin and Myoglobin. Comparison with Human Neuroglobin

PubMed Central

Giordano, Daniela; Boron, Ignacio; Abbruzzetti, Stefania; Van Leuven, Wendy; Nicoletti, Francesco P.; Forti, Flavio; Bruno, Stefano; Cheng, C-H. Christina; Moens, Luc; di Prisco, Guido; Nadra, Alejandro D.; Estrin, Darío; Smulevich, Giulietta; Dewilde, Sylvia; Viappiani, Cristiano; Verde, Cinzia

2012-01-01

The Antarctic icefish Chaenocephalus aceratus lacks the globins common to most vertebrates, hemoglobin and myoglobin, but has retained neuroglobin in the brain. This conserved globin has been cloned, over-expressed and purified. To highlight similarities and differences, the structural features of the neuroglobin of this colourless-blooded fish were compared with those of the well characterised human neuroglobin as well as with the neuroglobin from the retina of the red blooded, hemoglobin and myoglobin-containing, closely related Antarctic notothenioid Dissostichus mawsoni. A detailed structural and functional analysis of the two Antarctic fish neuroglobins was carried out by UV-visible and Resonance Raman spectroscopies, molecular dynamics simulations and laser-flash photolysis. Similar to the human protein, Antarctic fish neuroglobins can reversibly bind oxygen and CO in the Fe2+ form, and show six-coordination by distal His in the absence of exogenous ligands. A very large and structured internal cavity, with discrete docking sites, was identified in the modelled three-dimensional structures of the Antarctic neuroglobins. Estimate of the free-energy barriers from laser-flash photolysis and Implicit Ligand Sampling showed that the cavities are accessible from the solvent in both proteins. Comparison of structural and functional properties suggests that the two Antarctic fish neuroglobins most likely preserved and possibly improved the function recently proposed for human neuroglobin in ligand multichemistry. Despite subtle differences, the adaptation of Antarctic fish neuroglobins does not seem to parallel the dramatic adaptation of the oxygen carrying globins, hemoglobin and myoglobin, in the same organisms. PMID:23226490

Assembly of Triblock Amphiphilic Peptides into One-Dimensional Aggregates and Network Formation.

PubMed

Ozgur, Beytullah; Sayar, Mehmet

2016-10-06

Peptide assembly plays a key role in both neurological diseases and development of novel biomaterials with well-defined nanostructures. Synthetic model peptides provide a unique platform to explore the role of intermolecular interactions in the assembly process. A triblock peptide architecture designed by the Hartgerink group is a versatile system which relies on Coulomb interactions, hydrogen bonding, and hydrophobicity to guide these peptides' assembly at three different length scales: β-sheets, double-wall ribbon-like aggregates, and finally a highly porous network structure which can support gels with ≤1% by weight peptide concentration. In this study, by using molecular dynamics simulations of a structure based implicit solvent coarse grained model, we analyzed this hierarchical assembly process. Parametrization of our CG model is based on multiple-state points from atomistic simulations, which enables this model to represent the conformational adaptability of the triblock peptide molecule based on the surrounding medium. Our results indicate that emergence of the double-wall β-sheet packing mechanism, proposed in light of the experimental evidence, strongly depends on the subtle balance of the intermolecular forces. We demonstrate that, even though backbone hydrogen bonding dominates the early nucleation stages, depending on the strength of the hydrophobic and Coulomb forces, alternative structures such as zero-dimensional aggregates with two β-sheets oriented orthogonally (which we refer to as a cross-packed structure) and β-sheets with misoriented hydrophobic side chains are also feasible. We discuss the implications of these competing structures for the three different length scales of assembly by systematically investigating the influence of density, counterion valency, and hydrophobicity.

Massively parallel unsupervised single-particle cryo-EM data clustering via statistical manifold learning

PubMed Central

Wu, Jiayi; Ma, Yong-Bei; Congdon, Charles; Brett, Bevin; Chen, Shuobing; Xu, Yaofang; Ouyang, Qi

2017-01-01

Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the assessment of structural heterogeneity. However, traditional algorithms for unsupervised classification, such as K-means clustering and maximum likelihood optimization, may classify images into wrong classes with decreasing signal-to-noise-ratio (SNR) in the image data, yet demand increased computational costs. Overcoming these limitations requires further development of clustering algorithms for high-performance cryo-EM data processing. Here we introduce an unsupervised single-particle clustering algorithm derived from a statistical manifold learning framework called generative topographic mapping (GTM). We show that unsupervised GTM clustering improves classification accuracy by about 40% in the absence of input references for data with lower SNRs. Applications to several experimental datasets suggest that our algorithm can detect subtle structural differences among classes via a hierarchical clustering strategy. After code optimization over a high-performance computing (HPC) environment, our software implementation was able to generate thousands of reference-free class averages within hours in a massively parallel fashion, which allows a significant improvement on ab initio 3D reconstruction and assists in the computational purification of homogeneous datasets for high-resolution visualization. PMID:28786986

Massively parallel unsupervised single-particle cryo-EM data clustering via statistical manifold learning.

PubMed

Wu, Jiayi; Ma, Yong-Bei; Congdon, Charles; Brett, Bevin; Chen, Shuobing; Xu, Yaofang; Ouyang, Qi; Mao, Youdong

2017-01-01

Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the assessment of structural heterogeneity. However, traditional algorithms for unsupervised classification, such as K-means clustering and maximum likelihood optimization, may classify images into wrong classes with decreasing signal-to-noise-ratio (SNR) in the image data, yet demand increased computational costs. Overcoming these limitations requires further development of clustering algorithms for high-performance cryo-EM data processing. Here we introduce an unsupervised single-particle clustering algorithm derived from a statistical manifold learning framework called generative topographic mapping (GTM). We show that unsupervised GTM clustering improves classification accuracy by about 40% in the absence of input references for data with lower SNRs. Applications to several experimental datasets suggest that our algorithm can detect subtle structural differences among classes via a hierarchical clustering strategy. After code optimization over a high-performance computing (HPC) environment, our software implementation was able to generate thousands of reference-free class averages within hours in a massively parallel fashion, which allows a significant improvement on ab initio 3D reconstruction and assists in the computational purification of homogeneous datasets for high-resolution visualization.

Homology modeling of a Class A GPCR in the inactive conformation: A quantitative analysis of the correlation between model/template sequence identity and model accuracy.

PubMed

Costanzi, Stefano; Skorski, Matthew; Deplano, Alessandro; Habermehl, Brett; Mendoza, Mary; Wang, Keyun; Biederman, Michelle; Dawson, Jessica; Gao, Jia

2016-11-01

With the present work we quantitatively studied the modellability of the inactive state of Class A G protein-coupled receptors (GPCRs). Specifically, we constructed models of one of the Class A GPCRs for which structures solved in the inactive state are available, namely the β 2 AR, using as templates each of the other class members for which structures solved in the inactive state are also available. Our results showed a detectable linear correlation between model accuracy and model/template sequence identity. This suggests that the likely accuracy of the homology models that can be built for a given receptor can be generally forecasted on the basis of the available templates. We also probed whether sequence alignments that allow for the presence of gaps within the transmembrane domains to account for structural irregularities afford better models than the classical alignment procedures that do not allow for the presence of gaps within such domains. As our results indicated, although the overall differences are very subtle, the inclusion of internal gaps within the transmembrane domains has a noticeable a beneficial effect on the local structural accuracy of the domain in question. Copyright © 2016 Elsevier Inc. All rights reserved.

Different zinc(II) complex species and binding modes at Aβ N-terminus drive distinct long range cross-talks in the Aβ monomers.

PubMed

Pietropaolo, Adriana; Satriano, Cristina; Strano, Gaetano; La Mendola, Diego; Rizzarelli, Enrico

2015-12-01

The present study addresses the reconstruction of the free-energy landscapes of amyloid-beta1-42 (Aβ42) coordinated respectively with one and two zinc ions, to scrutinize whether different Aβ-zinc complex species, i.e., mononuclear and dinuclear metal complexes, induce different Aβ conformation features. We found a subtle switch of intramolecular interactions, depending both on the zinc coordination environment and on the peptide to zinc stoichiometric ratio. On the one side, hairpin-like structures are predominant in mononuclear complexes, where a salt-bridge that involves Lys28-Glu22 and Lys16-Asp23 is stabilized. On the other side, elongated conformations are instead stabilized in the dinuclear zinc complexes. Experimental studies of atomic force microscopy as well as of zinc-Aβ complex species distribution diagrams provide evidence that the theoretical calculations can be rationalized in terms of the correlation between the increased amount of amorphous aggregates and the Aβ/Zn(2+) ratio. Copyright © 2015 Elsevier Inc. All rights reserved.

X-Ray and UV Photoelectron Spectroscopy | Materials Science | NREL

Science.gov Websites

backsheet material, showing excellent quantitative agreement between measured and predicted peak area ratios quantitative agreement between measured and predicted peak area ratios. Subtle differences in polymer functionality are assessed by deviations from stoichiometry. Elemental Analysis Uses quantitative identification

How Do Health Care Providers Diagnose Klinefelter Syndrome?

MedlinePlus

... and when a diagnosis occurs: Few newborns and boys are tested for or diagnosed with KS. Although newborns in the United States are screened for some conditions, they are not screened for XXY or other sex-chromosome differences. In childhood, symptoms can be subtle ...

Probing Implicit Learning in Obsessive-Compulsive Disorder: Moderating Role of Medication on the Weather Prediction Task

PubMed Central

Kelmendi, Benjamin; Adams, Thomas; Jakubovski, Ewgeni; Hawkins, Keith A.; Coric, Vladimir; Pittenger, Christopher

2016-01-01

Deficits in implicit learning, a process by which knowledge is acquired accretively through practice independent of conscious awareness, have been implicated in Obsessive-Compulsive Disorder (OCD). The weather-prediction task (WPT) was used to assess implicit learning in 26 unmedicated patients with OCD and 23 healthy controls. An additional analysis compared these two groups with 25 medicated patients with OCD. In the comparison of unmedicated patients with healthy controls there was a subtle but statistically significant group-by-block interaction. Patients with OCD showed slower improvement in performance during the middle phase of learning. In a three-group comparison, there was no main effect of group; in post-hoc tests, medicated patients with OCD differed from unmedicated patients and were not different from healthy controls. Unmedicated patients with OCD have a subtle deficit in implicit learning in the WPT. This may be mitigated by pharmacotherapy, although prospective studies would be required to confirm this conclusion. PMID:27134820

The nature of combustion noise: Stochastic or chaotic?

NASA Astrophysics Data System (ADS)

Gupta, Vikrant; Lee, Min Chul; Li, Larry K. B.

2016-11-01

Combustion noise, which refers to irregular low-amplitude pressure oscillations, is conventionally thought to be stochastic. It has therefore been modeled using a stochastic term in the analysis of thermoacoustic systems. Recently, however, there has been a renewed interest in the validity of that stochastic assumption, with tests based on nonlinear dynamical theory giving seemingly contradictory results: some show combustion noise to be stochastic while others show it to be chaotic. In this study, we show that this contradiction arises because those tests cannot distinguish between noise amplification and chaos. We further show that although there are many similarities between noise amplification and chaos, there are also some subtle differences. It is these subtle differences, not the results of those tests, that should be the focus of analyses aimed at determining the true nature of combustion noise. Recognizing this is an important step towards improved understanding and modeling of combustion noise for the study of thermoacoustic instabilities. This work was supported by the Research Grants Council of Hong Kong (Project No. 16235716 and 26202815).

Spectral Characterization of Suspected Acid Deposition Damage in Red Spruce (picea Rubens) Stands from Vermont

NASA Technical Reports Server (NTRS)

Vogelmann, J. E.; Rock, B. N.

1985-01-01

In an attempt to demonstrate the utility of remote sensing systems to monitor sites of suspected acid rain deposition damage, intensive field activities, coupled with aircraft overflights, were centered on red spruce stands in Vermont during August and September of 1984. Remote sensing data were acquired using the Airborne Imaging Spectrometer, Thematic Mapper Simulator, Barnes Model 12 to 1000 Modular Multiband Radiometer and Spectron Engineering Spectrometer (the former two flown on the NASA C-130; the latter two on A Bell UH-1B Iroquois Helicopter). Field spectral data were acquired during the week of the August overflights using a high spectral resolution spectrometer and two broad-band radiometers. Preliminary analyses of these data indicate a number of spectral differences in vegetation between high and low damage sites. Some of these differences are subtle, and are observable only with high spectral resolution sensors; others are less subtle and are observable using broad-band sensors.

Surprising Ripple Effects: How Changing the SAT Score-Sending Policy for Low-Income Students Impacts College Access and Success

ERIC Educational Resources Information Center

Hurwitz, Michael; Mbekeani, Preeya P.; Nipson, Margaret M.; Page, Lindsay C.

2017-01-01

Subtle policy adjustments can induce relatively large "ripple effects." We evaluate a College Board initiative that increased the number of free SAT score reports available to low-income students and changed the time horizon for using these score reports. Using a difference-in-differences analytic strategy, we estimate that targeted…

Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease.

PubMed

Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai

2017-11-20

Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Wechsler Adult Intelligence Scale-Third Edition profiles and their relationship to self-reported outcome following traumatic brain injury.

PubMed

Harman-Smith, Yasmin E; Mathias, Jane L; Bowden, Stephen C; Rosenfeld, Jeffrey V; Bigler, Erin D

2013-01-01

Neuropsychological assessments of outcome after traumatic brain injury (TBI) are often unrelated to self-reported problems after TBI. The current study cluster-analyzed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) subtest scores from mild, moderate, and severe TBI (n=220) and orthopedic injury control (n=95) groups, to determine whether specific cognitive profiles are related to people's perceived outcomes after TBI. A two-stage cluster analysis produced 4- and 6-cluster solutions, with the 6-cluster solution better capturing subtle variations in cognitive functioning. The 6 clusters differed in the levels and profiles of cognitive performance, self-reported recovery, and education and injury severity. The findings suggest that subtle cognitive impairments after TBI should be interpreted in conjunction with patient's self-reported problems.

Customizing semen preservation protocols for individual dogs and individual species: sperm preservation beyond the state of the art.

PubMed

Farstad, W

2012-12-01

Sperm quality can be variable in morphometric and physiological attributes between males of different species, between males within species subtypes reared under different environmental conditions, between ejaculates of the same male or even between sperm populations within an ejaculate. Clinical semen evaluation is based on evaluation of whole ejaculates, which is not a chemically or physiologically well-defined entity, rather a collection of heterogeneous subpopulations giving different measurements and possessing different fertilizing potential. Identification of subpopulations with different motility patterns is important as well as characterizing the subtle structural changes underlying the motility differences observed. The ability to identify populations of sperm responding rapidly or failing to progress through the capacitation process may have clinical applications. Studies of lipid-phase fluidity of sperm membranes, mathematical modelling of membrane ion transport, role of modifying components and detergent-resistant microdomains are of particular interest. When customizing extenders to ejaculates from cryosensitive males or species, a thorough knowledge of species sperm membrane physiology and an assessment of the individual ejaculate's sperm populations are necessary. Structural differences have been found in sperm membranes between fox species with different cryosurvival potential of their spermatozoa. Supplementation of lipids and detergents in cryoextenders may influence membrane fluidity of the surviving spermatozoa in a species-dependent manner and influence capacitation. Immobilization of sperm prior to cryopreservation with subsequent slow release of sperm in the female genital tract may be a way to prolong the fertile life of sperm. In canids with a long oocyte maturation time, delayed capacitation may be beneficial. © 2012 Blackwell Verlag GmbH.

The posterolateral corner of the knee.

PubMed

Vinson, Emily N; Major, Nancy M; Helms, Clyde A

2008-02-01

The purpose of this article is to review the clinical importance and MRI appearances of injuries to the posterolateral corner of the knee. Injuries to the posterolateral corner structures of the knee can cause significant disability due to instability, cartilage degeneration, and cruciate graft failure. Becoming familiar with the anatomy of this region can improve one's ability to detect subtle abnormalities and can perhaps lead to improvements in diagnosing and understanding injuries to this area.

Diagnosis and management of dental wear.

PubMed

Harpenau, Lisa A; Noble, Warden H; Kao, Richard T

2011-04-01

Dental wear is loss of tooth structure resulting from erosion, attrition, abrasion, and, possibly, abfraction. Clinical/experimental data suggest no single damaging mechanism but rather simultaneous interaction of these destructive processes. The most important interaction is abrasion/attrition potentiated by dental erosion. Awareness of this pathosis is not well-appreciated by the public and dental professionals because the signs may be subtle. This article focuses on the recognition, diagnosis, and management of dental wear.

Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khare, B.; Krishnan, V.; Rajashankar, K.R.

2011-10-21

The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoringmore » of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a 'lid' in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y) motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the 'lid' mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis.« less

Neuromotor outcomes at school age after extremely low birth weight: early detection of subtle signs.

PubMed

Gidley Larson, Jennifer C; Baron, Ida Sue; Erickson, Kristine; Ahronovich, Margot D; Baker, Robin; Litman, Fern R

2011-01-01

Motor impairments are prevalent in children born at extremely low birth weight (ELBW; <1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born <26 weeks performed most poorly compared with those born 26-34 weeks and term-born. Subtle motor dysfunctions are detectable and quantifiable in ELBW children by school age, even in the presence of average cognition. Early age assessment of incoordination, motor speed, and overflow movements should aid initiation of timely therapies to prepare at-risk ELBW children for subsequent school entry and facilitate design of optimal early treatment strategies. (c) 2010 APA, all rights reserved.

Visualization of Hyperconjugation and Subsequent Structural Distortions through 3D Printing of Crystal Structures.

PubMed

Mithila, Farha J; Oyola-Reynoso, Stephanie; Thuo, Martin M; Atkinson, Manza Bj

2016-01-01

Structural distortions due to hyperconjugation in organic molecules, like norbornenes, are well captured through X-ray crystallographic data, but are sometimes difficult to visualize especially for those applying chemical knowledge and are not chemists. Crystal structure from the Cambridge database were downloaded and converted to .stl format. The structures were then printed at the desired scale using a 3D printer. Replicas of the crystal structures were accurately reproduced in scale and any resulting distortions were clearly visible from the macroscale models. Through space interactions or effect of through space hyperconjugation was illustrated through loss of symmetry or distortions thereof. The norbornene structures exhibits distortion that cannot be observed through conventional ball and stick modelling kits. We show that 3D printed models derived from crystallographic data capture even subtle distortions in molecules. We translate such crystallographic data into scaled-up models through 3D printing.

Subtle evidence for paleoseismicity in the cratonic interior, U.S. A

NASA Astrophysics Data System (ADS)

Jacobson, W. Z.; Cowan, C. A.; Runkel, A. C.

2009-12-01

Intrastratal deformation features in Cambrian-Ordovician boundary strata in southeastern Minnesota, U.S.A., may be evidence for mid-continent paleoseismicity. Deformation features are present tens of kilometers east of the Midcontinent Rift zone, and include sand blows, water escape, and convolute lamination, as well as more subtle structures indicative of sand-on-sand density contrasts. The stratigraphic interval of interest is the uppermost Jordan Formation (Furongian), a very fine- to coarse-grained quartzose sandstone, and the basal Oneota Formation (Tremadocian), a heterolithic sandstone and dolostone that grades upward into bedded dolostone. Along the Jordan-Oneota boundary, deformation features are extensive, and the result of sand liquefaction and fluidization. Upward migration of excess pore water was obstructed in places by shale drapes that locally ruptured, causing sand to be injected into overlying beds. Movement of sand in this manner created voids that were filled by a chaotic mixture of sand, shale, and pebbles that collapsed from above. Where upwardly percolating water was not confined by shale, intrastratal flow produced water escape pillars. Other deformation features are present up to ~3 m below the Jordan-Oneota boundary, in well-sorted, pure quartzose sandstone. These features are inconspicuous because of the uniform texture and minerology of the sediment, and some were previously interpreted as synsedimentary phenomena. These features are common along foreset boundaries in large-scale (>3 m) cross-strata, and include cm-scale digitate interfaces (interfingering) and in situ rounded forms interpreted as sand-on-sand boudinage. They formed from density contrasts between individual foresets within the cross-bedded sand. The top of the lower foreset was less dense but more viscous than the base of the succeeding foreset. Such contrasts were the result of subtle packing and grain size differences formed during the avalanche process during dune migration. We interpret the trigger for deformation, however, to be a post-depositional (post-Oneota) event because of the association of these subtle features with the more obvious liquefaction features in the immediately overlying boundary strata (and the increased intensity of deformation along foresets upward toward the boundary). Although these features cannot be unambiguously attributed to a paleoseismic event, some other common possibilities can be eliminated, including slumping and loading by sediment, tides, and storm waves. These intrastratal deformation features are documented in one outcrop in southeastern Minnesota. The subtlety of some of these features suggests that similar features may have been overlooked in nearby outcrops. Indeed, we are now revisiting unusual features in some localities that we previously interpreted as synsedimentary phenomena. Seismites may be difficult to generate, and to recognize, in quartoze sandstones of the mid-continent due to the lack of significantly thick clay beds to serve as permeability barriers, and the homogenous textural and mineralogical attributes of these units.

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiac structure and function across the glycemic spectrum in elderly men and women free of prevalent heart disease: the Atherosclerosis Risk In the Community study.

PubMed

Skali, Hicham; Shah, Amil; Gupta, Deepak K; Cheng, Susan; Claggett, Brian; Liu, Jiankang; Bello, Natalie; Aguilar, David; Vardeny, Orly; Matsushita, Kunihiro; Selvin, Elizabeth; Solomon, Scott

2015-05-01

Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia. We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses. In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus. © 2015 American Heart Association, Inc.

Supporting the Future Air Traffic Control Projection Process

NASA Technical Reports Server (NTRS)

Davison, Hayley J.; Hansman, R. John, Jr.

2002-01-01

In air traffic control, projecting what the air traffic situation will be over the next 30 seconds to 30 minutes is a key process in identifying conflicts that may arise so that evasive action can be taken upon discovery of these conflicts. A series of field visits in the Boston and New York terminal radar approach control (TRACON) facilities and in the oceanic air traffic control facilities in New York and Reykjavik, Iceland were conducted to investigate the projection process in two different ATC domains. The results from the site visits suggest that two types of projection are currently used in ATC tasks, depending on the type of separation minima and/or traffic restriction and information display used by the controller. As technologies improve and procedures change, care should be taken by designers to support projection through displays, automation, and procedures. It is critical to prevent time/space mismatches between interfaces and restrictions. Existing structure in traffic dynamics could be utilized to provide controllers with useful behavioral models on which to build projections. Subtle structure that the controllers are unable to internalize could be incorporated into an ATC projection aid.

CFD Analyses and Jet-Noise Predictions of Chevron Nozzles with Vortex Stabilization

NASA Technical Reports Server (NTRS)

Dippold, Vance

2008-01-01

The wind computational fluid dynamics code was used to perform a series of analyses on a single-flow plug nozzle with chevrons. Air was injected from tubes tangent to the nozzle outer surface at three different points along the chevron at the nozzle exit: near the chevron notch, at the chevron mid-point, and near the chevron tip. Three injection pressures were used for each injection tube location--10, 30, and 50 psig-giving injection mass flow rates of 0.1, 0.2, and 0.3 percent of the nozzle mass flow. The results showed subtle changes in the jet plume s turbulence and vorticity structure in the region immediately downstream of the nozzle exit. Distinctive patterns in the plume structure emerged from each injection location, and these became more pronounced as the injection pressure was increased. However, no significant changes in centerline velocity decay or turbulent kinetic energy were observed in the jet plume as a result of flow injection. Furthermore, computational acoustics calculations performed with the JeNo code showed no real reduction in jet noise relative to the baseline chevron nozzle.

Development of the Attitudes to Domestic Violence Questionnaire for Children and Adolescents.

PubMed

Fox, Claire L; Gadd, David; Sim, Julius

2015-09-01

To provide a more robust assessment of the effectiveness of a domestic abuse prevention education program, a questionnaire was developed to measure children's attitudes to domestic violence. The aim was to develop a short questionnaire that would be easy to use for practitioners but, at the same time, sensitive enough to pick up on subtle changes in young people's attitudes. We therefore chose to ask children about different situations in which they might be willing to condone domestic violence. In Study 1, we tested a set of 20 items, which we reduced by half to a set of 10 items. The factor structure of the scale was explored and its internal consistency was calculated. In Study 2, we tested the factor structure of the 10-item Attitudes to Domestic Violence (ADV) Scale in a separate calibration sample. Finally, in Study 3, we then assessed the test-retest reliability of the 10-item scale. The ADV Questionnaire is a promising tool to evaluate the effectiveness of domestic abuse education prevention programs. However, further development work is necessary. © The Author(s) 2014.

Problems in understanding the structure and assembly of viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, J.

1997-12-01

Though viruses infect the cells of all groups of animals, plants, and microorganisms, their structures follow a limited number of general themes; spherical or cylindrical shells built of hundreds of repeated protein subunits enclosing a nucleic acid - DNA or RNA - genome. Since the 1960s it has been known that the protein shells of spherical viruses in fact conform to icosahedral symmetry or to subtle deviations from icosahedral symmetry. The construction of the shell lattices and the transformations they go through in the different stages of the viral life cycle are not fully understood. The shells contain the nucleicmore » in a highly condensed state, of unknown coiling/organization. Features of the well studied bacterial viruses will be reviewed, with examples from adenoviruses, herpesviruses, poliovirus, and HIV. The emergence of new viral disease has led to increased interest in the development of agents which interfere with virus reproduction at the level of the assembly or function of the organized particle. Recently computational approaches to the problem of virus assembly have made important contributions to clarifying shell assembly processes. 1 ref.« less

Red, green, blue equals 1, 2, 3: Digit-color synesthetes can use structured digit information to boost recall of color sequences.

PubMed

Teichmann, A Lina; Nieuwenstein, Mark R; Rich, Anina N

2015-01-01

Digit-color synesthetes report experiencing colors when perceiving letters and digits. The conscious experience is typically unidirectional (e.g., digits elicit colors but not vice versa) but recent evidence shows subtle bidirectional effects. We examined whether short-term memory for colors could be affected by the order of presentation reflecting more or less structure in the associated digits. We presented a stream of colored squares and asked participants to report the colors in order. The colors matched each synesthete's colors for digits 1-9 and the order of the colors corresponded either to a sequence of numbers (e.g., [red, green, blue] if 1 = red, 2 = green, 3 = blue) or no systematic sequence. The results showed that synesthetes recalled sequential color sequences more accurately than pseudo-randomized colors, whereas no such effect was found for the non-synesthetic controls. Synesthetes did not differ from non-synesthetic controls in recall of color sequences overall, providing no evidence of a general advantage in memory for serial recall of colors.

Zebrafish AID is capable of deaminating methylated deoxycytidines

PubMed Central

Abdouni, Hala; King, Justin J.; Suliman, Mussa; Quinlan, Matthew; Fifield, Heather; Larijani, Mani

2013-01-01

Activation-induced cytidine deaminase (AID) deaminates deoxycytidine (dC) to deoxyuracil (dU) at immunoglobulin loci in B lymphocytes to mediate secondary antibody diversification. Recently, AID has been proposed to also mediate epigenetic reprogramming by demethylating methylated cytidines (mC) possibly through deamination. AID overexpression in zebrafish embryos was shown to promote genome demethylation through G:T lesions, implicating a deamination-dependent mechanism. We and others have previously shown that mC is a poor substrate for human AID. Here, we examined the ability of bony fish AID to deaminate mC. We report that zebrafish AID was unique among all orthologs in that it efficiently deaminates mC. Analysis of domain-swapped and mutant AID revealed that mC specificity is independent of the overall high-catalytic efficiency of zebrafish AID. Structural modeling with or without bound DNA suggests that efficient deamination of mC by zebrafish AID is likely not due to a larger catalytic pocket allowing for better fit of mC, but rather because of subtle differences in the flexibility of its structure. PMID:23585279

Random and Block Sulfonated Polyaramides as Advanced Proton Exchange Membranes

DOE PAGES

Kinsinger, Corey L.; Liu, Yuan; Liu, Feilong; ...

2015-10-09

We present here the experimental and computational characterization of two novel copolyaramide proton exchange membranes (PEMs) with higher conductivity than Nafion at relatively high temperatures, good mechanical properties, high thermal stability, and the capability to operate in low humidity conditions. The random and block copolyaramide PEMs are found to possess different ion exchange capacities (IEC) in addition to subtle structural and morphological differences, which impact the stability and conductivity of the membranes. SAXS patterns indicate the ionomer peak for the dry block copolymer resides at q = 0.1 Å –1, which increases in amplitude when initially hydrated to 25% relativemore » humidity, but then decrease in amplitude with additional hydration. This pattern is hypothesized to signal the transport of water into the polymer matrix resulting in a reduced degree of phase separation. Coupled to these morphological changes, the enhanced proton transport characteristics and structural/mechanical stability for the block copolymer are hypothesized to be primarily due to the ordered structure of ionic clusters that create connected proton transport pathways while reducing swelling upon hydration. Interestingly, the random copolymer did not possess an ionomer peak at any of the hydration levels investigated, indicating a lack of any significant ionomer structure. The random copolymer also demonstrated higher proton conductivity than the block copolymer, which is opposite to the trend normally seen in polymer membranes. However, it has reduced structural/mechanical stability as compared to the block copolymer. In conclusion, this reduction in stability is due to the random morphology formed by entanglements of polymer chains and the adverse swelling characteristics upon hydration. Therefore, the block copolymer with its enhanced proton conductivity characteristics, as compared to Nafion, and favorable structural/mechanical stability, as compared to the random copolymer, represents a viable alternative to current proton exchange membranes.« less

Developmental Regression in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rogers, Sally J.

2004-01-01

The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences.…

Artificial-epitope mapping for CK-MB assay.

PubMed

Tai, Dar-Fu; Ho, Yi-Fang; Wu, Cheng-Hsin; Lin, Tzu-Chieh; Lu, Kuo-Hao; Lin, Kun-Shian

2011-06-07

A quantitative method using artificial antibody to detect creatine kinases was developed. Linear epitope sequences were selected based on an artificial-epitope mapping strategy. Nine different MIPs corresponding to the selected peptides were then fabricated on QCM chips. The subtle conformational changes were also recognized by these chips.

Medical Surveillance Programs for Aircraft Maintenance Personnel Performing Nondestructive Inspection and Testing

DTIC Science & Technology

2005-11-01

visible and fl uorescent inspection techniques, while radiography relies on the individual’s ability to detect subtle differences in contrast either...binocular measurement of visual acuity may better predict a person’s functional capability in the workplace . However, measurement of monocular acuities

Leveraging Failure in Design Research

ERIC Educational Resources Information Center

Lobato, Joanne; Walters, C. David; Hohensee, Charles; Gruver, John; Diamond, Jaime Marie

2015-01-01

Even in the resource-rich, more ideal conditions of many design-based classroom interventions, unexpected events can lead to disappointing results in student learning. However, if later iterations in a design research study are more successful, the previous failures can provide opportunities for comparisons to reveal subtle differences in…

Quantitative analysis of pre-and postsynaptic sex differences in the nucleus accumbens

PubMed Central

Forlano, Paul M.; Woolley, Catherine S.

2010-01-01

The nucleus accumbens (NAc) plays a central role in motivation and reward. While there is ample evidence for sex differences in addiction-related behaviors, little is known about the neuroanatomical substrates that underlie these sexual dimorphisms. We investigated sex differences in synaptic connectivity of the NAc by evaluating pre- and postsynaptic measures in gonadally intact male and proestrous female rats. We used DiI labeling and confocal microscopy to measure dendritic spine density, spine head size, dendritic length and branching of medium spiny neurons (MSNs) in the NAc, and quantitative immunofluorescence to measure glutamatergic innervation using pre- (vesicular glutamate transporter 1 and 2) and postsynaptic (post synaptic density 95) markers, as well as dopaminergic innervation of the NAc. We also utilized electron microscopy to complement the above measures. Clear but subtle sex differences were identified, namely in distal dendritic spine density and the proportion of large spines on MSNs, both of which are greater in females. Sex differences in spine density and spine head size are evident in both the core and shell subregions, but are stronger in the core. This study is the first demonstration of neuroanatomical sex differences in the NAc and provides evidence that structural differences in synaptic connectivity and glutamatergic input may contribute to behavioral sex differences in reward and addiction. PMID:20151363

A hidden markov model derived structural alphabet for proteins.

PubMed

Camproux, A C; Gautier, R; Tufféry, P

2004-06-04

Understanding and predicting protein structures depends on the complexity and the accuracy of the models used to represent them. We have set up a hidden Markov model that discretizes protein backbone conformation as series of overlapping fragments (states) of four residues length. This approach learns simultaneously the geometry of the states and their connections. We obtain, using a statistical criterion, an optimal systematic decomposition of the conformational variability of the protein peptidic chain in 27 states with strong connection logic. This result is stable over different protein sets. Our model fits well the previous knowledge related to protein architecture organisation and seems able to grab some subtle details of protein organisation, such as helix sub-level organisation schemes. Taking into account the dependence between the states results in a description of local protein structure of low complexity. On an average, the model makes use of only 8.3 states among 27 to describe each position of a protein structure. Although we use short fragments, the learning process on entire protein conformations captures the logic of the assembly on a larger scale. Using such a model, the structure of proteins can be reconstructed with an average accuracy close to 1.1A root-mean-square deviation and for a complexity of only 3. Finally, we also observe that sequence specificity increases with the number of states of the structural alphabet. Such models can constitute a very relevant approach to the analysis of protein architecture in particular for protein structure prediction.

Crystal Structure of the Leishmania Major Phosphodiesterase LmjPDEB1 and Insight into the Design of hte Parasite-Selective Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang,H.; Yan, Z.; Geng, J.

2007-01-01

Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 Angstroms resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bondmore » with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.« less

Ground state of Ho atoms on Pt(111) metal surfaces: Implications for magnetism

NASA Astrophysics Data System (ADS)

Karbowiak, M.; Rudowicz, C.

2016-05-01

We investigated the ground state of Ho atoms adsorbed on the Pt(111) surface, for which conflicting results exist. The density functional theory (DFT) calculations yielded the Ho ground state as | Jz=±8 > . Interpretation of x-ray absorption spectroscopy and x-ray magnetic circular dichroism spectra and the magnetization curves indicated the ground state as | Jz=±6 > . Superposition model is employed to predict the crystal-field (CF) parameters based on the structural data for the system Ho/Pt(111) obtained from the DFT modeling. Simultaneous diagonalization of the free-ion (HFI) and the trigonal CF Hamiltonian (HCF) within the whole configuration 4 f10 of H o3 + ion was performed. The role of the trigonal CF terms, neglected in the pure uniaxial CF model used previously for interpretation of experimental spectra, is found significant, whereas the sixth-rank CF terms may be neglected in agreement with the DFT predictions. The results provide substantial support for the experimental designation of the | Jz=±6 > ground state, albeit with subtle difference due to admixture of other | Jz> states, but run against the DFT-based designation of the | Jz=±8 > ground state. A subtle splitting of the ground energy level with the state (predominantly), | Jz=±6 > is predicted. This paper provides better insight into the single-ion magnetic behavior of the Ho/Pt(111) system by helping to resolve the controversy concerning the Ho ground state. Experimental techniques with greater resolution powers are suggested for direct confirmation of this splitting and C3 v symmetry experienced by the Ho atom.

Sex differences in the outcomes of stent implantation in mini-swine model.

PubMed

Kunio, Mie; Wong, Gee; Markham, Peter M; Edelman, Elazer R

2018-01-01

Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation). Histomorphological parameters were evaluated from vascular specimens at 3-365 days after stent implantation and evaluated values were compared between female and male groups. While neointima formation at all times after implantation was invariant to sex, statistically significant differences between female and male groups were observed in injury, inflammation, adventitial fibrosis, and neointimal fibrin deposition. These differences were observed independently, i.e., for different procedure types and at different follow-up timings. Only subtle temporal sex-related differences were observed in extent and timing of resolution of inflammation and fibrin clearance. These subtle sex-related differences may be increasingly important as interventional devices meld novel materials that erode and innovations in drug delivery. Erodible materials may act differently if inflammation has a different temporal sequence with sex, and drug distribution after balloon or stent delivery might be different if the fibrin clearance speaks to different modes of pharmacokinetics in male and female swine.

COMPUTER SIMULATION STUDY OF AMYLOID FIBRIL FORMATION BY PALINDROMIC SEQUENCES IN PRION PEPTIDES

PubMed Central

Wagoner, Victoria; Cheon, Mookyung; Chang, Iksoo; Hall, Carol

2011-01-01

We simulate the aggregation of large systems containing palindromic peptides from the Syrian hamster prion protein SHaPrP 113–120 (AGAAAAGA) and the mouse prion protein MoPrP 111–120 (VAGAAAAGAV) and eight sequence variations: GAAAAAAG, (AG)4, A8, GAAAGAAA, A10, V10, GAVAAAAVAG, and VAVAAAAVAV The first two peptides are thought to act as the Velcro that holds the parent prion proteins together in amyloid structures and can form fibrils themselves. Kinetic events along the fibrillization pathway influence the types of structures that occur and variations in the sequence affect aggregation kinetics and fibrillar structure. Discontinuous molecular dynamics simulations using the PRIME20 force field are performed on systems containing 48 peptides starting from a random coil configuration. Depending on the sequence, fibrillar structures form spontaneously over a range of temperatures, below which amorphous aggregates form and above which no aggregation occurs. AGAAAAGA forms well organized fibrillar structures whereas VAGAAAAGAV forms less well organized structures that are partially fibrillar and partially amorphous. The degree of order in the fibrillar structure stems in part from the types of kinetic events leading up to its formation, with AGAAAAGA forming less amorphous structures early in the simulation than VAGAAAAGAV. The ability to form fibrils increases as the chain length and the length of the stretch of hydrophobic residues increase. However as the hydrophobicity of the sequence increases, the ability to form well-ordered structures decreases. Thus, longer hydrophobic sequences form slightly disordered aggregates that are partially fibrillar and partially amorphous. Subtle changes in sequence result in slightly different fibril structures. PMID:21557317

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases.

PubMed

Lohman, Jeremy R; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N; Shen, Ben

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases

PubMed Central

Lohman, Jeremy R.; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N.; Shen, Ben

2015-01-01

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs. PMID:26420866

The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly

NASA Astrophysics Data System (ADS)

Mainwaring, David E.; Nguyen, Song Ha; Webb, Hayden; Jakubov, Timur; Tobin, Mark; Lamb, Robert N.; Wu, Alex H.-F.; Marchant, Richard; Crawford, Russell J.; Ivanova, Elena P.

2016-03-01

While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08542j

Analysis of subtle auditory dysfunctions in young normal-hearing subjects affected by Williams syndrome.

PubMed

Paglialonga, Alessia; Barozzi, Stefania; Brambilla, Daniele; Soi, Daniela; Cesarani, Antonio; Spreafico, Emanuela; Tognola, Gabriella

2014-11-01

To assess if young subjects affected by Williams syndrome (WS) with normal middle ear functionality and normal hearing thresholds might have subtle auditory dysfunctions that could be detected by using clinically available measurements. Otoscopy, acoustic reflexes, tympanometry, pure-tone audiometry, and distortion product otoacoustic emissions (DPOAEs) were measured in a group of 13 WS subjects and in 13 age-matched, typically developing control subjects. Participants were required to have normal otoscopy, A-type tympanogram, normal acoustic reflex thresholds, and pure-tone thresholds≤15 dB HL at 0.5, 1, and 2 kHz bilaterally. To limit the possible influence of middle ear status on DPOAE recordings, we analyzed only data from ears with pure-tone thresholds≤15 dB HL across all octave frequencies in the range 0.25-8 kHz, middle ear pressure (MEP)>-50 daPa, static compliance (SC) in the range 0.3-1.2 cm3, and ear canal volume (ECV) in the range 0.2-2 ml, and we performed analysis of covariance to remove the possible effects of middle ear variables on DPOAEs. No differences in mean hearing thresholds, SC, ECV, and gradient were observed between the two groups, whereas significantly lower MEP values were found in WS subjects as well as significantly decreased DPOAEs up to 3.2 kHz after adjusting for differences in middle ear status. Results revealed that WS subjects with normal hearing thresholds (≤15 dB HL) and normal middle ear functionality (MEP>-50 daPa, SC in the range 0.3-1.2 cm3, ECV in the range 0.2-2 ml) might have subtle auditory dysfunctions that can be detected by using clinically available methods. Overall, this study points out the importance of using otoacoustic emissions as a complement to routine audiological examinations in individuals with WS to detect, before the onset of hearing loss, possible subtle auditory dysfunctions so that patients can be early identified, better monitored, and promptly treated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Physical stability comparisons of IgG1-Fc variants: effects of N-glycosylation site occupancy and Asp/Gln residues at site Asn 297

PubMed Central

KIM, JAE HYUN; JOSHI, SANGEETA B.; MIDDAUGH, C. RUSSELL; TOLBERT, THOMAS J.; VOLKIN, DAVID B.

2014-01-01

The structural integrity and conformational stability of various IgG1-Fc proteins produced from the yeast Pichia pastoris with different glycosylation site occupancy (di-, mono-, and non- glycosylated) was determined. In addition, the physical stability profiles of three different forms of non-glycosylated Fc molecules (varying amino acid residues at site 297 in the CH2 domain due to point mutations and enzymatic digestion of the Fc glycoforms) were also examined. The physical stability of these IgG1-Fc glycoproteins was examined as a function of pH and temperature by high throughput biophysical analysis using multiple techniques combined with data visualization tools (three index empirical phase diagrams and radar charts). Across the pH range of 4.0 to 6.0, the di- and mono- glycosylated forms of the IgG1-Fc showed the highest and lowest levels of physical stability respectively, with the non-glycosylated forms showing intermediate stability depending on solution pH. In the aglycosylated Fc proteins, the introduction of Asp (D) residues at site 297 (QQ vs. DN vs. DD forms) resulted in more subtle changes in structural integrity and physical stability depending on solution pH. The utility of evaluating the conformational stability profile differences between the various IgG1-Fc glycoproteins is discussed in the context of analytical comparability studies. PMID:24740840

Surface properties of adipocyte lipid-binding protein: Response to lipid binding, and comparison with homologous proteins.

PubMed

LiCata, V J; Bernlohr, D A

1998-12-01

Adipocyte lipid-binding protein (ALBP) is one of a family of intracellular lipid-binding proteins (iLBPs) that bind fatty acids, retinoids, and other hydrophobic ligands. The different members of this family exhibit a highly conserved three-dimensional structure; and where structures have been determined both with (holo) and without (apo) bound lipid, observed conformational changes are extremely small (Banaszak, et al., 1994, Adv. Prot. Chem. 45, 89; Bernlohr, et al., 1997, Annu. Rev. Nutr. 17, 277). We have examined the electrostatic, hydrophobic, and water accessible surfaces of ALBP in the apo form and of holo forms with a variety of bound ligands. These calculations reveal a number of previously unrecognized changes between apo and holo ALBP, including: 1) an increase in the overall protein surface area when ligand binds, 2) expansion of the binding cavity when ligand is bound, 3) clustering of individual residue exposure increases in the area surrounding the proposed ligand entry portal, and 4) ligand-binding dependent variation in the topology of the electrostatic potential in the area surrounding the ligand entry portal. These focused analyses of the crystallographic structures thus reveal a number of subtle but consistent conformational and surface changes that might serve as markers for differential targeting of protein-lipid complexes within the cell. Most changes are consistent from ligand to ligand, however there are some ligand-specific changes. Comparable calculations with intestinal fatty-acid-binding protein and other vertebrate iLBPs show differences in the electrostatic topology, hydrophobic topology, and in localized changes in solvent exposure near the ligand entry portal. These results provide a basis toward understanding the functional and mechanistic differences among these highly structurally homologous proteins. Further, they suggest that iLBPs from different tissues exhibit one of two predominant end-state structural distributions of the ligand entry portal.

Molecular Docking, Molecular Dynamics, and Structure–Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists

PubMed Central

2017-01-01

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure–activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3–7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design. PMID:28125215

Dissociation of recombinant prion autocatalysis from infectivity.

PubMed

Noble, Geoffrey P; Supattapone, Surachai

2015-01-01

Within the mammalian prion field, the existence of recombinant prion protein (PrP) conformers with self-replicating (ie. autocatalytic) activity in vitro but little to no infectious activity in vivo challenges a key prediction of the protein-only hypothesis of prion replication--that autocatalytic PrP conformers should be infectious. To understand this dissociation of autocatalysis from infectivity, we recently performed a structural and functional comparison between a highly infectious and non-infectious pair of autocatalytic recombinant PrP conformers derived from the same initial prion strain. (1) We identified restricted, C-terminal structural differences between these 2 conformers and provided evidence that these relatively subtle differences prevent the non-infectious conformer from templating the conversion of native PrP(C) substrates containing a glycosylphosphatidylinositol (GPI) anchor. (1) In this article we discuss a model, consistent with these findings, in which recombinant PrP, lacking post-translational modifications and associated folding constraints, is capable of adopting a wide variety of autocatalytic conformations. Only a subset of these recombinant conformers can be adopted by post-translationally modified native PrP(C), and this subset represents the recombinant conformers with high specific infectivity. We examine this model's implications for the generation of highly infectious recombinant prions and the protein-only hypothesis of prion replication.

Interfacial coupling and polarization of perovskite ABO3 heterostructures

NASA Astrophysics Data System (ADS)

Wu, Lijun; Wang, Zhen; Zhang, Bangmin; Yu, Liping; Chow, G. M.; Tao, Jing; Han, Myung-Geun; Guo, Hangwen; Chen, Lina; Plummer, E. W.; Zhang, Jiandi; Zhu, Yimei

2017-02-01

Interfaces with subtle difference in atomic and electronic structures in perovskite ABO3 heterostructures often yield intriguingly different properties, yet their exact roles remain elusive. In this article, we report an integrated study of unusual transport, magnetic, and structural properties of Pr0.67Sr0.33MnO3 (PSMO) films and La0.67Sr0.33MnO3 (LSMO) films of various thicknesses on SrTiO3 (STO) substrate. In particular, using atomically resolved imaging and electron energy-loss spectroscopy (EELS), we measured interface related local lattice distortion, BO6 octahedral rotation and cation-anion displacement induced polarization. In the very thin PSMO film, an unexpected interface-induced ferromagnetic polaronic insulator phase was observed during the cubic-to-tetragonal phase transition of the substrate STO, due to the enhanced electron-phonon interaction and atomic disorder in the film. On the other hand, for the very thin LSMO films we observed a remarkably deep polarization in non-ferroelectric STO substrate near the interface. Combining the experimental results with first principles calculations, we propose that the observed deep polarization is induced by an electric field originating from oxygen vacancies that extend beyond a dozen unit-cells from the interface, thus providing important evidence of the role of defects in the emergent interface properties of transition metal oxides.

Advantages of synchrotron radiation circular dichroism spectroscopy to study intrinsically disordered proteins.

PubMed

Kumagai, Patricia S; DeMarco, Ricardo; Lopes, Jose L S

2017-10-01

The unordered secondary structural content of an intrinsically disordered protein (IDP) is susceptible to conformational changes induced by many different external factors, such as the presence of organic solvents, removal of water, changes in temperature, binding to partner molecules, and interaction with lipids and/or other ligands. In order to characterize the high-flexibility nature of an IDP, circular dichroism (CD) spectroscopy is a particularly useful method due to its capability of monitoring both subtle and remarkable changes in different environments, relative ease in obtaining measurements, the small amount of sample required, and the capability for sample recovery (sample not damaged) and others. Using synchrotron radiation as the light source for CD spectroscopy represents the state-of-the-art version of this technique with feasibility of accessing the lower wavelength UV region, and therefore presenting a series of advantages over conventional circular dichroism (cCD) to monitor a protein conformational behavior, check protein stability, detect ligand binding, and many others. In this paper, we have performed a comparative study using cCD and SRCD methods for investigating the secondary structure and the conformational behavior of natively unfolded proteins: MEG-14 and soybean trypsin inhibitor. We show that the SRCD technique greatly improves the analysis and accuracy of the studies on the conformations of IDPs.

Time-dependent photon heat transport through a mesoscopic Josephson device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Wen-Ting; Zhao, Hong-Kang, E-mail: zhaohonk@bit.edu.cn

The time-oscillating photon heat current through a dc voltage biased mesoscopic Josephson Junction (MJJ) has been investigated by employing the nonequilibrium Green’s function approach. The Landauer-like formula of photon heat current has been derived in both of the Fourier space and its time-oscillating versions, where Coulomb interaction, self inductance, and magnetic flux take effective roles. Nonlinear behaviors are exhibited in the photon heat current due to the quantum nature of MJJ and applied external dc voltage. The magnitude of heat current decreases with increasing the external bias voltage, and subtle oscillation structures appear as the superposition of different photon heatmore » branches. The overall period of heat current with respect to time is not affected by Coulomb interaction, however, the magnitude and phase of it vary considerably by changing the Coulomb interaction. - Highlights: • The time-oscillating photon heat current through a mesoscopic Josephson Junction has been investigated. • The Landauer-like formula of photon heat current has been derived by the nonequilibrium Green’s function approach. • Nonlinear behaviors are exhibited in the photon heat current resulting from the self inductance and Coulomb interaction. • The oscillation structure of heat current is composed of the superposition of oscillations with different periods.« less

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia.

PubMed

Yang, Yaling; Raine, Adrian; Han, Chen-Bo; Schug, Robert A; Toga, Arthur W; Narr, Katherine L

2010-04-30

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, the hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 x 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. Copyright @ 2009 Elsevier Ireland Ltd. All rights reserved.

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia

PubMed Central

Raine, Adrian; Han, Chen-Bo; Schug, Robert A.; Toga, Arthur W.; Narr, Katherine L.

2010-01-01

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 × 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. PMID:20227253

Functional video-based analysis of 3D cardiac structures generated from human embryonic stem cells.

PubMed

Nitsch, Scarlett; Braun, Florian; Ritter, Sylvia; Scholz, Michael; Schroeder, Insa S

2018-05-01

Human embryonic stem cells (hESCs) differentiated into cardiomyocytes (CM) often develop into complex 3D structures that are composed of various cardiac cell types. Conventional methods to study the electrophysiology of cardiac cells are patch clamp and microelectrode array (MEAs) analyses. However, these methods are not suitable to investigate the contractile features of 3D cardiac clusters that detach from the surface of the culture dishes during differentiation. To overcome this problem, we developed a video-based motion detection software relying on the optical flow by Farnebäck that we call cBRA (cardiac beat rate analyzer). The beating characteristics of the differentiated cardiac clusters were calculated based on the local displacement between two subsequent images. Two differentiation protocols, which profoundly differ in the morphology of cardiac clusters generated and in the expression of cardiac markers, were used and the resulting CM were characterized. Despite these differences, beat rates and beating variabilities could be reliably determined using cBRA. Likewise, stimulation of β-adrenoreceptors by isoproterenol could easily be identified in the hESC-derived CM. Since even subtle changes in the beating features are detectable, this method is suitable for high throughput cardiotoxicity screenings. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Interfacial Coupling-Induced Ferromagnetic Insulator Phase in Manganite Film

DOE PAGES

Zhang, Bangmin; Wu, Lijun; Yin, Wei-Guo; ...

2016-06-08

Interfaces with subtle differences in atomic and electronic structures in perovskite ABO 3 heterostructures often yield intriguingly different properties, yet their exact roles remain elusive. Here, we report an integrated study of unusual transport, magnetic, and structural properties of Pr 0.67Sr 0.33MnO 3 film on SrTiO 3 substrate. The variations in the out-of-plane lattice constant and BO 6 octahedral rotation across the Pr 0.67Sr 0.33MnO 3/SrTiO 3 interface strongly depend on the thickness of the Pr 0.67Sr 0.33MnO 3 film. In the 12-nm film, a new interface-sensitive ferromagnetic polaronic insulator (FI') phase is formed during the cubic-to-tetragonal phase transition ofmore » SrTiO 3, apparently due to the enhanced electron–phonon interaction and atomic disorder in the film. The transport properties of the FI' phase in the 30-nm film are masked because of the reduced interfacial coupling and smaller interface-to-volume ratio. In conclusion, this work demonstrates how thickness-dependent interfacial coupling leads to the formation of a theoretically predicted ferromagnetic–polaronic insulator, as illustrated in a new phase diagram, that is otherwise ferromagnetic metal (FM) in bulk form.« less

Interfacial Coupling-Induced Ferromagnetic Insulator Phase in Manganite Film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bangmin; Wu, Lijun; Yin, Wei-Guo

Interfaces with subtle differences in atomic and electronic structures in perovskite ABO 3 heterostructures often yield intriguingly different properties, yet their exact roles remain elusive. Here, we report an integrated study of unusual transport, magnetic, and structural properties of Pr 0.67Sr 0.33MnO 3 film on SrTiO 3 substrate. The variations in the out-of-plane lattice constant and BO 6 octahedral rotation across the Pr 0.67Sr 0.33MnO 3/SrTiO 3 interface strongly depend on the thickness of the Pr 0.67Sr 0.33MnO 3 film. In the 12-nm film, a new interface-sensitive ferromagnetic polaronic insulator (FI') phase is formed during the cubic-to-tetragonal phase transition ofmore » SrTiO 3, apparently due to the enhanced electron–phonon interaction and atomic disorder in the film. The transport properties of the FI' phase in the 30-nm film are masked because of the reduced interfacial coupling and smaller interface-to-volume ratio. In conclusion, this work demonstrates how thickness-dependent interfacial coupling leads to the formation of a theoretically predicted ferromagnetic–polaronic insulator, as illustrated in a new phase diagram, that is otherwise ferromagnetic metal (FM) in bulk form.« less

Africa and International Policy Making for Lifelong Learning: Textual Revelations

ERIC Educational Resources Information Center

Preece, Julia

2013-01-01

This paper discusses the relationship between international agendas for lifelong learning and financial aid for low income countries, especially those on the African continent. It argues that there are subtle differences in terminology written by policymakers respectively in Europe and South Africa for lifelong learning but that international…

A Curious Reality: Exploring the Paintings of Philip C. Curtis

ERIC Educational Resources Information Center

Stephens, Pamela; Walkup, Nancy

2011-01-01

Many of the paintings of 20th-century American artist Philip C. Curtis defy clear classification. Curtis's artworks often show dreamlike and fantastical qualities and are therefore frequently pigeonholed as Surrealistic. While this classification is not completely erroneous, it fails to acknowledge some subtle differences between Curtis's artwork…

Language Ability of Students with Emotional Disturbance: Discrepancies between Teacher Ratings and Direct Assessment

ERIC Educational Resources Information Center

Chow, Jason C.; Hollo, Alexandra

2018-01-01

Language impairment often goes unidentified in students with behavioral disorders, perhaps in part because different forms of problem behavior deflect adult attention from more subtle language deficits. Therefore, attention to teachers' perception of students' language and behavioral performance is merited. The present study examines agreement…

Learning Strategies and Reading Literacy among Chinese and Finnish Adolescents: Evidence of Suppression

ERIC Educational Resources Information Center

Cai, Yuyang; Zhu, Xinhua

2017-01-01

Many arguments have been advanced in the context of the predictive correlation between learning strategies and reading achievement. There is insufficient understanding, however, of the subtle ways in which different types of learning strategies (i.e. memorisation, elaboration and control strategies) function in facilitating students' reading…

European Starlings Are Capable of Discriminating Subtle Size Asymmetries in Paired Stimuli

ERIC Educational Resources Information Center

Swaddle, John P.; Johnson, Charles W.

2007-01-01

Small deviations from bilateral symmetry (fluctuating asymmetries) are cues to fitness differences in some animals. Therefore, researchers have considered whether animals use these small asymmetries as visual cues to determine appropriate behavioral responses (e.g., mate preferences). However, there have been few systematic studies of animals'…

Zen and the Art of Management

ERIC Educational Resources Information Center

Pascale, Richard Tanner

1978-01-01

A study of Japanese-managed companies in the U.S. and Japan found that their decision-making processes are not much different from American companies. However, an eastern perspective on management and organizational communication emphasizes the value of the subtle arts employed by successful Japanese and American managers alike. (JG)

‘I wouldn’t say it’s sexism, except that … It’s all these little subtle things’: Healthcare scientists’ accounts of gender in healthcare science laboratories

PubMed Central

Learmonth, Mark

2013-01-01

We explore healthcare scientists’ accounts of men in healthcare science laboratories. By focussing on subtle masculinist actions that women find disadvantageous to them, we seek to extend knowledge about women’s under-representation in senior positions in healthcare science – despite women being in the majority at junior levels. We maintain that healthcare science continues to be dominated by taken-for-granted masculinities that marginalize women, keeping them in their ‘place’. Our aim is to make visible the subtle practices that are normally invisible by showing masculinities in action. Principally using feminist analyses, our findings show that both women and men are often unaware of taken-for-granted masculinist actions, and even when women do notice, they rarely challenge the subtle sexist behaviour.

Crowding, Entropic Forces, and Confinement: Crucial Factors for Structures and Functions in the Cell Nucleus.

PubMed

Hancock, R

2018-04-01

The view of the cell nucleus as a crowded system of colloid particles and that chromosomes are giant self-avoiding polymers is stimulating rapid advances in our understanding of its structure and activities, thanks to concepts and experimental methods from colloid, polymer, soft matter, and nano sciences and to increased computational power for simulating macromolecules and polymers. This review summarizes current understanding of some characteristics of the molecular environment in the nucleus, of how intranuclear compartments are formed, and of how the genome is highly but precisely compacted, and underlines the crucial, subtle, and sometimes unintuitive effects on structures and reactions of entropic forces caused by the high concentration of macromolecules in the nucleus.

Molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with cyanide biodegradation by Serratia marcescens.

PubMed

Kushwaha, Madhulika; Kumar, Virender; Mahajan, Rishi; Bhalla, Tek Chand; Chatterjee, Subhankar; Akhter, Yusuf

2018-05-09

The present study provides molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with degradation of cyanide compounds, using Serratia marcescens RL2b as a model organism. Resting cells harvested after 20 h achieved complete degradation of 12 mmol l - 1 cyanide in approximately 10 h. High-performance liquid chromatography analysis of reaction samples revealed formation of formamide as the only end product, which confirmed the presence of cyanide hydratase activity in S. marcescens RL2b. Comparative structural analysis with the other nitrilase family proteins, which was carried out using a sequence of cyanide hydratase from a phylogenetically related strain S. marcescens WW4, also revealed subtle but significant differences in amino acid residues of the substrate-binding pocket and catalytic triad (Cys-Lys-Glu).

Molecular mechanical studies of proflavine and acridine orange intercalation.

PubMed Central

Dearing, A; Weiner, P; Kollman, P A

1981-01-01

Previous workers have reported that proflavine and acridine orange form various structurally different complexes with the dinucleoside phosphates rCpG and dCpG, with uniform C3'-endo and mixed C3'-endo (3'-5') C2'-endo sugar puckers being observed. We present theoretical calculations, based on the method of molecular mechanics, which support the experimental observations. The results suggest that the mixed C3'-edo (3'-5') C2'-endo pucker conformation isi intrinsically more stable than the uniform C3'-endo conformation, but that the additional stabilisation gained from specific, hydrogen bonding, interactions between nucleic acid and solvent, or intramolecularly within the nucleic acid, can lead to the adoption of the latter conformation, or of variants between the two. The role played by hydrogen bonding between amino-groups and nucleic acid phosphate appears more subtle than previously supposed. PMID:7232221

Ultrafast studies of coexisting electronic order in cuprate superconductors

NASA Astrophysics Data System (ADS)

Hinton, James; Thewalt, Eric; Alpichshev, Zhanybek; Sternbach, Aaron; McLeod, Alex; Ji, L.; Veit, Mike; Dorrow, Chelsey; Koralek, Jake; Xhao, Xudong; Barisic, Neven; Kemper, Alexander; Gedik, Nuh; Greven, Martin; Basov, Dimitri; Orenstein, Joe

The cuprate family of high temperature superconductors displays a variety of electronic phases which emerge when charge carriers are added to the antiferromagnetic parent compound. These electronic phases are characterized by subtle differences in the low energy electronic excitations. Ultrafast time-resolved reflectivity (TRR) provides an ideal tool for investigating the cuprate phase diagram, as small changes in the electronic structure can produce significant contrast in the non-equilibrium reflectivity. Here we present TRR measurements of cuprate superconductors, focusing on the model single-layer cuprate HgBa2CuO4+δ. We observe a cusp-like feature in the quasiparticle lifetime near the superconducting transition temperature Tc. This feature can be understood using a model of coherently-mixed charge-density wave and superconducting pairing. We propose extending this technique to the nanoscale using ultrafast scattering scanning near-field microscopy (u-SNOM). This will allow us to explore how these electronic phases coexist and compete in real-space.

Dispersion-cancelled biological imaging with quantum-inspired interferometry

PubMed Central

Mazurek, M. D.; Schreiter, K. M.; Prevedel, R.; Kaltenbaek, R.; Resch, K. J.

2013-01-01

Quantum information science promises transformative impact over a range of key technologies in computing, communication, and sensing. A prominent example uses entangled photons to overcome the resolution-degrading effects of dispersion in the medical-imaging technology, optical coherence tomography. The quantum solution introduces new challenges: inherently low signal and artifacts, additional unwanted signal features. It has recently been shown that entanglement is not a requirement for automatic dispersion cancellation. Such classical techniques could solve the low-signal problem, however they all still suffer from artifacts. Here, we introduce a method of chirped-pulse interferometry based on shaped laser pulses, and use it to produce artifact-free, high-resolution, dispersion-cancelled images of the internal structure of a biological sample. Our work fulfills one of the promises of quantum technologies: automatic-dispersion-cancellation interferometry in biomedical imaging. It also shows how subtle differences between a quantum technique and its classical analogue may have unforeseen, yet beneficial, consequences. PMID:23545597

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Interactive Particle Visualization

NASA Astrophysics Data System (ADS)

Gribble, Christiaan P.

Particle-based simulation methods are used to model a wide range of complex phenomena and to solve time-dependent problems of various scales. Effective visualizations of the resulting state will communicate subtle changes in the three-dimensional structure, spatial organization, and qualitative trends within a simulation as it evolves. This chapter discusses two approaches to interactive particle visualization that satisfy these goals: one targeting desktop systems equipped with programmable graphics hardware, and the other targeting moderately sized multicore systems using packet-based ray tracing.

Angiogenesis - a crucial step in breast cancer growth, progression and dissemination by Raman imaging

NASA Astrophysics Data System (ADS)

Kopeć, Monika; Abramczyk, Halina

2018-06-01

Combined micro-Raman imaging and AFM imaging are efficient methods for analyzing human tissue due to their high spatial and spectral resolution as well as sensitivity to subtle chemical, structural and topographical changes. The aim of this study was to determine biochemical composition and mechanical topography around blood vessels in the tumor mass of human breast tissue. Significant alterations of the chemical composition and structural architecture around the blood vessel were found compared to the normal breast tissue. A pronounced increase of collagen-fibroblast-glycocalyx network, as well as enhanced lactic acid, and glycogen activity in patients affected by breast cancer were reported.

Interpersonal sensitivity, bullying victimization and paranoid ideation among help-seeking adolescents and young adults.

PubMed

Masillo, Alice; Valmaggia, Lucia R; Saba, Riccardo; Brandizzi, Martina; Lo Cascio, Nella; Telesforo, Ludovica; Venturini, Paola; Izzo, Aniello; Mattioli, M Teresa; D'Alema, Marco; Girardi, Paolo; Fiori Nastro, Paolo

2017-05-30

The effects of a negative interpersonal experience, such as bullying victimization in childhood and adolescence, can be strong and long lasting. Bullying victimization is associated with paranoid ideation and suspiciousness. Few studies have focused on personality traits of victims of bullying. The aim of this study is to investigate whether a particular personality trait called interpersonal sensitivity may be related to suspiciousness in those who experienced bullying victimization. The study sample consisted of 147 help-seeking adolescents (mean age 17 years) selected after a screening phase (Prodromal Questionnaire) and evaluated with the Structured Interview for Psychosis-risk Syndromes (SIPS). All participants were specifically asked if they had experienced either psychological bullying or physical bullying, and they completed the Interpersonal Sensitivity Measure (IPSM). Of the whole sample, 30 (20%) participants had experienced psychological bullying or physical bullying at least once in their life. Performing a multiple regression, bullying victimization was found to be an independent predictor of subtle paranoid ideation and suspiciousness. Interpersonal sensitivity was also found to be an independent predictor of subtle paranoid ideation; in particular, two IPSM subscales, fragile inner-self and separation anxiety, showed a significant correlation with subtle paranoid ideation. Our results confirmed that bullying victimization is a negative interpersonal experience associated with paranoid ideation and suspiciousness. However, being overly sensitive and having negative beliefs about the self as fragile and vulnerable to threat also lead to a tendency to attribute experiences as externally caused and, in turn, facilitate the formation and maintenance of paranoid ideation. © 2017 John Wiley & Sons Australia, Ltd.

Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR

NASA Astrophysics Data System (ADS)

Varkey, Jobin; Langen, Ralf

2017-07-01

The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single protein can generate different type of membrane curvatures using specific conformations for specific membrane structures and how EPR is a versatile tool well-suited to analyze subtle alterations in structures under such modifying conditions which otherwise would have been difficult using other biophysical tools.

fMRI investigation of sentence comprehension by eye and by ear: modality fingerprints on cognitive processes.

PubMed

Michael, E B; Keller, T A; Carpenter, P A; Just, M A

2001-08-01

The neural substrate underlying reading vs. listening comprehension of sentences was compared using fMRI. One way in which this issue was addressed was by comparing the patterns of activation particularly in cortical association areas that classically are implicated in language processing. The precise locations of the activation differed between the two modalities. In the left inferior frontal gyrus (Broca's area), the activation associated with listening was more anterior and inferior than the activation associated with reading, suggesting more semantic processing during listening comprehension. In the left posterior superior and middle temporal region (roughly, Wernicke's area), the activation for listening was closer to primary auditory cortex (more anterior and somewhat more lateral) than the activation for reading. In several regions, the activation was much more left lateralized for reading than for listening. In addition to differences in the location of the activation, there were also differences in the total amount of activation in the two modalities in several regions. A second way in which the modality comparison was addressed was by examining how the neural systems responded to comprehension workload in the two modalities by systematically varying the structural complexity of the sentences to be processed. Here, the distribution of the workload increase associated with the processing of additional structural complexity was very similar across the two input modalities. The results suggest a number of subtle differences in the cognitive processing underlying listening vs. reading comprehension. Copyright 2001 Wiley-Liss, Inc.

LES FOR SIMULATING THE GAS EXCHANGE PROCESS IN A SPARK IGNITION ENGINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ameen, Muhsin M; yang, xiaofeng; kuo, tang-wei

2015-01-01

The gas exchange process is known to be a significant source of cyclic variability in Internal Combustion Engines (ICE). Traditionally, Large Eddy Simulations (LES) are expected to capture these cycle-to-cycle variations. This paper reports a numerical effort to establish best practices for capturing cyclic variability with LES tools in a Transparent Combustion Chamber (TCC) spark ignition engine. The main intention is to examine the sensitivity of cycle averaged mean and Root Mean Square (RMS) flow fields and Proper Orthogonal Decomposition (POD) modes to different computational hardware, adaptive mesh refinement (AMR) and LES sub-grid scale (SGS) models, since these aspects havemore » received little attention in the past couple of decades. This study also examines the effect of near-wall resolution on the predicted wall shear stresses. LES is pursued with commercially available CONVERGE code. Two different SGS models are tested, a one-equation eddy viscosity model and dynamic structure model. The results seem to indicate that both mean and RMS fields without any SGS model are not much different than those with LES models, either one-equation eddy viscosity or dynamic structure model. Computational hardware results in subtle quantitative differences, especially in RMS distributions. The influence of AMR on both mean and RMS fields is negligible. The predicted shear stresses near the liner walls is also found to be relatively insensitive to near-wall resolution except in the valve curtain region.« less

Buccal Swabbing as a Noninvasive Method To Determine Bacterial, Archaeal, and Eukaryotic Microbial Community Structures in the Rumen

PubMed Central

Kirk, Michelle R.; Jonker, Arjan; McCulloch, Alan

2015-01-01

Analysis of rumen microbial community structure based on small-subunit rRNA marker genes in metagenomic DNA samples provides important insights into the dominant taxa present in the rumen and allows assessment of community differences between individuals or in response to treatments applied to ruminants. However, natural animal-to-animal variation in rumen microbial community composition can limit the power of a study considerably, especially when only subtle differences are expected between treatment groups. Thus, trials with large numbers of animals may be necessary to overcome this variation. Because ruminants pass large amounts of rumen material to their oral cavities when they chew their cud, oral samples may contain good representations of the rumen microbiota and be useful in lieu of rumen samples to study rumen microbial communities. We compared bacterial, archaeal, and eukaryotic community structures in DNAs extracted from buccal swabs to those in DNAs from samples collected directly from the rumen by use of a stomach tube for sheep on four different diets. After bioinformatic depletion of potential oral taxa from libraries of samples collected via buccal swabs, bacterial communities showed significant clustering by diet (R = 0.37; analysis of similarity [ANOSIM]) rather than by sampling method (R = 0.07). Archaeal, ciliate protozoal, and anaerobic fungal communities also showed significant clustering by diet rather than by sampling method, even without adjustment for potentially orally associated microorganisms. These findings indicate that buccal swabs may in future allow quick and noninvasive sampling for analysis of rumen microbial communities in large numbers of ruminants. PMID:26276109

Can Lighting Influence Self-Disclosure?

PubMed

Mehta, Veli; Mukherjee, Sumitava; Manjaly, Jaison A

2017-01-01

With the advent of social networks where people disclose a lot of their information and opinions publicly, this research attempted to re-look at the effect of environmental lighting on willingness and actual disclosure of personal information. Previous literatures mostly addressed counseling setups and the findings were mixed. In order to clarify the effect of lighting on self-disclosure, two experiments were conducted with reported willingness to disclose (Experiment 1) as well as actual disclosure (Experiment 2) on a range of topics like social issues, body, money, work, and personality. While quite a handful of studies have reported differences in disclosure from very subtle environmental lighting manipulations, in both experiments we could not find any effect of ambient room lighting conditions on self-disclosure. These results call for caution both in over-interpreting subtle environmental effects and in increased generalization of perceptual metaphors to actual behavior.

Harnessing the Interaction Continuum for Subtle Assisted Living

PubMed Central

García-Herranz, Manuel; Olivera, Fernando; Haya, Pablo; Alamán, Xavier

2012-01-01

People interact with each other in many levels of attention, intention and meaning. This Interaction Continuum is used daily to deal with different contexts, adapting the interaction to communication needs and available resources. Nevertheless, computer-supported interaction has mainly focused on the most direct, explicit and intrusive types of human to human Interaction such as phone calls, emails, or video conferences. This paper presents the results of exploring and exploiting the potentials of undemanding interaction mechanisms, paying special attention to subtle communication and background interaction. As we argue the benefits of this type of interaction for people with special needs, we present a theoretical framework to define it and propose a proof of concept based on Augmented Objects and a color codification mechanism. Finally, we evaluate and analyze the strengths and limitations of such approach with people with cognitive disabilities. PMID:23012573

Dentists versus auto mechanics: are there ethical differences?

PubMed

Riley, Crystal

2013-01-01

The different ethical perspectives of dentists and auto mechanics include primary concern, billing procedures, advertising, emergency care, the level of autonomy granted to their patients/ clients, the amount of disclosure given to their patients/clients, the ability to judge the work of others, and the freedom to pursue romantic relationships with their patients/clients. In analyzing these differences, one finds dentists to have much greater ethical obligations than auto mechanics. There are subtle differences between the ethical expectations of Canadian and United States dentists.

2-d and 1-d Nanomaterials Construction through Peptide Computational Design and Solution Assembly

NASA Astrophysics Data System (ADS)

Pochan, Darrin

Self-assembly of molecules is an attractive materials construction strategy due to its simplicity in application. By considering peptidic molecules in the bottom-up materials self-assembly design process, one can take advantage of inherently biomolecular attributes; intramolecular folding events, secondary structure, and electrostatic/H-bonding/hydrophobic interactions to define hierarchical material structure and consequent properties. Importantly, while biomimicry has been a successful strategy for the design of new peptide molecules for intermolecular assembly, computational tools have been developed to de novo design peptide molecules required for construction of pre-determined, desired nanostructures and materials. A new system comprised of coiled coil bundle motifs theoretically designed to assemble into designed, one and two-dimensional nanostructures will be introduced. The strategy provides the opportunity for arbitrary nanostructure formation, i.e. structures not observed in nature, with peptide molecules. Importantly, the desired nanostructure was chosen first while the peptides needed for coiled coil formation and subsequent nanomaterial formation were determined computationally. Different interbundle, two-dimensional nanostructures are stabilized by differences in amino acid composition exposed on the exterior of the coiled coil bundles. Computation was able to determine molecules required for different interbundle symmetries within two-dimensional sheets stabilized by subtle differences in amino acid composition of the inherent peptides. Finally, polymers were also created through covalent interactions between bundles that allowed formation of architectures spanning flexible network forming chains to ultra-stiff polymers, all with the same building block peptides. The success of the computational design strategy is manifested in the nanomaterial results as characterized by electron microscopy, scattering methods, and biophysical techniques. Support from NSF DMREF program under awards DMR-1234161 and DMR-1235084.

Social relationship difficulties in autism and reactive attachment disorder: Improving diagnostic validity through structured assessment.

PubMed

Davidson, Claire; O'Hare, Anne; Mactaggart, Fiona; Green, Jonathan; Young, David; Gillberg, Christopher; Minnis, Helen

2015-05-01

Autism Spectrum Disorder (ASD) versus Reactive Attachment Disorder (RAD) is a common diagnostic challenge for clinicians due to overlapping difficulties with social relationships. RAD is associated with neglect or maltreatment whereas ASD is not: accurate differential diagnosis is therefore critical. Very little research has investigated the relationship between the two, and it is unknown if standardised measures are able to discriminate between ASD and RAD. The current study aimed to address these issues. Fifty eight children with ASD, and no history of maltreatment, were group matched on age with 67 children with RAD. Group profiles on multi-informant measures of RAD were investigated and group differences explored. Discriminant function analysis determined assessment features that best discriminated between the two groups. Although, according to parent report, children with ASD presented with significantly fewer indiscriminate friendliness behaviours compared to the RAD group (p<0.001), 36 children with ASD appeared to meet core RAD criteria. However, structured observation clearly demonstrated that features were indicative of ASD and not RAD for all but 1 of these 36 children. Children with RAD and children with ASD may demonstrate similar social relationship difficulties but there appears to be a difference in the social quality of the interactions between the groups. In most cases it was possible to differentiate between children with ASD and children with RAD via structured observation. Nevertheless, for a small proportion of children with ASD, particularly those whose difficulties may be more subtle, our current standardised measures, including structured observation, may not be effective in differentiating RAD from ASD. Copyright © 2015. Published by Elsevier Ltd.

Oxytocin enhances pupil dilation and sensitivity to ‘hidden’ emotional expressions

PubMed Central

Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-01-01

Sensing others’ emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and ‘hidden’ emotional expressions and related the results to individual differences in sensitivity to others’ subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or ‘sharpened’ evaluative processing of others’ positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin’s prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin’s effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation. PMID:22648957

Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions.

PubMed

Leknes, Siri; Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-10-01

Sensing others' emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and 'hidden' emotional expressions and related the results to individual differences in sensitivity to others' subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others' positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin's prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin's effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation.

Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis

PubMed Central

Kret, Mariska E.; Broekens, Joost

2018-01-01

Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of stimulus intensity. Men, however, more strongly perceived non-target emotions to be present than women. In addition, we also found that the lower scores of men in self-reported EI was not related to their actual perception of target emotions, but it was to the perception of non-target emotions. PMID:29370198

Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis.

PubMed

Fischer, Agneta H; Kret, Mariska E; Broekens, Joost

2018-01-01

Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of stimulus intensity. Men, however, more strongly perceived non-target emotions to be present than women. In addition, we also found that the lower scores of men in self-reported EI was not related to their actual perception of target emotions, but it was to the perception of non-target emotions.

Electronic structures of WAlO(y) and WAlO(y)(-) (y = 2-4) determined by anion photoelectron spectroscopy and density functional theory calculations.

PubMed

Mann, Jennifer E; Waller, Sarah E; Jarrold, Caroline Chick

2012-07-28

The anion photoelectron spectra of WAlO(y)(-) (y = 2-4) are presented and assigned based on results of density functional theory calculations. The WAlO(2)(-) and WAlO(3)(-) spectra are both broad, with partially resolved vibrational structure. In contrast, the WAlO(4)(-) spectrum features well-resolved vibrational structure with contributions from three modes. There is reasonable agreement between experiment and theory for all oxides, and calculations are in particular validated by the near perfect agreement between the WAlO(4)(-) photoelectron spectrum and a Franck-Condon simulation based on computationally determined spectroscopic parameters. The structures determined from this study suggest strong preferential W-O bond formation, and ionic bonding between Al(+) and WO(y)(-2) for all anions. Neutral species are similarly ionic, with WAlO(2) and WAlO(3) having electronic structure that suggests Al(+) ionically bound to WO(y)(-) and WAlO(4) being described as Al(+2) ionically bound to WO(4)(-2). The doubly-occupied 3sp hybrid orbital localized on the Al center is energetically situated between the bonding O-local molecular orbitals and the anti- or non-bonding W-local molecular orbitals. The structures determined in this study are very similar to structures recently determined for the analogous MoAlO(y)(-)/MoAlO(y) cluster series, with subtle differences found in the electronic structures [S. E. Waller, J. E. Mann, E. Hossain, M. Troyer, and C. C. Jarrold, J. Chem. Phys. 137, 024302 (2012)].

Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.

PubMed

Ruiz, Federico M; Scholz, Barbara A; Buzamet, Eliza; Kopitz, Jürgen; André, Sabine; Menéndez, Margarita; Romero, Antonio; Solís, Dolores; Gabius, Hans-Joachim

2014-03-01

Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 β-strand of the β-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. © 2014 FEBS.

Controllable reflection properties of nanocomposite photonic crystals constructed by semiconductor nanocrystallites and natural periodic bio-matrices.

PubMed

Han, Jie; Su, Huilan; Song, Fang; Zhang, Di; Chen, Zhixin

2010-10-01

In this contribution, the subtle periodic nanostructures in butterfly wings and peacock feathers are applied as natural PhC matrices to in situ embed CdS nanocrystallites (nano-CdS) on the structure surface via a convenient solution process. The resulting nano-CdS/natural PhCs nanocomposites show typical 1D, quasi 1D and 2D PhC structures at the nanoscale, which is inherited from the corresponding natural periodic bio-matrices. Moreover, their reflection properties are investigated and show dependence on PhC type, structure parameter, loading amount, as well as collecting angle. This work suggests that natural periodic bio-structures could be perfect matrices to construct novel nanocomposite PhCs, whose photonic band structures are tunable and thus achieve controllable optical properties. Related ideas could inspire the design and synthesis of future nanocomposite PhCs.

Cd in SnO: Probing structural effects on the electronic structure of doped oxide semiconductors through the electric field gradient at the Cd nucleus

NASA Astrophysics Data System (ADS)

Errico, Leonardo A.; Rentería, Mario; Petrilli, Helena M.

2007-04-01

We perform an ab initio study of the electric field gradient (EFG) at the nucleus of Cd impurities at substitutional Sn sites in crystalline SnO. The full-potential linearized-augmented plane wave and the projector augmented wave methods used here allow us to treat the electronic structure of the doped system and the atomic relaxations introduced by the impurities in the host in a fully self-consistent way using a supercell approach in a state-of-the-art way. Effects of the impurity charge state on the electronic and structural properties are also discussed. Since the EFG is a very subtle quantity, its determination is very useful to probe ground-state properties such as the charge density. We show that the EFG is very sensitive to structural relaxations induced by the impurity. Our theoretical predictions are compared with available experimental results.

Anticorrelation between polar lattice instability and superconductivity in the Weyl semimetal candidate MoTe2

NASA Astrophysics Data System (ADS)

Takahashi, H.; Akiba, T.; Imura, K.; Shiino, T.; Deguchi, K.; Sato, N. K.; Sakai, H.; Bahramy, M. S.; Ishiwata, S.

2017-03-01

The relation between the polar structural instability and superconductivity in a Weyl semimetal candidate MoTe2 has been clarified by finely controlled physical and chemical pressure. The physical pressure as well as the chemical pressure, i.e., the Se substitution for Te, enhances the superconducting transition temperature Tc at around the critical pressure where the polar structure transition disappears. From the heat capacity and thermopower measurements, we ascribe the significant enhancement of Tc at the critical pressure to a subtle modification of the phonon dispersion or the semimetallic band structure upon the polar-to-nonpolar transition. On the other hand, the physical pressure, which strongly reduces the interlayer distance, is more effective on the suppression of the polar structural transition and the enhancement of Tc as compared with the chemical pressure, which emphasizes the importance of the interlayer coupling on the structural and superconducting instability in MoTe2.

Hypoglycemia-Associated EEG Changes Following Antecedent Hypoglycemia in Type 1 Diabetes Mellitus.

PubMed

Sejling, Anne-Sophie; Kjaer, Troels W; Pedersen-Bjergaard, Ulrik; Remvig, Line S; Frandsen, Christian S; Hilsted, Linda; Faber, Jens; Holst, Jens Juul; Tarnow, Lise; Møller, Jakob Skadkær; Nielsen, Martin N; Thorsteinsson, Birger; Juhl, Claus B

2017-02-01

Recurrent hypoglycemia has been shown to blunt hypoglycemia symptom scores and counterregulatory hormonal responses during subsequent hypoglycemia. We therefore studied whether hypoglycemia-associated electroencephalogram (EEG) changes are affected by an antecedent episode of hypoglycemia. Twenty-four patients with type 1 diabetes mellitus (10 with normal hypoglycemia awareness, 14 with hypoglycemia unawareness) were studied on 2 consecutive days by hyperinsulinemic glucose clamp at hypoglycemia (2.0-2.5 mmol/L) during a 1-h period. EEG was recorded, cognitive function assessed, and hypoglycemia symptom scores and counterregulatory hormonal responses were obtained. Twenty-one patients completed the study. Hypoglycemia-associated EEG changes were identified on both days with no differences in power or frequency distribution in the theta, alpha, or the combined theta-alpha band during hypoglycemia on the 2 days. Similar degree of cognitive dysfunction was also present during hypoglycemia on both days. When comparing the aware and unaware group, there were no differences in the hypoglycemia-associated EEG changes. There were very subtle differences in cognitive function between the two groups on day 2. The symptom response was higher in the aware group on both days, while only subtle differences were seen in the counterregulatory hormonal response. Antecedent hypoglycemia does not affect hypoglycemia-associated EEG changes in patients with type 1 diabetes mellitus.

CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study

PubMed Central

Cabral Soares, Fernanda; de Oliveira, Thaís Cristina Galdino; de Macedo, Liliane Dias e Dias; Tomás, Alessandra Mendonça; Picanço-Diniz, Domingos Luiz Wanderley; Bento-Torres, João; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

2015-01-01

Objective The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging. PMID:25565785

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

PubMed

Danias, Peter G; Tritos, Nicholas A; Stuber, Matthias; Kissinger, Kraig V; Salton, Carol J; Manning, Warren J

2003-07-01

Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Mammographic density measured as changes in tissue structure caused by HRT

NASA Astrophysics Data System (ADS)

Raundahl, Jakob; Loog, Marco; Nielsen, Mads

2006-03-01

Numerous studies have investigated the relation between mammographic density and breast cancer risk. These studies indicate that women with high breast density have a four to six fold risk increase. An investigation of whether or not this relation is causal is important for, e.g., hormone replacement therapy (HRT), which has been shown to actually increase the density. No gold standard for automatic assessment of mammographic density exists. Manual methods such as Wolfe patterns and BI-RADS are helpful for communication of diagnostic sensitivity, but they are both time consuming and crude. They may be sufficient in certain cases and for single measurements, but for serial, temporal analysis it is necessary to be able to detect more subtle changes and, in addition, to be more reproducible. In this work an automated method for measuring the effect of HRT w.r.t. changes in biological density in the breast is presented. This measure is a novel measure, which provides structural information orthogonal to intensity-based methods. Hessian eigenvalues at different scales are used as features and a clustering of these is employed to divide a mammogram into four structurally different areas. Subsequently, based on the relative size of the areas, a density score is determined. In the experiments, two sets of mammograms of 50 patients from a double blind, placebo controlled HRT experiment were used. The change in density for the HRT group, measured with the new method, was significantly higher (p = 0.0002) than the change in the control group.

A Miniature Fiber-Optic Sensor for High-Resolution and High-Speed Temperature Sensing in Ocean Environment

DTIC Science & Technology

2015-11-05

the SMF is superior when it comes to remote sensing in far and deep ocean. As an initial test , the real-time temperature structure within the water...4 ℃. The high resolution guarantees the visualization of subtle variation in the local water. To test the response time of the proposed sensor, the... Honey , "Optical trubulence in the sea," in Underwater Photo-optical Instrumentation Applications SPIE, 49-55 (1972). [6] J. D. Nash, D. R. Caldwell, M

Spin glass in semiconducting KFe 1.05 Ag 0.88 Te 2 single crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, Hyejin; Lei, Hechang; Klobes, B.

2015-05-01

We report discovery of KFe 1.05 Ag 0.88 Te 2 single crystals with semiconducting spin glass ground state. Composition and structure analyses suggest nearly stoichiometric I 4 / mmm space group but allow for the existence of vacancies, absent in long-range semiconducting antiferromagnet KFe 0.85 Ag 1.15 Te 2 . The subtle change in stoichometry in Fe-Ag sublattice changes magnetic ground state but not conductivity, giving further insight into the semiconducting gap mechanism.

To list or not to list? The value and detriment of freelisting in ethnobotanical studies.

PubMed

Zambrana, Narel Y Paniagua; Bussmann, Rainer W; Hart, Robbie E; Huanca, Araceli L Moya; Soria, Gere Ortiz; Vaca, Milton Ortiz; Álvarez, David Ortiz; Morán, Jorge Soria; Morán, María Soria; Chávez, Saúl; Moreno, Bertha Chávez; Moreno, Gualberto Chávez; Roca, Oscar; Siripi, Erlin

2018-04-01

Although freelisting and semi-structured interviews are widespread methods in ethnobotany, few studies quantitatively examine how these methods may bias results. Using a comprehensive ethnobotanical inventory of palm species, uses and names in the Chácobo tribe of Bolivia, we show that interviews elicit more items than freelists, but the effect is sensitive to sample size, item type and data categorization. This implies that even subtle methodological choices may greatly affect reported results.

Assessment of Detection and Refinement Strategies for de novo Protein Structures using Force Field and Statistical Potentials

DTIC Science & Technology

2007-01-01

energy landscape of real proteins . As such, real proteins may have a subtle free energy gradient toward the native that requires long folding times...some leaning, however slight, toward the lowest free - energy basin .9 One caveat in the connection between the scoring funnel and the folding funnel is... protein sets. The average DFIRE-AA scores from each cluster were ranked, and the lowest- energy conformers from each of the top 16 clusters

Biogenesis: number mysticism in protein thinking.

PubMed

Klotz, I M

1993-10-01

Historically, great minds have been tantalized by the idea that integers contain hidden, subtle meanings that could give us deep insights into natural (and supernatural) phenomena. Numerological analysis has been used in religion, mythology, and the sciences. In the field of proteins, integers played a stimulating role during early struggles to unravel structure, but they ultimately proved constrictive and misleading. In contrast, the introduction of imaginary (or complex) numbers into the algebra and numerical analysis of ligand-protein affinities can open new perspectives into such interactions.

The Many Faces of Constructivist Discussion

ERIC Educational Resources Information Center

Golding, Clinton

2011-01-01

Although constructivist discussions in the classroom are often treated as if they were all of the same kind, in this paper I argue that there are subtle but important distinctions that need to be made. An analysis of these distinctions shows that there is a continuum of different constructivist discussions. At one extreme are teacher-directed…

"The Types of Kids We Get Are Different"--The Distinguishing Characteristics of School Choosers in Detroit, Michigan

ERIC Educational Resources Information Center

Hamlin, Daniel

2018-01-01

Providing improved educational options for low-income African American families has been one of the primary objectives of the charter school movement. However, among demographically similar families, school choosers may possess subtle advantages compared to nonchoosers, leading to biased estimates of charter school performance in nonexperimental…

Character Portrayals and Social Values in TV Commercials.

ERIC Educational Resources Information Center

Scheibe, Cynthia L.; Condry, John C.

In order to investigate the nature of character portrayals in U.S. television commercials, a content analysis was done on a random sample of 2,604 U.S. television commercials which were videotaped in March 1981. This analysis included both demographic characteristics and more subtle aspects of gender differences, such as concerns, relationships…

Subtle temperature differences may well determine who wins: a story of three submerged aquatic plant species

USDA-ARS?s Scientific Manuscript database

As temperatures increases globally, shifts in the distribution of plant species are expected, with unknown effects on invasive species abundance. It is then of value to understand the role increased temperature may have on invasive species. Although nonhomeothermic organisms are the mercy of environ...

Profiling of dehydropyrrolizidine alkaloids and their N-oxides in herbarium-preserved specimens of Amsinckia species using HPLC-esi(+)MS

USDA-ARS?s Scientific Manuscript database

Species of the Amsinckia genus (Boraginaceae) are known to produce potentially hepato-, pneumo-, and/or genotoxic dehydropyrrolizidine alkaloids. However, the taxonomic differentiation of Amsinckia species can be very subtle and there seems to be marked differences in toxicity toward grazing livesto...

A Value Analysis of the 1980 Presidential Debate.

ERIC Educational Resources Information Center

Hochel, Sandra

Although Democrat Jimmy Carter and Republican Ronald Reagan appealed to many of the same basic American values in the 1980 presidential campaign debate, there were some subtle but major differences in their value appeals. Other than attempting to convince his audience that his policies had been and would be successful and that Reagan's policies…

Words Matter: A Semantic Differential Study of Recreation, Leisure, Play, Activity, and Sport

ERIC Educational Resources Information Center

Schlag, Paul A.; Yoder, Daniel G.; Sheng, Zhaohui

2015-01-01

Beyond the standard definitions found in the dictionary, words commonly used in the recreation field have subtle, yet powerful connotations of which senders and receivers of information may not be consciously aware. These words elicit different conscious and subconscious reactions that likely bear significant consequences for recreation agencies…

Using Network Science Measures to Predict the Lexical Decision Performance of Adults Who Stutter

ERIC Educational Resources Information Center

Castro, Nichol; Pelczarski, Kristin M.; Vitevitch, Michael S.

2017-01-01

Purpose: Methods from network science have examined various aspects of language processing. Clinical populations may also benefit from these novel analyses. Phonological and lexical factors have been examined in adults who stutter (AWS) as potential contributing factors to stuttering, although differences reported are often subtle. We reexamined…

Formal Attributes of Television Commercials: Subtle Ways of Transmitting Sex Stereotypes.

ERIC Educational Resources Information Center

Welch, Renate L.; And Others

Differences in formal aspects of television commercials aimed at boys and those aimed at girls were investigated. Formal attributes were defined as production techniques such as action, pace, visual effects, dialogue and narration, background music and sound effects. Two aspects of content were also examined: aggressive behavior and the gender of…

The Campus Climate Revisited: Chilly for Women Faculty, Administrators, and Graduate Students.

ERIC Educational Resources Information Center

Sandler, Bernice R.; Hall, Roberta M.

The professional climate often experienced by women faculty and administrators is reported, along with some consideration to the experiences of graduate and professional students. Attention is focused on subtle ways in which women are treated differently and common behaviors that create a chilly professional climate. The information was obtained…

Using Radar Charts with Qualitative Evaluation: Techniques to Assess Change in Blended Learning

ERIC Educational Resources Information Center

Kaczynski, Dan; Wood, Leigh; Harding, Ansie

2008-01-01

When university academics implement changes in learning, such as introducing blended learning, it is conventional practice to examine and evaluate the impact of the resulting curriculum reform. Judging the worth and impact of an educational development is a complex task involving subtle differences in learning. Qualitative methods to explore these…

Menstrual cycle phase affects discrimination of infant cuteness.

PubMed

Lobmaier, Janek S; Probst, Fabian; Perrett, David I; Heinrichs, Markus

2015-04-01

Recent studies have shown that women are more sensitive than men to subtle cuteness differences in infant faces. It has been suggested that raised levels in estradiol and progesterone may be responsible for this advantage. We compared young women's sensitivity to computer-manipulated baby faces varying in cuteness. Thirty-six women were tested once during ovulation and once during the luteal phase of their menstrual cycle. In a two alternative forced-choice experiment, participants chose the baby which they thought was cuter (Task 1), younger (Task 2), or the baby that they would prefer to babysit (Task 3). Saliva samples to assess levels of estradiol, progesterone and testosterone were collected at each test session. During ovulation, women were more likely to choose the cuter baby than during the luteal phase, in all three tasks. These results suggest that cuteness discrimination may be driven by cyclic hormonal shifts. However none of the measured hormones were related to increased cuteness sensitivity. We speculate that other hormones than the ones measured here might be responsible for the increased sensitivity to subtle cuteness differences during ovulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Fractal Complexity-Based Feature Extraction Algorithm of Communication Signals

NASA Astrophysics Data System (ADS)

Wang, Hui; Li, Jingchao; Guo, Lili; Dou, Zheng; Lin, Yun; Zhou, Ruolin

How to analyze and identify the characteristics of radiation sources and estimate the threat level by means of detecting, intercepting and locating has been the central issue of electronic support in the electronic warfare, and communication signal recognition is one of the key points to solve this issue. Aiming at accurately extracting the individual characteristics of the radiation source for the increasingly complex communication electromagnetic environment, a novel feature extraction algorithm for individual characteristics of the communication radiation source based on the fractal complexity of the signal is proposed. According to the complexity of the received signal and the situation of environmental noise, use the fractal dimension characteristics of different complexity to depict the subtle characteristics of the signal to establish the characteristic database, and then identify different broadcasting station by gray relation theory system. The simulation results demonstrate that the algorithm can achieve recognition rate of 94% even in the environment with SNR of -10dB, and this provides an important theoretical basis for the accurate identification of the subtle features of the signal at low SNR in the field of information confrontation.

Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.

PubMed

Delaforge, Elise; Kragelj, Jaka; Tengo, Laura; Palencia, Andrés; Milles, Sigrid; Bouvignies, Guillaume; Salvi, Nicola; Blackledge, Martin; Jensen, Malene Ringkjøbing

2018-01-24

Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions, or binding through highly dynamic, so-called fuzzy, complexes. The vast majority of experimental information about IDP binding modes have been inferred from crystal structures of proteins in complex with short peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the conformational dynamics experienced by the IDP in the bound state. Knowledge of the dynamics of IDP complexes is of fundamental importance to understand how IDPs engage in highly specific interactions without concomitantly high binding affinity. Here, we combine rotating-frame R 1ρ , Carr-Purcell-Meiboom Gill relaxation dispersion as well as chemical exchange saturation transfer to decipher the dynamic interaction profile of an IDP in complex with its partner. We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38α and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38α, leading to a complex displaying significantly different dynamics across the bound regions.

Self-Assembly of Nanoparticles and Origin of Life

NASA Astrophysics Data System (ADS)

Kotov, Nicholas

Inorganic nanoparticles (NPs) have the ability to self-organize into variety of extended and terminal structures, as do many molecular and nanoscale compounds, given a sufficient number of translational and rotational degrees of freedom. Analysis of experimental data for all NPs (metal, semiconductor, ceramic ..) indicate a general trend of self-assembly under a much wider range of conditions and having much broader structural variability than building blocks from organic matter. Remarkably, the internal organization of self-assembled structures spontaneously produced by NPs rival in complexity and functional sophistication to those found in biology. Multiscale collective effects make NP-NP interactions no less fascinating than those of naturally occurring proteins. In this talk, I will address the following questions: 1. What are the differences and similarities of NP self-organization compared with similar phenomena involving organic and biological building blocks? 2. What are the forces and related theoretical assumptions essential for NP interactions? 3. What is the significance of NP self-assembly for understanding emergence of life? In this context, self-organization of chiral nanostructures will illustrate the importance of subtle anisotropic effects stemming from collective behavior of NPs and non-additivity of their interactions. Chirality transfer from circularly-polarized photons to NPs and its relationship to the origin of homochirality on Earth, spontaneous compartmentalization (protocells), and out-of-equilibrium chemical synthesis in nanoassemblies.

Changes in microbial communities along redox gradients in polygonized Arctic wet tundra soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipson, David A.; Raab, Theodore K.; Parker, Melanie

2015-07-21

This study investigated how microbial community structure and diversity varied with depth and topography in ice wedge polygons of wet tundra of the Arctic Coastal Plain in northern Alaska, and what soil variables explain these patterns. We observed strong changes in community structure and diversity with depth, and more subtle changes between areas of high and low topography, with the largest differences apparent near the soil surface. These patterns are most strongly correlated with redox gradients (measured using the ratio of reduced Fe to total Fe in acid extracts as a proxy): conditions grew more reducing with depth and weremore » most oxidized in shallow regions of polygon rims. Organic matter and pH also changed with depth and topography, but were less effective predictors of the microbial community structure and relative abundance of specific taxa. Of all other measured variables, lactic acid concentration was the best, in combination with redox, for describing the microbial community. We conclude that redox conditions are the dominant force in shaping microbial communities in this landscape. Oxygen and other electron acceptors allowed for the greatest diversity of microbes: at depth the community was reduced to a simpler core of anaerobes, dominated by fermenters ( Bacteroidetes and Firmicutes).« less

Changes in microbial communities along redox gradients in polygonized Arctic wet tundra soils.

PubMed

Lipson, David A; Raab, Theodore K; Parker, Melanie; Kelley, Scott T; Brislawn, Colin J; Jansson, Janet

2015-08-01

This study investigated how microbial community structure and diversity varied with depth and topography in ice wedge polygons of wet tundra of the Arctic Coastal Plain in northern Alaska and what soil variables explain these patterns. We observed strong changes in community structure and diversity with depth, and more subtle changes between areas of high and low topography, with the largest differences apparent near the soil surface. These patterns are most strongly correlated with redox gradients (measured using the ratio of reduced Fe to total Fe in acid extracts as a proxy): conditions grew more reducing with depth and were most oxidized in shallow regions of polygon rims. Organic matter and pH also changed with depth and topography but were less effective predictors of the microbial community structure and relative abundance of specific taxa. Of all other measured variables, lactic acid concentration was the best, in combination with redox, for describing the microbial community. We conclude that redox conditions are the dominant force in shaping microbial communities in this landscape. Oxygen and other electron acceptors allowed for the greatest diversity of microbes: at depth the community was reduced to a simpler core of anaerobes, dominated by fermenters (Bacteroidetes and Firmicutes). © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Spatial analysis of temperature (BHT/DST) data and consequences for heat-flow determination in sedimentary basins

USGS Publications Warehouse

Forster, A.; Merriam, D.F.; Davis, J.C.

1997-01-01

Large numbers of bottom-hole temperatures (BHTs) and temperatures measured during drill-stem tests (DSTs) are available in areas explored for hydrocarbons, but their usefulness for estimating geothermal gradients and heat-flow density is limited. We investigated a large data set of BHT and DST measurements taken in boreholes in the American Midcontinent, a geologically uniform stable cratonic area, and propose an empirical correction for BHTs based on relationships between BHTs, DSTs, and thermal logs. This empirical correction is compared with similar approaches determined for other areas. The data were analyzed by multivariate statistics prior to the BHT correction to identify anomalous measurements and quantify external influences. Spatial patterns in temperature measurements for major stratigraphic units outline relations to regional structure. Comparision of temperature and structure trend-surface residuals reveals a relationship between temperature highs and local structure highs. The anticlines, developed by continuous but intermittent movement of basement fault blocks in the Late Paleozoic, are subtle features having closures of 10-30 m and contain relatively small hydrocarbon reservoirs. The temperature anomalies of the order of 5-7 ??C may reflect fluids moving upward along fractures and faults, rather than changes in thermal conductivity resulting from different pore fluids. ?? Springer-Verlag 1997.

Spatial analysis of temperature (BHT/DST) data and consequences for heat-flow determination in sedimentary basins

USGS Publications Warehouse

Forster, A.; Merriam, D.F.; Davis, J.C.

1997-01-01

Large numbers of bottom-hole temperatures (BHTs) and temperatures measured during drill-stem tests (DSTs) are available in areas explored for hydrocarbons, but their usefulness for estimating geothermal gradients and heat-flow density is limited. We investigated a large data set of BHT and DST measurements taken in boreholes in the American Midcontinent, a geologically uniform stable cratonic area, and propose an empirical correction for BHTs based on relationships between BHTs, DSTs, and thermal logs. This empirical correction is compared with similar approaches determined for other areas. The data were analyzed by multivariate statistics prior to the BHT correction to identify anomalous measurements and quantify external influences. Spatial patterns in temperature measurements for major stratigraphic units outline relations to regional structure. Comparision of temperature and structure trend-surface residuals reveals a relationship between temperature highs and local structure highs. The anticlines, developed by continuous but intermittent movement of basement fault blocks in the Late Paleozoic, are subtle features having closures of 10-30 m and contain relatively small hydrocarbon reservoirs. The temperature anomalies of the order of 5-7??C may reflect fluids moving upward along fractures and faults, rather than changes in thermal conductivity resulting from different pore fluids.

Ab Initio Modeling of Structure and Properties of Single and Mixed Alkali Silicate Glasses.

PubMed

Baral, Khagendra; Li, Aize; Ching, Wai-Yim

2017-10-12

A density functional theory (DFT)-based ab initio molecular dynamics (AIMD) has been applied to simulate models of single and mixed alkali silicate glasses with two different molar concentrations of alkali oxides. The structural environments and spatial distributions of alkali ions in the 10 simulated models with 20% and 30% of Li, Na, K and equal proportions of Li-Na and Na-K are studied in detail for subtle variations among the models. Quantum mechanical calculations of electronic structures, interatomic bonding, and mechanical and optical properties are carried out for each of the models, and the results are compared with available experimental observation and other simulations. The calculated results are in good agreement with the experimental data. We have used the novel concept of using the total bond order density (TBOD), a quantum mechanical metric, to characterize internal cohesion in these glass models. The mixed alkali effect (MAE) is visible in the bulk mechanical properties but not obvious in other physical properties studied in this paper. We show that Li doping deviates from expected trend due to the much stronger Li-O bonding than those of Na and K doping. The approach used in this study is in contrast with current studies in alkali-doped silicate glasses based only on geometric characterizations.

Joint inversion of seismic and gravity data for imaging seismic velocity structure of the crust and upper mantle beneath Utah, United States

DOE PAGES

Syracuse, Ellen Marie; Zhang, Haijiang; Maceira, Monica

2017-07-11

Here, we present a method for using any combination of body wave arrival time measurements, surface wave dispersion observations, and gravity data to simultaneously invert for three-dimensional P- and S-wave velocity models. The simultaneous use of disparate data types takes advantage of the differing sensitivities of each data type, resulting in a comprehensive and higher resolution three-dimensional geophysical model. In a case study for Utah, we combine body waves first arrivals mainly from the USArray Transportable Array, Rayleigh wave group and phase velocity dispersion data, and Bouguer gravity anomalies to invert for crustal and upper mantle structure of the region.more » Results show clear delineations, visible in both P- and S-wave velocities, between the three main tectonic provinces in the region. In conclusion, without the inclusion of the surface wave and gravity constraints, these delineations are less clear, particularly for S-wave velocities. Indeed, checkerboard tests confirm that the inclusion of the additional datasets dramatically improves S-wave velocity recovery, with more subtle improvements to P-wave velocity recovery, demonstrating the strength of the method in successfully recovering seismic velocity structure from multiple types of constraints.« less

Comparing the conformational behavior of a series of diastereomeric cyclic urea HIV-1 inhibitors using the low mode:monte carlo conformational search method.

PubMed

Parish, Carol A; Yarger, Matthew; Sinclair, Kent; Dure, Myrianne; Goldberg, Alla

2004-09-23

The conformational flexibility of a series of diastereomeric cyclic urea HIV-1 protease inhibitors has been examined using the Low Mode:Monte Carlo conformational search method. Force fields were validated by a comparison of the energetic ordering of the minimum energy structures on the AMBER/GBSA(water), OPLSAA/GBSA(water) and HF/6-311G/SCRF(water) surfaces. The energetic ordering of the minima on the OPLSAA /GBSA(water) surface was in better agreement with the quantum calculations than the ordering on the AMBER/GBSA(water) surface. An ensemble of low energy structures was generated using OPLSAA/GBSA(water) and used to compare the molecular shape and flexibility of each diastereomer to the experimentally determined binding affinities and crystal structures of closely related systems. The results indicate that diastereomeric solution-phase energetic stability, conformational rigidity and ability to adopt a chair conformation correlate strongly with experimental binding affinities. Rigid body docking suggests that all of the diastereomers adopt solution-phase conformations suitable for alignment with the HIV-1 protease; however, these results indicate that the binding affinities are dependent upon subtle differences in the P1/P1' and P2/P2' substituent orientations.

Joint inversion of seismic and gravity data for imaging seismic velocity structure of the crust and upper mantle beneath Utah, United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syracuse, Ellen Marie; Zhang, Haijiang; Maceira, Monica

Here, we present a method for using any combination of body wave arrival time measurements, surface wave dispersion observations, and gravity data to simultaneously invert for three-dimensional P- and S-wave velocity models. The simultaneous use of disparate data types takes advantage of the differing sensitivities of each data type, resulting in a comprehensive and higher resolution three-dimensional geophysical model. In a case study for Utah, we combine body waves first arrivals mainly from the USArray Transportable Array, Rayleigh wave group and phase velocity dispersion data, and Bouguer gravity anomalies to invert for crustal and upper mantle structure of the region.more » Results show clear delineations, visible in both P- and S-wave velocities, between the three main tectonic provinces in the region. In conclusion, without the inclusion of the surface wave and gravity constraints, these delineations are less clear, particularly for S-wave velocities. Indeed, checkerboard tests confirm that the inclusion of the additional datasets dramatically improves S-wave velocity recovery, with more subtle improvements to P-wave velocity recovery, demonstrating the strength of the method in successfully recovering seismic velocity structure from multiple types of constraints.« less

Bootstrapping white matter segmentation, Eve++

NASA Astrophysics Data System (ADS)

Plassard, Andrew; Hinton, Kendra E.; Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M.; Landman, Bennett A.

2015-03-01

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

Evaluation of Atlas-Based White Matter Segmentation with Eve.

PubMed

Plassard, Andrew J; Hinton, Kendra E; Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M; Landman, Bennett A

2015-03-20

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

Cobalt(II) sheet-like systems based on diacetic ligands: from subtle structural variances to different magnetic behaviors.

PubMed

Fabelo, Oscar; Pasán, Jorge; Cañadillas-Delgado, Laura; Delgado, Fernando S; Lloret, Francesc; Julve, Miguel; Ruiz-Pérez, Catalina

2009-07-06

The preparation, X-ray crystallography, and magnetic investigation of the compounds [Co(H(2)O)(2)(phda)](n) (1), [Co(phda)](n) (2), and [Co(chda)](n) (3) [H(2)phda = 1,4-phenylenediacetic acid and H(2)chda = 1,1-cyclohexanediacetic acid] are described herein. The cobalt atoms in this series are six- (1) and four-coordinated (2 and 3) in distorted octahedral (CoO(6)) and tetrahedral (CoO(4)) environments. The structures of 1-3 consists of rectangular-grids which are built up by sheets of cobalt atoms linked through anti-syn carboxylate bridges, giving rise to either a three-dimensional structure across the phenyl ring (1 and 2) or to regularly stacked layers with the cyclohexyl groups acting as organic separators (3). The magnetic properties of 1-3 were investigated as a function of the temperature and the magnetic field. Ferromagnetic coupling between the six-coordinate cobalt(II) ions across the anti-syn carboxylate bridge occurs in 1 (J = +1.2 cm(-1)) whereas antiferromagnetic coupling among the tetrahedral cobalt(II) centers within the sheets is observed in 2 and 3 [J = -1.63 (2) and -1.70 cm(-1) (3)] together with a spin-canted structure in 3 giving rise a long-range magnetic ordering (T(c) = 7.5 K).

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohman, Jeremy; Ma, Ming; Osipiuk, Jerzy

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representationmore » of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.« less

Approach for discrimination and quantification of electroactive species: kinetics difference revealed by higher harmonics of Fourier transformed sinusoidal voltammetry.

PubMed

Fang, Yishan; Huang, Xinjian; Wang, Lishi

2015-01-06

Discrimination and quantification of electroactive species are traditionally realized by a potential difference which is mainly determined by thermodynamics. However, the resolution of this approach is limited to tens of millivolts. In this paper, we described an application of Fourier transformed sinusoidal voltammetry (FT-SV) that provides a new approach for discrimination and quantitative evaluation of electroactive species, especially thermodynamic similar ones. Numerical simulation indicates that electron transfer kinetics difference between electroactive species can be revealed by the phase angle of higher order harmonics of FT-SV, and the difference can be amplified order by order. Thus, even a very subtle kinetics difference can be amplified to be distinguishable at a certain order of harmonics. This method was verified with structurally similar ferrocene derivatives which were chosen as the model systems. Although these molecules have very close redox potential (<10 mV), discrimination and selective detection were achieved by as high as the thirteenth harmonics. The results demonstrated the feasibility and reliability of the method. It was also implied that the combination of the traditional thermodynamic method and this kinetics method can form a two-dimension resolved detection method, and it has the potential to extend the resolution of voltammetric techniques to a new level.

The Cultural Evolution of Structured Languages in an Open-Ended, Continuous World.

PubMed

Carr, Jon W; Smith, Kenny; Cornish, Hannah; Kirby, Simon

2017-05-01

Language maps signals onto meanings through the use of two distinct types of structure. First, the space of meanings is discretized into categories that are shared by all users of the language. Second, the signals employed by the language are compositional: The meaning of the whole is a function of its parts and the way in which those parts are combined. In three iterated learning experiments using a vast, continuous, open-ended meaning space, we explore the conditions under which both structured categories and structured signals emerge ex nihilo. While previous experiments have been limited to either categorical structure in meanings or compositional structure in signals, these experiments demonstrate that when the meaning space lacks clear preexisting boundaries, more subtle morphological structure that lacks straightforward compositionality-as found in natural languages-may evolve as a solution to joint pressures from learning and communication. Copyright © 2016 The Authors. Cognitive Science published by Wiley Periodicals, Inc. on behalf of Cognitive Science Society.