Use of Crystal Structure Informatics for Defining the Conformational Space Needed for Predicting Crystal Structures of Pharmaceutical Molecules.

PubMed

Iuzzolino, Luca; Reilly, Anthony M; McCabe, Patrick; Price, Sarah L

2017-10-10

Determining the range of conformations that a flexible pharmaceutical-like molecule could plausibly adopt in a crystal structure is a key to successful crystal structure prediction (CSP) studies. We aim to use conformational information from the crystal structures in the Cambridge Structural Database (CSD) to facilitate this task. The conformations produced by the CSD Conformer Generator are reduced in number by considering the underlying rotamer distributions, an analysis of changes in molecular shape, and a minimal number of molecular ab initio calculations. This method is tested for five pharmaceutical-like molecules where an extensive CSP study has already been performed. The CSD informatics-derived set of crystal structure searches generates almost all the low-energy crystal structures previously found, including all experimental structures. The workflow effectively combines information on individual torsion angles and then eliminates the combinations that are too high in energy to be found in the solid state, reducing the resources needed to cover the solid-state conformational space of a molecule. This provides insights into how the low-energy solid-state and isolated-molecule conformations are related to the properties of the individual flexible torsion angles.

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori.

PubMed

An, Doo Ri; Im, Ha Na; Jang, Jun Young; Kim, Hyoun Sook; Kim, Jieun; Yoon, Hye Jin; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar; Kim, Soon-Jong; Suh, Se Won

2016-01-01

Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3 peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d-carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To provide a basis for understanding molecular functions of Csd1 and Csd2, we have carried out their structural characterizations. We have discovered that (i) Csd2 exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We have determined crystal structures of the Csd2121-308 homodimer and the heterodimer between Csd1125-312 and Csd2121-308. Overall structures of Csd1125-312 and Csd2121-308 monomers are similar to each other, consisting of a helical domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key role in the formation of homodimers or heterodimers. The Csd1 LytM domain contains a catalytic site with a Zn2+ ion, which is coordinated by three conserved ligands and two water molecules, whereas the Csd2 LytM domain has incomplete metal ligands and no metal ion is bound. Structural knowledge of these proteins sheds light on the events that regulate the cell wall in H. pylori.

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori

PubMed Central

An, Doo Ri; Im, Ha Na; Jang, Jun Young; Kim, Hyoun Sook; Kim, Jieun; Yoon, Hye Jin; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar; Kim, Soon-Jong

2016-01-01

Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3 peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d-carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To provide a basis for understanding molecular functions of Csd1 and Csd2, we have carried out their structural characterizations. We have discovered that (i) Csd2 exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We have determined crystal structures of the Csd2121–308 homodimer and the heterodimer between Csd1125–312 and Csd2121–308. Overall structures of Csd1125–312 and Csd2121–308 monomers are similar to each other, consisting of a helical domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key role in the formation of homodimers or heterodimers. The Csd1 LytM domain contains a catalytic site with a Zn2+ ion, which is coordinated by three conserved ligands and two water molecules, whereas the Csd2 LytM domain has incomplete metal ligands and no metal ion is bound. Structural knowledge of these proteins sheds light on the events that regulate the cell wall in H. pylori. PMID:27711177

Characterising non-covalent interactions with the Cambridge Structural Database.

PubMed

Lommerse, J P; Taylor, R

1997-02-01

This review describes how the CSD can be used to study non-covalent interactions. Several different types of information may be obtained. First, the relative frequencies of various interactions can be studied; for example, we have shown that the terminal oxygen atoms of phosphate groups accept hydrogen bonds far more often than the linkage oxygens. Secondly, information can be obtained about the geometries of nonbonded contacts; for example, hydrogen bonds to P-O groups rarely form along the extension of the P-O bond, whereas short contacts between oxygen and carbon-bound iodine show a strong preference for linear C-I ... O angles. Thirdly, the CSD can be searched for novel interactions which may be exploited in inhibitor design; for example, the I ... O contacts just mentioned, and N-H ... pi hydrogen bonds. Finally, the CSD can suggest synthetic targets for medicinal chemistry; for example, molecules containing delocalised electron deficient groups such as trimethylammonium, pyridinium, thaizolium and dinitrophenyl have a good chance of binding to an active-site tryptophan. Although the CSD contains small-molecule crystal structures, not protein-ligand complexes, there is considerable evidence that the contacts seen in the two types of structures are similar. We have illustrated this a number of times in the present review and additional evidence has been given previously by Klebe. The major advantages of the CSD are its size, diversity and experimental accuracy. For these reasons, it is a useful tool for modellers engaged in rational inhibitor design.

Hydrogen-bond landscapes, geometry and energetics of squaric acid and its mono- and dianions: a Cambridge Structural Database, IsoStar and computational study.

PubMed

Allen, Frank H; Cruz-Cabeza, Aurora J; Wood, Peter A; Bardwell, David A

2013-10-01

As part of a programme of work to extend central-group coverage in the Cambridge Crystallographic Data Centre's (CCDC) IsoStar knowledge base of intermolecular interactions, we have studied the hydrogen-bonding abilities of squaric acid (H2SQ) and its mono- and dianions (HSQ(-) and SQ(2-)) using the Cambridge Structural Database (CSD) along with dispersion-corrected density functional theory (DFT-D) calculations for a range of hydrogen-bonded dimers. The -OH and -C=O groups of H2SQ, HSQ(-) and SQ(2-) are potent donors and acceptors, as indicated by their hydrogen-bond geometries in available crystal structures in the CSD, and by the attractive energies calculated for their dimers with acetone and methanol, which were used as model acceptors and donors. The two anions have sufficient examples in the CSD for their addition as new central groups in IsoStar. It is also shown that charge- and resonance-assisted hydrogen bonds involving H2SQ and HSQ(-) are similar in strength to those made by carboxylate COO(-) acceptors, while hydrogen bonds made by the dianion SQ(2-) are somewhat stronger. The study reinforces the value of squaric acid and its anions as cocrystal formers and their actual and potential importance as isosteric replacements for carboxylic acid and carboxylate functions.

Survey and analysis of crystal polymorphism in organic structures

PubMed Central

Kaur, Ramanpreet

2018-01-01

With the intention of producing the most comprehensive treatment of the prevalence of crystal polymorphism among structurally characterized materials, all polymorphic compounds flagged as such within the Cambridge Structural Database (CSD) are analysed and a list of crystallographically characterized organic polymorphic compounds is assembled. Classifying these structures into subclasses of anhydrates, salts, hydrates, non-hydrated solvates and cocrystals reveals that there are significant variations in polymorphism prevalence as a function of crystal type, a fact which has not previously been recognized in the literature. It is also shown that, as a percentage, polymorphic entries are decreasing temporally within the CSD, with the notable exception of cocrystals, which continue to rise at a rate that is a constant fraction of the overall entries. Some phenomena identified that require additional scrutiny include the relative prevalence of temperature-induced phase transitions among organic salts and the paucity of polymorphism in crystals with three or more chemical components. PMID:29765601

The impact of counselor self-disclosure on clients: a meta-analytic review of experimental and quasi-experimental research.

PubMed

Henretty, Jennifer R; Currier, Joseph M; Berman, Jeffrey S; Levitt, Heidi M

2014-04-01

In an attempt to make sense of contradictory findings, meta-analysis was used to review 53 studies that examined counselor self-disclosure (CSD) vs. nondisclosure. CSD, overall, was found to have a favorable impact on clients/participants, with clients/participants having favorable perceptions of disclosing counselors and rating themselves more likely to disclose to counselors who had self-disclosed. Specifically, CSD that (a) revealed similarity between client and counselor; (b) was of negative content valence; or (c) was related to intra- or, especially, extratherapy experiences, had favorable impacts on clients/participants compared with nondisclosure. These types of disclosure resulted in more favorable perceptions of the counselor, especially in the area of professional attractiveness. CSD that revealed similarity between client and counselor also had a favorable impact on clients'/participants' allegiance-specifically, on their willingness to return-to disclosing counselors. Significant moderators of the impact of CSD on clients included researcher bias for or against CSD, type of "session" (e.g., written transcript, interview, real session), timing of CSD (whether before or after client self-disclosure), verb tense of extratherapy CSD, experimental setting, type of control group, and the number of CSDs in the experiment. Clinical implications include that CSD may be beneficial for building rapport, strengthening alliance, and eliciting client disclosure, with similar CSD being especially beneficial. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The Crystal Structure and Small-Angle X-Ray Analysis of CsdL/TcdA Reveal a New tRNA Binding Motif in the MoeB/E1 Superfamily

PubMed Central

López-Estepa, Miguel; Ardá, Ana; Savko, Martin; Round, Adam; Shepard, William E.; Bruix, Marta; Coll, Miquel; Fernández, Francisco J.; Jiménez-Barbero, Jesús; Vega, M. Cristina

2015-01-01

Cyclic N 6-threonylcarbamoyladenosine (‘cyclic t6A’, ct6A) is a non-thiolated hypermodification found in transfer RNAs (tRNAs) in bacteria, protists, fungi and plants. In bacteria and yeast cells ct6A has been shown to enhance translation fidelity and efficiency of ANN codons by improving the faithful discrimination of aminoacylated tRNAs by the ribosome. To further the understanding of ct6A biology we have determined the high-resolution crystal structures of CsdL/TcdA in complex with AMP and ATP, an E1-like activating enzyme from Escherichia coli, which catalyzes the ATP-dependent dehydration of t6A to form ct6A. CsdL/TcdA is a dimer whose structural integrity and dimer interface depend critically on strongly bound K+ and Na+ cations. By using biochemical assays and small-angle X-ray scattering we show that CsdL/TcdA can associate with tRNA with a 1:1 stoichiometry and with the proper position and orientation for the cyclization of t6A. Furthermore, we show by nuclear magnetic resonance that CsdL/TcdA engages in transient interactions with CsdA and CsdE, which, in the latter case, involve catalytically important residues. These short-lived interactions may underpin the precise channeling of sulfur atoms from cysteine to CsdL/TcdA as previously characterized. In summary, the combination of structural, biophysical and biochemical methods applied to CsdL/TcdA has afforded a more thorough understanding of how the structure of this E1-like enzyme has been fine tuned to accomplish ct6A synthesis on tRNAs while providing support for the notion that CsdA and CsdE are able to functionally interact with CsdL/TcdA. PMID:25897750

Structural investigation of the β-cyclodextrin complexes with chiral bicyclic monoterpenes - Influence of the functionality group on the host-guest stoichiometry

NASA Astrophysics Data System (ADS)

Ceborska, Magdalena

2017-10-01

The crystal structures of the complexes of β-cyclodextrin with (+)- and (-)-camphors are presented. The comparison of the obtained crystal structures with available data for other complexes of β-cyclodextrin with chiral bicyclic monoterpenes (hydrocarbon (+)-fenchene and alcohols: (-)-isopinocampheol, and (+)-, and (-)-borneols) obtained from Cambridge Structural Database (CSD) shows the trend of alcohols to form dimeric complexes of 2:3 stoichiometry, while hydrocarbons and ketones prefer to form 2:2 host-guest inclusion complexes.

Insights into the Structure of Dimeric RNA Helicase CsdA and Indispensable Role of Its C-Terminal Regions

DOE PAGES

Xu, Ling; Wang, Lijun; Peng, Junhui; ...

2017-12-05

CsdA has been proposed to be essential for the biogenesis of ribosome and gene regulation after cold shock. However, the structure of CsdA and the function of its long C-terminal regions are still unclear. For this study, we solved all of the domain structures of CsdA and found two previously uncharacterized auxiliary domains: a dimerization domain (DD) and an RNA-binding domain (RBD). Small-angle X-ray scattering experiments helped to track the conformational flexibilities of the helicase core domains and C-terminal regions. Biochemical assays revealed that DD is indispensable for stabilizing the CsdA dimeric structure. We also demonstrate for the first timemore » that CsdA functions as a stable dimer at low temperature. The C-terminal regions are critical for RNA binding and efficient enzymatic activities. CsdA_RBD could specifically bind to the regions with a preference for single-stranded G-rich RNA, which may help to bring the helicase core to unwind the adjacent duplex.« less

Insights into the Structure of Dimeric RNA Helicase CsdA and Indispensable Role of Its C-Terminal Regions

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

Xu, Ling; Wang, Lijun; Peng, Junhui

CsdA has been proposed to be essential for the biogenesis of ribosome and gene regulation after cold shock. However, the structure of CsdA and the function of its long C-terminal regions are still unclear. For this study, we solved all of the domain structures of CsdA and found two previously uncharacterized auxiliary domains: a dimerization domain (DD) and an RNA-binding domain (RBD). Small-angle X-ray scattering experiments helped to track the conformational flexibilities of the helicase core domains and C-terminal regions. Biochemical assays revealed that DD is indispensable for stabilizing the CsdA dimeric structure. We also demonstrate for the first timemore » that CsdA functions as a stable dimer at low temperature. The C-terminal regions are critical for RNA binding and efficient enzymatic activities. CsdA_RBD could specifically bind to the regions with a preference for single-stranded G-rich RNA, which may help to bring the helicase core to unwind the adjacent duplex.« less

Insights into the Structure of Dimeric RNA Helicase CsdA and Indispensable Role of Its C-Terminal Regions.

PubMed

Xu, Ling; Wang, Lijun; Peng, Junhui; Li, Fudong; Wu, Lijie; Zhang, Beibei; Lv, Mengqi; Zhang, Jiahai; Gong, Qingguo; Zhang, Rongguang; Zuo, Xiaobing; Zhang, Zhiyong; Wu, Jihui; Tang, Yajun; Shi, Yunyu

2017-12-05

CsdA has been proposed to be essential for the biogenesis of ribosome and gene regulation after cold shock. However, the structure of CsdA and the function of its long C-terminal regions are still unclear. Here, we solved all of the domain structures of CsdA and found two previously uncharacterized auxiliary domains: a dimerization domain (DD) and an RNA-binding domain (RBD). Small-angle X-ray scattering experiments helped to track the conformational flexibilities of the helicase core domains and C-terminal regions. Biochemical assays revealed that DD is indispensable for stabilizing the CsdA dimeric structure. We also demonstrate for the first time that CsdA functions as a stable dimer at low temperature. The C-terminal regions are critical for RNA binding and efficient enzymatic activities. CsdA_RBD could specifically bind to the regions with a preference for single-stranded G-rich RNA, which may help to bring the helicase core to unwind the adjacent duplex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

PubMed

Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

2014-07-22

Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

The HART II International Workshop: An Assessment of the State-of-the-Art in Comprehensive Code Prediction

NASA Technical Reports Server (NTRS)

vanderWall, Berend G.; Lim, Joon W.; Smith, Marilyn J.; Jung, Sung N.; Bailly, Joelle; Baeder, James D.; Boyd, D. Douglas, Jr.

2013-01-01

Significant advancements in computational fluid dynamics (CFD) and their coupling with computational structural dynamics (CSD, or comprehensive codes) for rotorcraft applications have been achieved recently. Despite this, CSD codes with their engineering level of modeling the rotor blade dynamics, the unsteady sectional aerodynamics and the vortical wake are still the workhorse for the majority of applications. This is especially true when a large number of parameter variations is to be performed and their impact on performance, structural loads, vibration and noise is to be judged in an approximate yet reliable and as accurate as possible manner. In this article, the capabilities of such codes are evaluated using the HART II International Workshop database, focusing on a typical descent operating condition which includes strong blade-vortex interactions. A companion article addresses the CFD/CSD coupled approach. Three cases are of interest: the baseline case and two cases with 3/rev higher harmonic blade root pitch control (HHC) with different control phases employed. One setting is for minimum blade-vortex interaction noise radiation and the other one for minimum vibration generation. The challenge is to correctly predict the wake physics-especially for the cases with HHC-and all the dynamics, aerodynamics, modifications of the wake structure and the aero-acoustics coming with it. It is observed that the comprehensive codes used today have a surprisingly good predictive capability when they appropriately account for all of the physics involved. The minimum requirements to obtain these results are outlined.

Comment on "Can assimilation of crowdsourced data in hydrological modelling improve flood prediction?" by Mazzoleni et al. (2017)

NASA Astrophysics Data System (ADS)

Viero, Daniele P.

2018-01-01

Citizen science and crowdsourcing are gaining increasing attention among hydrologists. In a recent contribution, Mazzoleni et al. (2017) investigated the integration of crowdsourced data (CSD) into hydrological models to improve the accuracy of real-time flood forecasts. The authors used synthetic CSD (i.e. not actually measured), because real CSD were not available at the time of the study. In their work, which is a proof-of-concept study, Mazzoleni et al. (2017) showed that assimilation of CSD improves the overall model performance; the impact of irregular frequency of available CSD, and that of data uncertainty, were also deeply assessed. However, the use of synthetic CSD in conjunction with (semi-)distributed hydrological models deserves further discussion. As a result of equifinality, poor model identifiability, and deficiencies in model structure, internal states of (semi-)distributed models can hardly mimic the actual states of complex systems away from calibration points. Accordingly, the use of synthetic CSD that are drawn from model internal states under best-fit conditions can lead to overestimation of the effectiveness of CSD assimilation in improving flood prediction. Operational flood forecasting, which results in decisions of high societal value, requires robust knowledge of the model behaviour and an in-depth assessment of both model structure and forcing data. Additional guidelines are given that are useful for the a priori evaluation of CSD for real-time flood forecasting and, hopefully, for planning apt design strategies for both model calibration and collection of CSD.

Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase

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

An, Doo Ri; Kim, Hyoun Sook; Seoul National University, Seoul 151 742

2015-03-01

H. pylori Csd3 (HP0506), together with other peptidoglycan hydrolases, plays an important role in determining cell shape. Its crystal structure in the latent state is reported. Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by themore » trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its d, d-endopeptidase activity cleaves the d-Ala{sup 4}-mDAP{sup 3} peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a d, d-carboxypeptidase that cleaves off the terminal d-Ala{sup 5} from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn{sup 2+} ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.« less

Software engineering capability for Ada (GRASP/Ada Tool)

NASA Technical Reports Server (NTRS)

Cross, James H., II

1995-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada Source code. A new Motif compliant graphical user interface has been developed for the GRASP/Ada prototype.

A chiral diamine: practical implications of a three-stereoisomer cocrystallization.

PubMed

Dolinar, Brian S; Samedov, Kerim; Maloney, Andrew G P; West, Robert; Khrustalev, Victor N; Guzei, Ilia A

2018-01-01

A brief comparison of seven straightforward methods for molecular crystal-volume estimation revealed that their precisions are comparable. A chiral diamine, N 2 ,N 3 -bis[2,6-bis(propan-2-yl)phenyl]butane-2,3-diamine, C 28 H 44 N 2 , has been used to illustrate the application of the methods. Three stereoisomers of the diamine cocrystallize in the centrosymmetric space group P2 1 /c with Z' = 1.5. The molecules occupying general positions are RR and SS, whereas that residing on an inversion center is meso. This is one of only ten examples of three stereoisomers with two asymmetric atoms cocrystallizing together reported to the Cambridge Structural Database (CSD). The conformations of the SS/RR and meso molecules differ considerably and lead to statistically significantly different C(asymmetric)-C(asymmetric) bond lengths in the diastereomers. An advanced Python script-based CSD searching technique for chiral compounds is presented.

The use of small-molecule structures to complement protein–ligand crystal structures in drug discovery

PubMed Central

Cole, Jason C.

2017-01-01

Many ligand-discovery stories tell of the use of structures of protein–ligand complexes, but the contribution of structural chemistry is such a core part of finding and improving ligands that it is often overlooked. More than 800 000 crystal structures are available to the community through the Cambridge Structural Database (CSD). Individually, these structures can be of tremendous value and the collection of crystal structures is even more helpful. This article provides examples of how small-molecule crystal structures have been used to complement those of protein–ligand complexes to address challenges ranging from affinity, selectivity and bioavailability though to solubility. PMID:28291759

[Barriers and facilitators to health care coordination in two integrated health care organizations in Catalonia (Spain)].

PubMed

Vargas Lorenzo, Ingrid; Vázquez Navarrete, M Luisa

2007-01-01

To analyze 2 integrated delivery systems (IDS) in Catalonia and identify areas for future development to improve their effectiveness. An exploratory, descriptive, qualitative study was carried out based on case studies by means of document analysis and semi-structured individual interviews. A criterion sample of cases and, for each case, of documents and informants was selected. Study cases consisted of the Consorci Sanitari del Maresme (CSdM) and the Consorci Sanitari de Terrassa/Fundació Hospital Sant Llàtzer (FHSLL). A total of 127 documents were analyzed and 29 informants were interviewed: IDS managers (n = 10), technical staff (n = 5), operational unit managers (n = 5) and health professionals (n = 9). Content analysis was conducted, with mixed generation of categories and segmentation by cases and subjects. CSdM and CSdT/FHSLL are health care organizations with backward vertical integration, total services production, and real (CSdM) and virtual (CSdT/FHSLL) ownership. Funds are allocated by care level. The governing body is centralized in CSdM and decentralized in CSdT/FHSLL. In both organizations, the global objectives are oriented toward improving coordination and efficiency but are not in line with those of the operational units. Both organizations present a functional structure with integration of support functions and utilize mechanisms for collaboration between care levels based on work processes standardization. Both IDS present facilitators and barriers to health care coordination. To improve coordination, changes in external elements (payment mechanism) and in internal elements (governing body role, organizational structure and coordination mechanisms) are required.

Comparison of structure, function and regulation of plant cold shock domain proteins to bacterial and animal cold shock domain proteins.

PubMed

Chaikam, Vijay; Karlson, Dale T

2010-01-01

The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs. [BMB reports 2010; 43(1): 1-8].

Sparkle/AM1 Parameters for the Modeling of Samarium(III) and Promethium(III) Complexes.

PubMed

Freire, Ricardo O; da Costa, Nivan B; Rocha, Gerd B; Simas, Alfredo M

2006-01-01

The Sparkle/AM1 model is extended to samarium(III) and promethium(III) complexes. A set of 15 structures of high crystallographic quality (R factor < 0.05 Å), with ligands chosen to be representative of all samarium complexes in the Cambridge Crystallographic Database 2004, CSD, with nitrogen or oxygen directly bonded to the samarium ion, was used as a training set. In the validation procedure, we used a set of 42 other complexes, also of high crystallographic quality. The results show that this parametrization for the Sm(III) ion is similar in accuracy to the previous parametrizations for Eu(III), Gd(III), and Tb(III). On the other hand, promethium is an artificial radioactive element with no stable isotope. So far, there are no promethium complex crystallographic structures in CSD. To circumvent this, we confirmed our previous result that RHF/STO-3G/ECP, with the MWB effective core potential (ECP), appears to be the most efficient ab initio model chemistry in terms of coordination polyhedron crystallographic geometry predictions from isolated lanthanide complex ion calculations. We thus generated a set of 15 RHF/STO-3G/ECP promethium complex structures with ligands chosen to be representative of complexes available in the CSD for all other trivalent lanthanide cations, with nitrogen or oxygen directly bonded to the lanthanide ion. For the 42 samarium(III) complexes and 15 promethium(III) complexes considered, the Sparkle/AM1 unsigned mean error, for all interatomic distances between the Ln(III) ion and the ligand atoms of the first sphere of coordination, is 0.07 and 0.06 Å, respectively, a level of accuracy comparable to present day ab initio/ECP geometries, while being hundreds of times faster.

GRASP/Ada 95: Reverse Engineering Tools for Ada

NASA Technical Reports Server (NTRS)

Cross, James H., II

1996-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical application. This report provides an overview of the GRASP/Ada project with an emphasis on the current update.

Determinants and materno-fetal outcomes related to cesarean section delivery in private and public hospitals in low- and middle-income countries: a systematic review and meta-analysis protocol.

PubMed

Beogo, Idrissa; Mendez Rojas, Bomar; Gagnon, Marie-Pierre

2017-01-14

Despite the well-established morbidity, mortality, long-term effects, and unnecessary extra-cost burden associated with cesarean section delivery (CSD) worldwide, its rate has grown exponentially. This has become a great topical challenge for the international healthcare community and individual countries. Estimated at three times the acceptable rate as defined by the World Health Organization in 1985, the continued upward trend has been fuelled by higher income countries. Some low- and middle-income countries (LMICs) have now taken the lead, and the factors contributing to this situation are poorly understood. The expansion of the private healthcare sector may be playing a significant role. Distinguishing between the public and private hospitals' role is critical in this investigation as it has not yet been approached. This review aims to systematically synthesize knowledge on the determinants of the CSD rate rise in private and public hospitals in LMICs and to investigate materno-fetal and materno-infant outcomes of CSD in perinatal period, between private and public hospitals. We will include studies published in English, French, Spanish, and Portuguese since 2000, using any experimental design, including randomized controlled trials (RCTs), non-RCTs, quasi-experimental, before and after studies, and interrupted time series. Outcomes of interest are the determinants of CSD and materno-fetal and materno-infant outcomes. We will only include studies carried out in private and public hospitals in LMICs. The literature searches will be conducted in the following databases: MEDLINE, Embase, CINAHL, Cochrane database, LILACS, and HINARI. We will also include unpublished studies in the gray literature (theses and technical reports). Using the two-person approach, two independent review authors will screen eligible articles, extract data, and assess risk of bias. Disagreements will be resolved through discussion with a third author. Results will be presented as structured summaries of the included studies. If possible, a meta-analysis will be conducted and, subsequently, an analysis for heterogeneity will be implemented. The proposed systematic review of the CSD rate rise will provide up-to-date evidence in regard to differences in proportions, determinants, and materno-fetal and materno-infant outcomes in perinatal period, between private and public hospitals in LMICs. We believe that this knowledge synthesis will help to shed light on the evidence and support evidence-informed decision-making with a view to addressing the issue in LMICs. PROSPERO CRD42016036871.

Three-dimensional analysis by electron diffraction methods of nanocrystalline materials.

PubMed

Gammer, Christoph; Mangler, Clemens; Karnthaler, Hans-Peter; Rentenberger, Christian

2011-12-01

To analyze nanocrystalline structures quantitatively in 3D, a novel method is presented based on electron diffraction. It allows determination of the average size and morphology of the coherently scattering domains (CSD) in a straightforward way without the need to prepare multiple sections. The method is applicable to all kinds of bulk nanocrystalline materials. As an example, the average size of the CSD in nanocrystalline FeAl made by severe plastic deformation is determined in 3D. Assuming ellipsoidal CSD, it is deduced that the CSD have a width of 19 ± 2 nm, a length of 18 ± 1 nm, and a height of 10 ± 1 nm.

Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles

NASA Astrophysics Data System (ADS)

Czylkowski, R.; Karolak-Wojciechowska, J.; Mrozek, A.; Yalçin, I.; Aki-Şener, E.

2001-12-01

The mutual position of two pharmacophoric elements in flexible biologically active molecules depends on the spacer conformation. This is true even for a two-atomic chain put to use as a spacer. It was established for 2-substituted-benzoxazoles containing two aromatic centres joined by -CH2-X- (X=S or O). From crystallographic studies of four molecules it was found that the role of heteroatom is essential for the whole molecule conformation. The spacer with X=S adopts the (-)synclinal conformation while for X=O the (+)antiperiplanar one. Such preferences were also found in the statistical data from Cambridge Structural Database (CSD).

Two rhodamine 6G derivative compounds: a structural and fluorescence single-crystal study.

PubMed

Di Paolo, Matias; Bossi, Mariano L; Baggio, Ricardo; Suarez, Sebastián A

2016-10-01

The synthesis, characterization, structural analysis and fluorescence properties of two rhodamine 6G derivatives are described, namely a propargylamine derivative, 3',6'-bis(ethylamino)-2',7'-dimethyl-2-(methylcyanide)spiro[isoindole-1,9'-xanthen]-3(2H)-one (I), and a γ-aminobutyric acid (GABA) derivative, 3',6'-bis(ethylamino)-2',7'-dimethyl-3-oxospiro[isoindole-1,9'-xanthen]-2(3H)-yl)butyricacid (II). Both structures are compared with four similar ones from the Cambridge Structural Database (CSD), and the interactions involved in the stabilization are analyzed using the atoms in molecules (AIM) theory. Finally, a single-crystal in-situ reaction study is presented, carried out by fluorescence methods, which enabled the `opening' of the spirolactam ring in the solid phase.

Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe.

PubMed

Cainzos-Achirica, Miguel; Varas-Lorenzo, Cristina; Pottegård, Anton; Asmar, Joelle; Plana, Estel; Rasmussen, Lotte; Bizouard, Geoffray; Forns, Joan; Hellfritzsch, Maja; Zint, Kristina; Perez-Gutthann, Susana; Pladevall-Vila, Manel

2018-03-23

To report and discuss estimated prevalence of potential off-label use and associated methodological challenges using a case study of dabigatran. Observational, cross-sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients). August 2011 to August 2015. Two definitions were used to estimate potential off-label use: a broad definition of on-label prescribing using codes for disease indication (eg, atrial fibrillation [AF]), and a restrictive definition excluding patients with conditions for which dabigatran is not indicated (eg, valvular AF). Prevalence estimates under the broad definition ranged from 5.7% (CPRD-HES) to 34.0% (CSD-LPD) and, under the restrictive definition, from 17.4% (CPRD-HES) to 44.1% (CSD-LPD). For the majority of potential off-label users, no diagnosis potentially related to anticoagulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off-label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources. Estimates of potential off-label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES-linkable estimates are likely to be the most accurate. Copyright © 2018 John Wiley & Sons, Ltd.

Distinct impacts of reductive soil disinfestation and chemical soil disinfestation on soil fungal communities and memberships.

PubMed

Zhao, Jun; Zhou, Xing; Jiang, Anqi; Fan, Juanzi; Lan, Tao; Zhang, Jinbo; Cai, Zucong

2018-06-21

Soil disinfestation is an important agricultural practice to conquer soil-borne diseases and thereby ensure crop productivity. Reductive soil disinfestation (RSD) had been developed as an environmentally friendly alternative to chemical soil disinfestation (CSD). However, the differences between CSD and RSD on soil-borne pathogen suppression and fungal community structure remain poorly understood. In this work, five treatments, i.e., untreated soil (CK), CSD with 0.5 t ha -1 dazomet (DZ), RSD with 10 t ha -1 ethanol (ET), 15 t ha -1 sugarcane bagasse (SB), and 15 t ha -1 bean dregs (BD), were performed to investigate their influences on disinfestation efficiency, fungal abundance, diversity, and community structure via quantitative PCR and high-throughput sequencing. RSD-related treatments, especially the BD treatment, effectively alleviated soil acidification and salinization. The fungal abundance and microbial activity considerably increased in the BD treatment and significantly declined in the DZ treatment as compared to the CK treatment. Moreover, both CSD and RSD-related treatments significantly inhibited the population of Fusarium oxysporum and the relative abundance of genus Fusarium. Fungal community structure was notably altered by CSD and RSD practices. Furthermore, both CSD and RSD harbored a distinct unique microbiome, with the DZ treatment dominated by the genus Mortierella and BD treatment predominated by the genera Zopfiella, Chaetomium, and Penicillium. Taken together, these results indicate that the BD treatment could considerably alleviate the soil deterioration, improve soil microbial activity, and reassemble a non-pathogen unique microbiome that have more disease-suppressive agents and thus might be a promising disinfestation practice to control soil-borne disease in monoculture system.

The development of a program analysis environment for Ada: Reverse engineering tools for Ada

NASA Technical Reports Server (NTRS)

Cross, James H., II

1991-01-01

The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

CH/π interactions in metal-porphyrin complexes with pyrrole and chelate rings as hydrogen acceptors.

PubMed

Medaković, Vesna B; Bogdanović, Goran A; Milčić, Miloš K; Janjić, Goran V; Zarić, Snežana D

2012-12-01

CH/π interactions in metal porphyrinato complexes were studied by analyzing data in crystal structures from the Cambridge Structural Database (CSD) and by quantum chemical calculations. The analysis of the data in the CSD shows that both five-membered pyrrole and six-membered chelate rings form CH/π interactions. The interactions occur more frequently with five-membered rings. The analysis of distances in crystal structures and calculated energies show stronger interactions with six-membered chelate rings, indicating that a larger number of interactions with five-membered rings are not the consequence of stronger interactions, but better accessibility of five-membered pyrrole rings. The calculated energies of the interactions with positions in six-membered rings are -2.09 to -2.83 kcal/mol, while the energies with five-membered rings are -2.05 to -2.26 kcal/mol. The results reveal that stronger interactions of six-membered rings are the consequence of stronger electrostatic interactions. Substituents on the porphyrin ring significantly strengthen the interactions. Substituents on the six-membered ring strengthen the interaction energy by about 20%. The results show that CH/π interactions play an important role in molecular recognition of metalloporphyrins. The significant influence of the substituents on interaction energies can be very important for the design of model systems in bioinorganic chemistry. Copyright © 2012 Elsevier Inc. All rights reserved.

Validations of Coupled CSD/CFD and Particle Vortex Transport Method for Rotorcraft Applications: Hover, Transition, and High Speed Flights

NASA Technical Reports Server (NTRS)

Anusonti-Inthra, Phuriwat

2010-01-01

This paper presents validations of a novel rotorcraft analysis that coupled Computational Fluid Dynamics (CFD), Computational Structural Dynamics (CSD), and Particle Vortex Transport Method (PVTM) methodologies. The CSD with associated vehicle trim analysis is used to calculate blade deformations and trim parameters. The near body CFD analysis is employed to provide detailed near body flow field information which is used to obtain high-fidelity blade aerodynamic loadings. The far field wake dominated region is simulated using the PVTM analysis which provides accurate prediction of the evolution of the rotor wake released from the near body CFD domains. A loose coupling methodology between the CSD and CFD/PVTM modules are used with appropriate information exchange amongst the CSD/CFD/PVTM modules. The coupled CSD/CFD/PVTM methodology is used to simulate various rotorcraft flight conditions (i.e. hover, transition, and high speed flights), and the results are compared with several sets of experimental data. For the hover condition, the results are compared with hover data for the HART II rotor tested at DLR Institute of Flight Systems, Germany. For the forward flight conditions, the results are validated with the UH-60A flight test data.

Bent CNN bond of diazo compounds, RR'(Cdbnd N+dbnd N-)

NASA Astrophysics Data System (ADS)

Akita, Motoko; Takahashi, Mai; Kobayashi, Keiji; Hayashi, Naoto; Tukada, Hideyuki

2013-02-01

The reaction of ninhydrin with benzophenone hydrazone afforded 2-diazo-3-diphenylmethylenehydrazono-1-indanone 1 and 2-diazo-1,3-bis(diphenylmethylenehydrazono)indan 2. X-ray crystal structure analyses of these products showed that the diazo functional group Cdbnd N+dbnd N- of 1 is bent by 172.9°, while that of 2 has a linear geometry. The crystal structure data of diazo compounds have been retrieved from the Cambridge Structural Database (CSD), which hit 177 entries to indicate that the angle of 172.9° in 1 lies in one of the most bent structures. The CSD search also indicated that diazo compounds consisting of a distorted diazo carbon tend to bend the Cdbnd N+dbnd N- bond. On the basis of DFT calculations (B3LYP/6-311++G(d,p)) of model compounds, it was revealed that the bending of the CNN bond is principally induced by steric factors and that the neighboring carbonyl group also plays a role in bending toward the carbonyl side owing to an electrostatic attractive interaction. The potential surface along the path of Cdbnd N+dbnd N- bending in 2-diazopropane shows a significantly shallow profile with only 4 kcal/mol needed to bend the Cdbnd N+dbnd N- bond from 180° to 160°. Thus, the bending of the diazo group in 1 is reasonable as it is provided with all of the factors for facile bending disclosed in this investigation.

Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review

PubMed Central

Ciofi-Silva, Caroline Lopes; Hansen, Lisbeth Lima; Almeida, Alda Graciele Claudio dos Santos; Kawagoe, Julia Yaeko; Padoveze, Maria Clara; Graziano, Kazuko Uchikawa

2016-01-01

ABSTRACT Objective: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. Method: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. Results: the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. Conclusions: there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed. PMID:27598374

Genetic variation and recombination of RdRp and HSP 70h genes of Citrus tristeza virus isolates from orange trees showing symptoms of citrus sudden death disease.

PubMed

Gomes, Clarissa P C; Nagata, Tatsuya; de Jesus, Waldir C; Neto, Carlos R Borges; Pappas, Georgios J; Martin, Darren P

2008-01-16

Citrus sudden death (CSD), a disease that rapidly kills orange trees, is an emerging threat to the Brazilian citrus industry. Although the causal agent of CSD has not been definitively determined, based on the disease's distribution and symptomatology it is suspected that the agent may be a new strain of Citrus tristeza virus (CTV). CTV genetic variation was therefore assessed in two Brazilian orange trees displaying CSD symptoms and a third with more conventional CTV symptoms. A total of 286 RNA-dependent-RNA polymerase (RdRp) and 284 heat shock protein 70 homolog (HSP70h) gene fragments were determined for CTV variants infecting the three trees. It was discovered that, despite differences in symptomatology, the trees were all apparently coinfected with similar populations of divergent CTV variants. While mixed CTV infections are common, the genetic distance between the most divergent population members observed (24.1% for RdRp and 11.0% for HSP70h) was far greater than that in previously described mixed infections. Recombinants of five distinct RdRp lineages and three distinct HSP70h lineages were easily detectable but respectively accounted for only 5.9 and 11.9% of the RdRp and HSP70h gene fragments analysed and there was no evidence of an association between particular recombinant mosaics and CSD. Also, comparisons of CTV population structures indicated that the two most similar CTV populations were those of one of the trees with CSD and the tree without CSD. We suggest that if CTV is the causal agent of CSD, it is most likely a subtle feature of population structures within mixed infections and not merely the presence (or absence) of a single CTV variant within these populations that triggers the disease.

Update of GRASP/Ada reverse engineering tools for Ada

NASA Technical Reports Server (NTRS)

Cross, James H., II

1993-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical application. An overview of the GRASP/Ada project with an emphasis on the current update is provided.

A CFD/CSD Interaction Methodology for Aircraft Wings

NASA Technical Reports Server (NTRS)

Bhardwaj, Manoj K.

1997-01-01

With advanced subsonic transports and military aircraft operating in the transonic regime, it is becoming important to determine the effects of the coupling between aerodynamic loads and elastic forces. Since aeroelastic effects can contribute significantly to the design of these aircraft, there is a strong need in the aerospace industry to predict these aero-structure interactions computationally. To perform static aeroelastic analysis in the transonic regime, high fidelity computational fluid dynamics (CFD) analysis tools must be used in conjunction with high fidelity computational structural fluid dynamics (CSD) analysis tools due to the nonlinear behavior of the aerodynamics in the transonic regime. There is also a need to be able to use a wide variety of CFD and CSD tools to predict these aeroelastic effects in the transonic regime. Because source codes are not always available, it is necessary to couple the CFD and CSD codes without alteration of the source codes. In this study, an aeroelastic coupling procedure is developed which will perform static aeroelastic analysis using any CFD and CSD code with little code integration. The aeroelastic coupling procedure is demonstrated on an F/A-18 Stabilator using NASTD (an in-house McDonnell Douglas CFD code) and NASTRAN. In addition, the Aeroelastic Research Wing (ARW-2) is used for demonstration of the aeroelastic coupling procedure by using ENSAERO (NASA Ames Research Center CFD code) and a finite element wing-box code (developed as part of this research).

Update of GRASP/Ada reverse engineering tools for Ada

NASA Technical Reports Server (NTRS)

Cross, James H., II

1992-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation of Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAS 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3, the prototype was evaluated by software engineering students at Auburn University and then updated with significant enhancements to the user interface including editing capabilities. Version 3.2 of the prototype was prepared for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical application.

Turing-like structures in a functional model of cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, A. Yu.; Verveyko, D. V.; Postnov, D. E.

2017-12-01

Cortical spreading depression (CSD) along with migraine waves and spreading depolarization events with stroke or injures are the front-line examples of extreme physiological behaviors of the brain cortex which manifest themselves via the onset and spreading of localized areas of neuronal hyperactivity followed by their depression. While much is known about the physiological pathways involved, the dynamical mechanisms of the formation and evolution of complex spatiotemporal patterns during CSD are still poorly understood, in spite of the number of modeling studies that have been already performed. Recently we have proposed a relatively simple mathematical model of cortical spreading depression which counts the effects of neurovascular coupling and cerebral blood flow redistribution during CSD. In the present study, we address the main dynamical consequences of newly included pathways, namely, the changes in the formation and propagation speed of the CSD front and the pattern formation features in two dimensions. Our most notable finding is that the combination of vascular-mediated spatial coupling with local regulatory mechanisms results in the formation of stationary Turing-like patterns during a CSD event.

Data-Driven High-Throughput Prediction of the 3D Structure of Small Molecules: Review and Progress

PubMed Central

Andronico, Alessio; Randall, Arlo; Benz, Ryan W.; Baldi, Pierre

2011-01-01

Accurate prediction of the 3D structure of small molecules is essential in order to understand their physical, chemical, and biological properties including how they interact with other molecules. Here we survey the field of high-throughput methods for 3D structure prediction and set up new target specifications for the next generation of methods. We then introduce COSMOS, a novel data-driven prediction method that utilizes libraries of fragment and torsion angle parameters. We illustrate COSMOS using parameters extracted from the Cambridge Structural Database (CSD) by analyzing their distribution and then evaluating the system’s performance in terms of speed, coverage, and accuracy. Results show that COSMOS represents a significant improvement when compared to the state-of-the-art, particularly in terms of coverage of complex molecular structures, including metal-organics. COSMOS can predict structures for 96.4% of the molecules in the CSD [99.6% organic, 94.6% metal-organic] whereas the widely used commercial method CORINA predicts structures for 68.5% [98.5% organic, 51.6% metal-organic]. On the common subset of molecules predicted by both methods COSMOS makes predictions with an average speed per molecule of 0.15s [0.10s organic, 0.21s metal-organic], and an average RMSD of 1.57Å [1.26Å organic, 1.90Å metal-organic], and CORINA makes predictions with an average speed per molecule of 0.13s [0.18s organic, 0.08s metal-organic], and an average RMSD of 1.60Å [1.13Å organic, 2.11Å metal-organic]. COSMOS is available through the ChemDB chemoinformatics web portal at: http://cdb.ics.uci.edu/. PMID:21417267

Standard atomic volumes in double-stranded DNA and packing in protein–DNA interfaces

PubMed Central

Nadassy, Katalin; Tomás-Oliveira, Isabel; Alberts, Ian; Janin, Joël; Wodak, Shoshana J.

2001-01-01

Standard volumes for atoms in double-stranded B-DNA are derived using high resolution crystal structures from the Nucleic Acid Database (NDB) and compared with corresponding values derived from crystal structures of small organic compounds in the Cambridge Structural Database (CSD). Two different methods are used to compute these volumes: the classical Voronoi method, which does not depend on the size of atoms, and the related Radical Planes method which does. Results show that atomic groups buried in the interior of double-stranded DNA are, on average, more tightly packed than in related small molecules in the CSD. The packing efficiency of DNA atoms at the interfaces of 25 high resolution protein–DNA complexes is determined by computing the ratios between the volumes of interfacial DNA atoms and the corresponding standard volumes. These ratios are found to be close to unity, indicating that the DNA atoms at protein–DNA interfaces are as closely packed as in crystals of B-DNA. Analogous volume ratios, computed for buried protein atoms, are also near unity, confirming our earlier conclusions that the packing efficiency of these atoms is similar to that in the protein interior. In addition, we examine the number, volume and solvent occupation of cavities located at the protein–DNA interfaces and compared them with those in the protein interior. Cavities are found to be ubiquitous in the interfaces as well as inside the protein moieties. The frequency of solvent occupation of cavities is however higher in the interfaces, indicating that those are more hydrated than protein interiors. Lastly, we compare our results with those obtained using two different measures of shape complementarity of the analysed interfaces, and find that the correlation between our volume ratios and these measures, as well as between the measures themselves, is weak. Our results indicate that a tightly packed environment made up of DNA, protein and solvent atoms plays a significant role in protein–DNA recognition. PMID:11504874

Remarkable features in lattice-parameter ratios of crystals. II. Monoclinic and triclinic crystals.

PubMed

de Gelder, R; Janner, A

2005-06-01

The frequency distributions of monoclinic crystals as a function of the lattice-parameter ratios resemble the corresponding ones of orthorhombic crystals: an exponential component, with more or less pronounced sharp peaks, with in general the most important peak at the ratio value 1. In addition, the distribution as a function of the monoclinic angle beta has a sharp peak at 90 degrees and decreases sensibly at larger angles. Similar behavior is observed for the three triclinic angular parameters alpha, beta and gamma, with characteristic differences between the organic and metal-organic, bio-macromolecular and inorganic crystals, respectively. The general behavior observed for the hexagonal, tetragonal, orthorhombic, monoclinic and triclinic crystals {in the first part of this series [de Gelder & Janner (2005). Acta Cryst. B61, 287-295] and in the present case} is summarized and commented. The data involved represent 366 800 crystals, with lattice parameters taken from the Cambridge Structural Database, CSD (294 400 entries), the Protein Data Bank, PDB (18 800 entries), and the Inorganic Crystal Structure Database, ICSD (53 600 entries). A new general structural principle is suggested.

Trends in active pharmaceutical ingredient salt selection based on analysis of the Orange Book database.

PubMed

Paulekuhn, G Steffen; Dressman, Jennifer B; Saal, Christoph

2007-12-27

The Orange Book database published by the U.S. Drug and Food Administration (FDA) was analyzed for the frequency of occurrence of different counterions used for the formation of pharmaceutical salts. The data obtained from the present analysis of the Orange Book are compared to reviews of the Cambridge Structural Database (CSD) and of the Martindale "The Extra Pharmacopoeia". As well as showing overall distributions of counterion usage, results are broken down into 5-year increments to identify trends in counterion selection. Chloride ions continue to be the most frequently utilized anionic counterions for the formation of salts as active pharmaceutical ingredients (APIs), while sodium ions are most widely utilized for the formation of salts starting from acidic molecules. A strong trend toward a wider variety of counterions over the past decade is observed. This trend can be explained by a stronger need to improve physical chemical properties of research and development compounds.

Reactivity of 12-tungstophosphoric acid and its inhibitor potency toward Na+/K+-ATPase: A combined 31P NMR study, ab initio calculations and crystallographic analysis.

PubMed

Bošnjaković-Pavlović, Nada; Bajuk-Bogdanović, Danica; Zakrzewska, Joanna; Yan, Zeyin; Holclajtner-Antunović, Ivanka; Gillet, Jean-Michel; Spasojević-de Biré, Anne

2017-11-01

Influence of 12-tungstophosphoric acid (WPA) on conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the presence of Na + /K + -ATPase was monitored by 31 P NMR spectroscopy. It was shown that WPA exhibits inhibitory effect on Na + /K + -ATPase activity. In order to study WPA reactivity and intermolecular interactions between WPA oxygen atoms and different proton donor types (D=O, N, C), we have considered data for WPA based compounds from the Cambridge Structural Database (CSD), the Crystallographic Open Database (COD) and the Inorganic Crystal Structure Database (ICSD). Binding properties of Keggin's anion in biological systems are illustrated using Protein Data Bank (PDB). This work constitutes the first determination of theoretical Bader charges on polyoxotungstate compound via the Atom In Molecule theory. An analysis of electrostatic potential maps at the molecular surface and charge of WPA, resulting from DFT calculations, suggests that the preferred protonation site corresponds to WPA bridging oxygen. These results enlightened WPA chemical reactivity and its potential biological applications such as the inhibition of the ATPase activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of carbon nanotube dispersion in fracture toughening of plasma sprayed aluminum oxide-carbon nanotube nanocomposite coating

NASA Astrophysics Data System (ADS)

Balani, Kantesh

Aluminum oxide (Al2O3, or alumina) is a conventional ceramic known for applications such as wear resistant coatings, thermal liners, heaters, crucibles, dielectric systems, etc. However applications of Al 2O3 are limited owing to its inherent brittleness. Due to its excellent mechanical properties and bending strength, carbon nanotubes (CNT) is an ideal reinforcement for Al2O3 matrix to improve its fracture toughness. The role of CNT dispersion in the fracture toughening of the plasma sprayed Al2O3-CNT nanocomposite coating is discussed in the current work. Pretreatment of powder feedstock is required for dispersing CNTs in the matrix. Four coatings namely spray dried Al2O 3 (A-SD), Al2O3 blended with 4wt.% CNT (A4C-B), composite spray dried Al2O3-4wt.% CNT (A4C-SD) and composite spray dried A1203-8wt.% CNT (A8C-SD), are synthesized by plasma spraying. Owing to extreme temperatures and velocities involved in the plasma spraying of ceramics, retention of CNTs in the resulting coatings necessitates optimizing plasma processing parameters using an inflight particle diagnostic sensor. A bimodal microstructure was obtained in the matrix that consists of fully melted and resolidified structure and solid state sintered structure. CNTs are retained both in the fully melted region and solid-state sintered regions of processed coatings. Fracture toughness of A-SD, A4C-B, A4C-SD and A8C-SD coatings was 3.22, 3.86, 4.60 and 5.04 MPa m1/2 respectively. This affirms the improvement of fracture toughness from 20% (in A4C-B coating) to 43% (in A4C-SD coating) when compared to the A-SD coating because of the CNT dispersion. Fracture toughness improvement from 43% (in A4C-SD) to 57% (in A8C-SD) coating is evinced because of the CNT content. Reinforcement by CNTs is described by its bridging, anchoring, hook formation, impact alignment, fusion with splat, and mesh formation. The Al2O3/CNT interface is critical in assisting the stress transfer and utilizing excellent mechanical properties of CNTs. Mathematical and computational modeling using ab-initio principle is applied to understand the wetting behavior at the Al2O 3/CNT interface. Contrasting storage modulus was obtained by nanoindentation (˜210, 250, 250-350 and 325-420 GPa in A-SD, A4C-B, A4C-SD, and A8C-SD coatings respectively) depicting the toughening associated with CNT content and dispersion.

Consumer Quality Index Chronic Skin Disease (CQI-CSD): a new instrument to measure quality of care from the patient's perspective.

PubMed

van Cranenburgh, O D; Krol, M W; Hendriks, M C P; de Rie, M A; Smets, E M A; de Korte, J; Sprangers, M A G

2015-10-01

Assessing quality of care from the patient's perspective is considered to be highly relevant. As a standardized instrument in dermatology was lacking, we developed a patient experience questionnaire regarding chronic skin disease care: the Consumer Quality Index Chronic Skin Disease (CQI-CSD). (i) To evaluate the dimensional structure of the CQI-CSD, (ii) to assess its ability to distinguish between hospitals according to patients' experiences with quality of care, (iii) to explore patients' experiences with dermatological care and priorities for quality improvement according to the patients, and (iv) to optimize the questionnaire based on psychometric results and stakeholders' input. In a cross-sectional study 5647 adult patients who received dermatological care in the past 12 months in 20 hospitals were randomly selected and invited to fill out the questionnaire. Overall 1160 of 3989 eligible respondents (29% response rate, 30-87 per hospital) were included for analysis. The CQI-CSD comprised seven scales with high internal consistency (Cronbach's α = 0·74-0·92). The instrument's discriminative power was limited. Patients were positive about the care provided by nurses and doctors, but the provision of information by healthcare providers, accessibility of care and patient involvement could be improved. We optimized the CQI-CSD, resulting in a revised questionnaire containing 65 items. In conclusion, the CQI-CSD is a useful instrument to measure patient experiences with dermatological care. © 2015 British Association of Dermatologists.

HART-II Acoustic Predictions using a Coupled CFD/CSD Method

NASA Technical Reports Server (NTRS)

Boyd, D. Douglas, Jr.

2009-01-01

This paper documents results to date from the Rotorcraft Acoustic Characterization and Mitigation activity under the NASA Subsonic Rotary Wing Project. The primary goal of this activity is to develop a NASA rotorcraft impulsive noise prediction capability which uses first principles fluid dynamics and structural dynamics. During this effort, elastic blade motion and co-processing capabilities have been included in a recent version of the computational fluid dynamics code (CFD). The CFD code is loosely coupled to computational structural dynamics (CSD) code using new interface codes. The CFD/CSD coupled solution is then used to compute impulsive noise on a plane under the rotor using the Ffowcs Williams-Hawkings solver. This code system is then applied to a range of cases from the Higher Harmonic Aeroacoustic Rotor Test II (HART-II) experiment. For all cases presented, the full experimental configuration (i.e., rotor and wind tunnel sting mount) are used in the coupled CFD/CSD solutions. Results show good correlation between measured and predicted loading and loading time derivative at the only measured radial station. A contributing factor for a typically seen loading mean-value offset between measured data and predictions data is examined. Impulsive noise predictions on the measured microphone plane under the rotor compare favorably with measured mid-frequency noise for all cases. Flow visualization of the BL and MN cases shows that vortex structures generated in the prediction method are consist with measurements. Future application of the prediction method is discussed.

NR2A contributes to genesis and propagation of cortical spreading depression in rats.

PubMed

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-03-22

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile.

NR2A contributes to genesis and propagation of cortical spreading depression in rats

PubMed Central

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-01-01

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID:27001011

XRD measurement of mean thickness, thickness distribution and strain for illite and illite-smectite crystallites by the Bertaut-Warren-Averbach technique

USGS Publications Warehouse

Drits, Victor A.; Eberl, Dennis D.; Środoń, Jan

1998-01-01

A modified version of the Bertaut-Warren-Averbach (BWA) technique (Bertaut 1949, 1950; Warren and Averbach 1950) has been developed to measure coherent scattering domain (CSD) sizes and strains in minerals by analysis of X-ray diffraction (XRD) data. This method is used to measure CSD thickness distributions for calculated and experimental XRD patterns of illites and illite-smectites (I-S). The method almost exactly recovers CSD thickness distributions for calculated illite XRD patterns. Natural I-S samples contain swelling layers that lead to nonperiodic structures in the c* direction and to XRD peaks that are broadened and made asymmetric by mixed layering. Therefore, these peaks cannot be analyzed by the BWA method. These difficulties are overcome by K-saturation and heating prior to X-ray analysis in order to form 10-Å periodic structures. BWA analysis yields the thickness distribution of mixed-layer crystals (coherently diffracting stacks of fundamental illite particles). For most I-S samples, CSD thickness distributions can be approximated by lognormal functions. Mixed-layer crystal mean thickness and expandability then can be used to calculate fundamental illite particle mean thickness. Analyses of the dehydrated, K-saturated samples indicate that basal XRD reflections are broadened by symmetrical strain that may be related to local variations in smectite interlayers caused by dehydration, and that the standard deviation of the strain increases regularly with expandability. The 001 and 002 reflections are affected only slightly by this strain and therefore are suited for CSD thickness analysis. Mean mixed-layer crystal thicknesses for dehydrated I-S measured by the BWA method are very close to those measured by an integral peak width method.

Chronic subjective dizziness: Analysis of underlying personality factors.

PubMed

Chiarella, G; Petrolo, C; Riccelli, R; Giofrè, L; Olivadese, G; Gioacchini, F M; Scarpa, A; Cassandro, E; Passamonti, L

2016-11-03

Chronic subjective dizziness (CSD) is characterized by persistent dizziness, unsteadiness, and hypersensitivity to one's own motion or exposure to complex visual stimuli. CSD may be triggered, in predisposed individuals with specific personality traits, by acute vestibular diseases. CSD is also thought to arise from failure to re-establish normal balance strategies after resolution of acute vestibular events which may be modulated by diathesis to develop anxiety and depression. To confirm the role of personality traits linked to anxiety and depression (i.e., neuroticism, introversion, low openness) as predisposing factors for CSD and to evaluate how individual differences in these personality traits are associated with CSD severity. We compared 19 CSD patients with 24 individuals who had suffered from periferal vestibular disorders (PVD) (i.e., Benign Paroxysmal Postural Vertigo or Vestibular Neuritis) but had not developed CSD as well as with 25 healthy controls (HC) in terms of personality traits, assessed via the NEO-PI-R questionnaire. CSD patients, relative to PVD patients and HCs, scored higher on the anxiety facet of neuroticism. Total neuroticism scores were also significantly associated with dizziness severity in CSD patients but not PVD patients. Pre-existing anxiety-related personality traits may promote and sustain the initial etiophatogenetic mechanisms linked with the development of CSD. Targeting anxiety-related mechanisms in CSD may be therefore a promising way to reduce the disability associated with CSD.

QTL Mapping of Sex Determination Loci Supports an Ancient Pathway in Ants and Honey Bees.

PubMed

Miyakawa, Misato O; Mikheyev, Alexander S

2015-11-01

Sex determination mechanisms play a central role in life-history characteristics, affecting mating systems, sex ratios, inbreeding tolerance, etc. Downstream components of sex determination pathways are highly conserved, but upstream components evolve rapidly. Evolutionary dynamics of sex determination remain poorly understood, particularly because mechanisms appear so diverse. Here we investigate the origins and evolution of complementary sex determination (CSD) in ants and bees. The honey bee has a well-characterized CSD locus, containing tandemly arranged homologs of the transformer gene [complementary sex determiner (csd) and feminizer (fem)]. Such tandem paralogs appear frequently in aculeate hymenopteran genomes. However, only comparative genomic, but not functional, data support a broader role for csd/fem in sex determination, and whether species other than the honey bee use this pathway remains controversial. Here we used a backcross to test whether csd/fem acts as a CSD locus in an ant (Vollenhovia emeryi). After sequencing and assembling the genome, we computed a linkage map, and conducted a quantitative trait locus (QTL) analysis of diploid male production using 68 diploid males and 171 workers. We found two QTLs on separate linkage groups (CsdQTL1 and CsdQTL2) that jointly explained 98.0% of the phenotypic variance. CsdQTL1 included two tandem transformer homologs. These data support the prediction that the same CSD mechanism has indeed been conserved for over 100 million years. CsdQTL2 had no similarity to CsdQTL1 and included a 236-kb region with no obvious CSD gene candidates, making it impossible to conclusively characterize it using our data. The sequence of this locus was conserved in at least one other ant genome that diverged >75 million years ago. By applying QTL analysis to ants for the first time, we support the hypothesis that elements of hymenopteran CSD are ancient, but also show that more remains to be learned about the diversity of CSD mechanisms.

Caffeine Treatment Prevented from Weight Regain after Calorie Shifting Diet Induced Weight Loss

PubMed Central

Davoodi, Sayed Hossein; Hajimiresmaiel, Seyed Javad; Ajami, Marjan; Mohseni-Bandpei, Anoushiravan; Ayatollahi, Seyyed Abdulmajid; Dowlatshahi, Kamran; Javedan, Gholamali; Pazoki-Toroudi, Hamidreza

2014-01-01

Low calorie diets are always difficult for obese subjects to follow and lead to metabolic and behavioral adaptation. Therefore, we evaluated the effect of caffeine treatment with calorie shifting diet (CSD) on weight loss. Female subjects (n=60; BMI≥25) completed 4-weeks control diet, 6-weeks CSD (3 repeated phases; each 2-weeks) and 4-weeks follow-up diet, with or without caffeine treatment (5 mg/Kg/day). The first 11 days of each phase included calorie restriction with four meals every day and 4 hours intervals. Significant weight and fat loss were observed after 4-weeks of CSD (5.7 ± 1.24 Kg and 4.84 ± 1.53 Kg) or CSD+Caffeine (7.57 ± 2.33 Kg and 5.24 ± 2.07 Kg) which was consistent for one month of the follow-up (CSD: 5.24 ± 1.83 Kg and 4.3 ± 1.62 Kg, CSD+Caffeine: 12.11 ± 2.31 Kg and 9.85 ± 1.6 Kg, p < 0.05 vs CSD group) and correlated to the restricted energy intake (p < 0.05). During three CSD phases, RMR tended to remain unchanged in both groups.While, CSD or CSD + Caffeine treatments, significantly decreased plasma glucose, total-cholesterol, and triacylglycerol (p < 0.05), even during follow-up period (p < 0.05). HDL-cholesterol was not changed by CSD. Feeling of hunger decreased and subject’s satisfaction increased after 4-weeks of CSD (p < 0.05) and remained low to the end of study, while satiety was not affected. Coffeine increased the effect of CSD on feeling of hunger and subject’s satisfaction after week 7 (p < 0.05 vs. CSD). These findings indicated that combination of caffeine treatment with CSD could be an effective alternative approach to weight and fat loss with small changes in RMR and improved tolerance of subjects to the new diet. PMID:25237367

Cortical spreading depression: An enigma

NASA Astrophysics Data System (ADS)

Miura, R. M.; Huang, H.; Wylie, J. J.

2007-08-01

The brain is a complex organ with active components composed largely of neurons, glial cells, and blood vessels. There exists an enormous experimental and theoretical literature on the mechanisms involved in the functioning of the brain, but we still do not have a good understanding of how it works on a gross mechanistic level. In general, the brain maintains a homeostatic state with relatively small ion concentration changes, the major ions being sodium, potassium, and chloride. Calcium ions are present in smaller quantities but still play an important role in many phenomena. Cortical spreading depression (CSD for short) was discovered over 60 years ago by A.A.P. Leão, a Brazilian physiologist doing his doctoral research on epilepsy at Harvard University, “Spreading depression of activity in the cerebral cortex," J. Neurophysiol., 7 (1944), pp. 359-390. Cortical spreading depression is characterized by massive changes in ionic concentrations and slow nonlinear chemical waves, with speeds on the order of mm/min, in the cortex of different brain structures in various experimental animals. In humans, CSD is associated with migraine with aura, where a light scintillation in the visual field propagates, then disappears, and is followed by a sustained headache. To date, CSD remains an enigma, and further detailed experimental and theoretical investigations are needed to develop a comprehensive picture of the diverse mechanisms involved in producing CSD. A number of mechanisms have been hypothesized to be important for CSD wave propagation. In this paper, we briefly describe several characteristics of CSD wave propagation, and examine some of the mechanisms that are believed to be important, including ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Continuum models of CSD, consisting of coupled nonlinear diffusion equations for the ion concentrations, and a discrete lattice-Boltzmann method approach will be described. Also, we will describe some open problems and remaining challenges.

Proteomic analysis of protein-protein interactions within the Cysteine Sulfinate Desulfinase Fe-S cluster biogenesis system.

PubMed

Bolstad, Heather M; Botelho, Danielle J; Wood, Matthew J

2010-10-01

Fe-S cluster biogenesis is of interest to many fields, including bioenergetics and gene regulation. The CSD system is one of three Fe-S cluster biogenesis systems in E. coli and is comprised of the cysteine desulfurase CsdA, the sulfur acceptor protein CsdE, and the E1-like protein CsdL. The biological role, biochemical mechanism, and protein targets of the system remain uncharacterized. Here we present that the active site CsdE C61 has a lowered pK(a) value of 6.5, which is nearly identical to that of C51 in the homologous SufE protein and which is likely critical for its function. We observed that CsdE forms disulfide bonds with multiple proteins and identified the proteins that copurify with CsdE. The identification of Fe-S proteins and both putative and established Fe-S cluster assembly (ErpA, glutaredoxin-3, glutaredoxin-4) and sulfur trafficking (CsdL, YchN) proteins supports the two-pathway model, in which the CSD system is hypothesized to synthesize both Fe-S clusters and other sulfur-containing cofactors. We suggest that the identified Fe-S cluster assembly proteins may be the scaffold and/or shuttle proteins for the CSD system. By comparison with previous analysis of SufE, we demonstrate that there is some overlap in the CsdE and SufE interactomes.

Structure-based Reassessment of the Caveolin Signaling Model: Do Caveolae Regulate Signaling Through Caveolin-Protein Interactions?

PubMed Central

Collins, Brett M.; Davis, Melissa J.; Hancock, John F.; Parton, Robert G.

2012-01-01

Summary Caveolin proteins drive formation of caveolae, specialized cell-surface microdomains that influence cell signaling. Signaling proteins are proposed to use conserved caveolin-binding motifs (CBMs) to associate with caveolae via the caveolin scaffolding domain (CSD). However, structural and bioinformatic analyses argue against such direct physical interactions: In the majority of signaling proteins, the CBM is buried and inaccessible. Putative CBMs do not form a common structure for caveolin recognition, are not enriched amongst caveolin-binding proteins, and are even more common in yeast, which lack caveolae. We propose that CBM/CSD-dependent interactions are unlikely to mediate caveolar signaling, and the basis for signaling effects should therefore be reassessed. PMID:22814599

Severity of complicated versus uncomplicated subthreshold depression: New evidence on the "Monotonicity Thesis" from the national comorbidity survey.

PubMed

Wakefield, Jerome C; Schmitz, Mark F

2017-04-01

"Complicated" subthreshold depression (CsD) includes at least one of six pathosuggestive "complicated" symptoms: >6 months duration, marked role impairment, sense of worthlessness, suicidal ideation, psychotic ideation, and psychomotor retardation. "Uncomplicated" subthreshold depression (UsD) has no complicated features. Whereas studies show that complicated (CMDD) versus uncomplicated (UMDD) major depression differ substantially in severity and prognosis, UsD and CsD severity has not been previously compared. This study evaluates UsD and CsD pathology validator levels and examines whether the complicated/uncomplicated distinction offers incremental concurrent validity over the standard number-of-symptoms dimension as a depression severity measure. Using nationally representative community data from the National Comorbidity Survey, seven depression lifetime history subgroups were identified: one MDD screener symptom (n=1432); UsD (n=430); CsD (n=611); UMDD (n=182); and CMDD with 5-6 symptoms (n=518), 7 symptoms (n=217), and 8-9 symptoms (n=291). Severity was evaluated using five concurrent pathology validators: suicide attempt, interference with life, help seeking, hospitalization, and generalized anxiety disorder. CsD validator levels are substantially higher than both UsD and UMDD levels, and similar to mild CMDD, disconfirming the "monotonicity thesis" that severity increase with symptom number. Complicated/uncomplicated status predicts severity, and when complicatedness is controlled, number of symptoms no longer predicts validator levels. Diagnoses were based on respondents' fallible retrospective symptom reports during a lay-administered structured interview, which may not yield diagnoses comparable to clinicians' assessments. CsD is more severe than UsD and comparable to mild MDD. Complicated status more validly indicates depression severity than the standard number-of-symptoms measure. Copyright © 2017 Elsevier B.V. All rights reserved.

High fidelity CFD-CSD aeroelastic analysis of slender bladed horizontal-axis wind turbine

NASA Astrophysics Data System (ADS)

Sayed, M.; Lutz, Th.; Krämer, E.; Shayegan, Sh.; Ghantasala, A.; Wüchner, R.; Bletzinger, K.-U.

2016-09-01

The aeroelastic response of large multi-megawatt slender horizontal-axis wind turbine blades is investigated by means of a time-accurate CFD-CSD coupling approach. A loose coupling approach is implemented and used to perform the simulations. The block- structured CFD solver FLOWer is utilized to obtain the aerodynamic blade loads based on the time-accurate solution of the unsteady Reynolds-averaged Navier-Stokes equations. The CSD solver Carat++ is applied to acquire the blade elastic deformations based on non-linear beam elements. In this contribution, the presented coupling approach is utilized to study the aeroelastic response of the generic DTU 10MW wind turbine. Moreover, the effect of the coupled results on the wind turbine performance is discussed. The results are compared to the aeroelastic response predicted by FLOWer coupled to the MBS tool SIMPACK as well as the response predicted by SIMPACK coupled to a Blade Element Momentum code for aerodynamic predictions. A comparative study among the different modelling approaches for this coupled problem is discussed to quantify the coupling effects of the structural models on the aeroelastic response.

Mathematical approaches to modeling of cortical spreading depression

NASA Astrophysics Data System (ADS)

Miura, Robert M.; Huang, Huaxiong; Wylie, Jonathan J.

2013-12-01

Migraine with aura (MwA) is a debilitating disease that afflicts about 25%-30% of migraine sufferers. During MwA, a visual illusion propagates in the visual field, then disappears, and is followed by a sustained headache. MwA was conjectured by Lashley to be related to some neurological phenomenon. A few years later, Leão observed electrophysiological waves in the brain that are now known as cortical spreading depression (CSD). CSD waves were soon conjectured to be the neurological phenomenon underlying MwA that had been suggested by Lashley. However, the confirmation of the link between MwA and CSD was not made until 2001 by Hadjikhani et al. [Proc. Natl. Acad. Sci. U.S.A. 98, 4687-4692 (2001)] using functional MRI techniques. Despite the fact that CSD has been studied continuously since its discovery in 1944, our detailed understandings of the interactions between the mechanisms underlying CSD waves have remained elusive. The connection between MwA and CSD makes the understanding of CSD even more compelling and urgent. In addition to all of the information gleaned from the many experimental studies on CSD since its discovery, mathematical modeling studies provide a general and in some sense more precise alternative method for exploring a variety of mechanisms, which may be important to develop a comprehensive picture of the diverse mechanisms leading to CSD wave instigation and propagation. Some of the mechanisms that are believed to be important include ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Discrete and continuum models of CSD consist of coupled nonlinear differential equations for the ion concentrations. In this review of the current quantitative understanding of CSD, we focus on these modeling paradigms and various mechanisms that are felt to be important for CSD.

[Cortical spreading depolarization phenomena in patients with traumatic and ischemic brain injuries. Results of a pilot study].

PubMed

Sueiras, M; Sahuquillo, J; García-López, B; Sánchez-Guerrero, Á; Poca, M A; Santamarina, E; Riveiro, M; Fabricius, M; Strong, A J

2014-10-01

To determine the frequency and duration of cortical spreading depolarization (CSD) and CSD-like episodes in patients with traumatic brain injury (TBI) and malignant middle cerebral artery infarction (MMCAI) requiring craniotomy. A descriptive observational study was carried out during 19 months. Neurocritical patients. Sixteen patients were included: 9 with MMCAI and 7 with moderate or severe TBI, requiring surgical treatment. A 6-electrode subdural electrocorticographic (ECoG) strip was placed onto the perilesional cortex. An analysis was made of the time profile and the number and duration of CSD and CSD-like episodes recorded from the ECoGs. Of the 16 patients enrolled, 9 presented episodes of CSD or CSD-like phenomena, of highly variable frequency and duration. Episodes of CSD and CSD-like phenomena are frequently detected in the ischemic penumbra and/or traumatic cortical regions of patients with MMCAI who require decompressive craniectomy or of patients with contusional TBI. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.

PubMed

Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Shimizu, Toshihiko; Toriumi, Haruki; Ebine, Taeko; Unekawa, Miyuki; Koh, Anri; Yoshimura, Akihiko; Suzuki, Norihiro

2017-03-01

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Psychometric Properties of the Consensus Sleep Diary in Those With Insomnia Disorder.

PubMed

Maich, Kristin H G; Lachowski, Angela M; Carney, Colleen E

2018-01-01

The Consensus Sleep Diary (CSD) is a standardized, prospective tool for tracking nightly subjective sleep. The current study evaluated the validity and utility of the CSD, with consideration for challenges inherent to psychometric evaluation of diary measures. Results showed that the CSD indices differentiated good sleepers from those with insomnia and were associated with similar objective indices and a subjective insomnia severity measure. The ability to detect treatment improvements after cognitive behavior therapy for insomnia (CBT-I) was tested by comparing pre- and post-CBT-I CSD indices with a subjective rating of insomnia symptom severity. Improvement in insomnia symptom severity was significantly related to improvement on the CSD indices. Completion rate of the CSD amongst participants across all 14 days was 99.8%. These findings provide support for the validity, clinical utility, and usability of the CSD.

Effects of garlic extract on spreading depression: In vitro and in vivo investigations.

PubMed

Marschollek, Claudia; Karimzadeh, Fariba; Jafarian, Maryam; Ahmadi, Milad; Mohajeri, Seyed Mohammad Reza; Rahimi, Sadegh; Speckmann, Erwin-Josef; Gorji, Ali

2017-02-01

The potential use of garlic for prevention and treatment of different types of headaches has been suggested by several medieval literatures. Cortical spreading depression (CSD), a propagating wave of neuroglial depolarization, was established as a target for anti-migraine drugs. This study was designed to investigate the effect of garlic extract on CSD in adult rats. CSD was induced by KCl microinjection in the somatosensory cortex. The effects of five different concentrations of garlic oil (1-500 μl/l) were tested on different characteristic features of CSD in necocortical slices. In in vivo experiments, the effects of garlic oil on electrophysiological and morphological changes induced by CSD were investigated. Garlic oil in a dose-dependent manner decreased the amplitude of CSD but not its duration and velocity in neocortical brain slices. Garlic oil at concentration of 500 μl/l reversibly reduced the amplitude of the field excitatory post-synaptic potentials and inhibited induction of long-term potentiation in the third layer of neocortical slices. In in vivo studies, systemic application of garlic oil (1 ml/l) for three consecutive days reduced the amplitude and repetition rate of CSD. Garlic oil also prevented of CSD-induced reactive astrocytosis in the neocortex. Garlic oil suppresses CSD, likely via inhibition of synaptic plasticity, and prevents its harmful effects on astrocyte. Further studies are required to identify the exact active ingredient(s) of garlic oil that inhibit CSD and may have the potential to use in treatment of CSD-related disorders.

Computational study on cortical spreading depression based on a generalized cellular automaton model

NASA Astrophysics Data System (ADS)

Chen, Shangbin; Hu, Lele; Li, Bing; Xu, Changcheng; Liu, Qian

2009-02-01

Cortical spreading depression (CSD) is an important neurophysiological phenomenon correlating with some neural disorders, such as migraine, cerebral ischemia and epilepsy. By now, we are still not clear about the mechanisms of CSD's initiation and propagation, also the relevance between CSD and those neural diseases. Nevertheless, characterization of CSD, especially the spatiotemporal evolution, will promote the understanding of the CSD's nature and mechanisms. Besides the previous experimental work on charactering the spatiotemporal evolution of CSD in rats by optical intrinsic signal imaging, a computational study based on a generalized cellular automaton (CA) model was proposed here. In the model, we exploited a generalized neighborhood connection rule: a central CA cell is related with a group of surrounding CA cells with different weight coefficients. By selecting special parameters, the generalized CA model could be transformed to the traditional CA models with von Neumann, Moore and hexagon neighborhood connection means. Hence, the new model covered several properties of CSD simulated in traditional CA models: 1) expanding from the origin site like a circular wave; 2) annihilation of two waves traveling in opposite directions after colliding; 3) wavefront of CSD breaking and recovering when and after encountering an obstacle. By setting different refractory period in the different CA lattice field, different connection coefficient in different direction within the defined neighborhood, inhomogeneous propagation of CSD was simulated with high fidelity. The computational results were analogous to the reported time-varying CSD waves by optical imaging. So, the generalized CA model would be useful to study CSD because of its intuitive appeal and computational efficiency.

Structural study of piracetam polymorphs and cocrystals: crystallography redetermination and quantum mechanics calculations.

PubMed

Tilborg, Anaëlle; Jacquemin, Denis; Norberg, Bernadette; Perpète, Eric; Michaux, Catherine; Wouters, Johan

2011-12-01

Pharmaceutical compounds are mostly developed as solid dosage forms containing a single-crystal form. It means that the selection of a particular crystal state for a given molecule is an important step for further clinical outlooks. In this context, piracetam, a pharmaceutical molecule known since the sixties for its nootropic properties, is considered in the present work. This molecule is analyzed using several experimental and theoretical approaches. First, the conformational space of the molecule has been systematically explored by performing a quantum mechanics scan of the two most relevant dihedral angles of the lateral chain. The predicted stable conformations have been compared to all the reported experimental geometries retrieved from the Cambridge Structural Database (CSD) covering polymorphs and cocrystals structures. In parallel, different batches of powders have been recrystallized. Under specific conditions, single crystals of polymorph (III) of piracetam have been obtained, an outcome confirmed by crystallographic analysis. © 2011 International Union of Crystallography. Printed in Singapore – all rights reserved.

Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

PubMed

Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

2015-07-16

Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

Resolution doubling in fluorescence microscopy with confocal spinning-disk image scanning microscopy.

PubMed

Schulz, Olaf; Pieper, Christoph; Clever, Michaela; Pfaff, Janine; Ruhlandt, Aike; Kehlenbach, Ralph H; Wouters, Fred S; Großhans, Jörg; Bunt, Gertrude; Enderlein, Jörg

2013-12-24

We demonstrate how a conventional confocal spinning-disk (CSD) microscope can be converted into a doubly resolving image scanning microscopy (ISM) system without changing any part of its optical or mechanical elements. Making use of the intrinsic properties of a CSD microscope, we illuminate stroboscopically, generating an array of excitation foci that are moved across the sample by varying the phase between stroboscopic excitation and rotation of the spinning disk. ISM then generates an image with nearly doubled resolution. Using conventional fluorophores, we have imaged single nuclear pore complexes in the nuclear membrane and aggregates of GFP-conjugated Tau protein in three dimensions. Multicolor ISM was shown on cytoskeletal-associated structural proteins and on 3D four-color images including MitoTracker and Hoechst staining. The simple adaptation of conventional CSD equipment allows superresolution investigations of a broad variety of cell biological questions.

Resolution doubling in fluorescence microscopy with confocal spinning-disk image scanning microscopy

PubMed Central

Schulz, Olaf; Pieper, Christoph; Clever, Michaela; Pfaff, Janine; Ruhlandt, Aike; Kehlenbach, Ralph H.; Wouters, Fred S.; Großhans, Jörg; Bunt, Gertrude; Enderlein, Jörg

2013-01-01

We demonstrate how a conventional confocal spinning-disk (CSD) microscope can be converted into a doubly resolving image scanning microscopy (ISM) system without changing any part of its optical or mechanical elements. Making use of the intrinsic properties of a CSD microscope, we illuminate stroboscopically, generating an array of excitation foci that are moved across the sample by varying the phase between stroboscopic excitation and rotation of the spinning disk. ISM then generates an image with nearly doubled resolution. Using conventional fluorophores, we have imaged single nuclear pore complexes in the nuclear membrane and aggregates of GFP-conjugated Tau protein in three dimensions. Multicolor ISM was shown on cytoskeletal-associated structural proteins and on 3D four-color images including MitoTracker and Hoechst staining. The simple adaptation of conventional CSD equipment allows superresolution investigations of a broad variety of cell biological questions. PMID:24324140

On signals of phase transitions in salmon population dynamics

PubMed Central

Krkošek, Martin; Drake, John M.

2014-01-01

Critical slowing down (CSD) reflects the decline in resilience of equilibria near a bifurcation and may reveal early warning signals (EWS) of ecological phase transitions. We studied CSD in the recruitment dynamics of 120 stocks of three Pacific salmon (Oncorhynchus spp.) species in relation to critical transitions in fishery models. Pink salmon (Oncorhynchus gorbuscha) exhibited increased variability and autocorrelation in populations that had a growth parameter, r, close to zero, consistent with EWS of extinction. However, models and data for sockeye salmon (Oncorhynchus nerka) indicate that portfolio effects from heterogeneity in age-at-maturity may obscure EWS. Chum salmon (Oncorhynchus keta) show intermediate results. The data do not reveal EWS of Ricker-type bifurcations that cause oscillations and chaos at high r. These results not only provide empirical support for CSD in some ecological systems, but also indicate that portfolio effects of age structure may conceal EWS of some critical transitions. PMID:24759855

Spatio-temporal cerebral blood flow perfusion patterns in cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.

2017-04-01

Cortical spreading depression (CSD) is an example of one of the most common abnormalities in biophysical brain functioning. Despite the fact that there are many mathematical models describing the cortical spreading depression (CSD), most of them do not take into consideration the role of redistribution of cerebral blood flow (CBF), that results in the formation of spatio-temporal patterns. The paper presents a mathematical model, which successfully explains the CBD role in the CSD process. Numerical study of this model has revealed the formation of stationary dissipative structures, visually analogous to Turing structures. However, the mechanism of their formation is not diffusion. We show these structures occur due to another type of spatial coupling, that is related to tissue perfusion rate. The proposed model predicts that at similar state of neurons the distribution of blood flow and oxygenation may by different. Currently, this effect is not taken into account when the Blood oxygen-level dependent (BOLD) contrast imaging used in functional magnetic resonance imaging (fMRI). Thus, the diagnosis on the BOLD signal can be ambiguous. We believe that our results can be used in the future for a more correct interpretation of the data obtained with fMRI, NIRS and other similar methods for research of the brain activity.

Epidemiology and outcomes of people with dementia, delirium, and unspecified cognitive impairment in the general hospital: prospective cohort study of 10,014 admissions.

PubMed

Reynish, Emma L; Hapca, Simona M; De Souza, Nicosha; Cvoro, Vera; Donnan, Peter T; Guthrie, Bruce

2017-07-27

Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission. Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined 'cognitive spectrum disorder' (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score < 8/10. Routine data for length of stay (LOS), mortality, and readmission were linked to examine associations with outcomes. A CSD was present in 38.5% of all patients admitted aged over 65, and in more than half of those aged over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9% delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5% unspecified cognitive impairment (AMT score < 8/10, no delirium, no known dementia). Of those with known dementia, 45.8% had delirium superimposed. Outcomes were worse in those with CSD compared to those without - LOS 25.0 vs. 11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1-year death or readmission 62.4% vs. 51.5% (all P < 0.01). There was relatively little difference by CSD type, although people with delirium superimposed on dementia had the longest LOS, and people with dementia the worst mortality at 1 year. CSD is common in older inpatients and associated with considerably worse outcomes, with little variation between different types of CSD. Healthcare systems should systematically identify and develop care pathways for older people with CSD admitted as medical emergencies, and avoid only focusing on condition-specific pathways such as those for dementia or delirium alone.

Caffeine does not affect susceptibility to cortical spreading depolarization in mice.

PubMed

Yalcin, Nilufer; Chen, Shih-Pin; Yu, Esther S; Liu, Tzu-Ting; Yen, Jiin-Cherng; Atalay, Yahya B; Qin, Tao; Celik, Furkan; van den Maagdenberg, Arn Mjm; Moskowitz, Michael A; Ayata, Cenk; Eikermann-Haerter, Katharina

2018-01-01

Several factors that modulate migraine, a common primary headache disorder, also affect susceptibility to cortical spreading depolarization (CSD). CSD is a wave of neuronal and glial depolarization and thought to underlie the migraine aura and possibly headache. Here, we tested whether caffeine, known to alleviate or trigger headache after acute exposure or chronic use/withdrawal, respectively, modulates CSD. We injected C57BL/6J mice with caffeine (30, 60, or 120 mg/kg; i.p.) once (acute) or twice per day for one or two weeks (chronic). Susceptibility to CSD was evaluated by measuring the electrical CSD threshold and by assessing KCl-induced CSD. Simultaneous laser Doppler flowmetry was used to assess CSD-induced cortical blood flow changes. Recordings were performed 15 min after caffeine/vehicle administration, or 24 h after the last dose of chronic caffeine in the withdrawal group. The latter paradigm was also tested in mice carrying the familial hemiplegic migraine type 1 R192Q missense mutation, considered a valid migraine model. Neither acute/chronic administration nor withdrawal of caffeine affected CSD susceptibility or related cortical blood flow changes, either in WT or R192Q mice. Hence, adverse or beneficial effects of caffeine on headache seem unrelated to CSD pathophysiology, consistent with the non-migrainous clinical presentation of caffeine-related headache.

Nucleotide variability at its limit? Insights into the number and evolutionary dynamics of the sex-determining specificities of the honey bee Apis mellifera.

PubMed

Lechner, Sarah; Ferretti, Luca; Schöning, Caspar; Kinuthia, Wanja; Willemsen, David; Hasselmann, Martin

2014-02-01

Deciphering the evolutionary processes driving nucleotide variation in multiallelic genes is limited by the number of genetic systems in which such genes occur. The complementary sex determiner (csd) gene in the honey bee Apis mellifera is an informative example for studying allelic diversity and the underlying evolutionary forces in a well-described model of balancing selection. Acting as the primary signal of sex determination, diploid individuals heterozygous for csd develop into females, whereas csd homozygotes are diploid males that have zero fitness. Examining 77 of the functional heterozygous csd allele pairs, we established a combinatorical criteria that provide insights into the minimum number of amino acid differences among those pairs. Given a data set of 244 csd sequences, we show that the total number of csd alleles found in A. mellifera ranges from 53 (locally) to 87 (worldwide), which is much higher than was previously reported (20). Using a coupon-collector model, we extrapolate the presence of in total 116-145 csd alleles worldwide. The hypervariable region (HVR) is of particular importance in determining csd allele specificity, and we provide for this region evidence of high evolutionary rate for length differences exceeding those of microsatellites. The proportion of amino acids driven by positive selection and the rate of nonsynonymous substitutions in the HVR-flanking regions reach values close to 1 but differ with respect to the HVR length. Using a model of csd coalescence, we identified the high originating rate of csd specificities as a major evolutionary force, leading to an origin of a novel csd allele every 400,000 years. The csd polymorphism frequencies in natural populations indicate an excess of new mutations, whereas signs of ancestral transspecies polymorphism can still be detected. This study provides a comprehensive view of the enormous diversity and the evolutionary forces shaping a multiallelic gene.

Nucleotide Variability at Its Limit? Insights into the Number and Evolutionary Dynamics of the Sex-Determining Specificities of the Honey Bee Apis mellifera

PubMed Central

Lechner, Sarah; Ferretti, Luca; Schöning, Caspar; Kinuthia, Wanja; Willemsen, David; Hasselmann, Martin

2014-01-01

Deciphering the evolutionary processes driving nucleotide variation in multiallelic genes is limited by the number of genetic systems in which such genes occur. The complementary sex determiner (csd) gene in the honey bee Apis mellifera is an informative example for studying allelic diversity and the underlying evolutionary forces in a well-described model of balancing selection. Acting as the primary signal of sex determination, diploid individuals heterozygous for csd develop into females, whereas csd homozygotes are diploid males that have zero fitness. Examining 77 of the functional heterozygous csd allele pairs, we established a combinatorical criteria that provide insights into the minimum number of amino acid differences among those pairs. Given a data set of 244 csd sequences, we show that the total number of csd alleles found in A. mellifera ranges from 53 (locally) to 87 (worldwide), which is much higher than was previously reported (20). Using a coupon-collector model, we extrapolate the presence of in total 116–145 csd alleles worldwide. The hypervariable region (HVR) is of particular importance in determining csd allele specificity, and we provide for this region evidence of high evolutionary rate for length differences exceeding those of microsatellites. The proportion of amino acids driven by positive selection and the rate of nonsynonymous substitutions in the HVR-flanking regions reach values close to 1 but differ with respect to the HVR length. Using a model of csd coalescence, we identified the high originating rate of csd specificities as a major evolutionary force, leading to an origin of a novel csd allele every 400,000 years. The csd polymorphism frequencies in natural populations indicate an excess of new mutations, whereas signs of ancestral transspecies polymorphism can still be detected. This study provides a comprehensive view of the enormous diversity and the evolutionary forces shaping a multiallelic gene. PMID:24170493

Cloning, Characterization and Expression Pattern Analysis of a Cytosolic Copper/Zinc Superoxide Dismutase (SaCSD1) in a Highly Salt Tolerant Mangrove (Sonneratia alba)

PubMed Central

Yang, Enze; Yi, Shanze; Bai, Fang; Niu, Dewei; Zhong, Junjie; Wu, Qiuhong; Chen, Shufang; Zhou, Renchao; Wang, Feng

2015-01-01

Mangroves are critical marine resources for their remarkable ability to tolerate seawater. Antioxidant enzymes play an especially significant role in eliminating reactive oxygen species and conferring abiotic stress tolerance. In this study, a cytosolic copper/zinc superoxide dismutase (SaCSD1) cDNA of Sonneratia alba, a mangrove species with high salt tolerance, was successfully cloned and then expressed in Escherichia coli Rosetta-gami (designated as SaCSD1). SaCSD1 comprised a complete open reading frame (ORF) of 459 bp which encoded a protein of 152 amino acids. Its mature protein is predicted to be 15.32 kDa and the deduced isoelectric point is 5.78. SaCSD1 has high sequence similarity (85%–90%) with the superoxide dismutase (CSD) of some other plant species. SaCSD1 was expressed with 30.6% yield regarding total protein content after being introduced into the pET-15b (Sma I) vector for expression in Rosetta-gami and being induced with IPTG. After affinity chromatography on Ni-NTA, recombinant SaCSD1 was obtained with 3.2-fold purification and a specific activity of 2200 U/mg. SaCSD1 showed good activity as well as stability in the ranges of pH between 3 and 7 and temperature between 25 and 55 °C. The activity of recombinant SaCSD1 was stable in 0.25 M NaCl, Dimethyl Sulphoxide (DMSO), glycerol, and chloroform, and was reduced to a great extent in β-mercaptoethanol, sodium dodecyl sulfate (SDS), H2O2, and phenol. Moreover, the SaCSD1 protein was very susceptive to pepsin digestion. Real-time Quantitative Polymerase Chain Reaction (PCR) assay demonstrated that SaCSD1 was expressed in leaf, stem, flower, and fruit organs, with the highest expression in fruits. Under 0.25 M and 0.5 M salt stress, the expression of SaCSD1 was down-regulated in roots, but up-regulated in leaves. PMID:26703583

Kingella kingae expresses four structurally distinct polysaccharide capsules that differ in their correlation with invasive disease

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

Starr, Kimberly F.; Porsch, Eric A.; Seed, Patrick C.

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), allmore » encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. Lastly, these results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease« less

Kingella kingae expresses four structurally distinct polysaccharide capsules that differ in their correlation with invasive disease

DOE PAGES

Starr, Kimberly F.; Porsch, Eric A.; Seed, Patrick C.; ...

2016-10-19

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), allmore » encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. Lastly, these results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease« less

Do the accelerating actions of tianeptine and l-arginine on cortical spreading depression interact? An electrophysiological analysis in young and adult rats.

PubMed

Maia, Luciana Maria Silva de Seixas; Amancio-Dos-Santos, Angela; Germano, Paula Catirina Pereira da Silva; Falcão, Anna Carolina Santos Marinho; Duda-de-Oliveira, Desirré; Guedes, Rubem Carlos Araújo

2017-05-22

In the rat, we previously demonstrated that serotonin-enhancing drugs impair cortical spreading depression (CSD) and that l-arginine (arginine) treatment enhances CSD. Here, we investigated the interaction between topical application of the serotonin uptake enhancer tianeptine and systemic arginine administration on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage 300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water-treated rats underwent CSD recording at 30-40days of age (young), while the other half was recorded at 90-120days (adult). Following baseline recording (four episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular portion of the intact dura mater for 10-min and then elicited CSD. This procedure was repeated three times. Compared to baseline values, CSD velocities and amplitudes following tianeptine application increased, and CSD duration decreased significantly (p<0.05) in both young and adult rats, regardless of treatment group. CSD acceleration caused by systemic treatment with arginine is in agreement with previous findings. Topical cortical application of tianeptine replicated the effect of systemic application, suggesting a cortically based mechanism for tianeptine's action. However, the absence of interaction between arginine and tianeptine treatments suggests that they probably act through separate mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular Characterization of Caveolin-induced Membrane Curvature*

PubMed Central

Ariotti, Nicholas; Rae, James; Leneva, Natalya; Ferguson, Charles; Loo, Dorothy; Okano, Satomi; Hill, Michelle M.; Walser, Piers; Collins, Brett M.; Parton, Robert G.

2015-01-01

The generation of caveolae involves insertion of the cholesterol-binding integral membrane protein caveolin-1 (Cav1) into the membrane, however, the precise molecular mechanisms are as yet unknown. We have speculated that insertion of the caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in interactions with signaling proteins, is crucial for caveola formation. We now define the core membrane-juxtaposed region of Cav1 and show that the oligomerization domain and CSD are protected by tight association with the membrane in both mature mammalian caveolae and a model prokaryotic system for caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed domain to be sufficient to maintain oligomerization as defined by polyhedral distortion of the caveolar membrane. Through mutagenesis we demonstrate the importance of the membrane association of the oligomerization domain/CSD for defined caveola biogenesis and furthermore, highlight the functional significance of the intramembrane domain and the CSD for defined caveolin-induced membrane deformation. Finally, we define the core structural domain of Cav1, constituting only 66 amino acids and of great potential to nanoengineering applications, which is required for caveolin-induced vesicle formation in a bacterial system. These results have significant implications for understanding the role of Cav1 in caveola formation and in regulating cellular signaling events. PMID:26304117

Molecular Characterization of Caveolin-induced Membrane Curvature.

PubMed

Ariotti, Nicholas; Rae, James; Leneva, Natalya; Ferguson, Charles; Loo, Dorothy; Okano, Satomi; Hill, Michelle M; Walser, Piers; Collins, Brett M; Parton, Robert G

2015-10-09

The generation of caveolae involves insertion of the cholesterol-binding integral membrane protein caveolin-1 (Cav1) into the membrane, however, the precise molecular mechanisms are as yet unknown. We have speculated that insertion of the caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in interactions with signaling proteins, is crucial for caveola formation. We now define the core membrane-juxtaposed region of Cav1 and show that the oligomerization domain and CSD are protected by tight association with the membrane in both mature mammalian caveolae and a model prokaryotic system for caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed domain to be sufficient to maintain oligomerization as defined by polyhedral distortion of the caveolar membrane. Through mutagenesis we demonstrate the importance of the membrane association of the oligomerization domain/CSD for defined caveola biogenesis and furthermore, highlight the functional significance of the intramembrane domain and the CSD for defined caveolin-induced membrane deformation. Finally, we define the core structural domain of Cav1, constituting only 66 amino acids and of great potential to nanoengineering applications, which is required for caveolin-induced vesicle formation in a bacterial system. These results have significant implications for understanding the role of Cav1 in caveola formation and in regulating cellular signaling events. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular identification and characterization of clustered regularly interspaced short palindromic repeat (CRISPR) gene cluster in Taylorella equigenitalis.

PubMed

Hara, Yasushi; Hayashi, Kyohei; Nakajima, Takuya; Kagawa, Shizuko; Tazumi, Akihiro; Moore, John E; Matsuda, Motoo

2013-09-01

Clustered regularly interspaced short palindromic repeats (CRISPRs), of approximately 10,000 base pairs (bp) in length, were shown to occur in the Japanese Taylorella equigenitalis strain, EQ59. The locus was composed of the putative CRISPRs-associated with 5 (cas5), RAMP csd1, csd2, recB, cas1, a leader region, 13 CRISPR consensus sequence repeats (each 32 bp; 5'-TCAGCCACGTTCGCGTGGCTGTGTGTTTAAAG-3'). These were in turn separated by 12 non repetitive unique spacer regions of similar length. In addition, a leader region, a transposase/IS protein, a leader region, and cas3 were also seen. All seven putative open reading frames carry their ribosome binding sites. Promoter consensus sequences at the -35 and -10 regions and putative intrinsic ρ-independent transcription terminator regions also occurred. A possible long overlap of 170 bp in length occurred between the recB and cas1 loci. Positive reverse transcription PCR signals of cas5, RAMP csd1, csd2-recB/cas1, and cas3 were generated. A putative secondary structure of the CRISPR consensus repeats was constructed. Following this, CRISPR results of the T. equigenitalis EQ59 isolate were subsequently compared with those from the Taylorella asinigenitalis MCE3 isolate.

Differential regulation of cell functions by CSD peptide subdomains

PubMed Central

2013-01-01

Background In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82–101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A). Methods Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients. Results Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide. Conclusions Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types. PMID:24011378

Differential regulation of cell functions by CSD peptide subdomains.

PubMed

Reese, Charles; Dyer, Shanice; Perry, Beth; Bonner, Michael; Oates, James; Hofbauer, Ann; Sessa, William; Bernatchez, Pascal; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley; Tourkina, Elena

2013-09-08

In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82-101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A). Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients. Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide. Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types.

Evolution of the complementary sex-determination gene of honey bees: balancing selection and trans-species polymorphisms.

PubMed

Cho, Soochin; Huang, Zachary Y; Green, Daniel R; Smith, Deborah R; Zhang, Jianzhi

2006-11-01

The mechanism of sex determination varies substantively among evolutionary lineages. One important mode of genetic sex determination is haplodiploidy, which is used by approximately 20% of all animal species, including >200,000 species of the entire insect order Hymenoptera. In the honey bee Apis mellifera, a hymenopteran model organism, females are heterozygous at the csd (complementary sex determination) locus, whereas males are hemizygous (from unfertilized eggs). Fertilized homozygotes develop into sterile males that are eaten before maturity. Because homozygotes have zero fitness and because common alleles are more likely than rare ones to form homozygotes, csd should be subject to strong overdominant selection and negative frequency-dependent selection. Under these selective forces, together known as balancing selection, csd is expected to exhibit a high degree of intraspecific polymorphism, with long-lived alleles that may be even older than the species. Here we sequence the csd genes as well as randomly selected neutral genomic regions from individuals of three closely related species, A. mellifera, Apis cerana, and Apis dorsata. The polymorphic level is approximately seven times higher in csd than in the neutral regions. Gene genealogies reveal trans-species polymorphisms at csd but not at any neutral regions. Consistent with the prediction of rare-allele advantage, nonsynonymous mutations are found to be positively selected in csd only in early stages after their appearances. Surprisingly, three different hypervariable repetitive regions in csd are present in the three species, suggesting variable mechanisms underlying allelic specificities. Our results provide a definitive demonstration of balancing selection acting at the honey bee csd gene, offer insights into the molecular determinants of csd allelic specificities, and help avoid homozygosity in bee breeding.

Motivating factors influencing choice of major in undergraduates in communication sciences and disorders.

PubMed

Keshishian, Flora; McGarr, Nancy S

2012-04-01

The purposes of this study were to determine: (1) whether background factors influence the choice of Communication Sciences and Disorders (CSD) as an academic major; (2) what motivates students to major in CSD; (3) the relationship between motivation to pursue CSD as a major and the attractiveness of the major; and (4) whether motivation influences the perceived value of a career in CSD. A survey of 143 undergraduates was created and administered to assess motivational factors that influence the choice of major. The participants had diverse ethnic/racial and cultural backgrounds and were enrolled in CSD courses in the Liberal Arts College of St John's University, a US American Institution in Queens, New York. Preliminary analyses indicated that ethnic/racial background and family income had no statistically significant relationship to motivations, attractiveness of CSD as a major, or career value of CSD as a major. Students scored highest on Intrinsic motivation factor (e.g., enjoy interacting with people) and the lowest on Science motivation (e.g., interested in science). Student confidence (e.g., in reaching career goals) was an important predictor in the perception of the career value of a CSD. Results of this study provide further insight into curriculum development and recruiting strategies.

Exploring the role of microglia in cortical spreading depression in neurological disease

PubMed Central

Suzuki, Norihiro

2017-01-01

Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly propagating (2–5 mm/min) wave of rapid, near-complete depolarization of neurons and astrocytes followed by a period of electrical suppression of a distinct population of cortical neurons. Not only has CSD been implicated in brain migraine aura, but CSD-like events have also been detected in stroke and traumatic injury. CSD causes a considerable perturbation of the ionic environment in the brain, which may be readily detected by microglia. Although CSD is known to activate microglia, the role of microglial activation in CSD-related neurological disorders remains poorly understood. In this article, we first provide an overview of microglial development and the multiple functions of microglia. Then, we review existing data on the relationship between microglia and CSD and discuss the relevance of CSD-induced microglial activation in neurological disease. PMID:28155572

Bridging the gap between continuous sedation until death and physician-assisted death: a focus group study in nursing homes in Flanders, Belgium.

PubMed

Rys, Sam; Deschepper, Reginald; Mortier, Freddy; Deliens, Luc; Bilsen, Johan

2015-06-01

The distinction between continuous sedation until death (CSD) and physician-assisted death (PAD) has become a topic of medical ethical debate. We conducted 6 focus groups to examine how nursing home clinicians perceive this distinction. For some, the difference is clear whereas others consider CSD a form of euthanasia. Another group situates CSD between pain relief and ending life. Arguments for these perspectives refer to the following themes: intention, dosage of sedative drugs, unconsciousness, and the pace of the dying process. Generally, CSD is considered emotionally easier to deal with since it entails a gradual dying process. Nursing home clinicians have diverging perceptions of the relation between CSD and PAD; some consider CSD to be more than a purely palliative measure, that is, also as a means to hasten death. © The Author(s) 2014.

Isotopomer-selective spectra of a single intact H2O molecule in the Cs+(D2O)5H2O isotopologue: Going beyond pattern recognition to harvest the structural information encoded in vibrational spectra

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

Wolke, Conrad T.; Fournier, Joseph A.; Miliordos, Evangelos

We report the vibrational signatures of a single H2O water molecule occupying distinct sites of the hydration network in the Cs+(H2O)6 cluster. This is accomplished using isotopomer selective IR-IR hole-burning on the Cs+(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs+(D2O)6 ion. The OH stretching pattern of the Cs+(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structuralmore » information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs+(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs+(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy (ZPE). With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions.« less

Oral bioavailability enhancement of β-lapachone, a poorly soluble fast crystallizer, by cocrystal, amorphous solid dispersion, and crystalline solid dispersion.

PubMed

Liu, Chengyu; Liu, Zhengsheng; Chen, Yuejie; Chen, Zhen; Chen, Huijun; Pui, Yipshu; Qian, Feng

2018-03-01

The aim of this paper was to compare the in vitro dissolution and in vivo bioavailability of three solubility enhancement technologies for β-lapachone (LPC), a poorly water soluble compound with extremely high crystallization propensity. LPC cocrystal was prepared by co-grinding LPC with resorcinol. LPC crystalline and amorphous solid dispersions (CSD and ASD) were obtained by spray drying with Poloxamer 188 and HPMC-AS, respectively. The cocrystal structure was solved by single crystal x-ray diffraction. All formulations were characterized by WAXRD, DSC, POM and SEM. USP II and intrinsic dissolution studies were used to compare the in vitro dissolution of these formulations, and a crossover dog pharmacokinetic study was used to compare their in vivo bioavailability. An 1:1 LPC-resorcinol cocrystal with higher solubility and faster dissolution rate was obtained, yet it converted to LPC crystal rapidly in solution. LPC/HPMC-AS ASD was confirmed to be amorphous and uniform, while the crystal and crystallite sizes of LPC in CSD were found to be ∼1-3 μm and around 40 nm, respectively. These formulations performed similarly during USP II dissolution, while demonstrated dramatically different oral bioavailability of ∼32%, ∼5%, and ∼1% in dogs, for CSD, co-crystal, and ASD, respectively. CSD showed the fastest intrinsic dissolution rate among the three. The three formulations showed poor IVIVC which could be due to rapid and unpredictable crystallization kinetics. Considering all the reasons, we conclude that for molecules with extremely high crystallization tendency that cannot be inhibited by any pharmaceutical excipients, size-reduction technologies such as CSD could be advantageous for oral bioavailability enhancement in vivo than technologies only generating transient but not sustained supersaturation. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

PubMed Central

Green, A Laine; Gu, Pengfei; De Felice, Milena; Dodick, David; Ossipov, Michael H; Porreca, Frank

2014-01-01

Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans. PMID:24335852

CSD Fans and Disjointed CSD Bundles: Recovery of The Spatial Sample Locations from CSD Ensembles

NASA Astrophysics Data System (ADS)

Marsh, B. D.; Zieg, M. J.

2001-05-01

Volcanic rock captures magmatic time through eruption and quenching, but its spatial connection to the parent magma has been scrambled. It is an aliquot of magma from an unknown position within the magmatic body, and its relation to other coeval and comagmatic samples is also unknown. P-T determinations, although invaluable are not precise enough to arrange successive samples with any real certainty within the magmatic regime. This is a severe limitation in using lavas to infer magma chamber processes. We have developed a technique that allows the relative spatial order of comagmatic samples in the magmatic environment to be recovered. The method rests on a recent advance in CSD analysis. We have been able to show that CSD slope (S) and intercept (I) are linked through a universal relation (Zieg and Marsh, 2001, sub. J. Pet.). The CSDs of all igneous rocks fall on this I-S curve. Moreover, it can also be shown that CSD slope is inversely related to mean crystal size (S=1/Lm) and also that mean crystal size is the product of mean growth rate (G) and solidification time (Dt). That is, Lm = GDt. (The exact form of this growth law is completely arbitrary.). Because the rate of solidification front (SF) advance decreases as it propagates inward, local solidification time increases and so does mean crystal size, but nucleation rate must, in accordance with the universal I-S relation, decrease. The CSD slope thus must decrease systematically inward in the body, and a series of spatially contiguous CSDs thus form a fan. (This solves the mystery of CSD pivot points and of the often noticed correlation between CSD slope and intercept (Marsh et al., 1995 EOS).) A series of fanning CSDs for the Sudbury norite melt sheet match exactly the CSD fan calculated from the I - S relation. CSD slope decreases inward from the margins of the body as Lm increases due to increasing solidification time. Given a set of blind samples from a pluton, the order of the CSDs in a fan determines the relative position of the samples. And the maximum crystal size in each CSD measures the local solidification time, which indicates - through a generalized thermal model (Zieg & Marsh, 2001) - the true position in the body. That similar CSD fans are also found in active magmatic systems can be seen from the CSDs through the active upper SF of Makaopuhi lava lake (Cashman & Marsh, 1988). Here, however, the order of the fan is reversed. The steepest slope (smallest crystals) is deepest in the body, closest to the liquidus. Maximum crystal size and crystallinity decrease inward (increasing depth), and the order of the CSDs in the fan thus give the sample order within the SF. The reverse orders of active SF and pluton CSD fans are reconciled by realizing that the pluton CSD is set at the solidus, which means that the CSD continues to decrease in slope with increasing crystallization until it reaches the limit set by the thermal regime at the exact spatial position of the present solidus. This is a fundamentally important realization. It means that, because SFs reflect a thermal gradient, CSD fans record the progress of SFs. Many comagmatic volcanic suites (e.g., OPD 504B, Atka, Dome Mtn.) also show similar CSD fans. CSDs in comagmatic lava sequences that do not fall into a fan or belong to another fan may represent separate batches of the same parent body or different magmas with different histories. These CSDs often fall into two groups: Those of similar slope and different intercept and those of the same intercept but different slope. We call these disjointed bundles and discuss their interpretation.

The Sex Determination Gene Shows No Founder Effect in the Giant Honey Bee, Apis dorsata

PubMed Central

Yan, Wei Yu; Wu, Xiao Bo; Zeng, Zhi Jiang; Huang, Zachary Y.

2012-01-01

Background All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland. Methodology/Principal Findings We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia. Conclusions/Significance Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species. PMID:22511940

Deep Sequencing Analysis of RNAs from Citrus Plants Grown in a Citrus Sudden Death-Affected Area Reveals Diverse Known and Putative Novel Viruses.

PubMed

Matsumura, Emilyn E; Coletta-Filho, Helvecio D; Nouri, Shahideh; Falk, Bryce W; Nerva, Luca; Oliveira, Tiago S; Dorta, Silvia O; Machado, Marcos A

2017-04-24

Citrus sudden death (CSD) has caused the death of approximately four million orange trees in a very important citrus region in Brazil. Although its etiology is still not completely clear, symptoms and distribution of affected plants indicate a viral disease. In a search for viruses associated with CSD, we have performed a comparative high-throughput sequencing analysis of the transcriptome and small RNAs from CSD-symptomatic and -asymptomatic plants using the Illumina platform. The data revealed mixed infections that included Citrus tristeza virus (CTV) as the most predominant virus, followed by the Citrus sudden death-associated virus (CSDaV), Citrus endogenous pararetrovirus (CitPRV) and two putative novel viruses tentatively named Citrus jingmen-like virus (CJLV), and Citrus virga-like virus (CVLV). The deep sequencing analyses were sensitive enough to differentiate two genotypes of both viruses previously associated with CSD-affected plants: CTV and CSDaV. Our data also showed a putative association of the CSD-symptomatic plants with a specific CSDaV genotype and a likely association with CitPRV as well, whereas the two putative novel viruses showed to be more associated with CSD-asymptomatic plants. This is the first high-throughput sequencing-based study of the viral sequences present in CSD-affected citrus plants, and generated valuable information for further CSD studies.

The sex determination gene shows no founder effect in the giant honey bee, Apis dorsata.

PubMed

Liu, Zhi Yong; Wang, Zi Long; Yan, Wei Yu; Wu, Xiao Bo; Zeng, Zhi Jiang; Huang, Zachary Y

2012-01-01

All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland. We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia. Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species.

Group Independent Component Analysis (gICA) and Current Source Density (CSD) in the study of EEG in ADHD adults.

PubMed

Ponomarev, Valery A; Mueller, Andreas; Candrian, Gian; Grin-Yatsenko, Vera A; Kropotov, Juri D

2014-01-01

To investigate the performance of the spectral analysis of resting EEG, Current Source Density (CSD) and group independent components (gIC) in diagnosing ADHD adults. Power spectra of resting EEG, CSD and gIC (19 channels, linked ears reference, eyes open/closed) from 96 ADHD and 376 healthy adults were compared between eyes open and eyes closed conditions, and between groups of subjects. Pattern of differences in gIC and CSD spectral power between conditions was approximately similar, whereas it was more widely spatially distributed for EEG. Size effect (Cohen's d) of differences in gIC and CSD spectral power between groups of subjects was considerably greater than in the case of EEG. Significant reduction of gIC and CSD spectral power depending on conditions was found in ADHD patients. Reducing power in a wide frequency range in the fronto-central areas is a common phenomenon regardless of whether the eyes were open or closed. Spectral power of local EEG activity isolated by gICA or CSD in the fronto-central areas may be a suitable marker for discrimination of ADHD and healthy adults. Spectral analysis of gIC and CSD provides better sensitivity to discriminate ADHD and healthy adults. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Electronegativity Equalization Method: Parameterization and Validation for Large Sets of Organic, Organohalogene and Organometal Molecule

PubMed Central

Vařeková, Radka Svobodová; Jiroušková, Zuzana; Vaněk, Jakub; Suchomel, Šimon; Koča, Jaroslav

2007-01-01

The Electronegativity Equalization Method (EEM) is a fast approach for charge calculation. A challenging part of the EEM is the parameterization, which is performed using ab initio charges obtained for a set of molecules. The goal of our work was to perform the EEM parameterization for selected sets of organic, organohalogen and organometal molecules. We have performed the most robust parameterization published so far. The EEM parameterization was based on 12 training sets selected from a database of predicted 3D structures (NCI DIS) and from a database of crystallographic structures (CSD). Each set contained from 2000 to 6000 molecules. We have shown that the number of molecules in the training set is very important for quality of the parameters. We have improved EEM parameters (STO-3G MPA charges) for elements that were already parameterized, specifically: C, O, N, H, S, F and Cl. The new parameters provide more accurate charges than those published previously. We have also developed new parameters for elements that were not parameterized yet, specifically for Br, I, Fe and Zn. We have also performed crossover validation of all obtained parameters using all training sets that included relevant elements and confirmed that calculated parameters provide accurate charges.

Ion diffusion may introduce spurious current sources in current-source density (CSD) analysis.

PubMed

Halnes, Geir; Mäki-Marttunen, Tuomo; Pettersen, Klas H; Andreassen, Ole A; Einevoll, Gaute T

2017-07-01

Current-source density (CSD) analysis is a well-established method for analyzing recorded local field potentials (LFPs), that is, the low-frequency part of extracellular potentials. Standard CSD theory is based on the assumption that all extracellular currents are purely ohmic, and thus neglects the possible impact from ionic diffusion on recorded potentials. However, it has previously been shown that in physiological conditions with large ion-concentration gradients, diffusive currents can evoke slow shifts in extracellular potentials. Using computer simulations, we here show that diffusion-evoked potential shifts can introduce errors in standard CSD analysis, and can lead to prediction of spurious current sources. Further, we here show that the diffusion-evoked prediction errors can be removed by using an improved CSD estimator which accounts for concentration-dependent effects. NEW & NOTEWORTHY Standard CSD analysis does not account for ionic diffusion. Using biophysically realistic computer simulations, we show that unaccounted-for diffusive currents can lead to the prediction of spurious current sources. This finding may be of strong interest for in vivo electrophysiologists doing extracellular recordings in general, and CSD analysis in particular. Copyright © 2017 the American Physiological Society.

The doublesex gene integrates multi-locus complementary sex determination signals in the Japanese ant, Vollenhovia emeryi.

PubMed

Miyakawa, Misato Okamoto; Tsuchida, Koji; Miyakawa, Hitoshi

2018-03-01

A female diploid, male haploid sex determination system (haplodiploidy) is found in hymenopteran taxa, such as ants, wasps, bees and sawflies. In this system, a single, complementary sex-determination (sl-CSD) locus functions as the primary sex-determination signal. In the taxa that has evolved this system, females and males are heterozygous and hemi/homozygous at the CSD locus, respectively. While the sl-CSD system enables females to alter sex ratios in the nest, it carries a high cost in terms of inbreeding, as individuals that are homozygous at the CSD locus become sterile diploid males. To counter this risk, some of hymenopteran species have evolved a multi-locus CSD (ml-CSD) system, which effectively reduces the proportion of sterile males. However, the mechanism by which these multiple primary signals are integrated and how they affect the terminal sex-differentiation signal of the molecular cascade have not yet been clarified. To resolve these questions, we examined the molecular cascade in the Japanese ant Vollenhovia emeryi, which we previously confirmed has two CSD loci. Here, we showed that the sex-determination gene, doublesex (dsx), which is highly conserved among phylogenetically distant taxa, is responsible for integrating two CSD signals in V. emeryi. After identifying and characterizing dsx, genotypes containing two CSD loci and splicing patterns of dsx were found to correspond to the sexual phenotype, suggesting that two primary signals are integrated into dsx. These findings will facilitate future molecular and functional studies of the sex determination cascade in V. emeryi, and shed light on the evolution and diversification of sex determination systems in insects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Similar but not the same: insights into the evolutionary history of paralogous sex-determining genes of the dwarf honey bee Apis florea.

PubMed

Biewer, M; Lechner, S; Hasselmann, M

2016-01-01

Studying the fate of duplicated genes provides informative insight into the evolutionary plasticity of biological pathways to which they belong. In the paralogous sex-determining genes complementary sex determiner (csd) and feminizer (fem) of honey bee species (genus Apis), only heterozygous csd initiates female development. Here, the full-length coding sequences of the genes csd and fem of the phylogenetically basal dwarf honey bee Apis florea are characterized. Compared with other Apis species, remarkable evolutionary changes in the formation and localization of a protein-interacting (coiled-coil) motif and in the amino acids coding for the csd characteristic hypervariable region (HVR) are observed. Furthermore, functionally different csd alleles were isolated as genomic fragments from a random population sample. In the predicted potential specifying domain (PSD), a high ratio of πN/πS=1.6 indicated positive selection, whereas signs of balancing selection, commonly found in other Apis species, are missing. Low nucleotide diversity on synonymous and genome-wide, non-coding sites as well as site frequency analyses indicated a strong impact of genetic drift in A. florea, likely linked to its biology. Along the evolutionary trajectory of ~30 million years of csd evolution, episodic diversifying selection seems to have acted differently among distinct Apis branches. Consistently low amino-acid differences within the PSD among pairs of functional heterozygous csd alleles indicate that the HVR is the most important region for determining allele specificity. We propose that in the early history of the lineage-specific fem duplication giving rise to csd in Apis, A. florea csd stands as a remarkable example for the plasticity of initial sex-determining signals.

Anxious, introverted personality traits in patients with chronic subjective dizziness.

PubMed

Staab, Jeffrey P; Rohe, Daniel E; Eggers, Scott D Z; Shepard, Neil T

2014-01-01

Chronic subjective dizziness (CSD) is a neurotologic disorder of persistent non-vertiginous dizziness, unsteadiness, and hypersensitivity to one's own motion or exposure to complex visual stimuli. CSD usually follows acute attacks of vertigo or dizziness and is thought to arise from patients' failure to re-establish normal locomotor control strategies after resolution of acute vestibular symptoms. Pre-existing anxiety or anxiety diathesis may be risk factors for CSD. This study tested the hypothesis that patients with CSD are more likely than individuals with other chronic neurotologic illnesses to possess anxious, introverted personality traits. Data were abstracted retrospectively from medical records of 40 patients who underwent multidisciplinary neurotology evaluations for chronic dizziness. Twenty-four subjects had CSD. Sixteen had chronic medical conditions other than CSD plus co-existing anxiety disorders. Group differences in demographics, Dizziness Handicap Inventory (DHI) scores, Hospital Anxiety and Depression Scale (HADS) scores, DSM-IV diagnoses, personality traits measured with the NEO Personality Inventory - Revised (NEO-PI-R), and temperaments composed of NEO-PI-R facets were examined. There were no differences between groups in demographics, mean DHI or HADS-anxiety scores, or DSM-IV diagnoses. The CSD group had higher mean HADS-depression and NEO-PI-R trait anxiety, but lower NEO-PI-R extraversion, warmth, positive emotions, openness to feelings, and trust (all p<0.05). CSD subjects were significantly more likely than comparison subjects to have a composite temperament of high trait anxiety plus low warmth or excitement seeking. An anxious, introverted temperament is strongly associated with CSD and may be a risk factor for developing this syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Models for the mechanism for activating copper-zinc superoxide dismutase in the absence of the CCS Cu chaperone in Arabidopsis.

PubMed

Huang, Chien-Hsun; Kuo, Wen-Yu; Jinn, Tsung-Luo

2012-03-01

Copper-zinc superoxide dismutase (CuZnSOD; CSD) is an important antioxidant enzyme for oxidative stress protection. To date, two activation pathways have been identified in many species. One requiring the CCS, Cu chaperone for SOD, to insert Cu and activate CSD (referred to as CCS-dependent pathway), and the other works independently of CCS (referred to as CCS-independent pathway). In our previous study, we suggest an unidentified factor will work with glutathione (GSH) for CSD activation in the absence of the CCS. Here, two models of the CCS-independent mechanism are proposed. The role of the unidentified factor may work as a scaffold protein, which provides a platform for the CSD protein and Cu-GSH to interact, or as a Cu carrier, which itself can bind Cu and interact with CSD proteins. We also suggest that the CSD protein conformation at C-terminal is important in providing a docking site for unidentified factor to access.

B-mode sonographic criteria for differential diagnosis of cervicofacial lymphadenopathy in cat-scratch disease and toxoplasmosis.

PubMed

Ridder, Gerd Jürgen; Boedeker, Carsten Christof; Lee, Tao-Kwang Kevin; Sander, Anna

2003-04-01

Our purpose was to evaluate different sonographic parameters of cervicofacial lymphadenopathy caused by cat-scratch disease (CSD) and toxoplasmosis. By use of high-resolution B-mode sonography a total of 552 lymph nodes in the head and neck were detected between January 1997 and December 2001. There were 71 patients (422 lymph nodes) with CSD and 19 patients (130 lymph nodes) with toxoplasmosis. Sonographic variables, including 20 sonomorphologic features along with age and gender, were analyzed with multivariate logistic regression. Heterogenous lymph nodes were more often found in CSD (p =.003), and nonsharp nodal borders showed a significant association with CSD (p =.0005). Multivariate analysis identified sharpness of borders (p =.0001), S/L ratio (p =.0006), and type of lymphadenopathy (acute, abscessed, chronic) (p =.0006) as most significant for differentiating between CSD and toxoplasmosis. These results provide significant and useful criteria for ultrasonographic differentiation between CSD and toxoplasmosis. Copyright 2003 Wiley Periodicals, Inc.

Bridging dermatologists with patient advocacy organizations through smartphones.

PubMed

Kourosh, A Shadi; Schoenberg, Evan D; Dejace, Jean M; Bergstresser, Paul R

2014-03-01

Patient advocacy organizations seek to increase their benefits for patients with skin disease; low awareness and patient referrals among dermatologists have presented an obstacle to this. To determine whether the Skin Advocate iPhone App would increase awareness and referrals to patient advocacy organizations in the Coalition of Skin Diseases (CSD) among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations. We present results of an institutional review board-exempted investigation conducted among member organizations of the CSD and among dermatologists and dermatology residents in Texas from April 1, 2011, through March 31, 2013. Effects were measured in a blinded fashion subjectively through pre-intervention and post-intervention surveys and objectively through internal analytics that tracked downloads and use of the iPhone app, as well as pre-intervention and post-intervention numbers of registrations for CSD member organizations. The Skin Advocate iPhone App. Awareness and referrals to patient advocacy organizations in the CSD among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations. Throughout the study, mean app use ranged from 3.3 to 3.6 uses per user per month, maintaining the 3-fold improvement compared with self-reported referral for 90% of the study population and a 12-fold improvement for 64% of the study population. Our data revealed substantial improvement in self-reported physician awareness and referrals, and increased patient registrations for CSD organizations. The Skin Advocate iPhone App improved physician awareness and subsequent referrals to CSD member organizations.

Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine.

PubMed

Eising, Else; Shyti, Reinald; 't Hoen, Peter A C; Vijfhuizen, Lisanne S; Huisman, Sjoerd M H; Broos, Ludo A M; Mahfouz, Ahmed; Reinders, Marcel J T; Ferrari, Michel D; Tolner, Else A; de Vries, Boukje; van den Maagdenberg, Arn M J M

2017-05-01

Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α 1A subunit of voltage-gated Ca V 2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.

Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1.

PubMed

Weng, Ping; Zhang, Xiao-Tong; Sheng, Qiong; Tian, Wen-Fang; Chen, Jun-Liang; Yuan, Jia-Jia; Zhang, Ji-Ru; Pang, Qing-Feng

2017-06-20

Caveolin-1(Cav-1) scaffolding domain (CSD) peptides compete with the plasma membrane Cav-1, inhibit the interaction of the proteins and Cav-1, and re-store the functions of Cav-1 binding proteins. Heme oxygenase-1 (HO-1) binds to Cav-1 and its enzymatic activity was inhibited. In this study, we investigated the effect of CSD peptides on interaction between HO-1 and Cav-1, and on the HO-1 activity in vitro and in vivo. Our data showed that CSD peptides decreased the compartmentalization of HO-1 and Cav-1, and increased the HO-1 activity both in LPS-treated alveolar macrophages and in mice. Meanwhile, CSD peptides obviously ameliorated the pathology changes in mice and lowered the following injury indexes: the wet/dry ratio of lung tissues, total cell numbers in bronchoalveolar lavage fluid and lactate dehydrogenase activity in the serum. Mechanistically, it was firstly found that CSD peptides promoted alveolar macrophages polarization to M2 phenotype and inhibited the IκB degeneration. Furthermore, CSD peptides down-regulated the expression of IL-1β, IL-6, TNF-α, MCP-1, and iNOS in alveolar macrophages and in lung tissue. However, the protective role of CSD peptides on LPS-induced acute lung injury in mice could be abolished by zinc protoporphyrin IX (ZnPP, a HO-1 activity inhibitor). In summary, CSD peptides have beneficial anti-inflammatory effects by restoring the HO-1 activity suppressed by Cav-1 on plasma membrane.

Cortical spreading depression as a target for anti-migraine agents

PubMed Central

2013-01-01

Spreading depression (SD) is a slowly propagating wave of neuronal and glial depolarization lasting a few minutes, that can develop within the cerebral cortex or other brain areas after electrical, mechanical or chemical depolarizing stimulations. Cortical SD (CSD) is considered the neurophysiological correlate of migraine aura. It is characterized by massive increases in both extracellular K+ and glutamate, as well as rises in intracellular Na+ and Ca2+. These ionic shifts produce slow direct current (DC) potential shifts that can be recorded extracellularly. Moreover, CSD is associated with changes in cortical parenchymal blood flow. CSD has been shown to be a common therapeutic target for currently prescribed migraine prophylactic drugs. Yet, no effects have been observed for the antiepileptic drugs carbamazepine and oxcarbazepine, consistent with their lack of efficacy on migraine. Some molecules of interest for migraine have been tested for their effect on CSD. Specifically, blocking CSD may play an enabling role for novel benzopyran derivative tonabersat in preventing migraine with aura. Additionally, calcitonin gene-related peptide (CGRP) antagonists have been recently reported to inhibit CSD, suggesting the contribution of CGRP receptor activation to the initiation and maintenance of CSD not only at the classic vascular sites, but also at a central neuronal level. Understanding what may be lying behind this contribution, would add further insights into the mechanisms of actions for “gepants”, which may be pivotal for the effectiveness of these drugs as anti-migraine agents. CSD models are useful tools for testing current and novel prophylactic drugs, providing knowledge on mechanisms of action relevant for migraine. PMID:23879550

The use of current source density as electrophysiological correlates in neuropsychiatric disorders: a review of human studies

PubMed Central

Kamarajan, Chella; Pandey, Ashwini K.; Chorlian, David B.; Porjesz, Bernice

2014-01-01

The use of current source density (CSD), the Laplacian of the scalp surface voltage, to map the electrical activity of the brain is a powerful method in studies of cognitive and affective phenomena. During the last few decades, mapping of CSD has been successfully applied to characterize several neuropsychiatric conditions such as alcoholism, schizophrenia, depression, anxiety disorders, childhood/developmental disorders, and neurological conditions (i.e., epilepsy and brain lesions) using electrophysiological data from resting state and during cognitive performance. Use of CSD and Laplacian measures has proven effective in elucidating topographic and activation differences between groups: i) patients with a specific diagnosis vs. healthy controls, ii) subjects at high risk for a specific diagnosis vs. low risk or normal controls, and iii) patients with specific symptom(s) vs. patients without these symptom(s). The present review outlines and summarizes the studies that have employed CSD measures in investigating several neuropsychiatric conditions. The advantages and potential of CSD-based methods in clinical and research applications along with some of the limitations inherent in the CSD-based methods are discussed in the review, as well as future directions to expand the implementation of CSD to other potential clinical applications. As CSD methods have proved to be more advantageous than using scalp potential data to understand topographic and source activations, its clinical applications offer promising potential, not only for a better understanding of a range of psychiatric conditions, but also for a variety of focal neurological disorders, including epilepsy and other conditions involving brain lesions and surgical interventions. PMID:25448264

A Taxonomy of Consumer Satisfaction/Dissatisfaction Measures

ERIC Educational Resources Information Center

Andreasen, Alan R.

1977-01-01

Government and business have become more concerned with measuring market performance in terms of consumer satisfactions and dissatisfactions (CS/D). This research is concerned with the question of how one ought to measure CS/D. Offers a taxonomy of alternative CS/D measures and presents data from a national urban study of consumer complaints to…

Polyethylene glycol-conjugated chondroitin sulfate A derivative nanoparticles for tumor-targeted delivery of anticancer drugs.

PubMed

Lee, Jae-Young; Park, Ju-Hwan; Lee, Jeong-Jun; Lee, Song Yi; Chung, Suk-Jae; Cho, Hyun-Jong; Kim, Dae-Duk

2016-10-20

Polyethylene glycol (PEG)-decorated chondroitin sulfate A-deoxycholic acid (CSD) nanoparticles (NPs) were fabricated for the selective delivery of doxorubicin (DOX) to ovarian cancer. CSD-PEG was synthesized via amide bond formation between the NH2 group of methoxypolyethylene glycol amine and the COOH group of CSD. CSD-PEG/DOX NPs with a 247nm mean diameter, negative zeta potential, and >90% drug encapsulation efficiency were prepared. Sustained and pH-dependent DOX release profiles from CSD-PEG NPs were observed in dissolution tests. Endocytosis of NPs by SKOV-3 cells (CD44 receptor-positive human ovarian cancer cells), based on the CSA-CD44 receptor interaction, was determined by flow cytometry and confocal laser scanning microscopy (CLSM) studies. PEGylation of NPs also resulted in reduced drug clearance (CL) in vivo and improved relative bioavailability, compared to non-PEGylated NPs, as determined by the pharmacokinetic study performed after intravenous administration in rats. Developed CSD-PEG NPs can be a promising delivery vehicle for the therapy of CD44 receptor-expressing ovarian cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase.

PubMed

Fuertig, René; Azzinnari, Damiano; Bergamini, Giorgio; Cathomas, Flurin; Sigrist, Hannes; Seifritz, Erich; Vavassori, Stefano; Luippold, Andreas; Hengerer, Bastian; Ceci, Angelo; Pryce, Christopher R

2016-05-01

Psychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immune-inflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity to aversive stimuli. The present mouse study investigated effects of psychosocial stress as chronic social defeat (CSD) versus control-handling (CON) on: Pavlovian tone-shock fear conditioning, activation of the kynurenine pathway, and efficacy of a specific inhibitor (IDOInh) of the tryptophan-kynurenine catabolising enzyme indoleamine 2,3-dioxygenase (IDO1), in reversing CSD effects on the kynurenine pathway and fear. CSD led to excessive fear learning and memory, whilst repeated oral escitalopram (antidepressant and anxiolytic) reversed excessive fear memory, indicating predictive validity of the model. CSD led to higher blood levels of TNF-α, IFN-γ, kynurenine (KYN), 3-hydroxykynurenine (3-HK) and kynurenic acid, and higher KYN and 3-HK in amygdala and hippocampus. CSD was without effect on IDO1 gene or protein expression in spleen, ileum and liver, whilst increasing liver TDO2 gene expression. Nonetheless, oral IDOInh reduced blood and brain levels of KYN and 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyper-activity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring of Batch Industrial Crystallization with Growth, Nucleation, and Agglomeration. Part 2: Structure Design for State Estimation with Secondary Measurements

PubMed Central

2017-01-01

This work investigates the design of alternative monitoring tools based on state estimators for industrial crystallization systems with nucleation, growth, and agglomeration kinetics. The estimation problem is regarded as a structure design problem where the estimation model and the set of innovated states have to be chosen; the estimator is driven by the available measurements of secondary variables. On the basis of Robust Exponential estimability arguments, it is found that the concentration is distinguishable with temperature and solid fraction measurements while the crystal size distribution (CSD) is not. Accordingly, a state estimator structure is selected such that (i) the concentration (and other distinguishable states) are innovated by means of the secondary measurements processed with the geometric estimator (GE), and (ii) the CSD is estimated by means of a rigorous model in open loop mode. The proposed estimator has been tested through simulations showing good performance in the case of mismatch in the initial conditions, parametric plant-model mismatch, and noisy measurements. PMID:28890604

Monitoring of Batch Industrial Crystallization with Growth, Nucleation, and Agglomeration. Part 2: Structure Design for State Estimation with Secondary Measurements.

PubMed

Porru, Marcella; Özkan, Leyla

2017-08-30

This work investigates the design of alternative monitoring tools based on state estimators for industrial crystallization systems with nucleation, growth, and agglomeration kinetics. The estimation problem is regarded as a structure design problem where the estimation model and the set of innovated states have to be chosen; the estimator is driven by the available measurements of secondary variables. On the basis of Robust Exponential estimability arguments, it is found that the concentration is distinguishable with temperature and solid fraction measurements while the crystal size distribution (CSD) is not. Accordingly, a state estimator structure is selected such that (i) the concentration (and other distinguishable states) are innovated by means of the secondary measurements processed with the geometric estimator (GE), and (ii) the CSD is estimated by means of a rigorous model in open loop mode. The proposed estimator has been tested through simulations showing good performance in the case of mismatch in the initial conditions, parametric plant-model mismatch, and noisy measurements.

Mortality from Circulatory System Diseases among French Uranium Miners: A Nested Case-Control Study.

PubMed

Drubay, Damien; Caër-Lorho, Sylvaine; Laroche, Pierre; Laurier, Dominique; Rage, Estelle

2015-05-01

A significant association has been observed between radon exposure and cerebrovascular disease (CeVD) mortality among French uranium miners, but risk factors for circulatory system diseases (CSD) have not been previously considered. We conducted new analyses in the recently updated (through 2007) French cohort of uranium miners (n = 5,086), which included 442 deaths from CSD, 167 of them from ischemic heart disease (IHD) and 105 from CeVD. A nested case-control study was then set up to collect and investigate the influence of these risk factors on the relationships between mortality from CSD and occupational external gamma ray and internal ionizing radiation exposure (radon and long-lived radionuclides) in this updated cohort. The nested case-control study included miners first employed after 1955, still employed in 1976 and followed up through 2007. Individual information about CSD risk factors was collected from medical files for the 76 deaths from CSD (including 26 from IHD and 16 from CeVD) and 237 miners who had not died of CSD by the end of follow-up. The exposure-risk relationships were assessed with a Cox proportional hazard model weighted by the inverse sampling probability. A significant increase in all CSD and CeVD mortality risks associated with radon exposure was observed in the total cohort [hazard ratios: HRCSD/100 working level months (WLM) = 1.11, 95% confidence interval (1.01; 1.22) and HRCeVD/100 WLM = 1.25 (1.09; 1.43), respectively]. A nonsignificant exposure-risk relationship was observed for every type of cumulative ionizing radiation exposure and every end point [e.g., HRCSD/100WLM = 1.43 (0.71; 2.87)]. The adjustment for each CSD risk factor did not substantially change the exposure-risk relationships. When the model was adjusted for overweight, hypertension, diabetes, hypercholesterolemia and smoking status, the HR/100WLM for CSD, for example, was equal to 1.21 (0.54; 2.75); and when it was adjusted for risk factors selected with the Akaike information criterion, it was equal to 1.44 (0.66; 3.14). To our knowledge, this is the first study to use a uranium miner cohort to consider the major standard CSD risk factors in assessing the relationships between ionizing radiation exposure and the risk of death from these diseases. These results suggest that the significant relationship between CeVD risk and radon exposure observed in the total French cohort is probably not affected by the CSD risk factors. Extending the collection of information about CSD risk factors to a larger subsample would be useful to confirm this result.

Nuclear magnetic resonance characterization of metabolite disorder in orange trees caused by citrus sudden death disease.

PubMed

Prestes, Rosilene A; Colnago, Luiz A; Forato, Lucimara A; Carrilho, Emanuel; Bassanezi, Renato B; Wulff, Nelson A

2009-01-01

Citrus sudden death (CSD) is a new disease of sweet orange and mandarin trees grafted on Rangpur lime and Citrus volkameriana rootstocks. It was first seen in Brazil in 1999, and has since been detected in more than four million trees. The CSD causal agent is unknown and the current hypothesis involves a virus similar to Citrus tristeza virus or a new virus named Citrus sudden death-associated virus. CSD symptoms include generalized foliar discoloration, defoliation and root death, and, in most cases, it can cause tree death. One of the unique characteristics of CSD disease is the presence of a yellow stain in the rootstock bark near the bud union. This region also undergoes profound anatomical changes. In this study, we analyse the metabolic disorder caused by CSD in the bark of sweet orange grafted on Rangpur lime by nuclear magnetic resonance (NMR) spectroscopy and imaging. The imaging results show the presence of a large amount of non-functional phloem in the rootstock bark of affected plants. The spectroscopic analysis shows a high content of triacylglyceride and sucrose, which may be related to phloem blockage close to the bud union. We also propose that, without knowing the causal CSD agent, the determination of oil content in rootstock bark by low-resolution NMR can be used as a complementary method for CSD diagnosis, screening about 300 samples per hour.

Large-Scale Mass Spectrometry Imaging Investigation of Consequences of Cortical Spreading Depression in a Transgenic Mouse Model of Migraine

NASA Astrophysics Data System (ADS)

Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Abdelmoula, Walid M.; van Heiningen, Sandra H.; van Zeijl, Rene J.; Dijkstra, Jouke; Ferrari, Michel D.; Tolner, Else A.; McDonnell, Liam A.; van den Maagdenberg, Arn M. J. M.

2015-06-01

Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant ( t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations.

Aeroelastic analysis of bridge girder section using computer modeling

DOT National Transportation Integrated Search

2001-05-01

This report describes the numerical simulation of wind flow around bridges using the Finite Element Method (FEM) and the principles of Computational Fluid Dynamics (CFD) and Computational Structural Dynamics (CSD). Since, the suspension bridges are p...

Linear distributed source modeling of local field potentials recorded with intra-cortical electrode arrays.

PubMed

Hindriks, Rikkert; Schmiedt, Joscha; Arsiwalla, Xerxes D; Peter, Alina; Verschure, Paul F M J; Fries, Pascal; Schmid, Michael C; Deco, Gustavo

2017-01-01

Planar intra-cortical electrode (Utah) arrays provide a unique window into the spatial organization of cortical activity. Reconstruction of the current source density (CSD) underlying such recordings, however, requires "inverting" Poisson's equation. For inter-laminar recordings, this is commonly done by the CSD method, which consists in taking the second-order spatial derivative of the recorded local field potentials (LFPs). Although the CSD method has been tremendously successful in mapping the current generators underlying inter-laminar LFPs, its application to planar recordings is more challenging. While for inter-laminar recordings the CSD method seems reasonably robust against violations of its assumptions, is it unclear as to what extent this holds for planar recordings. One of the objectives of this study is to characterize the conditions under which the CSD method can be successfully applied to Utah array data. Using forward modeling, we find that for spatially coherent CSDs, the CSD method yields inaccurate reconstructions due to volume-conducted contamination from currents in deeper cortical layers. An alternative approach is to "invert" a constructed forward model. The advantage of this approach is that any a priori knowledge about the geometrical and electrical properties of the tissue can be taken into account. Although several inverse methods have been proposed for LFP data, the applicability of existing electroencephalographic (EEG) and magnetoencephalographic (MEG) inverse methods to LFP data is largely unexplored. Another objective of our study therefore, is to assess the applicability of the most commonly used EEG/MEG inverse methods to Utah array data. Our main conclusion is that these inverse methods provide more accurate CSD reconstructions than the CSD method. We illustrate the inverse methods using event-related potentials recorded from primary visual cortex of a macaque monkey during a motion discrimination task.

Linear distributed source modeling of local field potentials recorded with intra-cortical electrode arrays

PubMed Central

Schmiedt, Joscha; Arsiwalla, Xerxes D.; Peter, Alina; Verschure, Paul F. M. J.; Fries, Pascal; Schmid, Michael C.; Deco, Gustavo

2017-01-01

Planar intra-cortical electrode (Utah) arrays provide a unique window into the spatial organization of cortical activity. Reconstruction of the current source density (CSD) underlying such recordings, however, requires “inverting” Poisson’s equation. For inter-laminar recordings, this is commonly done by the CSD method, which consists in taking the second-order spatial derivative of the recorded local field potentials (LFPs). Although the CSD method has been tremendously successful in mapping the current generators underlying inter-laminar LFPs, its application to planar recordings is more challenging. While for inter-laminar recordings the CSD method seems reasonably robust against violations of its assumptions, is it unclear as to what extent this holds for planar recordings. One of the objectives of this study is to characterize the conditions under which the CSD method can be successfully applied to Utah array data. Using forward modeling, we find that for spatially coherent CSDs, the CSD method yields inaccurate reconstructions due to volume-conducted contamination from currents in deeper cortical layers. An alternative approach is to “invert” a constructed forward model. The advantage of this approach is that any a priori knowledge about the geometrical and electrical properties of the tissue can be taken into account. Although several inverse methods have been proposed for LFP data, the applicability of existing electroencephalographic (EEG) and magnetoencephalographic (MEG) inverse methods to LFP data is largely unexplored. Another objective of our study therefore, is to assess the applicability of the most commonly used EEG/MEG inverse methods to Utah array data. Our main conclusion is that these inverse methods provide more accurate CSD reconstructions than the CSD method. We illustrate the inverse methods using event-related potentials recorded from primary visual cortex of a macaque monkey during a motion discrimination task. PMID:29253006

Cesarean section scar diverticulum evaluation by saline contrast-enhanced magnetic resonance imaging: The relationship between variable parameters and longer menstrual bleeding.

PubMed

Yao, Min; Wang, Wenjing; Zhou, Jieru; Sun, Minghua; Zhu, Jialiang; Chen, Pin; Wang, Xipeng

2017-04-01

This study was conducted to determine a more accurate imaging method for the diagnosis of cesarean scar diverticulum (CSD) and to identify the parameters of CSD strongly associated with prolonged menstrual bleeding. We enrolled 282 women with a history of cesarean section (CS) who presented with prolonged menstrual bleeding between January 2012 and May 2015. Transvaginal ultrasound, general magnetic resonance imaging (MRI) and contrast-enhanced MRI were used to diagnose CSD. Five parameters were compared among the imaging modalities: length, width, depth and thickness of the remaining muscular layer (TRM) of CSD and the depth/TRM ratio. Correlation between the five parameters and days of menstrual bleeding was performed. Finally, multivariate analysis was used to determine the parameters associated with menstrual bleeding longer than 14 days. Contrast-enhanced MRI yielded greater length or width or thinner TRM of CSD compared with MRI and transvaginal ultrasound. CSD size did not significantly differ between women who had undergone one and two CSs. Correlation analysis revealed that CSD (P = 0.038) and TRM (P = 0.003) lengths were significantly associated with days of menstrual bleeding. Longer than 14 days of bleeding was defined by cut-off values of 2.15 mm for TRM and 13.85 mm for length. TRM and number of CSs were strongly associated with menstrual bleeding longer than 14 days. CE-MRI is a relatively accurate and efficient imaging method for the diagnosis of CSD. A cut-off value of TRM of 2.15 mm is the most important parameter associated with menstrual bleeding longer than 14 days. © 2017 Japan Society of Obstetrics and Gynecology.

Cortical spreading depression preconditioning mediates neuroprotection against ischemic stroke by inducing AMP-activated protein kinase-dependent autophagy in a rat cerebral ischemic/reperfusion injury model.

PubMed

Shen, Pingping; Hou, Shuai; Zhu, Mingqin; Zhao, Mingming; Ouyang, Yibing; Feng, Jiachun

2017-03-01

Cortical spreading depression (CSD), based on its similarities with peri-infarct depolarization, is an ideal model for investigating transformation from the ischemic penumbra to infarct core. However, the underlying mechanisms remain unclear. To our knowledge, this is the first study to use a middle cerebral artery occlusion ischemic-reperfusion (I/R) injury model to determine whether AMP-activated protein kinase (AMPK)-dependent autophagy contributes to the neuroprotection of CSD preconditioning in rat cortex. In this study, we topically applied a pledget soaked in 1 mol/L KCl solution on rat cortex for 2 h to elicite CSD or 1 mol/L NaCl solution as a control. The results demonstrated that CSD preconditioning significantly decreased the infarct volume, neurological deficits and neuronal apoptosis in the cortical penumbra of middle cerebral artery occlusion rats, which was inhibited by the autophagy inhibitor 3-methyladenine (3-MA, 200 nmol). Furthermore, CSD increased the protein levels of the autophagy markers LC3-II, Beclin-1 and the p-AMPK (Thr 172 )/AMPK ratio at 12 h and decreased P62 and p-P70S6K (Thr 389 ). Moreover, the AMPK inhibitor Compound C (20 mg/kg) down-regulated the LC3-II, p-AMPK (Thr 172 )/AMPK and ULK1 levels, up-regulated the P62 and p-P70S6K (Thr 389 ) levels induced by CSD. The neuroprotection of CSD is likely a result of AMPK-mediated autophagy activity and autophagy-induced neuronal cells apoptosis inhibition. These novel findings support a central role for AMPK and autophagy in CSD-induced ischemic tolerance. AMPK-mediated autophagy may represent a new target for stroke. © 2016 International Society for Neurochemistry.

Children's Social Desirability and Dietary Reports.

PubMed

Baxter, Suzanne Domel; Smith, Albert F; Litaker, Mark S; Baglio, Michelle L; Guinn, Caroline H; Shaffer, Nicole M

2004-01-01

We investigated telephone administration of the Children's Social Desirability (CSD) scale and our adaptation for children of the Social Desirability for Food scale (C-SDF). Each of 100 4th-graders completed 2 telephone interviews 28 days apart. CSD scores had adequate internal consistency and test-retest reliability, and a 14-item subset was identified that sufficiently measures the same construct. Our C-SDF scale performed less well in terms of internal consistency and test-retest reliability; factor analysis revealed 2 factors, 1 of which was moderately related to the CSD. The 14-item subset of the CSD scale may help researchers understand error in children's dietary reports.

Children's Social Desirability and Dietary Reports

PubMed Central

Baxter, Suzanne Domel; Smith, Albert F.; Litaker, Mark S.; Baglio, Michelle L.; Guinn, Caroline H.; Shaffer, Nicole M.

2005-01-01

We investigated telephone administration of the Children's Social Desirability (CSD) scale and our adaptation for children of the Social Desirability for Food scale (C-SDF). Each of 100 4th-graders completed 2 telephone interviews 28 days apart. CSD scores had adequate internal consistency and test—retest reliability, and a 14-item subset was identified that sufficiently measures the same construct. Our C-SDF scale performed less well in terms of internal consistency and test—retest reliability; factor analysis revealed 2 factors, 1 of which was moderately related to the CSD. The 14-item subset of the CSD scale may help researchers understand error in children's dietary reports. PMID:15068757

An Agenda for Improving Perioperative Code Status Discussion.

PubMed

Hickey, Thomas R; Cooper, Zara; Urman, Richard D; Hepner, David L; Bader, Angela M

2016-06-15

Code status discussions (CSDs) clarify patient preferences for cardiopulmonary resuscitation in the event of cardiac or respiratory arrest. CSDs are a key component of perioperative care, particularly at the end of life, and must be both patient-centered and shared. Physicians at all levels of training are insufficiently trained in and inappropriately perform CSD; this may be particularly true of perioperative physicians. In this article, we describe the difficulty of achieving a patient-centered, shared perioperative CSD in the case of a medical professional with a do-not-resuscitate order. We provide a brief background in cardiopulmonary resuscitation, do-not-resuscitate, and CSD before proposing an agenda for improving perioperative CSD.

Varied Presentation of Congenital Segmental Dilatation of the Intestine in Neonates: Report of Three Cases

PubMed Central

Rai, Binod Kumar; Mirza, Bilal; Hashim, Imran; Saleem, Muhammad

2016-01-01

Congenital segmental dilatation (CSD) of the intestine is a rare developmental anomaly characterized by sharply demarcated dilatation of a gastrointestinal segment and may present with intestinal obstruction. We report three cases of CSD of the intestine in neonates with varied presentation. First patient was mistaken as pneumoperitoneum on abdominal radiograph, which led to initial abdominal drain placement. The 2nd patient was a case of anorectal malformation associated with congenital pouch colon (CPC) and CSD of ileum; and the third case presented as neonatal intestinal obstruction and found to have CSD of ileum. All the patients were successfully managed in our department. PMID:27896163

Comparison of time-frequency distribution techniques for analysis of spinal somatosensory evoked potential.

PubMed

Hu, Y; Luk, K D; Lu, W W; Holmes, A; Leong, J C

2001-05-01

Spinal somatosensory evoked potential (SSEP) has been employed to monitor the integrity of the spinal cord during surgery. To detect both temporal and spectral changes in SSEP waveforms, an investigation of the application of time-frequency analysis (TFA) techniques was conducted. SSEP signals from 30 scoliosis patients were analysed using different techniques; short time Fourier transform (STFT), Wigner-Ville distribution (WVD), Choi-Williams distribution (CWD), cone-shaped distribution (CSD) and adaptive spectrogram (ADS). The time-frequency distributions (TFD) computed using these methods were assessed and compared with each other. WVD, ADS, CSD and CWD showed better resolution than STFT. Comparing normalised peak widths, CSD showed the sharpest peak width (0.13+/-0.1) in the frequency dimension, and a mean peak width of 0.70+/-0.12 in the time dimension. Both WVD and CWD produced cross-term interference, distorting the TFA distribution, but this was not seen with CSD and ADS. CSD appeared to give a lower mean peak power bias (10.3%+/-6.2%) than ADS (41.8%+/-19.6%). Application of the CSD algorithm showed both good resolution and accurate spectrograms, and is therefore recommended as the most appropriate TFA technique for the analysis of SSEP signals.

Supersaturation Control using Analytical Crystal Size Distribution Estimator for Temperature Dependent in Nucleation and Crystal Growth Phenomena

NASA Astrophysics Data System (ADS)

Zahari, Zakirah Mohd; Zubaidah Adnan, Siti; Kanthasamy, Ramesh; Saleh, Suriyati; Samad, Noor Asma Fazli Abdul

2018-03-01

The specification of the crystal product is usually given in terms of crystal size distribution (CSD). To this end, optimal cooling strategy is necessary to achieve the CSD. The direct design control involving analytical CSD estimator is one of the approaches that can be used to generate the set-point. However, the effects of temperature on the crystal growth rate are neglected in the estimator. Thus, the temperature dependence on the crystal growth rate needs to be considered in order to provide an accurate set-point. The objective of this work is to extend the analytical CSD estimator where Arrhenius expression is employed to cover the effects of temperature on the growth rate. The application of this work is demonstrated through a potassium sulphate crystallisation process. Based on specified target CSD, the extended estimator is capable of generating the required set-point where a proposed controller successfully maintained the operation at the set-point to achieve the target CSD. Comparison with other cooling strategies shows a reduction up to 18.2% of the total number of undesirable crystals generated from secondary nucleation using linear cooling strategy is achieved.

Characterization of the cDNA coding for rat brain cysteine sulfinate decarboxylase: brain and liver enzymes are identical proteins encoded by two distinct mRNAs.

PubMed

Tappaz, M; Bitoun, M; Reymond, I; Sergeant, A

1999-09-01

Cysteine sulfinate decarboxylase (CSD) is considered as the rate-limiting enzyme in the biosynthesis of taurine, a possible osmoregulator in brain. Through cloning and sequencing of RT-PCR and RACE-PCR products of rat brain mRNAs, a 2,396-bp cDNA sequence was obtained encoding a protein of 493 amino acids (calculated molecular mass, 55.2 kDa). The corresponding fusion protein showed a substrate specificity similar to that of the endogenous enzyme. The sequence of the encoded protein is identical to that encoded by liver CSD cDNA. Among other characterized amino acid decarboxylases, CSD shows the highest homology (54%) with either isoform of glutamic acid decarboxylase (GAD65 and GAD67). A single mRNA band, approximately 2.5 kb, was detected by northern blot in RNA extracts of brain, liver, and kidney. However, brain and liver CSD cDNA sequences differed in the 5' untranslated region. This indicates two forms of CSD mRNA. Analysis of PCR-amplified products of genomic DNA suggests that the brain form results from the use of a 3' alternative internal splicing site within an exon specifically found in liver CSD mRNA. Through selective RT-PCR the brain form was detected in brain only, whereas the liver form was found in liver and kidney. These results indicate a tissue-specific regulation of CSD genomic expression.

Prevalence of unilateral and bilateral deafness in border collies and association with phenotype.

PubMed

Platt, Simon; Freeman, Julia; di Stefani, Alberta; Wieczorek, Lara; Henley, William

2006-01-01

Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. A total of 2597 Border Collies from the United Kingdom. A retrospective study of Border Collies tested, during 1994-2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P = .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P = .007), after adjustment for phenotypic attributes. Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease.

Descendant root volume varies as a function of root type: estimation of root biomass lost during uprooting in Pinus pinaster.

PubMed

Danjon, Frédéric; Caplan, Joshua S; Fortin, Mathieu; Meredieu, Céline

2013-01-01

Root systems of woody plants generally display a strong relationship between the cross-sectional area or cross-sectional diameter (CSD) of a root and the dry weight of biomass (DWd) or root volume (Vd) that has grown (i.e., is descendent) from a point. Specification of this relationship allows one to quantify root architectural patterns and estimate the amount of material lost when root systems are extracted from the soil. However, specifications of this relationship generally do not account for the fact that root systems are comprised of multiple types of roots. We assessed whether the relationship between CSD and Vd varies as a function of root type. Additionally, we sought to identify a more accurate and time-efficient method for estimating missing root volume than is currently available. We used a database that described the 3D root architecture of Pinus pinaster root systems (5, 12, or 19 years) from a stand in southwest France. We determined the relationship between CSD and Vd for 10,000 root segments from intact root branches. Models were specified that did and did not account for root type. The relationships were then applied to the diameters of 11,000 broken root ends to estimate the volume of missing roots. CSD was nearly linearly related to the square root of Vd, but the slope of the curve varied greatly as a function of root type. Sinkers and deep roots tapered rapidly, as they were limited by available soil depth. Distal shallow roots tapered gradually, as they were less limited spatially. We estimated that younger trees lost an average of 17% of root volume when excavated, while older trees lost 4%. Missing volumes were smallest in the central parts of root systems and largest in distal shallow roots. The slopes of the curves for each root type are synthetic parameters that account for differentiation due to genetics, soil properties, or mechanical stimuli. Accounting for this differentiation is critical to estimating root loss accurately.

Descendant root volume varies as a function of root type: estimation of root biomass lost during uprooting in Pinus pinaster

PubMed Central

Danjon, Frédéric; Caplan, Joshua S.; Fortin, Mathieu; Meredieu, Céline

2013-01-01

Root systems of woody plants generally display a strong relationship between the cross-sectional area or cross-sectional diameter (CSD) of a root and the dry weight of biomass (DWd) or root volume (Vd) that has grown (i.e., is descendent) from a point. Specification of this relationship allows one to quantify root architectural patterns and estimate the amount of material lost when root systems are extracted from the soil. However, specifications of this relationship generally do not account for the fact that root systems are comprised of multiple types of roots. We assessed whether the relationship between CSD and Vd varies as a function of root type. Additionally, we sought to identify a more accurate and time-efficient method for estimating missing root volume than is currently available. We used a database that described the 3D root architecture of Pinus pinaster root systems (5, 12, or 19 years) from a stand in southwest France. We determined the relationship between CSD and Vd for 10,000 root segments from intact root branches. Models were specified that did and did not account for root type. The relationships were then applied to the diameters of 11,000 broken root ends to estimate the volume of missing roots. CSD was nearly linearly related to the square root of Vd, but the slope of the curve varied greatly as a function of root type. Sinkers and deep roots tapered rapidly, as they were limited by available soil depth. Distal shallow roots tapered gradually, as they were less limited spatially. We estimated that younger trees lost an average of 17% of root volume when excavated, while older trees lost 4%. Missing volumes were smallest in the central parts of root systems and largest in distal shallow roots. The slopes of the curves for each root type are synthetic parameters that account for differentiation due to genetics, soil properties, or mechanical stimuli. Accounting for this differentiation is critical to estimating root loss accurately. PMID:24167506

Corticosteroid Treatment for Prolonged Fever in Hepatosplenic Cat-Scratch Disease: A Case Study.

PubMed

Phan, Amanda; Castagnini, Luis A

2017-12-01

Hepatosplenic cat-scratch disease (CSD) may cause prolonged fever. We present the case of a 4-year-old boy with confirmed hepatosplenic CSD with fever lasting 3 months despite use of multiple different antimicrobial agents. The patient became afebrile soon after corticosteroid therapy was started. Our case indicates corticosteroids may be useful in patients with hepatosplenic CSD and prolonged fever.

Spatial and temporal analyses of citrus sudden death as a tool to generate hypotheses concerning its etiology.

PubMed

Bassanezi, Renato B; Bergamin Filho, Armando; Amorim, Lilian; Gimenes-Fernandes, Nelson; Gottwald, Tim R; Bové, Joseph M

2003-04-01

ABSTRACT Citrus sudden death (CSD), a new disease of unknown etiology that affects sweet orange grafted on Rangpur lime, was visually monitored for 14 months in 41 groves in Brazil. Ordinary runs analysis of CSD-symptomatic trees indicated a departure from randomness of symptomatic trees status among immediately adjacent trees mainly within rows. The binomial index of dispersion (D) and the intraclass correlation (k) for various quadrat sizes suggested aggregation of CSD-symptomatic trees for almost all plots within the quadrat sizes tested. Estimated parameters of the binary form of Taylor's power law provided an overall measure of aggregation of CSD-symptomatic trees for all quadrat sizes tested. Aggregation in each plot was dependent on disease incidence. Spatial autocorrelation analysis of proximity patterns suggested that aggregation often existed among quadrats of various sizes up to three lag distances; however, significant lag positions discontinuous from main proximity patterns were rare, indicating a lack of spatial association among discrete foci. Some asymmetry was also detected for some spatial autocorrelation proximity patterns, indicating that within-row versus across-row distributions are not necessarily equivalent. These results were interpreted to mean that the cause of the disease was most likely biotic and its dissemination was common within a local area of influence that extended to approximately six trees in all directions, including adjacent trees. Where asymmetry was indicated, this area of influence was somewhat elliptical. Longer-distance patterns were not detected within the confines of the plot sizes tested. Annual rates of CSD progress based on the Gompertz model ranged from 0.37 to 2.02. Numerous similarities were found between the spatial patterns of CSD and Citrus tristeza virus (CTV) described in the literature, both in the presence of the aphid vector, Toxoptera citricida. CSD differs from CTV in that symptoms occur in sweet orange grafted on Rangpur lime. Based on the symptoms of CSD and on its spatial and temporal patterns, our hypothesis is that CSD may be caused by a similar but undescribed pathogen such as a virus and probably vectored by insects such as aphids by similar spatial processes to those affecting CTV.

High power density solid oxide fuel cells

DOEpatents

Pham, Ai Quoc; Glass, Robert S.

2004-10-12

A method for producing ultra-high power density solid oxide fuel cells (SOFCs). The method involves the formation of a multilayer structure cells wherein a buffer layer of doped-ceria is deposited intermediate a zirconia electrolyte and a cobalt iron based electrode using a colloidal spray deposition (CSD) technique. For example, a cobalt iron based cathode composed of (La,Sr)(Co,Fe)O (LSCF) may be deposited on a zirconia electrolyte via a buffer layer of doped-ceria deposited by the CSD technique. The thus formed SOFC have a power density of 1400 mW/cm.sup.2 at 600.degree. C. and 900 mW/cm.sup.2 at 700.degree. C. which constitutes a 2-3 times increased in power density over conventionally produced SOFCs.

Assessment of ODOT culvert load rating spreadsheets for use in Michigan.

DOT National Transportation Integrated Search

2013-01-01

The project Assessment of ODOT Culvert Load Rating Spreadsheets for use in Michigan was : a short time-frame project funded by the Michigan Department of Transportation (MDOT) : through the Center for Structural Durability (CSD) at Michigan Tec...

Structural studies of crystalline forms of triamterene with carboxylic acid, GRAS and API molecules

PubMed Central

Rehman, Abida

2018-01-01

Pharmaceutical salt solvates (dimethyl sulfoxide, DMSO) of the drug triamterene with the coformers acetic, succinic, adipic, pimelic, azelaic and nicotinic acid and ibuprofen are prepared by liquid-assisted grinding and solvent-evaporative crystallization. The modified ΔpK a rule as proposed by Cruz-Cabeza [(2012 ▸). CrystEngComm, 14, 6362–6365] is in close agreement with the results of this study. All adducts were characterized by X-ray diffraction and thermal analytical techniques, including single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermal gravimetric analysis. Hydrogen-bonded motifs combined to form a variety of extended tapes and sheets. Analysis of the crystal structures showed that all adducts existed as salt solvates and contained the amino­pyridinium–carboxyl­ate heterodimer, except for the solvate containing triamterene, ibuprofen and DMSO, as a result of the presence of a strong and stable hemitriamterenium duplex. A search of the Cambridge Structural Database (CSD 5.36, Version 1.18) to determine the frequency of occurrence of the putative supramolecular synthons found in this study showed good agreement with previous work. PMID:29755747

Quantum mechanics models of the methanol dimer: OH⋯O hydrogen bonds of β-d-glucose moieties from crystallographic data.

PubMed

Cintrón, Michael Santiago; Johnson, Glenn P; French, Alfred D

2017-04-18

The interaction of two methanol molecules, simplified models of carbohydrates and cellulose, was examined using a variety of quantum mechanics (QM) levels of theory. Energy plots for hydrogen bonding distance (H⋯O) and angle (OH⋯O) were constructed. All but two experimental structures were located in stabilized areas on the vacuum phase energy plots. Each of the 399 models was analyzed with Bader's atoms-in-molecules (AIM) theory, which showed a widespread ability by the dimer models to form OH⋯O hydrogen bonds that have bond paths and Bond Critical Points. Continuum solvation calculations suggest that a portion of the energy-stabilized structures could occur in the presence of water. A survey of the Cambridge Structural Database (CSD) for all donor-acceptor interactions in β-D-glucose moieties examined the similarities and differences among the hydroxyl groups and acetal oxygen atoms that participate in hydrogen bonds. Comparable behavior was observed for the O2H, O3H, O4H, and O6H hydroxyls, acting either as acceptors or donors. Ring O atoms showed distinct hydrogen bonding behavior that favored mid-length hydrogen bonds. Published by Elsevier Ltd.

Chemical solution route to self-assembled epitaxial oxide nanostructures.

PubMed

Obradors, X; Puig, T; Gibert, M; Queraltó, A; Zabaleta, J; Mestres, N

2014-04-07

Self-assembly of oxides as a bottom-up approach to functional nanostructures goes beyond the conventional nanostructure formation based on lithographic techniques. Particularly, chemical solution deposition (CSD) is an ex situ growth approach very promising for high throughput nanofabrication at low cost. Whereas strain engineering as a strategy to define nanostructures with tight control of size, shape and orientation has been widely used in metals and semiconductors, it has been rarely explored in the emergent field of functional complex oxides. Here we will show that thermodynamic modeling can be very useful to understand the principles controlling the growth of oxide nanostructures by CSD, and some attractive kinetic features will also be presented. The methodology of strain engineering is applied in a high degree of detail to form different sorts of nanostructures (nanodots, nanowires) of the oxide CeO2 with fluorite structure which then is used as a model system to identify the principles controlling self-assembly and self-organization in CSD grown oxides. We also present, more briefly, the application of these ideas to other oxides such as manganites or BaZrO3. We will show that the nucleation and growth steps are essentially understood and manipulated while the kinetic phenomena underlying the evolution of the self-organized networks are still less widely explored, even if very appealing effects have been already observed. Overall, our investigation based on a CSD approach has opened a new strategy towards a general use of self-assembly and self-organization which can now be widely spread to many functional oxide materials.

The Fractal Behavior of Crystal Distribution of la Gloria Pluton, Chile

NASA Astrophysics Data System (ADS)

Gutiérrez, F. J.; Payacán, I. J.; Pasten, D.; Aravena, A.; Gelman, S. E.; Bachmann, O.; Parada, M. A.

2013-12-01

We utilize fractal analysis to study the spatial distributions of crystals in a 10 Ma granitic intrusion (La Gloria pluton) located in the central Chilean Andes. Previous work determined the crystal size distribution (CSD) and anisotropy of magnetic susceptibility (AMS) tensors throughout this pluton. Using orthogonal thin sections oriented along the AMS tensor axes, we have applied fractal analysis in three magmatic crystal families: plagioclase, ferromagnesian minerals (biotite and amphibole), and Fe-Ti oxides (magnetite with minor ilmenite). We find that plagioclase and ferromagnesian minerals have a Semi-logarithmic CSD (S-CSD), given by: log(n/n0)= -L/C (1) where n [mm-4], n0 [mm-4], L [mm] and C [mm] are crystal density, intercept (nucleation density; L=0), size of crystals (three axes) and characteristic length, respectively. In contrast, Fe-Ti oxides have a Fractal CSD (F-CSD, power law size distribution), given by: log(n)= - Dn log(L) + n1 (2) where Dn and n1 [log(mm-4)] are a non-dimensional proportionality constant and the logarithm of the initial crystallization density (n1 = log(n(L=1 mm))), respectively. Finally, we calculate the fractal dimension (D0) by applying the box-counting method on each crystal thin section image, using: log(N) = -D0 log(ɛ) (3) where N and ɛ are the number of boxes occupied by minerals and the length of the square box, respectively. Results indicate that D0 values (eq. 3) are well defined for all minerals, and are higher for plagioclase than for ferromagnesian minerals and lowest for Fe-Ti oxides. D0 values are correlated with n0 and -1/C for S-CSD (eq. 1), and with n1 values for F-CSD (eq. 2). These correlations between fractal dimensions with CSD parameters suggest crystal growth follows a fractal behaviour in magmatic systems. Fractal behaviour of CSD means that the spatial distribution of crystals follows an all-scale pattern as part of a self-organized magmatic system. We interpret S-CSD of plagioclase and ferromagnesian minerals as consequence of early to intermediate crystal growth, whereas F-CSD of magnetite is also a consequence of late magmatic equilibration by increasing of fine magnetite crystals (e.g. reaction of hornblende to magnetite plus actinolite, biotite and titanite). Acknowledgments. This research has been developed by the FONDECYT N°11100241 and PBCT-PDA07 projects granted by CONICYT (Chilean National Commission for Science and Technology). I.P. is supported by CONICYT magister grant N°22130729. F.G. and I.P. thank to FONDAP N°15090013 for supporting during the conference. D.P. acknowledges FONDECYT grant N° 3120237.

In vivo optical imaging of cortical spreading depression in rat

NASA Astrophysics Data System (ADS)

Chen, Shangbin; Li, Pengcheng; Luo, Weihua; Gong, Hui; Cheng, Haiying; Luo, Qingming

2003-12-01

Intrinsic optical signals imaging (IOSI) and laser speckle imaging (LSI) are both novel techniques for functional neuroimaging in vivo. Combining them to study cortical spreading depression (CSD) which is an important disease model for migraine and other neurological disorders. CSD were induced by pinprick in Sprague-Dawley rats. Intrinsic optical signals (IOS) at 540 nm showed CSD evolution happened in one hemisphere cortex at speeds of 3.7+/-0.4 mm/min, and the vasodilation closely correlated a four-phasic response. By LSI, we observed a transient and significant increase cerebral blood flow (CBF). In this paper, optical imaging would be showed as a powerful tool for describing the hemodynamic character during CSD in rat.

Improved Helicopter Rotor Performance Prediction through Loose and Tight CFD/CSD Coupling

NASA Astrophysics Data System (ADS)

Ickes, Jacob C.

Helicopters and other Vertical Take-Off or Landing (VTOL) vehicles exhibit an interesting combination of structural dynamic and aerodynamic phenomena which together drive the rotor performance. The combination of factors involved make simulating the rotor a challenging and multidisciplinary effort, and one which is still an active area of interest in the industry because of the money and time it could save during design. Modern tools allow the prediction of rotorcraft physics from first principles. Analysis of the rotor system with this level of accuracy provides the understanding necessary to improve its performance. There has historically been a divide between the comprehensive codes which perform aeroelastic rotor simulations using simplified aerodynamic models, and the very computationally intensive Navier-Stokes Computational Fluid Dynamics (CFD) solvers. As computer resources become more available, efforts have been made to replace the simplified aerodynamics of the comprehensive codes with the more accurate results from a CFD code. The objective of this work is to perform aeroelastic rotorcraft analysis using first-principles simulations for both fluids and structural predictions using tools available at the University of Toledo. Two separate codes are coupled together in both loose coupling (data exchange on a periodic interval) and tight coupling (data exchange each time step) schemes. To allow the coupling to be carried out in a reliable and efficient way, a Fluid-Structure Interaction code was developed which automatically performs primary functions of loose and tight coupling procedures. Flow phenomena such as transonics, dynamic stall, locally reversed flow on a blade, and Blade-Vortex Interaction (BVI) were simulated in this work. Results of the analysis show aerodynamic load improvement due to the inclusion of the CFD-based airloads in the structural dynamics analysis of the Computational Structural Dynamics (CSD) code. Improvements came in the form of improved peak/trough magnitude prediction, better phase prediction of these locations, and a predicted signal with a frequency content more like the flight test data than the CSD code acting alone. Additionally, a tight coupling analysis was performed as a demonstration of the capability and unique aspects of such an analysis. This work shows that away from the center of the flight envelope, the aerodynamic modeling of the CSD code can be replaced with a more accurate set of predictions from a CFD code with an improvement in the aerodynamic results. The better predictions come at substantially increased computational costs between 1,000 and 10,000 processor-hours.

Changes in hemodynamics and light scattering during cortical spreading depression

NASA Astrophysics Data System (ADS)

Li, Pengcheng; Yang, Yuanyuan; Luo, Qingming

2005-01-01

Cortical spreading depression (CSD) has been known to play an important role in the mechanism of migraine, stroke and brain injure. Optical imaging of intrinsic signals has been shown a powerful method for characterizing the spatial and temporal pattern of the propagation of CSD. However, the possible physiological mechanisms underlying the intrinsic optical signal (IOS) during CSD still remain incompletely understood. In this study, a spectroscopic recording of the change in optical intrinsic signal during CSD was performed and an analysis method based on the modified Beer-Lambert law was used to estimate the changes in the concentration of HbO2 and Hb, and changes in light scattering from the spectra data. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. In all experiments, four-phasic changes in optical reflectance were observed at 450 nm ~ 570 nm, and triphasic changes in optical reflectance were observed in the range of 570 nm ~750 nm. But at 750 nm ~ 850 nm, only biphasic changes of optical signal were detected. Converting the spectra data to the changes in light scattering and concentration of Hb and HbO2, we found that the CSD induced an initial increase in concentration of HbO2 (amplitude: 9.0+/-3.7%), which was 26.2+/-18.6 s earlier than the onset of increase of Hb concentration. Furthermore, the concentration of HbO2 showed a four-phasic change, whereas the concentration of Hb only showed a biphasic change. For the changes in light scattering during CSD, a triphasic change was observed.

Origin of a function by tandem gene duplication limits the evolutionary capability of its sister copy.

PubMed

Hasselmann, Martin; Lechner, Sarah; Schulte, Christina; Beye, Martin

2010-07-27

The most remarkable outcome of a gene duplication event is the evolution of a novel function. Little information exists on how the rise of a novel function affects the evolution of its paralogous sister gene copy, however. We studied the evolution of the feminizer (fem) gene from which the gene complementary sex determiner (csd) recently derived by tandem duplication within the honey bee (Apis) lineage. Previous studies showed that fem retained its sex determination function, whereas the rise of csd established a new primary signal of sex determination. We observed a specific reduction of nonsynonymous to synonymous substitution ratios in Apis to non-Apis fem. We found a contrasting pattern at two other genetically linked genes, suggesting that hitchhiking effects to csd, the locus under balancing selection, is not the cause of this evolutionary pattern. We also excluded higher synonymous substitution rates by relative rate testing. These results imply that stronger purifying selection is operating at the fem gene in the presence of csd. We propose that csd's new function interferes with the function of Fem protein, resulting in molecular constraints and limited evolvability of fem in the Apis lineage. Elevated silent nucleotide polymorphism in fem relative to the genome-wide average suggests that genetic linkage to the csd gene maintained more nucleotide variation in today's population. Our findings provide evidence that csd functionally and genetically interferes with fem, suggesting that a newly evolved gene and its functions can limit the evolutionary capability of other genes in the genome.

An analysis of current source density profiles activated by local stimulation in the mouse auditory cortex in vitro.

PubMed

Yamamura, Daiki; Sano, Ayaka; Tateno, Takashi

2017-03-15

To examine local network properties of the mouse auditory cortex in vitro, we recorded extracellular spatiotemporal laminar profiles driven by short electric local stimulation on a planar multielectrode array substrate. The recorded local field potentials were subsequently evaluated using current source density (CSD) analysis to identify sources and sinks. Current sinks are thought to be an indicator of net synaptic current in the small volume of cortex surrounding the recording site. Thus, CSD analysis combined with multielectrode arrays enabled us to compare mean synaptic activity in response to small current stimuli on a layer-by-layer basis. We also used senescence-accelerated mice (SAM), some strains of which show earlier onset of age-related hearing loss, to examine the characteristic spatiotemporal CSD profiles stimulated by electrodes in specific cortical layers. Thus, the CSD patterns were classified into several clusters based on stimulation sites in the cortical layers. We also found some differences in CSD patterns between the two SAM strains in terms of aging according to principle component analysis with dimension reduction. For simultaneous two-site stimulation, we modeled the obtained CSD profiles as a linear superposition of the CSD profiles to individual single-site stimulation. The model analysis indicated the nonlinearity of spatiotemporal integration over stimulus-driven activity in a layer-specific manner. Finally, on the basis of these results, we discuss the auditory cortex local network properties and the effects of aging on these mouse strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Caveolin-1 regulates chemokine receptor 5-mediated contribution of bone marrow-derived cells to dermal fibrosis

PubMed Central

Lee, Rebecca; Perry, Beth; Heywood, Jonathan; Reese, Charles; Bonner, Michael; Hatfield, Corey M.; Silver, Richard M.; Visconti, Richard P.; Hoffman, Stanley; Tourkina, Elena

2014-01-01

In fibrotic diseases caveolin-1 underexpression in fibroblasts results in collagen overexpression and in monocytes leads to hypermigration. These profibrotic behaviors are blocked by the caveolin-1 scaffolding domain peptide (CSD) which compensates for caveolin-1 deficiency. Monocytes and fibroblasts are related in that monocytes are the progenitors of fibrocytes (CD45+/Collagen I+ cells) that, in turn, are the progenitors of many fibroblasts in fibrotic tissues. In an additional anti-fibrotic activity, CSD blocks monocyte differentiation into fibrocytes. We studied a mouse fibrosis model (Pump Model) involving systemic bleomycin delivery that closely models scleroderma (SSc) in several ways, the most important of which for this study is that fibrosis is observed in the lungs, skin, and internal organs. We show here that dermal thickness is increased 2-fold in the Pump Model and that this effect is almost completely blocked by CSD (p < 0.001). Concomitantly, the subcutaneous fat layer becomes >80% thinner. This effect is also blocked by CSD (p < 0.001). Even in mice receiving vehicle instead of bleomycin, CSD increases the thickness of the fat layer. To study the mechanisms of action of bleomycin and CSD, we examined the accumulation of the chemokine receptor CCR5 and its ligands MIP1α and MIP1β in fibrotic tissue and their roles in monocyte migration. Fibrocytes and other leukocytes expressing CCR5 and its ligands were present at high levels in the fibrotic dermis of SSc patients and Pump Model mice while CSD blocked their accumulation in mouse dermis. Migration toward CCR5 ligands of SSc monocytes and Pump Model bone marrow cells was 3-fold greater than cells from control subjects. This enhanced migration was almost completely blocked by CSD. These results suggest that low monocyte caveolin-1 promotes fibrosis by enhancing the recruitment of fibrocytes and their progenitors into affected tissue. PMID:24966836

Nature and Strength of the Inner-Core H⋅⋅⋅H Interactions in Porphyrinoids.

PubMed

Singh, Ankit; Sahoo, Dipak Kumar; Sethi, Srikant Kumar; Jena, Subhrakant; Biswal, Himansu S

2017-12-15

Several recent publications have illustrated that electrostatic attraction is not solely responsible for strong hydrogen bonds. Even electropositive and less electronegative atoms such as Te and Se are capable of forming strong H-bonds. Herein, we provide evidence for intramolecular homopolar dihydrogen bonds [HOMO-DHBs; X-N(C)-H δ+ ⋅⋅⋅ δ+ H-N(C)-Y] in porphyrins and related compounds for the first time; these bonds are revealed by careful Cambridge Structural Database (CSD) exploration, quantum theory of atoms in molecules, compliance constant calculations, and natural bond orbital and noncovalent interaction (NCI) analysis. A search of the CSD showed that the inner-core hydrogen atom distances were less than 2.5 Å (sum of the van der Waals radii of two hydrogen atoms is 2.4 Å) in porphyrinoids, i.e. about 75 % of the cases. This suggested an attractive interaction between hydrogen atoms carrying a positive charge, which was further supported by quantum-chemical calculations. The HOMO-DHB energy in some cases was found to be as much as around 20 kJ mol -1 , which is comparable to that of any conventional H-bond energy such as for the NH 3 dimer. The interplay between hyperconjugative attraction and steric constraint favorably decided the strength of the HOMO-DHBs. We expect that HOMO-DHBs could be revealed in many more systems, such as corroles, phlorins, crown ethers, and constrained systems having hydrogen atoms in close contact, and could be an important noncovalent interaction to consider in supramolecular chemistry. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electronegativity equalization method: parameterization and validation for organic molecules using the Merz-Kollman-Singh charge distribution scheme.

PubMed

Jirousková, Zuzana; Vareková, Radka Svobodová; Vanek, Jakub; Koca, Jaroslav

2009-05-01

The electronegativity equalization method (EEM) was developed by Mortier et al. as a semiempirical method based on the density-functional theory. After parameterization, in which EEM parameters A(i), B(i), and adjusting factor kappa are obtained, this approach can be used for calculation of average electronegativity and charge distribution in a molecule. The aim of this work is to perform the EEM parameterization using the Merz-Kollman-Singh (MK) charge distribution scheme obtained from B3LYP/6-31G* and HF/6-31G* calculations. To achieve this goal, we selected a set of 380 organic molecules from the Cambridge Structural Database (CSD) and used the methodology, which was recently successfully applied to EEM parameterization to calculate the HF/STO-3G Mulliken charges on large sets of molecules. In the case of B3LYP/6-31G* MK charges, we have improved the EEM parameters for already parameterized elements, specifically C, H, N, O, and F. Moreover, EEM parameters for S, Br, Cl, and Zn, which have not as yet been parameterized for this level of theory and basis set, we also developed. In the case of HF/6-31G* MK charges, we have developed the EEM parameters for C, H, N, O, S, Br, Cl, F, and Zn that have not been parameterized for this level of theory and basis set so far. The obtained EEM parameters were verified by a previously developed validation procedure and used for the charge calculation on a different set of 116 organic molecules from the CSD. The calculated EEM charges are in a very good agreement with the quantum mechanically obtained ab initio charges. 2008 Wiley Periodicals, Inc.

Development of an aeroelastic methodology for surface morphing rotors

NASA Astrophysics Data System (ADS)

Cook, James R.

Helicopter performance capabilities are limited by maximum lift characteristics and vibratory loading. In high speed forward flight, dynamic stall and transonic flow greatly increase the amplitude of vibratory loads. Experiments and computational simulations alike have indicated that a variety of active rotor control devices are capable of reducing vibratory loads. For example, periodic blade twist and flap excitation have been optimized to reduce vibratory loads in various rotors. Airfoil geometry can also be modified in order to increase lift coefficient, delay stall, or weaken transonic effects. To explore the potential benefits of active controls, computational methods are being developed for aeroelastic rotor evaluation, including coupling between computational fluid dynamics (CFD) and computational structural dynamics (CSD) solvers. In many contemporary CFD/CSD coupling methods it is assumed that the airfoil is rigid to reduce the interface by single dimension. Some methods retain the conventional one-dimensional beam model while prescribing an airfoil shape to simulate active chord deformation. However, to simulate the actual response of a compliant airfoil it is necessary to include deformations that originate not only from control devices (such as piezoelectric actuators), but also inertial forces, elastic stresses, and aerodynamic pressures. An accurate representation of the physics requires an interaction with a more complete representation of loads and geometry. A CFD/CSD coupling methodology capable of communicating three-dimensional structural deformations and a distribution of aerodynamic forces over the wetted blade surface has not yet been developed. In this research an interface is created within the Fully Unstructured Navier-Stokes (FUN3D) solver that communicates aerodynamic forces on the blade surface to University of Michigan's Nonlinear Active Beam Solver (UM/NLABS -- referred to as NLABS in this thesis). Interface routines are developed for transmission of force and deflection information to achieve an aeroelastic coupling updated at each time step. The method is validated first by comparing the integrated aerodynamic work at CFD and CSD nodes to verify work conservation across the interface. Second, the method is verified by comparing the sectional blade loads and deflections of a rotor in hover and in forward flight with experimental data. Finally, stability analyses for pitch/plunge flutter and camber flutter are performed with comprehensive CSD/low-order-aerodynamics and tightly coupled CFD/CSD simulations and compared to analytical solutions of Peters' thin airfoil theory to verify proper aeroelastic behavior. The effects of simple harmonic camber actuation are examined and compared to the response predicted by Peters' finite-state (F-S) theory. In anticipation of active rotor experiments inside enclosed facilities, computational simulations are performed to evaluate the capability of CFD for accurately simulating flow inside enclosed volumes. A computational methodology for accurately simulating a rotor inside a test chamber is developed to determine the influence of test facility components and turbulence modeling and performance predictions. A number of factors that influence the physical accuracy of the simulation, such as temporal resolution, grid resolution, and aeroelasticity are also evaluated.

Fluid Structural Analysis of Human Cerebral Aneurysm Using Their Own Wall Mechanical Properties

PubMed Central

Valencia, Alvaro; Burdiles, Patricio; Ignat, Miguel; Mura, Jorge; Rivera, Rodrigo; Sordo, Juan

2013-01-01

Computational Structural Dynamics (CSD) simulations, Computational Fluid Dynamics (CFD) simulation, and Fluid Structure Interaction (FSI) simulations were carried out in an anatomically realistic model of a saccular cerebral aneurysm with the objective of quantifying the effects of type of simulation on principal fluid and solid mechanics results. Eight CSD simulations, one CFD simulation, and four FSI simulations were made. The results allowed the study of the influence of the type of material elements in the solid, the aneurism's wall thickness, and the type of simulation on the modeling of a human cerebral aneurysm. The simulations use their own wall mechanical properties of the aneurysm. The more complex simulation was the FSI simulation completely coupled with hyperelastic Mooney-Rivlin material, normal internal pressure, and normal variable thickness. The FSI simulation coupled in one direction using hyperelastic Mooney-Rivlin material, normal internal pressure, and normal variable thickness is the one that presents the most similar results with respect to the more complex FSI simulation, requiring one-fourth of the calculation time. PMID:24151523

Method of Fabrication of High Power Density Solid Oxide Fuel Cells

DOEpatents

Pham, Ai Quoc; Glass, Robert S.

2008-09-09

A method for producing ultra-high power density solid oxide fuel cells (SOFCs). The method involves the formation of a multilayer structure cells wherein a buffer layer of doped-ceria is deposited intermediate a zirconia electrolyte and a cobalt iron based electrode using a colloidal spray deposition (CSD) technique. For example, a cobalt iron based cathode composed of (La,Sr)(Co,Fe)O(LSCF) may be deposited on a zirconia electrolyte via a buffer layer of doped-ceria deposited by the CSD technique. The thus formed SOFC have a power density of 1400 mW/cm.sup.2 at 600.degree. C. and 900 mW/cm.sup.2 at 700.degree. C. which constitutes a 2-3 times increased in power density over conventionally produced SOFCs.

Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine.

PubMed

Bergamini, Giorgio; Cathomas, Flurin; Auer, Sandra; Sigrist, Hannes; Seifritz, Erich; Patterson, Michael; Gabriel, Cecilia; Pryce, Christopher R

2016-09-01

A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Specialty of prescribers associated with prescription opioid fatalities in Utah, 2002-2010.

PubMed

Porucznik, Christina A; Johnson, Erin M; Rolfs, Robert T; Sauer, Brian C

2014-01-01

Opioid adverse events are widespread, and deaths have been directly attributed to opioids prescribed by medical professionals. Little information exists on the amount of opioids various medical specialties prescribe and the opioid fatality rate that would be expected if prescription opioid-related deaths were independent of medical specialty. To compute the incidence of prescription opioid fatalities by medical specialty in Utah and to calculate the attributable risk (AR) of opioid fatality by medical specialty. Prevalence database study design linking the Utah Controlled Substance Database (CSD) for prescribing data with the Utah Medical Examiner data to identify prescription opioid fatalities. AR were calculated for each medical specialty and year. Opioid prescriptions are common with 23,302,892 recorded in the CSD for 2002-2010, 0.64% of which were associated with a fatality. We attached specialty to 90.2% of opioid prescriptions. Family medicine and internal medicine physicians wrote the largest proportion of prescriptions (24.1% and 10.8%) and were associated with the greatest number of prescription opioid fatalities. The number of active prescriptions at time of death decreased each year. The AR of fatality by provider specialty varied each year with some specialties, such as pain medicine and anesthesiology, consistently associated with more fatalities per 1,000 opioid prescriptions than internal medicine physicians the same year. Primary care providers were the most frequent prescribers and the most often associated with opioid fatalities and should be targeted for education about safe prescribing along with specialties that prescribe less frequently but are associated with a positive AR for opioid fatality. Wiley Periodicals, Inc.

Prevalence of deafness and association with coat variations in client-owned ferrets.

PubMed

Piazza, Stéphanie; Abitbol, Marie; Gnirs, Kirsten; Huynh, Minh; Cauzinille, Laurent

2014-05-01

To evaluate the prevalence of congenital sensorineural deafness (CSD) and its association with phenotypic markers in client-owned ferrets. Epidemiological study. 152 healthy European pet ferrets. Brainstem auditory evoked response tests were recorded in ferrets during general anesthesia. Phenotypic markers such as sex, coat color and pattern, coat length (Angora or not), and premature graying trait were assessed. Overall, 44 of the 152 (29%) ferrets were affected by CSD; 10 (7%) were unilaterally deaf, and 34 (22%) were bilaterally deaf. There was no association between CSD and sex or Angora trait, but a strong association between CSD and white patterned coat or premature graying was identified. All panda, American panda, and blaze ferrets were deaf. The ferrets in this study had a high prevalence of CSD that was strictly associated with coat color patterns, specifically white markings and premature graying. This seemed to be an emerging congenital defect in pet ferrets because white-marked coats are a popular new coat color. Breeders should have a greater awareness and understanding of this defect to reduce its prevalence for the overall benefit of the species.

Cat Scratch Disease

MedlinePlus

Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry the infection ... symptoms of CSD, call your doctor. Centers for Disease Control and Prevention

What is the best screening test for depression in chronic spinal pain patients?

PubMed

Choi, YunHee; Mayer, Tom G; Williams, Mark J; Gatchel, Robert J

2014-07-01

High prevalence rates of depression have been found in patients with chronic spinal disorder (CSD). The biopsychosocial model has become widely adopted and, with it, the role of psychopathology in the development and/or exacerbation of CSD has become increasingly recognized. Standardized diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), have been used to diagnose major depressive disorder (MDD). Many measures of MDD (and depressive symptom inventories) have been developed during the past 50 years, but their comparative utility in CSD populations is still unclear. To systemically compare the performance of depression screening questionnaires in detecting MDD among a large sample of patients with CSD. Prospective cohort study comparing the screening ability of four popular depression measures for diagnosing MDD against the "gold standard" Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), using a receiver operating characteristic (ROC) analysis in a CSD population. A consecutive cohort of 546 patients with CSD admitted to an interdisciplinary functional restoration program. Sensitivity, specificity, ROC curves, area under the curve (AUC), and optimal cutoff points that are most closely related to the prevalence rates of MDD, with balanced sensitivity and specificity analysis. Using the SCID-I diagnosis as a "gold standard," the ability of four screening measures in detecting MDD were compared. These included: the Beck Depression Inventory (BDI); Hamilton Rating Scale for Depression (HRSD); 9-Item Patient Health Questionnaire Depression Module (PHQ-9); and the Short Form-36 (SF-36). Of 542 CSD patients, 331 (61.1%) were diagnosed with MDD by the SCID-I. Results of the ROC analysis revealed that the BDI (AUC 0.768), HRSD (AUC 0.796), and PHQ-9 (AUC 0.768) have similar abilities to discriminate between depressed and nondepressed patients in this population. These depression measures outperformed the two mental health scales derived from the SF-36 (Mental Component Summary score/5-Item Mental Health Index; AUC 0.679-0.715). The optimal cut-off scores of 15 (for the BDI), 17 (for the HRSD), and 10 (for the PHQ-9) were also determined. Although the greatest overall accuracy (sensitivity of 81.3% and specificity of 65.4%) was obtained with the HRSD, it is the only clinician-administered instrument. Self-report measures of depression (the BDI and PHQ-9) showed comparable abilities to detect depression, only slightly less than the HRSD. Compared to the HRSD, both BDI and PHQ-9 are relatively short and easy to self-administer. The cut-off scores established in this study may be used to reliably determine whether a person should be evaluated more thoroughly for an MDD diagnosis. Using an acknowledged "gold standard," the HRSD, BDI and PHQ-9 showed similar validity to recommend their use for future clinical and research purposes. The SF-36 is less appropriate for diagnosing MDD. Copyright © 2014 Elsevier Inc. All rights reserved.

RGB camera-based imaging of cerebral tissue oxygen saturation, hemoglobin concentration, and hemodynamic spontaneous low-frequency oscillations in rat brain following induction of cortical spreading depression

PubMed Central

Mustari, Afrina; Nakamura, Naoki; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Nishidate, Izumi

2018-01-01

To evaluate cerebral hemodynamics and spontaneous low-frequency oscillations (SLFOs) of cerebral blood flow in rat brain, we investigated an imaging method using a digital RGB camera. In this method, the RGB values were converted into tristimulus values in the CIE (Commission Internationale de l’Eclairage) XYZ color space, which is compatible with the common RGB working spaces. Monte Carlo simulation for light transport in tissue was then used to specify the relationship among the tristimulus XYZ values and the concentrations of oxygenated hemoglobin (CHbO), deoxygenated hemoglobin (CHbR), and total hemoglobin (CHbT) and cerebral tissue oxygen saturation (StO2). Applying the fast Fourier transform to each pixel of the sequential images of CHbT along the timeline, SLFOs of cerebral blood volume were visualized as a spatial map of power spectral density (PSD) at specific frequencies related to vasomotion. To confirm the feasibility of this method, we performed in vivo experiments using exposed rat brain during a cortical spreading depression (CSD) evoked by topical application of KCl. Cerebral hemodynamic responses to CSD such as initial hypoperfusion, profound hyperemia, and post-CSD oligemia and hypoxemia were successfully visualized with this method. At the transition to the hyperemia phase from hypoperfusion, CHbO and StO2 were significantly increased, which implied vasodilatation in arterioles and increased cerebral blood volume in response to CSD. In the wake of the hyperemic phase, CHbO and CHbT were significantly reduced to 25 ± 12% and 3.5 ± 1% of baseline, respectively, suggesting long-lasting vasoconstriction after CSD. In this persistent oligemia, StO2 significantly dropped to at most 23 ± 12% of the level before CSD, indicating long-lasting hypoxemia. The PSD value of SLFOs in CHbT for arteriole regions during CSD was significantly reduced to 28 ± 20% of baseline with respect to the pre-CSD level, which was correlated with the reduction in StO2. The results showed the possibility of RGB camera-based diffuse reflectance spectroscopy imaging for evaluating cerebral hemodynamics and SLFOs under normal and pathologic conditions. PMID:29541495

Distribution and Characteristics of Seafloor Seepage Features in the Active Margin Offshore of SW Taiwan

NASA Astrophysics Data System (ADS)

Chen, T. T.; Hsu, H. H.; Liu, C. S.; Su, C. C.; Paull, C. K.; Chen, Y. H.; Caress, D. W.; Gwiazda, R.; Lundsten, E. M.

2017-12-01

In the active margin offshore of southwest (SW) Taiwan, west-vergent imbricated thrusts, folds and dipping strata are the main structural features. This is also the area where gas hydrates are widely distributed beneath the seafloor. Fluids from deep strata may migrate upwards along porous dipping layers or faults and then vent out to form seafloor seepage features in many of the gas hydrate prospects. A joint survey was conducted in May 2017 using MBARI mapping AUV and miniROV to investigate the seafloor seepage features. Numerous comet-shaped depressions (CSD) are mapped along flanks of several anticlinal ridges, and four carbonate mounds around CSD are observed from the ultra-high-resolution (1-m lateral resolution) bathymetry data collected by AUV. Samples of the carbonate mounds were collected by the mini-ROV, and their mineral compositions contain dolomite and ankerite. The AUV collected chirp sonar profiles and previously collected surface ship multichannel seismic reflection profiles across these seafloor features show that potential fluid migration pathways connect free gas trapped below the base of gas hydrate stability zone and the seafloor in the vicinity of these features. Our study suggests that the CSD could be an indicator of seafloor seepage and may be distribution widely in the active margin setting.

Design and optimization of production parameters for boric acid crystals with the crystallization process in an MSMPR crystallizer using FBRM® and PVM® technologies

NASA Astrophysics Data System (ADS)

Kutluay, Sinan; Şahin, Ömer; Ceyhan, A. Abdullah; İzgi, M. Sait

2017-06-01

In crystallization studies, newly developed technologies, such as Focused Beam Reflectance Measurement (FBRM) and Particle Vision and Measurement (PVM) are applied for determining on-line monitoring of a representation of the Chord Length Distribution (CLD) and observe the photographs of crystals respectively; moreover recently they are widely used. Properly installed, the FBRM ensures on-line determination of the CLD, which is statistically associated to the Crystal Size Distribution (CSD). In industrial crystallization, CSD and mean crystal size as well as external habit and internal structure are important characteristics for further use of the crystals. In this paper, the effect of residence time, stirring speed, feeding rate, supersaturation level and the polyelectrolytes such as anionic polyacrylamide (APAM) and non-ionic polyacrylamide (NPAM) on the CLD as well as the shape of boric acid crystals were investigated by using the FBRM G600 and the PVM V819 probes respectively in an MSMPR (Mixed Suspension Mixed Product Removal) crystallizer. The CSD and kinetic data were determined experimentally using continuous MSMPR crystallizer running at steady state. The population density of nuclei, the nucleation rate and the growth rate were determined from the experimental population balance distribution when the steady state was reached.

Development and Validation of a Multidisciplinary Tool for Accurate and Efficient Rotorcraft Noise Prediction (MUTE)

NASA Technical Reports Server (NTRS)

Liu, Yi; Anusonti-Inthra, Phuriwat; Diskin, Boris

2011-01-01

A physics-based, systematically coupled, multidisciplinary prediction tool (MUTE) for rotorcraft noise was developed and validated with a wide range of flight configurations and conditions. MUTE is an aggregation of multidisciplinary computational tools that accurately and efficiently model the physics of the source of rotorcraft noise, and predict the noise at far-field observer locations. It uses systematic coupling approaches among multiple disciplines including Computational Fluid Dynamics (CFD), Computational Structural Dynamics (CSD), and high fidelity acoustics. Within MUTE, advanced high-order CFD tools are used around the rotor blade to predict the transonic flow (shock wave) effects, which generate the high-speed impulsive noise. Predictions of the blade-vortex interaction noise in low speed flight are also improved by using the Particle Vortex Transport Method (PVTM), which preserves the wake flow details required for blade/wake and fuselage/wake interactions. The accuracy of the source noise prediction is further improved by utilizing a coupling approach between CFD and CSD, so that the effects of key structural dynamics, elastic blade deformations, and trim solutions are correctly represented in the analysis. The blade loading information and/or the flow field parameters around the rotor blade predicted by the CFD/CSD coupling approach are used to predict the acoustic signatures at far-field observer locations with a high-fidelity noise propagation code (WOPWOP3). The predicted results from the MUTE tool for rotor blade aerodynamic loading and far-field acoustic signatures are compared and validated with a variation of experimental data sets, such as UH60-A data, DNW test data and HART II test data.

A star in the eye: cat scratch neuroretinitis.

PubMed

Gajula, Viswanath; Kamepalli, Ravi; Kalavakunta, Jagadeesh K

2014-02-01

Neuroretinitis is one of the atypical presentations of Cat scratch disease (CSD). Fundoscopy showed star pattern macular exudates. CSD should be considered in patients who present with blurry vision and typical fundoscopic findings.

Strategic Rebalance of the Three Component Air Force

DTIC Science & Technology

2013-03-01

protect its ability to regenerate capabilities that might be needed to meet future, unforeseen demands, maintaining intellectual capital and rank structure...93 Air Reserve Personnel Center, “Continuum of Service,” myPers, https:// gum - crm.csd.disa.mil/app/answers/detail/a_id/19204/kw/continuum/p/16

Simultaneous imaging of intrinsic optical signals and cerebral vessel responses during cortical spreading depression in rats

NASA Astrophysics Data System (ADS)

Li, Pengcheng; Chen, Shangbin; Luo, Weihua; Luo, Qingming

2003-12-01

Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. We investigated the spatio-temporal characteristics of the intrinsic optical signals (IOS) at 570 nm and the cerebral blood vessel responses during CSD simultaneously by optical reflectance imaging in vivo. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. A four-phasic IOS response was observed at pial arteries and parenchymal sites in all experimental animals and an initial slight pial arteries dilation (21.5%+/-13.6%) and constriction (-4.2%+/-3.5%) precedes the dramatic dilation (69.2%+/-26.1%) of pial arterioles was recorded. Our experimental results show a high correlation (r = 0.89+/-0.025) between the IOS response and the diameter changes of the cerebral blood vessels during CSD in rats.

An invasive social insect overcomes genetic load at the sex locus.

PubMed

Gloag, Rosalyn; Ding, Guiling; Christie, Joshua R; Buchmann, Gabriele; Beekman, Madeleine; Oldroyd, Benjamin P

2016-11-07

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.

Cortical spreading depression occurs during elective neurosurgical procedures.

PubMed

Carlson, Andrew P; William Shuttleworth, C; Mead, Brittany; Burlbaw, Brittany; Krasberg, Mark; Yonas, Howard

2017-01-01

OBJECTIVE Cortical spreading depression (CSD) has been observed with relatively high frequency in the period following human brain injury, including traumatic brain injury and ischemic/hemorrhagic stroke. These events are characterized by loss of ionic gradients through massive cellular depolarization, neuronal dysfunction (depression of electrocorticographic [ECoG] activity) and slow spread (2-5 mm/min) across the cortical surface. Previous data obtained in animals have suggested that even in the absence of underlying injury, neurosurgical manipulation can induce CSD and could potentially be a modifiable factor in neurosurgical injury. The authors report their initial experience with direct intraoperative ECoG monitoring for CSD. METHODS The authors prospectively enrolled patients undergoing elective craniotomy for supratentorial lesions in cases in which the surgical procedure was expected to last > 2 hours. These patients were monitored for CSD from the time of dural opening through the time of dural closure, using a standard 1 × 6 platinum electrode coupled with an AC or full-spectrum DC amplifier. The data were processed using standard techniques to evaluate for slow potential changes coupled with suppression of high-frequency ECoG propagating across the electrodes. Data were compared with CSD validated in previous intensive care unit (ICU) studies, to evaluate recording conditions most likely to permit CSD detection, and identify likely events during the course of neurosurgical procedures using standard criteria. RESULTS Eleven patients underwent ECoG monitoring during elective neurosurgical procedures. During the periods of monitoring, 2 definite CSDs were observed to occur in 1 patient and 8 suspicious events were detected in 4 patients. In other patients, either no events were observed or artifact limited interpretation of the data. The DC-coupled amplifier system represented an improvement in stability of data compared with AC-coupled systems. Compared with more widely used postoperative ICU monitoring, there were additional challenges with artifact from saturation during bipolar cautery as well as additional noise peaks detected. CONCLUSIONS CSD can occur during elective neurosurgical procedures even in brain regions distant from the immediate operative site. ECoG monitoring with a DC-coupled full-spectrum amplifier seemed to provide the most stable signal despite significant challenges to the operating room environment. CSD may be responsible for some cases of secondary surgical injury. Though further studies on outcome related to the occurrence of these events is needed, efforts to decrease the occurrence of CSD by modification of anesthetic regimen may represent a novel target for study to increase the safety of neurosurgical procedures.

Bilateral sensory disturbance after cortical spreading depression revealed by fluorescence imaging of voltage-sensitive dye.

PubMed

Huang, Qin; Liu, Rui; Gui, Shen; Lu, Jinling; Li, Pengcheng

2018-03-07

Cortical spreading depression (CSD), a propagation wave of transient neuronal and glial depolarization followed by suppression of spontaneous brain activity, has been hypothesized to be the underlying mechanism of migraine aura and triggers the headache attack. Evidence from various animal models accumulates since its first discovery in 1944 and provides support for this hypothesis. In this paper, alterations of bilateral cortical responses are investigated in a mice migrainous model of CSD using voltage-sensitive dye imaging under hindlimb and cortical stimulation. After CSD induction in the right hemisphere, bilateral sensory responses evoked by left hindlimb stimulation dramatically decreases, whereas right hindlimb stimulation can still activate bilateral responses with an increased response of the left hemisphere and a well-preserved response of the right hemisphere. In addition, cortical neural excitability remains after CSD assessed by direct activation of the right hemisphere in spite of the sensory deficit under contralateral hindlimb stimulation. These results depict the sensory disturbance of bilateral hemispheres after CSD, which may be helpful in understanding how sensory disturbance occur during migraine aura. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combined quantum mechanics and molecular mechanics simulation of Ca2+/ammonia solution based on the ONIOM-XS method: Octahedral coordination and implication to biology

NASA Astrophysics Data System (ADS)

Kerdcharoen, Teerakiat; Morokuma, Keiji

2003-05-01

An extension of the ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics) method [M. Svensson, S. Humbel, R. D. J. Froese, T. Mutsubara, S. Sieber, and K. Morokuma, J. Phys. Chem. 100, 19357 (1996)] for simulation in the condensed phase, called ONIOM-XS (XS=eXtension to Solvation) [T. Kerdcharoen and K. Morokuma, Chem. Phys. Lett. 355, 257 (2002)], was applied to investigate the coordination of Ca2+ in liquid ammonia. A coordination number of 6 is found. Previous simulations based on pair potential or pair potential plus three-body correction gave values of 9 and 8.2, respectively. The new value is the same as the coordination number most frequently listed in the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). N-Ca-N angular distribution reveals a near-octahedral coordination structure. Inclusion of many-body interactions (which amounts to 25% of the pair interactions) into the potential energy surface is essential for obtaining reasonable coordination number. Analyses of the metal coordination in water, water-ammonia mixture, and in proteins reveals that cation/ammonia solution can be used to approximate the coordination environment in proteins.

Mapping Climate Science Information Needs and Networks in the Northwest, USA through Evaluating the Northwest Climate Science Center Climate Science Digest

NASA Astrophysics Data System (ADS)

Gergel, D. R.; Watts, L. H.; Salathe, E. P.; Mankowski, J. D.

2017-12-01

Climate science, already a highly interdisciplinary field, is rapidly evolving, and natural resource managers are increasingly involved in policymaking and adaptation decisions to address climate change that need to be informed by state-of-the-art climate science. Consequently, there is a strong demand for unique organizations that engender collaboration and cooperation between government, non-profit, academic and for-profit sectors that are addressing issues relating to natural resources management and climate adaptation and resilience. These organizations are often referred to as boundary organizations. The Northwest Climate Science Center (NW CSC) and the North Pacific Landscape Conservation Cooperative (NP LCC) are two such boundary organizations operating in different contexts. Together, the NW CSC and the NP LCC fulfill the need for sites of co-production between researchers and managers working on climate-related issues, and a key component of this work is a monthly climate science newsletter that includes recent climate science journal articles, reports, and climate-related events. Our study evaluates the effectiveness of the climate science digest (CSD) through a three-pronged approach: a) in-depth interviews with natural resource managers who use the CSD, b) poll questions distributed to CSD subscribers, and c) quantitative analysis of CSD effectiveness using analytics from MailChimp distribution. We aim to a) map the reach of the CSD across the Northwest and at a national level; b) understand the efficacy of the CSD at communicating climate science to diverse audiences; c) evaluate the usefulness of CSD content for diverse constituencies of subscribers; d) glean transferrable knowledge for future evaluations of boundary management tools; and e) establish a protocol for designing climate science newsletters for other agencies disseminating climate science information. We will present results from all three steps of our evaluation process and describe their implications for future evaluations of climate science communications products and other boundary management tools in the field of natural resources management.

Expanding the Use of Continuous Sedation Until Death: Moving Beyond the Last Resort for the Terminally Ill.

PubMed

LiPuma, Samuel H; DeMarco, Joseph P

2015-01-01

As currently practiced, the use of continuous sedation until death (CSD) is controlled by clinicians in a way that may deny patients a key choice in controlling their dying process. Ethical guidelines from the American Medical Association and the American Academy of Pain Medicine describe CSD as a "last resort," and a position statement from the American Academy of Hospice and Palliative Medicine describe it as "an intervention reserved for extreme situations." Accordingly, patients must progress to unremitting pain and suffering and reach a last-resort stage before the option to pursue CSD is considered. Alternatively, we present and defend a new guideline in which decisionally capable, terminally ill patients who have a life expectancy of less than six months may request CSD before being subjected to the refractory suffering of a treatment of "last resort." Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

In vitro and in vivo evaluation of 11C-SD5024, a novel PET radioligand for human brain imaging of cannabinoid CB1 receptors

PubMed Central

Tsujikawa, Tetsuya; Zoghbi, Sami S.; Hong, Jinsoo; Donohue, Sean R.; Jenko, Kimberly J.; Gladding, Robert L.; Halldin, Christer; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro

2013-01-01

We recently developed a novel cannabinoid subtype-1 (CB1) receptor radioligand 11C-SD5024 for brain imaging. This study aimed to evaluate 11C-SD5024 both in vitro and in vivo and compare it with the other CB1 receptor ligands previously used in humans, i.e., 11C-MePPEP, 11C-OMAR, 18F-MK-9470, and 18F-FMPEP-d2. In vitro experiments were performed to measure dissociation constant (Ki) in human brain and to measure the lipophilicity of five CB1 receptor ligands listed above. In vivo specific binding in monkeys was measured by comparing total distribution volume (VT) at baseline and after full receptor blockade. The kinetics of 11C-SD5024 in humans were evaluated in seven healthy subjects with compartmental modeling. SD5024 showed Ki=0.47 nM, which was at an intermediate level among the five CB1 receptor ligands. Lipophilicity (LogD7.4) was 3.79, which is appropriate for brain imaging. Monkey scans showed high proportion of specific binding: ~80% of VT. In humans, 11C-SD5024 showed peak brain uptake of 1.5–3 standardized uptake value, which was slightly higher than those of 11C-OMAR and 18F-MK-9470. One-compartment model showed good fitting, consistent with the vast majority of brain uptake being specific binding found in the monkey. Regional VT values were consistent with known distribution of CB1 receptors. VT calculated from 80 and 120 min of scan data were strongly correlated (R2=0.97), indicating that 80 min provided adequate information for quantitation and that the influence of radiometabolites was low. Intersubject variability for VT of 11C-SD5024 was 22%, which was low among the five radioligands and indicated precise measurement. In conclusion, 11C-SD5024 has appropriate affinity and lipophilicity, high specific binding, moderate brain uptake, and provides good precision to measure the binding. The results suggest that 11C-SD5024 is slightly better than or equivalent to 11C-OMAR and that both are suitable for clinical studies, especially those that involve two scans in one day. PMID:24076222

A multigene family related to chitin synthase genes of yeast in the opportunistic pathogen Aspergillus fumigatus.

PubMed

Mellado, E; Aufauvre-Brown, A; Specht, C A; Robbins, P W; Holden, D W

1995-02-06

Two approaches were used to isolate fragments of chitin synthase genes from the opportunistic human pathogen Aspergillus fumigatus. Firstly, regions of amino acid conservation in chitin synthases of Saccharomyces cerevisiae were used to design degenerate primers for amplification of portions of related genes, and secondly, a segment of the S. cerevisiae CSD2 gene was used to screen an A. fumigatus lambda genomic DNA library. the polymerase chain reaction (PCR)-based approach led to the identification of five different genes, designated chsA, chsB, chsC, chsD and chsE. chsA, chsB, and chsC fall into Classes I, II and III of the 'zymogen type' chitin synthases, respectively. The chsD fragment has approximately 35% amino acid sequence identity to both the zymogen type genes and the non-zymogen type CSD2 gene. chsF appears to be a homologue of CSD2, being 80% identical to CSD2 over 100 amino acids. An unexpected finding was the isolation by heterologous hybridization of another gene (chsE), which also has strong sequence similarity (54% identity at the amino acid level over the same region as chsF) to CSD2. Reverse transcriptase-PCR was used to show that each gene is expressed during hyphal growth in submerged cultures.

Semantic Location Extraction from Crowdsourced Data

NASA Astrophysics Data System (ADS)

Koswatte, S.; Mcdougall, K.; Liu, X.

2016-06-01

Crowdsourced Data (CSD) has recently received increased attention in many application areas including disaster management. Convenience of production and use, data currency and abundancy are some of the key reasons for attracting this high interest. Conversely, quality issues like incompleteness, credibility and relevancy prevent the direct use of such data in important applications like disaster management. Moreover, location information availability of CSD is problematic as it remains very low in many crowd sourced platforms such as Twitter. Also, this recorded location is mostly related to the mobile device or user location and often does not represent the event location. In CSD, event location is discussed descriptively in the comments in addition to the recorded location (which is generated by means of mobile device's GPS or mobile communication network). This study attempts to semantically extract the CSD location information with the help of an ontological Gazetteer and other available resources. 2011 Queensland flood tweets and Ushahidi Crowd Map data were semantically analysed to extract the location information with the support of Queensland Gazetteer which is converted to an ontological gazetteer and a global gazetteer. Some preliminary results show that the use of ontologies and semantics can improve the accuracy of place name identification of CSD and the process of location information extraction.

Comparative Soot Diagnostics: 1 Year Report

NASA Technical Reports Server (NTRS)

Urban, David L.; Griffin, DeVon W.; Gard, Melissa Y.

1998-01-01

The motivation for the Comparative Soot Diagnostics (CSD) experiment lies in the broad practical importance of understanding combustion generated particulate. Depending upon the circumstances, particulate matter can affect the durability and performance of combustion equipment, can be a pollutant, can be used to detect fires and, in the form of soot, can be the dominant source of radiant energy from flames. Bright sooty fires are desirable for efficient energy extraction in furnaces and power equipment. In contrast, soot-enhanced radiation is undesirable in many propulsion systems (e.g. jet engines). The non-buoyant structure of most flames of practical interest (turbulent) makes understanding of soot processes in low gravity flames important to our ability to predict fire behavior on earth. These studies also have direct applications to fire safety in human-crew spacecraft, since smoke is the indicator used for automated detection in current spacecraft. In addition, recent tests conducted on MIR showed that a candle in a truly quiescent spacecraft environment can burn for tens of minutes. Consequently, this test and many earlier tests have demonstrated that fires in spacecraft can be considered a credible risk. In anticipation of this risk, NASA has included fire detectors on Skylab, smoke detectors on the Space Shuttle (STS), and smoke detectors in the design for the International Space Station (ISS). In the CSD experiment, these smoke detectors were tested using, quasi-steady, low-gravity, particulate generating materials. Samples of the particulate were also obtained from these low-gravity sources. This experiment provides the first such measurements aimed toward understanding of soot processes here on earth and for the testing and design of advanced spacecraft smoke detection systems. This paper describes the operation and preliminary results of the CSD experiment which was was conducted in the Middeck Glovebox Facility (MGBX) on USMP-3. The objectives of CSD are to examine the particulate emission from a variety of pyrolyzing and combusting sources and to quantify the performance of several particulate-sensing diagnostic techniques. This paper presents the results of the microgravity portion of the CSD experiment. The results include the temporal response of the detectors and average sizes of the primary and aggregate particles captured on the thermophoretic probes. Complete assessment of the microgravity data and its combination with the normal-gravity data are still in process.

Phase Evolution of YBa2Cu3O7-x films by all-chemical solution deposition route for coated conductors

NASA Astrophysics Data System (ADS)

Zhao, Yue; Tang, Xiao; Wu, Wei; Grivel, Jean-Claude

2014-05-01

In order to understand the all-chemical-solution-deposition (CSD) processes for manufacturing coated conductors, we investigated the phase evolution of YBa2Cu3O7 (YBCO) films deposited by a low-fluorine metal-organic solution deposition (LF-MOD) method on CSD derived Ce0.9La0.1O2/Gd2Zr2O7/NiW. It is shown that the phase transition from the pyrolyzed film to fully converted YBCO film in the LF-MOD process is similar to that in typical trifluoroacetates-metal organic deposition (TFA-MOD) processes even though the amount of TFA in the solution is reduced by almost one half compared with typical TFA-MOD cases. Moreover, we found that the formation of impurities (mainly BaCeO3, NiWO4 and NiO) is strongly related to the annealing temperature, i.e., the diffusion controlled reactions become intensive from 760 oC, which might be connected with the poor structural and superconducting properties of the films deposited at high sintering temperatures. Based on these results, the optimized growth conditions of YBCO films were established, and a high critical current density (Jc) of about 2 MA/cm2 (77 K, self field) is achieved in a 200 nm thick YBCO film in the architecture made by our all CSD route.

The Organization of Correctional Education Services

ERIC Educational Resources Information Center

Gehring, Thom

2007-01-01

There have been five major types of correctional education organizations over the centuries: Sabbath school, traditional or decentralized, bureau, correctional school district (CSD), and integral education. The middle three are modern organizational patterns that can be implemented throughout a system: Decentralized, bureau, and CSD. The…

A reliability assessment of constrained spherical deconvolution-based diffusion-weighted magnetic resonance imaging in individuals with chronic stroke.

PubMed

Snow, Nicholas J; Peters, Sue; Borich, Michael R; Shirzad, Navid; Auriat, Angela M; Hayward, Kathryn S; Boyd, Lara A

2016-01-15

Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter properties after stroke. Novel work is utilizing constrained spherical deconvolution (CSD) to estimate complex intra-voxel fiber architecture unaccounted for with tensor-based fiber tractography. However, the reliability of CSD-based tractography has not been established in people with chronic stroke. Establishing the reliability of CSD-based DW-MRI in chronic stroke. High-resolution DW-MRI was performed in ten adults with chronic stroke during two separate sessions. Deterministic region of interest-based fiber tractography using CSD was performed by two raters. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract number, and tract volume were extracted from reconstructed fiber pathways in the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). Callosal fiber pathways connecting the primary motor cortices were also evaluated. Inter-rater and test-retest reliability were determined by intra-class correlation coefficients (ICCs). ICCs revealed excellent reliability for FA and ADC in ipsilesional (0.86-1.00; p<0.05) and contralesional hemispheres (0.94-1.00; p<0.0001), for CST and SLF fibers; and excellent reliability for all metrics in callosal fibers (0.85-1.00; p<0.05). ICC ranged from poor to excellent for tract number and tract volume in ipsilesional (-0.11 to 0.92; p≤0.57) and contralesional hemispheres (-0.27 to 0.93; p≤0.64), for CST and SLF fibers. Like other select DW-MRI approaches, CSD-based tractography is a reliable approach to evaluate FA and ADC in major white matter pathways, in chronic stroke. Future work should address the reproducibility and utility of CSD-based metrics of tract number and tract volume. Copyright © 2015 Elsevier B.V. All rights reserved.

Ozeane: Ergebnisse der 7. Sitzung der Kommission für nachhaltige Entwicklung (CSD) der Vereinten Nationen

NASA Astrophysics Data System (ADS)

Schlimm, Jutta; Stietzel, Hans-Joachim

1999-12-01

The 7th session of the United Nations Commission on Sustainable Development (CSD) was organised from 19 30 April in the UN Headquarters in New York. The Commission on Sustainable Development was established in 1992 with the aim to implement the comprehensive action programme of Agenda 21. The topics on the agenda of this year’s CSD session included: oceans, tourism as well as consumption and production patterms with a special focus on the oceans item. The 7th Session covered two weeks. It began with the so-called “High Level Segment” during the first week when 89 ministers and high-ranking government representatives stated their points of view on various themes-sometimes also in interaction with the chairman. Concerning the topic of oceans CSD 7 focussed on a few main items of special priority for the implementation of the Agenda 21, both during the preparatory “Intersessional Working Group” and in the final document. These main items are: the conservation and integrated as well as sustainable management of fisheries and marine resources, including the ecosystem of the oceans, the prevention of pollution and degradation of the marine environment through land-based and other acticities, the improvement of the scientific knowledge on oceans and the interaction between the oceans and the global climate system. The decisions of CSD 7 adressed detailed and for the major part concrete proposals for action, appeals or requests to the international organisations and the interntional community with regard to these main items. Summarizing the 7th session, it can be said that in the oceans sector CSD 7 was quite successful in fullilling the task to study the implementation of Agenda 21, to set priorities and to address actors and the necessary actions.

Neural activity tied to reading predicts individual differences in extended-text comprehension

PubMed Central

Mossbridge, Julia A.; Grabowecky, Marcia; Paller, Ken A.; Suzuki, Satoru

2013-01-01

Reading comprehension depends on neural processes supporting the access, understanding, and storage of words over time. Examinations of the neural activity correlated with reading have contributed to our understanding of reading comprehension, especially for the comprehension of sentences and short passages. However, the neural activity associated with comprehending an extended text is not well-understood. Here we describe a current-source-density (CSD) index that predicts individual differences in the comprehension of an extended text. The index is the difference in CSD-transformed event-related potentials (ERPs) to a target word between two conditions: a comprehension condition with words from a story presented in their original order, and a scrambled condition with the same words presented in a randomized order. In both conditions participants responded to the target word, and in the comprehension condition they also tried to follow the story in preparation for a comprehension test. We reasoned that the spatiotemporal pattern of difference-CSDs would reflect comprehension-related processes beyond word-level processing. We used a pattern-classification method to identify the component of the difference-CSDs that accurately (88%) discriminated good from poor comprehenders. The critical CSD index was focused at a frontal-midline scalp site, occurred 400–500 ms after target-word onset, and was strongly correlated with comprehension performance. Behavioral data indicated that group differences in effort or motor preparation could not explain these results. Further, our CSD index appears to be distinct from the well-known P300 and N400 components, and CSD transformation seems to be crucial for distinguishing good from poor comprehenders using our experimental paradigm. Once our CSD index is fully characterized, this neural signature of individual differences in extended-text comprehension may aid the diagnosis and remediation of reading comprehension deficits. PMID:24223540

Caveolin-1 Regulates Leukocyte Behaviour in Fibrotic Lung Disease

PubMed Central

Tourkina, Elena; Richard, Mathieu; Oates, James; Hofbauer, Ann; Bonner, Michael; Gööz, Pal; Visconti, Richard; Zhang, Jing; Znoyko, Sergei; Hatfield, Corey M.; Silver, Richard M.; Hoffman, Stanley

2010-01-01

Objectives Reduced caveolin-1 levels in scleroderma lung fibroblasts and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. We now evaluate whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and scleroderma patients and examine the consequences of this deficiency and its reversal. Methods Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, we examined caveolin-1 levels in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue. To validate our results in human disease and identify caveolin-1-regulated molecular mechanisms, we isolated monocytes and neutrophils from scleroderma patients and control subjects and evaluated caveolin-1, ERK, JNK, p38, CXCR4, and MMP-9 expression/activation. We also studied these parameters in monocytes treated with cytokines or CSD peptide. Results Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression is diminished in monocytes and CSD peptide inhibits leucocyte recruitment into the lungs. These observations are relevant to human disease. Scleroderma monocytes and neutrophils contain less caveolin-1 and more activated ERK, JNK, and p38 than their normal counterparts. CSD peptide treatment reverses ERK, JNK, and p38 hyperactivation. Scleroderma monocytes also overexpress CXCR4 and MMP-9. The overexpression of CXCR4 and MMP-9 is inhibited by the CSD peptide. Cytokine treatment of normal monocytes causes adoption of the scleroderma phenotype: low caveolin-1, high CXCR4 and MMP-9, and signaling molecule hyperactivation. Conclusions Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as a promising therapeutic target in scleroderma. PMID:20410070

Detection of Spiroplasma citri by droplet digital PCR

USDA-ARS?s Scientific Manuscript database

Spiroplasmas are motile, helical bacteria belonging to the Class Mollicutes, a group of prokaryotics with no cell wall and phylogenetically related to Gram-positive bacteria. Spiroplasma citri is the first-cultured spiroplasma and causal agent of citrus stubborn disease (CSD). Detection of CSD is di...

Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression.

PubMed

Yıldırım, Timur; Eylen, Alpaslan; Lule, Sevda; Erdener, Sefik Evren; Vural, Atay; Karatas, Hulya; Ozveren, Mehmet Faik; Dalkara, Turgay; Gursoy-Ozdemir, Yasemin

2015-01-01

Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.

Non-uniform cosine modulated filter banks using meta-heuristic algorithms in CSD space.

PubMed

Kalathil, Shaeen; Elias, Elizabeth

2015-11-01

This paper presents an efficient design of non-uniform cosine modulated filter banks (CMFB) using canonic signed digit (CSD) coefficients. CMFB has got an easy and efficient design approach. Non-uniform decomposition can be easily obtained by merging the appropriate filters of a uniform filter bank. Only the prototype filter needs to be designed and optimized. In this paper, the prototype filter is designed using window method, weighted Chebyshev approximation and weighted constrained least square approximation. The coefficients are quantized into CSD, using a look-up-table. The finite precision CSD rounding, deteriorates the filter bank performances. The performances of the filter bank are improved using suitably modified meta-heuristic algorithms. The different meta-heuristic algorithms which are modified and used in this paper are Artificial Bee Colony algorithm, Gravitational Search algorithm, Harmony Search algorithm and Genetic algorithm and they result in filter banks with less implementation complexity, power consumption and area requirements when compared with those of the conventional continuous coefficient non-uniform CMFB.

Non-uniform cosine modulated filter banks using meta-heuristic algorithms in CSD space

PubMed Central

Kalathil, Shaeen; Elias, Elizabeth

2014-01-01

This paper presents an efficient design of non-uniform cosine modulated filter banks (CMFB) using canonic signed digit (CSD) coefficients. CMFB has got an easy and efficient design approach. Non-uniform decomposition can be easily obtained by merging the appropriate filters of a uniform filter bank. Only the prototype filter needs to be designed and optimized. In this paper, the prototype filter is designed using window method, weighted Chebyshev approximation and weighted constrained least square approximation. The coefficients are quantized into CSD, using a look-up-table. The finite precision CSD rounding, deteriorates the filter bank performances. The performances of the filter bank are improved using suitably modified meta-heuristic algorithms. The different meta-heuristic algorithms which are modified and used in this paper are Artificial Bee Colony algorithm, Gravitational Search algorithm, Harmony Search algorithm and Genetic algorithm and they result in filter banks with less implementation complexity, power consumption and area requirements when compared with those of the conventional continuous coefficient non-uniform CMFB. PMID:26644921

The Microscopic Representation of Complex Oscopic Phenomena Critical Slowing Down - a Blessing in Disguise

NASA Astrophysics Data System (ADS)

Solomon, S.

The following sections are included: * The Microscopic Representation Paradigm * CSD Appearance and Measurement * Elimination of CSD as Understanding of oscopic Dynamics * MicRep Use in Multiscale Phenomena * Conclusions * Acknowledgements * References * Notes Added in Proof: Visualization Experiments * References Added in Proof

Complementary Sex Determination in the Parasitic Wasp Diachasmimorpha longicaudata

PubMed Central

Carabajal Paladino, Leonela; Muntaabski, Irina; Lanzavecchia, Silvia; Le Bagousse-Pinguet, Yoann; Viscarret, Mariana; Juri, Marianela; Fueyo-Sánchez, Luciana; Papeschi, Alba; Cladera, Jorge; Bressa, María José

2015-01-01

We studied the sex determination in Diachasmimorpha longicaudata, a parasitoid braconid wasp widely used as biological control agent of fruit pest tephritid flies. We tested the complementary sex determination hypothesis (CSD) known in at least 60 species of Hymenoptera. According to CSD, male or female development depends on the allelic composition of one sex locus (single-locus CSD) or multiple sex loci (multiple-locus CSD). Hemizygote individuals are normal haploid males, and heterozygotes for at least one sex locus are normal diploid females, but homozygotes for all the sex loci are diploid males. In order to force the occurrence of diploid males in D. longicaudata, we established highly inbred lines and examined their offspring using chromosome counting, flow cytometry, and sex ratio analysis. We found that when mother-son crosses were studied, this wasp produced about 20% of diploid males out of the total male progeny. Our results suggest that this parasitoid may represent the second genus with multiple-locus CSD in Hymenoptera. Knowledge about the sex determination system in D. longicaudata is relevant for the improvement of mass rearing protocols of this species. This information also provides the necessary background for further investigations on the underlying molecular mechanisms of sex determination in this species, and a better insight into the evolution of this pathway in Hymenoptera in particular and insects in general. PMID:25789748

Single-locus complementary sex determination in the inbreeding wasp Euodynerus foraminatus Saussure (Hymenoptera: Vespidae).

PubMed

Stahlhut, J K; Cowan, D P

2004-03-01

The Hymenoptera have arrhenotokous haplodiploidy in which males normally develop from unfertilized eggs and are haploid, while females develop from fertilized eggs and are diploid. Multiple sex determination systems are known to underlie haplodiploidy, and the best understood is single-locus complementary sex determination (sl-CSD) in which sex is determined at a single polymorphic locus. Individuals heterozygous at the sex locus develop as females; individuals that are hemizygous (haploid) or homozygous (diploid) at the sex locus develop as males. sl-CSD can be detected with inbreeding experiments that produce diploid males in predictable proportions as well as sex ratio shifts due to diploid male production. This sex determination system is considered incompatible with inbreeding because the ensuing increase in homozygosity increases the production of diploid males that are inviable or infertile, imposing a high cost on matings between close relatives. However, in the solitary hunting wasp Euodynerus foraminatus, a species suspected of having sl-CSD, inbreeding may be common due to a high incidence of sibling matings at natal nests. In laboratory crosses with E. foraminatus, we find that sex ratios and diploid male production (detected as microsatellite heterozygosity) are consistent with sl-CSD, but not with other sex determination systems. This is the first documented example of sl-CSD in a hymenopteran with an apparent natural history of inbreeding, and thus presents a paradox for our understanding of hymenopteran genetics.

Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex.

PubMed

Piilgaard, Henning; Lauritzen, Martin

2009-09-01

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is the mechanism of migraine, and involved in progressive neuronal injury in stroke and head trauma. Here we tested the hypothesis that single episodes of CSD induced acute hypoxia, and prolonged impairment of neurovascular and neurometabolic coupling. Cortical spreading depression was induced in rat frontal cortex, whereas cortical electrical activity and local field potentials (LFPs) were recorded by glass microelectrodes, cerebral blood flow (CBF) by laser-Doppler flowmetry, and tissue oxygen tension (tpO(2)) with polarographic microelectrodes. Cortical spreading depression increased cerebral metabolic rate of oxygen (CMRO(2)) by 71%+/-6.7% and CBF by 238%+/-48.1% for 1 to 2 mins. For the following 2 h, basal tpO(2) and CBF were reduced whereas basal CMRO(2) was persistently elevated by 8.1%+/-2.9%. In addition, within first hour after CSD we found impaired neurovascular coupling (LFP versus CBF), whereas neurometabolic coupling (LFP versus CMRO(2)) remained unaffected. Impaired neurovascular coupling was explained by both reduced vascular reactivity and suppressed function of cortical inhibitory interneurons. The protracted effects of CSD on basal CMRO(2) and neurovascular coupling may contribute to cellular dysfunction in patients with migraine and acutely injured cerebral cortex.

Testing constrained sequential dominance models of neutrinos

NASA Astrophysics Data System (ADS)

Björkeroth, Fredrik; King, Stephen F.

2015-12-01

Constrained sequential dominance (CSD) is a natural framework for implementing the see-saw mechanism of neutrino masses which allows the mixing angles and phases to be accurately predicted in terms of relatively few input parameters. We analyze a class of CSD(n) models where, in the flavour basis, two right-handed neutrinos are dominantly responsible for the ‘atmospheric’ and ‘solar’ neutrino masses with Yukawa couplings to ({ν }e,{ν }μ ,{ν }τ ) proportional to (0,1,1) and (1,n,n-2), respectively, where n is a positive integer. These coupling patterns may arise in indirect family symmetry models based on A 4. With two right-handed neutrinos, using a χ 2 test, we find a good agreement with data for CSD(3) and CSD(4) where the entire Pontecorvo-Maki-Nakagawa-Sakata mixing matrix is controlled by a single phase η, which takes simple values, leading to accurate predictions for mixing angles and the magnitude of the oscillation phase | {δ }{CP}| . We carefully study the perturbing effect of a third ‘decoupled’ right-handed neutrino, leading to a bound on the lightest physical neutrino mass {m}1{{≲ }}1 meV for the viable cases, corresponding to a normal neutrino mass hierarchy. We also discuss a direct link between the oscillation phase {δ }{CP} and leptogenesis in CSD(n) due to the same see-saw phase η appearing in both the neutrino mass matrix and leptogenesis.

The protective effect of 20(S)-protopanaxadiol (PPD) against chronic sleep deprivation (CSD)-induced memory impairments in mice.

PubMed

Lu, Cong; Lv, Jingwei; Dong, Liming; Jiang, Ning; Wang, Yan; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

2018-03-01

Sleep deprivation (SD) is associated with oxidative stress that causes learning and memory impairment. 20(S)-Protopanaxadiol (PPD), one of the protopanaxadiol-type saponins, has antioxidant and neuroprotective effect. This study was designed to research the protective effect of PPD against cognitive deficits induced by chronic sleep deprivation (CSD) in mice. The CSD model was induced by subjecting the mice to our self-made Sleep Interruption Apparatus (SIA) continuously for 14 days. The memory enhancing effects of PPD were evaluated by behavioral tests and the related mechanism was further explored by observing the oxidative stress changes in the cortex and hippocampus of mice. The results revealed that PPD (20 and 40 μmol/kg, i.p.) administration significantly improved the cognitive performance of CSD model mice in object location recognition experiment, novel object recognition task and Morris water maze test. Furthermore, PPD effectively restored the levels/activities of antioxidant defense biomarkers in the cortex and hippocampus, including the superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, glutathione (GSH), and lipid peroxidation (LPO). In conclusion, PPD could attenuate cognitive deficits induced by CSD, and the neuroprotective effect of PPD might be mediated by alleviation of oxidative stress. It was assumed that PPD has the potential to be a neuroprotective substance for cognition dysfunction. Copyright © 2018 Elsevier Inc. All rights reserved.

Cat-scratch disease: ocular manifestations and visual outcome.

PubMed

Curi, André L L; Machado, Danuza; Heringer, Gustavo; Campos, Wesley Ribeiro; Lamas, Cristiane; Rozental, Tatiana; Gutierres, Alexandro; Orefice, Fernando; Lemos, Elba

2010-10-01

To describe the intra-ocular manifestations of cat-scratch disease (CSD) found at two uveitis reference centers in Brazil. Retrospective case series study. Review of clinical records of patients diagnosed with CSD in the Uveitis Department of São Geraldo Hospital and the Ophthalmology Department of the Instituto de Pesquisa Clínica Evandro Chagas-FIOCRUZ, from 2001 to 2008. In the 8-year period, 24 patients with the diagnosis of CSD were identified. Twelve patients were male and 12 female. The mean age was 27.04 years (range 7-56). Sixteen patients (66.6%) presented with a history of a cat scratch and all patients reported cat exposure. Visual acuity ranged from counting fingers to 1.0 in the affected eye. Thirteen patients presented with bilateral disease. Sixteen (66.6%) patients complained of systemic symptoms, including fever, lymphadenopathy, liver and spleen enlargement and rash. All patients presented with serum antibodies (IgG) to Bartonella henselae. Thirty-seven eyes were affected. The most common findings were small areas of retinal infiltrates which occurred in 11 eyes (29.7%) and angiomatous lesions which occurred in nine eyes (24.3%). Neuroretinitis occurred in only six eyes (16.2%). The most common findings of CSD in our study were retinal infiltrates and angiomatous lesions. CSD patients may present with significant visual loss. Patients may benefit from systemic treatment with antibiotics.

CuLi2Sn and Cu2LiSn: Characterization by single crystal XRD and structural discussion towards new anode materials for Li-ion batteries.

PubMed

Fürtauer, Siegfried; Effenberger, Herta S; Flandorfer, Hans

2014-12-01

The stannides CuLi 2 Sn (CSD-427095) and Cu 2 LiSn (CSD-427096) were synthesized by induction melting of the pure elements and annealing at 400 °C. The phases were reinvestigated by X-ray powder and single-crystal X-ray diffractometry. Within both crystal structures the ordered CuSn and Cu 2 Sn lattices form channels which host Cu and Li atoms at partly mixed occupied positions exhibiting extensive vacancies. For CuLi 2 Sn, the space group F-43m. was verified (structure type CuHg 2 Ti; a =6.295(2) Å; wR 2 ( F ²)=0.0355 for 78 unique reflections). The 4( c ) and 4( d ) positions are occupied by Cu atoms and Cu+Li atoms, respectively. For Cu 2 LiSn, the space group P 6 3 / mmc was confirmed (structure type InPt 2 Gd; a =4.3022(15) Å, c =7.618(3) Å; wR 2 ( F ²)=0.060 for 199 unique reflections). The Cu and Li atoms exhibit extensive disorder; they are distributed over the partly occupied positions 2( a ), 2( b ) and 4( e ). Both phases seem to be interesting in terms of application of Cu-Sn alloys as anode materials for Li-ion batteries.

Learning Conservation and Sustainable Development: An Interdisciplinary Approach

Treesearch

John Schelhas; James P. Lassoie

2001-01-01

Conservation aud sustainable development (CSD) represent one of the most important new ways of thinking in natural resource management and policy. Cornell University has developed an iuterdisciplinary graduate minor to include this approach in its curriculum. The concept of CSD involves working toward environmental, social, and economic goals simultaneously. Although...

Cas5d Protein Processes Pre-crRNA and Assembles into a Cascade-like Interference Complex in Subtype I-C/Dvulg CRISPR-Cas System

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

Nam, Ki Hyun; Haitjema, Charles; Liu, Xueqi

Clustered regularly interspaced short palindromic repeats (CRISPRs), together with an operon of CRISPR-associated (Cas) proteins, form an RNA-based prokaryotic immune system against exogenous genetic elements. Cas5 family proteins are found in several type I CRISPR-Cas systems. Here, we report the molecular function of subtype I-C/Dvulg Cas5d from Bacillus halodurans. We show that Cas5d cleaves pre-crRNA into unit length by recognizing both the hairpin structure and the 3 single stranded sequence in the CRISPR repeat region. Cas5d structure reveals a ferredoxin domain-based architecture and a catalytic triad formed by Y46, K116, and H117 residues. We further show that after pre-crRNA processing,more » Cas5d assembles with crRNA, Csd1, and Csd2 proteins to form a multi-sub-unit interference complex similar to Escherichia coli Cascade (CRISPR-associated complex for antiviral defense) in architecture. Our results suggest that formation of a crRNA-presenting Cascade-like complex is likely a common theme among type I CRISPR subtypes.« less

Project Document Change/Revision Log for CSD Originated Document Number CSD-A-945

NASA Technical Reports Server (NTRS)

Chullen, Cinda

1969-01-01

The EMU (Extravehicular Mobility Unit) Garments and associated hardware were evaluated to determine if they are qualified for use in the first Lunar Landing Mission, Apollo XI (s/c 107/LM-5). It has been determined that the subject equipment is qualified for this application as summarized in this report.

Research-Based Curriculum, Pedagogy, and Assessment in a Deaf Bilingual Program

ERIC Educational Resources Information Center

Peterson, Laura

2012-01-01

The California School for the Deaf (CSD), Fremont, is a deaf-centered bilingual program. CSD's approach to curriculum development, instructional pedagogy, and assessment integrates best practices in deaf education, bilingual education, and general education. The goals of the program are outlined in the Expected School-wide Learning Results which…

The significance of Bartonella henselae bacterias for oncological diagnosis in children.

PubMed

Mazur-Melewska, Katarzyna; Jończyk-Potoczna, Katarzyna; Mania, Anna; Kemnitz, Paweł; Szydłowski, Jarosław; Służewski, Wojciech; Figlerowicz, Magdalena

2015-01-01

Cat-scratch disease (CSD) is a common infection in children; however, the wide spectrum of its clinical picture may lead to delayed diagnosis. An unusual presentation of CSD includes in the differential diagnosis malignant diseases, Epstein-Barr and cytomegalovirus infections, tuberculosis, and mycobacterioses. The diagnostic procedure is difficult, and it is important to consider CSD as the etiology of untypical lesion. We present the analysis of 22 immunocompetent children treated with the clinical diagnosis of CSD in our hospital. Their ages were 2 to 16 years (mean 9.15 ± 2.2 years). Four of them presented classical papulas at admission time. Asymmetric, local lymphadenopathy was present in 16 patients. Five children, who presented an untypical course of CSD mimicking the oncological process, were analysed carefully. There were 3 patients with skull osteomyelitis, 1 with inflammation of the parotid gland, and 1 with an extra peripharyngeal mass. The diagnosis in these children was based on epidemiological, radiological, serological, and histological factors. About 25 % of children with bartonellosis present an untypical spectrum of symptoms, including the lack of documented cat contact, primary lesions, or peripheral lymphadenopathy. Radiological methods like USG, CT, MRI present the unspecific masses, but they are not enough to distinguish the Bartonella inflammatory and oncological process. The final diagnosis was based on a histological method with additional polymerase chain reaction test. CSD should be considered in differential diagnosis of any patient with untypical lesions located on the head, neck, and upper extremities.

Leveraging knowledge engineering and machine learning for microbial bio-manufacturing.

PubMed

Oyetunde, Tolutola; Bao, Forrest Sheng; Chen, Jiung-Wen; Martin, Hector Garcia; Tang, Yinjie J

2018-05-03

Genome scale modeling (GSM) predicts the performance of microbial workhorses and helps identify beneficial gene targets. GSM integrated with intracellular flux dynamics, omics, and thermodynamics have shown remarkable progress in both elucidating complex cellular phenomena and computational strain design (CSD). Nonetheless, these models still show high uncertainty due to a poor understanding of innate pathway regulations, metabolic burdens, and other factors (such as stress tolerance and metabolite channeling). Besides, the engineered hosts may have genetic mutations or non-genetic variations in bioreactor conditions and thus CSD rarely foresees fermentation rate and titer. Metabolic models play important role in design-build-test-learn cycles for strain improvement, and machine learning (ML) may provide a viable complementary approach for driving strain design and deciphering cellular processes. In order to develop quality ML models, knowledge engineering leverages and standardizes the wealth of information in literature (e.g., genomic/phenomic data, synthetic biology strategies, and bioprocess variables). Data driven frameworks can offer new constraints for mechanistic models to describe cellular regulations, to design pathways, to search gene targets, and to estimate fermentation titer/rate/yield under specified growth conditions (e.g., mixing, nutrients, and O 2 ). This review highlights the scope of information collections, database constructions, and machine learning techniques (such as deep learning and transfer learning), which may facilitate "Learn and Design" for strain development. Copyright © 2018. Published by Elsevier Inc.

Physical exercise counteracts the increase in velocity of propagation of cortical spreading depression imposed by early over-nutrition in rats.

PubMed

Monteiro, Heloísa Mirelle Costa; de Mendonça, Débora Carneiro; Sousa, Mariana Séfora Bezerra; Amancio-Dos-Santos, Angela

2018-06-01

This investigation studied whether physical exercise could modulate cortical spreading depression (CSD) propagation velocity in adult rat offspring from dams that had received a high-fat (HF) diet during lactation. Wistar male rats suckled by dams fed either control (C) or HF diet ad libitum. After weaning, pups received standard laboratory chow. From 40 to 60 days of life, half of the animals exercised on a treadmill (group E); the other half remained sedentary (group S). Two additional HF groups (E and S) received fluoxetine (F; 10 mg/kg/day, orogastrically) from 40 to 60 days of life (groups HF/EF and HF/F). At 40 days of life, rats from the maternal HF diet presented higher weight, thoracic circumference, and Lee Index than C animals and remained heavier at 60 days of life. Physical exercise decreased abdominal circumference. HF diet increased CSD propagation velocity (mean ± SD; mm/min) in sedentaries (HF/S 3.47 ± 0.31 versus C/S 3.24 ± 0.26). Treadmill exercise decelerated CSD propagation in both groups C/E (2.94 ± 0.28) and HF/E (2.97 ± 0.40). Fluoxetine alone decreased CSD propagation (HF/F 2.88 ± 0.45) compared with HF/S group. The combination of fluoxetine + exercise under HF condition (2.98 ± 0.27) was similar to HF/E group. Physical exercise is able to reduce CSD propagation velocity in rat adult brains even when they have suffered over-nourishing during lactation. The effects of exercise alone or fluoxetine alone on CSD were similar to the effects of fluoxetine + exercise, under the HF condition. Data reinforce malnutrition during lactation modifies cortical electrophysiology even when the HF condition no longer exists.

Neonatal treatment with monosodium glutamate lastingly facilitates spreading depression in the rat cortex.

PubMed

Lima, Cássia Borges; Soares, Geórgia de Sousa Ferreira; Vitor, Suênia Marcele; Castellano, Bernardo; Andrade da Costa, Belmira Lara da Silveira; Guedes, Rubem Carlos Araújo

2013-09-17

Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human food to enhance flavor. MSG can affect the morphological and electrophysiological organization of the brain. This effect is more severe during brain development. Here, we investigated the electrophysiological and morphological effects of MSG in the developing rat brain by characterizing changes in the excitability-related phenomenon of cortical spreading depression (CSD) and microglial reaction. From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no treatment (naïve group; n=5) every other day. At 45-60 days, CSD was recorded on two cortical points for 4h. The CSD parameters velocity, and amplitude and duration of the negative potential change were calculated. Fixative-perfused brain sections were immunolabeled with anti-IBA-1 antibodies to identify and quantify cortical microglia. MSG-4 rats presented significantly higher velocities (4.59 ± 0.34 mm/min) than the controls (saline, 3.84 ± 0.20mm/min; naïve, 3.71 ± 0.8mm/min) and MSG-2 group (3.75 ± 0.10mm/min). The amplitude (8.8 ± 2.2 to 11.2 ± 1.9 mV) and duration (58.2 ± 7.1 to 73.6 ± 6.0s) of the negative slow potential shift was similar in all groups. MSG-treatment dose-dependently increased the microglial immunolabeling. The results demonstrate a novel, dose-dependent action of MSG in the developing brain, characterized by acceleration of CSD and significant microglial reaction in the cerebral cortex. The CSD effect indicates that MSG can influence cortical excitability, during brain development, as evaluated by CSD acceleration. Data suggest caution when consuming MSG, especially in developing organisms. © 2013.

Caveolin-1 regulates leucocyte behaviour in fibrotic lung disease.

PubMed

Tourkina, Elena; Richard, Mathieu; Oates, James; Hofbauer, Ann; Bonner, Michael; Gööz, Pal; Visconti, Richard; Zhang, Jing; Znoyko, Sergei; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

2010-06-01

Reduced caveolin-1 levels in lung fibroblasts from patients with scleroderma and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. This study was undertaken to determine whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and patients with scleroderma and to examine the consequences of this deficiency and its reversal. Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, the levels of caveolin-1 in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue were examined. To validate the results in human disease and to identify caveolin-1-regulated molecular mechanisms, monocytes and neutrophils were isolated from patients with scleroderma and control subjects and caveolin-1, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, CXC chemokine receptor 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9) expression/activation were evaluated. These parameters were also studied in monocytes treated with cytokines or CSD peptide. Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression was diminished in monocytes and CSD peptide inhibited leucocyte recruitment into the lungs. These observations are relevant to human disease. Monocytes and neutrophils from patients with scleroderma contained less caveolin-1 and more activated ERK, JNK and p38 than those from control subjects. Treatment with CSD peptide reversed ERK, JNK and p38 hyperactivation. Scleroderma monocytes also overexpressed CXCR4 and MMP-9, which was inhibited by the CSD peptide. Cytokine treatment of normal monocytes caused adoption of the scleroderma phenotype (low caveolin-1, high CXCR4 and MMP-9 and signalling molecule hyperactivation). Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as a promising therapeutic target in scleroderma.

A high-throughput core sampling device for the evaluation of maize stalk composition

PubMed Central

2012-01-01

Background A major challenge in the identification and development of superior feedstocks for the production of second generation biofuels is the rapid assessment of biomass composition in a large number of samples. Currently, highly accurate and precise robotic analysis systems are available for the evaluation of biomass composition, on a large number of samples, with a variety of pretreatments. However, the lack of an inexpensive and high-throughput process for large scale sampling of biomass resources is still an important limiting factor. Our goal was to develop a simple mechanical maize stalk core sampling device that can be utilized to collect uniform samples of a dimension compatible with robotic processing and analysis, while allowing the collection of hundreds to thousands of samples per day. Results We have developed a core sampling device (CSD) to collect maize stalk samples compatible with robotic processing and analysis. The CSD facilitates the collection of thousands of uniform tissue cores consistent with high-throughput analysis required for breeding, genetics, and production studies. With a single CSD operated by one person with minimal training, more than 1,000 biomass samples were obtained in an eight-hour period. One of the main advantages of using cores is the high level of homogeneity of the samples obtained and the minimal opportunity for sample contamination. In addition, the samples obtained with the CSD can be placed directly into a bath of ice, dry ice, or liquid nitrogen maintaining the composition of the biomass sample for relatively long periods of time. Conclusions The CSD has been demonstrated to successfully produce homogeneous stalk core samples in a repeatable manner with a throughput substantially superior to the currently available sampling methods. Given the variety of maize developmental stages and the diversity of stalk diameter evaluated, it is expected that the CSD will have utility for other bioenergy crops as well. PMID:22548834

Interfacing comprehensive rotorcraft analysis with advanced aeromechanics and vortex wake models

NASA Astrophysics Data System (ADS)

Liu, Haiying

This dissertation describes three aspects of the comprehensive rotorcraft analysis. First, a physics-based methodology for the modeling of hydraulic devices within multibody-based comprehensive models of rotorcraft systems is developed. This newly proposed approach can predict the fully nonlinear behavior of hydraulic devices, and pressure levels in the hydraulic chambers are coupled with the dynamic response of the system. The proposed hydraulic device models are implemented in a multibody code and calibrated by comparing their predictions with test bench measurements for the UH-60 helicopter lead-lag damper. Predicted peak damping forces were found to be in good agreement with measurements, while the model did not predict the entire time history of damper force to the same level of accuracy. The proposed model evaluates relevant hydraulic quantities such as chamber pressures, orifice flow rates, and pressure relief valve displacements. This model could be used to design lead-lag dampers with desirable force and damping characteristics. The second part of this research is in the area of computational aeroelasticity, in which an interface between computational fluid dynamics (CFD) and computational structural dynamics (CSD) is established. This interface enables data exchange between CFD and CSD with the goal of achieving accurate airloads predictions. In this work, a loose coupling approach based on the delta-airloads method is developed in a finite-element method based multibody dynamics formulation, DYMORE. To validate this aerodynamic interface, a CFD code, OVERFLOW-2, is loosely coupled with a CSD program, DYMORE, to compute the airloads of different flight conditions for Sikorsky UH-60 aircraft. This loose coupling approach has good convergence characteristics. The predicted airloads are found to be in good agreement with the experimental data, although not for all flight conditions. In addition, the tight coupling interface between the CFD program, OVERFLOW-2, and the CSD program, DYMORE, is also established. The ability to accurately capture the wake structure around a helicopter rotor is crucial for rotorcraft performance analysis. In the third part of this thesis, a new representation of the wake vortex structure based on Non-Uniform Rational B-Spline (NURBS) curves and surfaces is proposed to develop an efficient model for prescribed and free wakes. NURBS curves and surfaces are able to represent complex shapes with remarkably little data. The proposed formulation has the potential to reduce the computational cost associated with the use of Helmholtz's law and the Biot-Savart law when calculating the induced flow field around the rotor. An efficient free-wake analysis will considerably decrease the computational cost of comprehensive rotorcraft analysis, making the approach more attractive to routine use in industrial settings.

Multiple approaches to valuation of conservation design and low-impact development features in residential subdivisions.

PubMed

Bowman, Troy; Tyndall, John C; Thompson, Janette; Kliebenstein, James; Colletti, Joe P

2012-08-15

Residents, developers and civic officials are often faced with difficult decisions about appropriate land uses in and around metropolitan boundaries. Urban expansion brings with it the potential for negative environmental impacts, but there are alternatives, such as conservation subdivision design (CSD) or low-impact development (LID), which offer the possibility of mitigating some of these effects at the development site. Many urban planning jurisdictions across the Midwest do not currently have any examples of these designs and lack information to identify public support or barriers to use of these methods. This is a case study examining consumer value for conservation and low-impact design features in one housing market by using four different valuation techniques to estimate residents' willingness to pay for CSD and LID features in residential subdivisions. A contingent valuation survey of 1804 residents in Ames, IA assessed familiarity with and perceptions of subdivision development and used an ordered value approach to estimate willingness to pay for CSD and LID features. A majority of residents were not familiar with CSD or LID practices. Residents indicated a willingness to pay for most CSD and LID features with the exception of clustered housing. Gender, age, income, familiarity with LID practices, perceptions of attractiveness of features and the perceived effect of CSD and LID features on ease of future home sales were important factors influencing residents' willingness to pay. A hypothetical referendum measured willingness to pay for tax-funded conservation land purchases and estimated that a property tax of around $50 would be the maximum increase that would pass. Twenty-seven survey respondents participated in a subsequent series of experimental real estate negotiations that used an experimental auction mechanism to estimate willingness to pay for CSD and LID features. Participants indicated that clustered housing (with interspersed preserved forest or open space areas), rain gardens, and neighborhood streams with a forested buffer were the features they were most willing to pay for. Participants were not willing to pay for neighborhood streams without buffers. Finally, a spatial hedonic price model using 2093 homes in Ames, IA was used to estimate the effect of public and private open space on housing values. The model indicated that presence of neighborhood association-owned forest and water features as well as proximity to public parks had significant positive effects on housing prices. However, proximity to a public lake had a negative effect on home values. The four methods used in this study include both stated and revealed preference techniques. Although the relative magnitude of value expressed varied, all methods indicated that residents value CSD and LID subdivision features. Subdivision features that included explicit environmental benefits were also consistently preferred over features that did not. Familiarity with alternative designs was an important factor influencing resident willingness to pay for neighborhood features, and developers and civic officials should consider ways to educate citizens about CSD and LID development techniques to increase interest in these designs. Published by Elsevier Ltd.

Disseminated cat-scratch disease: case report and review of the literature.

PubMed

Chang, Chih-Chen; Lee, Chia-Jie; Ou, Liang-Shiou; Wang, Chao-Jan; Huang, Yhu-Chering

2016-08-01

Cat scratch disease (CSD) can present as a systemic disease in 5-10% of cases and lead to various disease entities. A previously healthy 16-month-old boy presented with fever for 7 days without other obvious symptoms. Abdominal computed tomography scan demonstrated enlarged right inguinal lymph nodes and multiple small round hypodensities in the spleen. Despite antibiotic treatment for 1 week, the fever persisted and the intrasplenic lesions progressed. Inguinal lymph node biopsy confirmed CSD by immunohistochemistry staining. The diagnosis of CSD was also supported by a history of contact, imaging and serological findings. The patient recovered after treatment with azithromycin for a total of 5 weeks and, in serial follow-up, the hepatosplenic micro-abscesses resolved after 4th months.

Disseminated cat-scratch disease: case report and review of the literature.

PubMed

Chang, Chih-Chen; Lee, Chia-Jie; Ou, Liang-Shiou; Wang, Chao-Jan; Huang, Yhu-Chering

2016-01-12

Cat scratch disease (CSD) can present as a systemic disease in 5-10% of cases and lead to various disease entities. A previously healthy 16-month-old boy presented with fever for 7 days without other obvious symptoms. Abdominal computed tomography scan demonstrated enlarged right inguinal lymph nodes and multiple small round hypodensities in the spleen. Despite antibiotic treatment for 1 week, the fever persisted and the intrasplenic lesions progressed. Inguinal lymph node biopsy confirmed CSD by immunohistochemistry staining. The diagnosis of CSD was also supported by a history of contact, imaging and serological findings. The patient recovered after treatment with azithromycin for a total of 5 weeks and, in serial follow-up, the hepatosplenic micro-abscesses resolved after 4th months.

Maternal brain response to own baby-cry is affected by cesarean section delivery

PubMed Central

Swain, James E.; Tasgin, Esra; Mayes, Linda C.; Feldman, Ruth; Constable, R. Todd; Leckman, James F.

2011-01-01

A range of early circumstances surrounding the birth of a child affects peripartum hormones, parental behavior and infant wellbeing. One of these factors, which may lead to postpartum depression, is the mode of delivery: vaginal delivery (VD) or cesarean section delivery (CSD). To test the hypothesis that CSD mothers would be less responsive to own baby-cry stimuli than VD mothers in the immediate postpartum period, we conducted functional magnetic resonance imaging, 2–4 weeks after delivery, of the brains of six mothers who delivered vaginally and six who had an elective CSD. VD mothers’ brains were significantly more responsive than CSD mothers’ brains to their own baby-cry in the superior and middle temporal gyri, superior frontal gyrus, medial fusiform gyrus, superior parietal lobe, as well as regions of the caudate, thalamus, hypothalamus, amygdala and pons. Also, within preferentially active regions of VD brains, there were correlations across all 12 mothers with out-of-magnet variables. These include correlations between own baby-cry responses in the left and right lenticular nuclei and parental preoccupations (r = .64, p < .05 and .67, p < .05 respectively), as well as in the superior frontal cortex and Beck depression inventory (r = .78, p < .01). First this suggests that VD mothers are more sensitive to own baby-cry than CSD mothers in the early postpartum in sensory processing, empathy, arousal, motivation, reward and habit-regulation circuits. Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby-cry. PMID:18771508

Multichannel fiber-based diffuse reflectance spectroscopy for the rat brain exposed to a laser-induced shock wave: comparison between ipsi- and contralateral hemispheres

NASA Astrophysics Data System (ADS)

Miyaki, Mai; Kawauchi, Satoko; Okuda, Wataru; Nawashiro, Hiroshi; Takemura, Toshiya; Sato, Shunichi; Nishidate, Izumi

2015-03-01

Due to considerable increase in the terrorism using explosive devices, blast-induced traumatic brain injury (bTBI) receives much attention worldwide. However, little is known about the pathology and mechanism of bTBI. In our previous study, we found that cortical spreading depolarization (CSD) occurred in the hemisphere exposed to a laser- induced shock wave (LISW), which was followed by long-lasting hypoxemia-oligemia. However, there is no information on the events occurred in the contralateral hemisphere. In this study, we performed multichannel fiber-based diffuse reflectance spectroscopy for the rat brain exposed to an LISW and compared the results for the ipsilateral and contralateral hemispheres. A pair of optical fibers was put on the both exposed right and left parietal bone; white light was delivered to the brain through source fibers and diffuse reflectance signals were collected with detection fibers for both hemispheres. An LISW was applied to the left (ipsilateral) hemisphere. By analyzing reflectance signals, we evaluated occurrence of CSD, blood volume and oxygen saturation for both hemispheres. In the ipsilateral hemispheres, we observed the occurrence of CSD and long-lasting hypoxemia-oligemia in all rats examined (n=8), as observed in our previous study. In the contralateral hemisphere, on the other hand, no occurrence of CSD was observed, but we observed oligemia in 7 of 8 rats and hypoxemia in 1 of 8 rats, suggesting a mechanism to cause hypoxemia or oligemia or both that is (are) not directly associated with CSD in the contralateral hemisphere.

Aquaporin-4 Regulates the Velocity and Frequency of Cortical Spreading Depression in Mice

PubMed Central

Yao, Xiaoming; Smith, Alex J.; Jin, Byung-Ju; Zador, Zsolt; Manley, Geoffrey T.; Verkman, A.S.

2016-01-01

The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K+ concentration ([K+]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K+]e and ECS volume affect the velocity, frequency and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4+/+) and AQP4-deficient (AQP4−/−) mice. Contrary to initial expectations, both the velocity and frequency of CSD were significantly reduced in AQP4−/− mice when compared to AQP4+/+ mice, by 22% and 32%, respectively. Measurement of [K+]e with K+-selective microelectrodes demonstrated an increase to ~35 mM during spreading depolarizations in both AQP4+/+ and AQP4−/− mice, but the rates of [K+]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4−/− mice. ECS volume fraction measured by trimethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4+/+ mice, and 0.23 to 0.063 in AQP4−/− mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4−/− mice was primarily a consequence of the slowed increase in [K+]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K+]e and ECS volume dynamics accelerate CSD propagation. PMID:25944186

Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C

PubMed Central

Müller, Thomas; Rasool, Insha; Heinz-Erian, Peter; Mildenberger, Eva; Hülstrunk, Christian; Müller, Andreas; Michaud, Laurent; Koot, Bart G P; Ballauff, Antje; Vodopiutz, Julia; Rosipal, Stefan; Petersen, Britt-Sabina; Franke, Andre; Fuchs, Irene; Witt, Heiko; Zoller, Heinz; Janecke, Andreas R; Visweswariah, Sandhya S

2016-01-01

Objective Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing. Design We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies. Results We identified novel de novo missense mutations in GUCY2C, the gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One patient developed severe, early-onset IBD and chronic arthritis at 4 years of age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable enterotoxin. Mutations in GUCY2C were present in different intracellular domains of GC-C, and were activating mutations that enhanced intracellular cyclic guanosine monophosphate accumulation in a ligand-independent and ligand-stimulated manner, following heterologous expression in HEK293T cells. Conclusions Dominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD. PMID:25994218

Complementary sex determination, inbreeding depression and inbreeding avoidance in a gregarious sawfly.

PubMed

Harper, K E; Bagley, R K; Thompson, K L; Linnen, C R

2016-11-01

Although most Hymenoptera reproduce via arrhenotokous haplodiploidy, the underlying genetic mechanisms vary. Of these, the most widespread mechanism appears to be single-locus complementary sex determination (sl-CSD), in which individuals that are diploid and heterozygous at a sex-determining locus are female, and individuals that are homozygous or hemizygous are male. Because inbreeding increases the probability of producing diploid males, which are often sterile or inviable, sl-CSD can generate substantial inbreeding depression. To counteract this, Hymenoptera with traits that promote inbreeding, such as gregariousness, may evolve one or more of the following: inbreeding avoidance, functional diploid males or alternative sex determination mechanisms. Here, we investigate sex determination, inbreeding depression and inbreeding avoidance in Neodiprion lecontei, a gregarious, pine-feeding sawfly in the family Diprionidae. First, via inbreeding experiments and flow cytometry, we demonstrate that this species has CSD. By modeling expected sex ratios under different conditions, we also show that our data are consistent with sl-CSD. Second, via tracking survival in inbred and outbred families, we demonstrate that inbred families have reduced larval survival and that this mortality is partly attributable to the death of diploid males. Third, using a no-choice mating assay, we demonstrate that females are less willing to mate with siblings than nonsiblings. Together, these results suggest that inbreeding depression stemming from CSD has shaped mating behavior in N. lecontei. These results also set the stage for future comparative work that will investigate the interplay between sex determination, ecology and behavior in additional diprionid species that vary in larval gregariousness.

Complementary sex determination, inbreeding depression and inbreeding avoidance in a gregarious sawfly

PubMed Central

Harper, K E; Bagley, R K; Thompson, K L; Linnen, C R

2016-01-01

Although most Hymenoptera reproduce via arrhenotokous haplodiploidy, the underlying genetic mechanisms vary. Of these, the most widespread mechanism appears to be single-locus complementary sex determination (sl-CSD), in which individuals that are diploid and heterozygous at a sex-determining locus are female, and individuals that are homozygous or hemizygous are male. Because inbreeding increases the probability of producing diploid males, which are often sterile or inviable, sl-CSD can generate substantial inbreeding depression. To counteract this, Hymenoptera with traits that promote inbreeding, such as gregariousness, may evolve one or more of the following: inbreeding avoidance, functional diploid males or alternative sex determination mechanisms. Here, we investigate sex determination, inbreeding depression and inbreeding avoidance in Neodiprion lecontei, a gregarious, pine-feeding sawfly in the family Diprionidae. First, via inbreeding experiments and flow cytometry, we demonstrate that this species has CSD. By modeling expected sex ratios under different conditions, we also show that our data are consistent with sl-CSD. Second, via tracking survival in inbred and outbred families, we demonstrate that inbred families have reduced larval survival and that this mortality is partly attributable to the death of diploid males. Third, using a no-choice mating assay, we demonstrate that females are less willing to mate with siblings than nonsiblings. Together, these results suggest that inbreeding depression stemming from CSD has shaped mating behavior in N. lecontei. These results also set the stage for future comparative work that will investigate the interplay between sex determination, ecology and behavior in additional diprionid species that vary in larval gregariousness. PMID:27381325

Distancing sedation in end-of-life care from physician-assisted suicide and euthanasia

PubMed Central

Soh, Tze Ling Gwendoline Beatrice; Krishna, Lalit Kumar Radha; Sim, Shin Wei; Yee, Alethea Chung Peng

2016-01-01

Lipuma equates continuous sedation until death (CSD) to physician-assisted suicide/euthanasia (PAS/E) based on the premise that iatrogenic unconsciousness negates social function and, thus, personhood, leaving a patient effectively ‘dead’. Others have extrapolated upon this position further, to suggest that any use of sedation and/or opioids at the end of life would be analogous to CSD and thus tantamount to PAS/E. These posits sit diametrically opposite to standard end-of-life care practices. This paper will refute Lipuma’s position and the posits borne from it. We first show that prevailing end-of-life care guidelines require proportional and monitored use of sedatives and/or opioids to attenuate fears that the use of such treatment could hasten death. These guidelines also classify CSD as a last resort treatment, employed only when symptoms prove intractable, and not amenable to all standard treatment options. Furthermore, CSD is applied only when deemed appropriate by a multidisciplinary palliative medicine team. We also show that empirical data based on local views of personhood will discount concerns that iatrogenic unconsciousness is tantamount to a loss of personhood and death. PMID:27211055

Effects of sciatic nerve stimulation on the propagation of cortical spreading depression

NASA Astrophysics Data System (ADS)

Sun, Xiaoli; Yu, Zhidong; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

2008-02-01

Cortical spreading depression (CSD) is an important pathological model of migraine and is related to other neural disorders, such as cerebral ischemia and epilepsy. It has been reported that brain stimulation is a quite effective way to treat neural diseases. However, direct stimulation could cause harm to brain. If peripheral nerve stimulation could have the same treatment, it would be essential to investigate the mechanisms of peripheral nerve and the study of sciatic nerve stimulation would have profound clinical meaning. In this paper, we used optical intrinsic signal imaging (OISI) and extracellular electrophysiologic recording techniques to study the effects of sciatic nerve stimulation on the propagation of CSD. We found that: (1) continuous sciatic nerve stimulation on rats caused a decrease in light intensity on the whole cortex, which meant an increase in cerebral blood volume(CBV); (2) the spreading velocity of CSD declined from 3.63+/- 0.272 mm/min to 3.06+/-0.260 mm/min during sciatic nerve stimulation, compared with that without sciatic nerve stimulation. In summary, data suggests that sciatic nerve stimulation elicits a response of cortex and causes a slowdown in the propagation of CSD.

Distancing sedation in end-of-life care from physician-assisted suicide and euthanasia.

PubMed

Soh, Tze Ling Gwendoline Beatrice; Krishna, Lalit Kumar Radha; Sim, Shin Wei; Yee, Alethea Chung Peng

2016-05-01

Lipuma equates continuous sedation until death (CSD) to physician-assisted suicide/euthanasia (PAS/E) based on the premise that iatrogenic unconsciousness negates social function and, thus, personhood, leaving a patient effectively 'dead'. Others have extrapolated upon this position further, to suggest that any use of sedation and/or opioids at the end of life would be analogous to CSD and thus tantamount to PAS/E. These posits sit diametrically opposite to standard end-of-life care practices. This paper will refute Lipuma's position and the posits borne from it. We first show that prevailing end-of-life care guidelines require proportional and monitored use of sedatives and/or opioids to attenuate fears that the use of such treatment could hasten death. These guidelines also classify CSD as a last resort treatment, employed only when symptoms prove intractable, and not amenable to all standard treatment options. Furthermore, CSD is applied only when deemed appropriate by a multidisciplinary palliative medicine team. We also show that empirical data based on local views of personhood will discount concerns that iatrogenic unconsciousness is tantamount to a loss of personhood and death. Copyright: © Singapore Medical Association.

Pathology and causes of death in stranded humpback whales (Megaptera novaeangliae) from Brazil.

PubMed

Groch, Kátia Regina; Díaz-Delgado, Josué; Marcondes, Milton C C; Colosio, Adriana Castaldo; Santos-Neto, Elitieri B; Carvalho, Vítor Luz; Boos, Gisele Silva; Oliveira de Meirelles, Ana Carolina; Ramos, Hernani Gomes da Cunha; Guimarães, Juliana Plácido; Borges, João Carlos Gomes; Vergara-Parente, Jociery Einhardt; St Leger, Judy A; Fernández, Antonio; Catão-Dias, José Luiz

2018-01-01

This study describes the pathologic findings of 24 humpback whales (Megaptera novaeangliae) found stranded along the Brazilian coast from 2004 to 2016. Eighteen (75%) animals evaluated were found stranded alive. From these, 13 died naturally on shore and five were euthanized. Six died at sea and were washed ashore. Of the 24, 19 (79.2%) were calves, four (16.7%) were juveniles, and one (4.2%) was an adult. The most probable cause of stranding and/or death (CSD) was determined in 23/24 (95.8%) individuals. In calves, CSD included neonatal respiratory distress (13/19; 68.4%), infectious disease (septicemia, omphaloarteritis and urachocystitis; 3/19; 15.8%), trauma of unknown origin (2/19; 10.5%), and vehicular trauma (vessel strike; 1/19; 5.3%). In juveniles and adult individuals, CSD was: emaciation (2/5; 40%), sunlight-thermal burn shock (1/5; 20%); and discospondylitis (1/5; 20%). In one juvenile, the CSD was undetermined (1/5; 20%). This study integrates novel findings and published case reports to delineate the pathology of a South-western Atlantic population of humpback whales. This foundation will aid in the assessment of the population health and establish a baseline for development of conservation policies.

Pathology and causes of death in stranded humpback whales (Megaptera novaeangliae) from Brazil

PubMed Central

Díaz-Delgado, Josué; Marcondes, Milton C. C.; Colosio, Adriana Castaldo; Santos-Neto, Elitieri B.; Carvalho, Vítor Luz; Boos, Gisele Silva; Oliveira de Meirelles, Ana Carolina; Ramos, Hernani Gomes da Cunha; Guimarães, Juliana Plácido; Borges, João Carlos Gomes; Vergara-Parente, Jociery Einhardt; St. Leger, Judy A.; Fernández, Antonio; Catão-Dias, José Luiz

2018-01-01

This study describes the pathologic findings of 24 humpback whales (Megaptera novaeangliae) found stranded along the Brazilian coast from 2004 to 2016. Eighteen (75%) animals evaluated were found stranded alive. From these, 13 died naturally on shore and five were euthanized. Six died at sea and were washed ashore. Of the 24, 19 (79.2%) were calves, four (16.7%) were juveniles, and one (4.2%) was an adult. The most probable cause of stranding and/or death (CSD) was determined in 23/24 (95.8%) individuals. In calves, CSD included neonatal respiratory distress (13/19; 68.4%), infectious disease (septicemia, omphaloarteritis and urachocystitis; 3/19; 15.8%), trauma of unknown origin (2/19; 10.5%), and vehicular trauma (vessel strike; 1/19; 5.3%). In juveniles and adult individuals, CSD was: emaciation (2/5; 40%), sunlight-thermal burn shock (1/5; 20%); and discospondylitis (1/5; 20%). In one juvenile, the CSD was undetermined (1/5; 20%). This study integrates novel findings and published case reports to delineate the pathology of a South-western Atlantic population of humpback whales. This foundation will aid in the assessment of the population health and establish a baseline for development of conservation policies. PMID:29768405

Does the choice of the crystal structure influence the results of the periodic DFT calculations? A case of glycine alpha polymorph GIPAW NMR parameters computations.

PubMed

Szeleszczuk, Łukasz; Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika

2018-05-30

Glycine is a common amino acid with relatively complex chemistry in solid state. Although several polymorphs (α, β, δ, γ, ε) of crystalline glycine are known, for NMR spectroscopy the most important is a polymorph, which is used as a standard for calibration of spectrometer performance and therefore it is intensively studied by both experimental methods and theoretical computation. The great scientific interest in a glycine results in a large number of crystallographic information files (CIFs) deposited in Cambridge Structural Database (CSD). The aim of this study was to evaluate the influence of the chosen crystal structure of α glycine obtained in different crystallographic experimental conditions (temperature, pressure and source of radiation of α glycine) on the results of periodic DFT calculation. For this purpose the total of 136 GIPAW calculations of α glycine NMR parameters were performed, preceded by the four approaches ("SP", "only H", "full", "full+cell") of structure preparation. The analysis of the results of those computations performed on the representative group of 34 structures obtained at various experimental conditions revealed that though the structures were generally characterized by good accuracy (R < 0.05 for most of them) the results of the periodic DFT calculations performed using the unoptimized structures differed significantly. The values of the standard deviations of the studied NMR parameters were in most cases decreasing with the number of optimized parameters. The most accurate results (of the calculations) were in most cases obtained using the structures with solely hydrogen atoms positions optimized. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

The laminar and temporal structure of stimulus information in the phase of field potentials of auditory cortex.

PubMed

Szymanski, Francois D; Rabinowitz, Neil C; Magri, Cesare; Panzeri, Stefano; Schnupp, Jan W H

2011-11-02

Recent studies have shown that the phase of low-frequency local field potentials (LFPs) in sensory cortices carries a significant amount of information about complex naturalistic stimuli, yet the laminar circuit mechanisms and the aspects of stimulus dynamics responsible for generating this phase information remain essentially unknown. Here we investigated these issues by means of an information theoretic analysis of LFPs and current source densities (CSDs) recorded with laminar multi-electrode arrays in the primary auditory area of anesthetized rats during complex acoustic stimulation (music and broadband 1/f stimuli). We found that most LFP phase information originated from discrete "CSD events" consisting of granular-superficial layer dipoles of short duration and large amplitude, which we hypothesize to be triggered by transient thalamocortical activation. These CSD events occurred at rates of 2-4 Hz during both stimulation with complex sounds and silence. During stimulation with complex sounds, these events reliably reset the LFP phases at specific times during the stimulation history. These facts suggest that the informativeness of LFP phase in rat auditory cortex is the result of transient, large-amplitude events, of the "evoked" or "driving" type, reflecting strong depolarization in thalamo-recipient layers of cortex. Finally, the CSD events were characterized by a small number of discrete types of infragranular activation. The extent to which infragranular regions were activated was stimulus dependent. These patterns of infragranular activations may reflect a categorical evaluation of stimulus episodes by the local circuit to determine whether to pass on stimulus information through the output layers.

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

PubMed

Shimizu, Tomohisa; Hishikawa, Tomohito; Nishihiro, Shingo; Shinji, Yukei; Takasugi, Yuji; Haruma, Jun; Hiramatsu, Masafumi; Kawase, Hirokazu; Sato, Sachiko; Mizoue, Ryoichi; Takeda, Yoshimasa; Sugiu, Kenji; Morimatsu, Hiroshi; Date, Isao

2018-01-01

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P 50 ) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage. CONCLUSIONS CSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

Atypical manifestation of cat-scratch disease: isolated epigastric pain in an immunocompetent, 12-year-old child.

PubMed

Kayemba-Kay's, Simon; Kovács, Tamas; Rakotoharinandrasana, Iarolalao; Benosman, Sidi Mohamed

2015-07-01

We present a 12-year-old immunocompetent girl with hepato splenic cat-scratch disease (CSD). Her sole inaugural complaint was isolated epigastric pain. She fully recovered, with normalized abdominal CT scan following 2 weeks course of Azythromycin®. CSD should be included in differential diagnosis in children with epigastric pain, especially in those with domestic pets.

A multi-fidelity framework for physics based rotor blade simulation and optimization

NASA Astrophysics Data System (ADS)

Collins, Kyle Brian

New helicopter rotor designs are desired that offer increased efficiency, reduced vibration, and reduced noise. Rotor Designers in industry need methods that allow them to use the most accurate simulation tools available to search for these optimal designs. Computer based rotor analysis and optimization have been advanced by the development of industry standard codes known as "comprehensive" rotorcraft analysis tools. These tools typically use table look-up aerodynamics, simplified inflow models and perform aeroelastic analysis using Computational Structural Dynamics (CSD). Due to the simplified aerodynamics, most design studies are performed varying structural related design variables like sectional mass and stiffness. The optimization of shape related variables in forward flight using these tools is complicated and results are viewed with skepticism because rotor blade loads are not accurately predicted. The most accurate methods of rotor simulation utilize Computational Fluid Dynamics (CFD) but have historically been considered too computationally intensive to be used in computer based optimization, where numerous simulations are required. An approach is needed where high fidelity CFD rotor analysis can be utilized in a shape variable optimization problem with multiple objectives. Any approach should be capable of working in forward flight in addition to hover. An alternative is proposed and founded on the idea that efficient hybrid CFD methods of rotor analysis are ready to be used in preliminary design. In addition, the proposed approach recognizes the usefulness of lower fidelity physics based analysis and surrogate modeling. Together, they are used with high fidelity analysis in an intelligent process of surrogate model building of parameters in the high fidelity domain. Closing the loop between high and low fidelity analysis is a key aspect of the proposed approach. This is done by using information from higher fidelity analysis to improve predictions made with lower fidelity models. This thesis documents the development of automated low and high fidelity physics based rotor simulation frameworks. The low fidelity framework uses a comprehensive code with simplified aerodynamics. The high fidelity model uses a parallel processor capable CFD/CSD methodology. Both low and high fidelity frameworks include an aeroacoustic simulation for prediction of noise. A synergistic process is developed that uses both the low and high fidelity frameworks together to build approximate models of important high fidelity metrics as functions of certain design variables. To test the process, a 4-bladed hingeless rotor model is used as a baseline. The design variables investigated include tip geometry and spanwise twist distribution. Approximation models are built for metrics related to rotor efficiency and vibration using the results from 60+ high fidelity (CFD/CSD) experiments and 400+ low fidelity experiments. Optimization using the approximation models found the Pareto Frontier anchor points, or the design having maximum rotor efficiency and the design having minimum vibration. Various Pareto generation methods are used to find designs on the frontier between these two anchor designs. When tested in the high fidelity framework, the Pareto anchor designs are shown to be very good designs when compared with other designs from the high fidelity database. This provides evidence that the process proposed has merit. Ultimately, this process can be utilized by industry rotor designers with their existing tools to bring high fidelity analysis into the preliminary design stage of rotors. In conclusion, the methods developed and documented in this thesis have made several novel contributions. First, an automated high fidelity CFD based forward flight simulation framework has been built for use in preliminary design optimization. The framework was built around an integrated, parallel processor capable CFD/CSD/AA process. Second, a novel method of building approximate models of high fidelity parameters has been developed. The method uses a combination of low and high fidelity results and combines Design of Experiments, statistical effects analysis, and aspects of approximation model management. And third, the determination of rotor blade shape variables through optimization using CFD based analysis in forward flight has been performed. This was done using the high fidelity CFD/CSD/AA framework and method mentioned above. While the low and high fidelity predictions methods used in the work still have inaccuracies that can affect the absolute levels of the results, a framework has been successfully developed and demonstrated that allows for an efficient process to improve rotor blade designs in terms of a selected choice of objective function(s). Using engineering judgment, this methodology could be applied today to investigate opportunities to improve existing designs. With improvements in the low and high fidelity prediction components that will certainly occur, this framework could become a powerful tool for future rotorcraft design work. (Abstract shortened by UMI.)

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

PubMed

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.

PubMed

Saengjaroentham, Chonlawan; Supornsilpchai, Weera; Ji-Au, Wilawan; Srikiatkhachorn, Anan; Maneesri-le Grand, Supang

2015-02-01

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.

Congenital Sodium Diarrhea: A Form of Intractable Diarrhea, With a Link to Inflammatory Bowel Disease.

PubMed

Janecke, Andreas R; Heinz-Erian, Peter; Müller, Thomas

2016-08-01

Congenital diarrheal disorders (CDDs) represent a group of challenging clinical conditions for pediatricians because of the severity of the presentation and the broad range of possible differential diagnoses. CDDs arise from alterations in the transport of nutrients and electrolytes across the intestinal mucosa, from enterocyte and enteroendocrine cell differentiation and/or polarization defects, and from the modulation of the intestinal immune response. Advances were made recently in deciphering the etiology and pathophysiology of one of these disorders, congenital sodium diarrhea (CSD). CSD refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. A syndromic form of CSD features choanal and intestinal atresias as well as recurrent corneal erosions. Small bowel histology frequently detects an epithelial "tufting" dysplasia. It is autosomal recessively inherited, and caused by SPINT2 mutations. The nonsyndromic form of CSD can be caused by dominant activating mutations in GUCY2C, encoding intestinal receptor guanylate cyclase C (GC-C), and by autosomal recessive SLC9A3 loss-of-function mutations. SLC9A3 encodes Na/H antiporter 3, the major intestinal brush border Na/H exchanger, and a downstream target of GC-C. A number of patients with GUCY2C and SLC9A3 mutations developed inflammatory bowel disease. Both the number of recognized CDD forms as well as the number of underlying disease genes are gradually increasing. Knowledge of these CDD genes enables noninvasive, next-generation gene panel-based testing to facilitate an early diagnosis in CDD. Primary Na/H antiporter 3 and GC-C malfunction is implicated as a predisposition for inflammatory bowel disease in subset of patients.

An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

Potassium-induced cortical spreading depression bilaterally suppresses the electroencephalogram but only ipsilaterally affects red blood cell velocity in intraparenchymal capillaries.

PubMed

Unekawa, Miyuki; Tomita, Yutaka; Toriumi, Haruki; Masamoto, Kazuto; Kanno, Iwao; Suzuki, Norihiro

2013-04-01

Cortical spreading depression (CSD) is a repetitive, propagating profile of mass depolarization of neuronal and glial cells, followed by sustained suppression of spontaneous neuronal activity. We have reported a long-lasting suppressive effect on red blood cell (RBC) velocities in intraparenchymal capillaries. Here, to test the hypothesis that the prolonged decrease of RBC velocity in capillaries is due to suppression of neuronal activity, we measured CSD-elicited changes in the electroencephalogram (EEG) as an index of neuronal activity. In isoflurane-anesthetized rats, DC potential, EEG, partial pressure of oxygen (PO₂), and cerebral blood flow (CBF) were simultaneously recorded in the temporo-parietal region. The velocities of fluorescently labeled RBCs were evaluated by high-speed camera laser scanning confocal fluorescence microscopy with our original software, KEIO-IS2. Transient deflection of DC potential and PO₂ and increase of CBF were repeatedly detected only in the ipsilateral hemisphere following topical KCl application. On the other hand, the relative spectral power of EEG was reduced bilaterally, showing the lowest value at 5 min after KCl application, when the other parameters had already returned to the baseline after the passage of CSD. Mean RBC velocity in capillaries was slightly but significantly reduced during and after passage of CSD in the ipsilateral hemisphere but did not change in the contralateral hemisphere in the same rats. We suggest that mass depolarization of neuronal and glial cells might transiently decelerate RBCs in nearby capillaries, but the sustained reduction of ipsilateral RBC velocity might be a result of the prolonged effect of CSD, not of neuronal suppression alone. Copyright © 2013 Wiley Periodicals, Inc.

Annular tautomerism: experimental observations and quantum mechanics calculations.

PubMed

Cruz-Cabeza, Aurora J; Schreyer, Adrian; Pitt, William R

2010-06-01

The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomeric relative stabilities. The calculated relative energies of tautomers were compared to relative abundances within the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB). The work was focussed on 84 annular tautomeric forms of 34 common ring systems. Good agreement was found between the calculations and the experimental data even if the quantity of these data was limited in many cases. The QM results were compared to those produced by much faster semiempirical calculations. In a search for other sources of the useful experimental data, the relative numbers of known compounds in which prototropic positions were often substituted by heavy atoms were also analysed. A scheme which groups all annular tautomeric transformations into 10 classes was developed. The scheme was designed to encompass a comprehensive set of known and theoretically possible tautomeric ring systems generated as part of a previous study. General trends across analogous ring systems were detected as a result. The calculations and statistics collected on crystallographic data as well as the general trends observed should be useful for the better modelling of annular tautomerism in the applications such as computer-aided drug design, small molecule crystal structure prediction, the naming of compounds and the interpretation of protein-small molecule crystal structures.

Annular tautomerism: experimental observations and quantum mechanics calculations

NASA Astrophysics Data System (ADS)

Cruz-Cabeza, Aurora J.; Schreyer, Adrian; Pitt, William R.

2010-06-01

The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomeric relative stabilities. The calculated relative energies of tautomers were compared to relative abundances within the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB). The work was focussed on 84 annular tautomeric forms of 34 common ring systems. Good agreement was found between the calculations and the experimental data even if the quantity of these data was limited in many cases. The QM results were compared to those produced by much faster semiempirical calculations. In a search for other sources of the useful experimental data, the relative numbers of known compounds in which prototropic positions were often substituted by heavy atoms were also analysed. A scheme which groups all annular tautomeric transformations into 10 classes was developed. The scheme was designed to encompass a comprehensive set of known and theoretically possible tautomeric ring systems generated as part of a previous study. General trends across analogous ring systems were detected as a result. The calculations and statistics collected on crystallographic data as well as the general trends observed should be useful for the better modelling of annular tautomerism in the applications such as computer-aided drug design, small molecule crystal structure prediction, the naming of compounds and the interpretation of protein—small molecule crystal structures.

Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum).

PubMed

Satoh, Akira; Cummings, Gillian M C; Bryant, Susan V; Gardiner, David M

2010-01-15

The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment. Copyright 2009 Elsevier Inc. All rights reserved.

Selective amotivation deficits following chronic psychosocial stress in mice.

PubMed

Tsai Cabal, Alejandro; Ioanas, Horea-Ioan; Seifritz, Erich; Saab, Bechara J

2017-01-15

Amotivation is a major symptom of several psychiatric disorders. However, which specific motivations are most affected in various illnesses is not well understood. In major depressive disorder (MDD), anecdotal evidence suggests the motivation to explore may be especially affected, but direct evidence from either patients or animal models is lacking. To investigate the potential for, and nature of, exploratory drive deficits in MDD, we subjected mice to a chronic social defeat (CSD) manipulation that gives rise to a MDD-like behavioural ensemble, and performed a behavioural battery to examine bodyweight homeostasis, ambulation, anxiety, exploratory behaviour motivated by either novelty or fear, and short-term memory. Consistent with previous reports, we found a disruption of bodyweight homeostasis and reduced ambulation following CSD treatment, but we found no evidence for anxiogenic effects or impairments in short-term memory. Surprisingly, we also observed profoundly delayed and diminished exploration of novel, safe space following CSD, while exploration motivated by fear remained intact. These results extend our knowledge of the behavioural phenotypes in mice resulting from CSD by homing in on specific motivational drives. In MDD patients, reduced exploration could compound disease symptomatology by preventing engagement in what could be rewarding exploration experiences, and targeting deficits in the motivation to explore may represent a novel avenue for treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

PubMed Central

Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John

2011-01-01

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves. PMID:21045864

Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.

PubMed

Tower, Amanda M; Frishman, Gary N

2013-01-01

The gynecologic sequelae due to deficient uterine scar healing after cesarean section are only recently being identified and described. These include conditions such as abnormal bleeding, pelvic pain, infertility, and cesarean scar ectopic pregnancy, as well as a potentially higher risk of complications and difficulties during gynecologic procedures such as uterine evacuation, hysterectomy, endometrial ablation, and insertion of an intrauterine device. The proposed mechanism of abnormal uterine bleeding is a pouch or "isthmocele" in the lower uterine segment that causes delayed menstrual bleeding. The prevalence of symptomatic or clinically relevant cesarean scar defects (CSDs) ranges from 19.4% to 88%. Possible risk factors for CSD include number of cesarean sections, uterine position, labor before cesarean section, and surgical technique used to close the uterine incision. There are no accepted guidelines for the diagnostic criteria of CSD. We propose that a CSD be defined on transvaginal ultrasound or saline infusion sonohysterography as a triangular hypoechoic defect in the myometrium at the site of the previous hysterotomy. We also propose a classification system to aid in standardized classification for future research. Surgical techniques for repair of CSD include laparoscopic excision, resectoscopic treatment, vaginal revision, and endometrial ablation. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

Posterior segment involvement in cat-scratch disease: A case series.

PubMed

Tolou, C; Mahieu, L; Martin-Blondel, G; Ollé, P; Matonti, F; Hamid, S; Benouaich, X; Debard, A; Cassagne, M; Soler, V

2015-12-01

Cat-scratch disease (CSD) is a systemic infectious disease. The most well-known posterior segment presentation is neuroretinitis with a macular star. In this study, we present a case series emphasising the heterogeneity of the disease and the various posterior segment manifestations. A retrospective case series of consecutive patients presenting with posterior segment CSD, over a 5-year period (2010 to 2015), at two ophthalmological centres in Midi-Pyrénées. Twelve patients (17 eyes) were included, of whom 11 (92%) presented with rapidly decreasing visual acuity, with 6 of these (50%) extremely abrupt. CSD was bilateral in 5 (42% of all patients). Posterior manifestations were: 12 instances of optic nerve edema (100%), 8 of focal chorioretinitis (67%) and only 6 of the classic macular edema with macular star (25% at first examination, but 50% later). Other ophthalmological complications developed in three patients; one developed acute anterior ischemic optic neuropathy, one a retrohyaloid hemorrhage and one a branch retinal artery occlusion, all secondary to occlusive focal vasculitis adjacent to focal chorioretinitis. Classical neuroretinitis with macular star is not the only clinical presentation of CSD. Practitioners should screen for Bartonella henselae in all patients with papillitis or focal chorioretinitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

An Assessment of Comprehensive Code Prediction State-of-the-Art Using the HART II International Workshop Data

NASA Technical Reports Server (NTRS)

vanderWall, Berend G.; Lim, Joon W.; Smith, Marilyn J.; Jung, Sung N.; Bailly, Joelle; Baeder, James D.; Boyd, D. Douglas, Jr.

2012-01-01

Despite significant advancements in computational fluid dynamics and their coupling with computational structural dynamics (= CSD, or comprehensive codes) for rotorcraft applications, CSD codes with their engineering level of modeling the rotor blade dynamics, the unsteady sectional aerodynamics and the vortical wake are still the workhorse for the majority of applications. This is especially true when a large number of parameter variations is to be performed and their impact on performance, structural loads, vibration and noise is to be judged in an approximate yet reliable and as accurate as possible manner. In this paper, the capabilities of such codes are evaluated using the HART II Inter- national Workshop data base, focusing on a typical descent operating condition which includes strong blade-vortex interactions. Three cases are of interest: the baseline case and two cases with 3/rev higher harmonic blade root pitch control (HHC) with different control phases employed. One setting is for minimum blade-vortex interaction noise radiation and the other one for minimum vibration generation. The challenge is to correctly predict the wake physics - especially for the cases with HHC - and all the dynamics, aerodynamics, modifications of the wake structure and the aero-acoustics coming with it. It is observed that the comprehensive codes used today have a surprisingly good predictive capability when they appropriately account for all of the physics involved. The minimum requirements to obtain these results are outlined.

Improved computational treatment of transonic flow about swept wings

NASA Technical Reports Server (NTRS)

Ballhaus, W. F.; Bailey, F. R.; Frick, J.

1976-01-01

Relaxation solutions to classical three-dimensional small-disturbance (CSD) theory for transonic flow about lifting swept wings are reported. For such wings, the CSD theory was found to be a poor approximation to the full potential equation in regions of the flow field that are essentially two-dimensional in a plane normal to the sweep direction. The effect of this deficiency on the capture of embedded shock waves in terms of (1) the conditions under which shock waves can exist and (2) the relations they must satisfy when they do exist is emphasized. A modified small-disturbance (MSD) equation, derived by retaining two previously neglected terms, was proposed and shown to be a consistent approximation to the full potential equation over a wider range of sweep angles. The effect of these extra terms is demonstrated by comparing CSD, MSD, and experimental wing surface pressures.

An expanded model and application of the combined effect of crystal-size distribution and crystal shape on the relative viscosity of magmas

NASA Astrophysics Data System (ADS)

Klein, Johannes; Mueller, Sebastian P.; Helo, Christoph; Schweitzer, Silja; Gurioli, Lucia; Castro, Jonathan M.

2018-05-01

This study examines the combined effect of crystal-size distributions (CSD) and crystal shape on the rheology of vesicle free magmatic suspensions and provides the first practical application of an empirical model to estimate the relative effect of crystal content and CSD's on the viscosity of magma directly from textural image analysis of natural rock samples in the form of a user-friendly texture-rheology spreadsheet calculator. We extend and apply established relationships between the maximum packing fraction ϕm of a crystal bearing suspension and both its rheological properties and the polydispersity γ of a CSD. By using analogue rotational rheometric experiments with glass fibres and glass flakes in silicone oil acting as magma equivalent, this study also provides new insights in the relationship between ϕm and the aspect ratio rp of suspended particles.

IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice

PubMed Central

Schwenk, Robert; Nikki, Jennifer; Rein, Lisa; Spaccapelo, Roberta; Crisanti, Andrea; Wightman, Paul D.; Ockenhouse, Christian F.; Dutta, Sheetij

2014-01-01

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive TH1/TH2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans. PMID:25343487

Short communication: Estimates of genetic parameters for dairy fertility in New Zealand.

PubMed

Amer, P R; Stachowicz, K; Jenkins, G M; Meier, S

2016-10-01

Reproductive performance of dairy cows in a seasonal calving system is especially important as cows are required to achieve a 365-d calving interval. Prior research with a small data set has identified that the genetic evaluation model for fertility could be enhanced by replacing the binary calving rate trait (CR42), which gives the probability of a cow calving within the first 42d since the planned start of calving at second, third, and fourth calving, with a continuous version, calving season day (CSD), including a heifer calving season day trait expressed at first calving, removing milk yield, retaining a probability of mating trait (PM21) which gives the probability of a cow being mated within the first 21d from the planned start of mating, and first lactation body condition score (BCS), and including gestation length (GL). The aim of this study was to estimate genetic parameters for the proposed new model using a larger data set and compare these with parameters used in the current system. Heritability estimates for CSD and PM21 ranged from 0.013 to 0.019 and from 0.031 to 0.058, respectively. For the 2 traits that correspond with the ones used in the current genetic evaluation system (mating trait, PM21 and BCS) genetic correlations were lower in this study compared with previous estimates. Genetic correlations between CSD and PM21 across different parities were also lower than the correlations between CR42 and PM21 reported previously. The genetic correlation between heifer CSD and CSD in first parity was 0.66. Estimates of genetic correlations of BCS with CSD were higher than those with PM21. For GL, direct heritability was estimated to be 0.67, maternal heritability was 0.11, and maternal repeatability was 0.22. Direct GL had moderate to high and favorable genetic correlations with evaluated fertility traits, whereas corresponding residual correlations remain low, which makes GL a useful candidate predictor trait for fertility in a multiple trait evaluation. The superiority of direct GL genetic component over the maternal GL component for predicting fertility was demonstrated. Future work planned in this area includes the implementation and testing of this new model on national fertility data. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of modal layering in granites: a case study from the Carna Pluton, Connemara, Ireland

NASA Astrophysics Data System (ADS)

McKenzie, Kirsty; McCarthy, William; Hunt, Emma

2016-04-01

Modal layering in igneous rocks uniquely record dynamic processes operating in magma chambers and also host a large proportion of Earth's strategic mineral deposits. This research investigates the origin of biotite modal layering and primary pseudo-sedimentary structures in felsic magmas, by using a combination of Crystal Size Distribution (CSD) analysis and Electron Probe Microanalysis (EPMA) to determine the mechanisms responsible for the development of these structures in the Carna Pluton, Connemara, Ireland. The Carna Pluton is a composite granodiorite intrusion and is one of five plutons comprising the Galway Granite Complex (425 - 380 Ma). Prominent 30 cm thick modal layers are defined by sharp basal contacts to a biotite-rich (20%) granite, which grades upward over 10 cm into biotite-poor, alkali-feldspar megacrystic granite. The layering strikes parallel to, and dips 30-60° N toward the external pluton contact. Pseudo-sedimentary structures (cross-bedding, flame structures, slumping and crystal graded bedding) are observed within these layers. Petrographic observations indicate the layers contain euhedral biotite and fresh undeformed quartz and feldspar. Throughout the pluton, alkali-feldspar phenocrysts define a foliation that is sub-parallel to the strike of biotite modal layers. Together these observations indicate that the intrusion's concentric foliation, biotite layers and associated structures formed in the magmatic state and due to a complex interaction between magma flow and crystallisation processes. Biotite CSDs (>250 crystals per sample) were determined for nine samples across three biotite-rich layers in a single unit. Preliminary CSD results suggest biotite within basal contacts accumulated via fractional crystallisation within an upward-growing crystal pile, likely reflecting the yield strength of the magma as a limiting factor to gravitational settling of biotite. This is supported by the abrupt decrease in mean biotite crystal size across the contact, compared to the biotite crystals in the megacrystic granite below. CSD results provide additional evidence for in-situ textural coarsening of biotite. This study proposes a new model for the crystallisation dynamics of the Carna Pluton. During emplacement, 2 - 5 cm alkali-feldspar megacrysts were aligned and fractional crystallisation was the primary mechanism driving the formation of biotite modal layers. Pseudo-sedimentary structures are interpreted to have formed due to the entrainment of biotite crystals within a necessarily highly fluid magma chamber. However, this interpretation is difficult to reconcile with the high viscosities commonly associated with granitic melts. To test this hypothesis, ongoing EPMA analysis on biotite F content and Fe/(Fe+Mg) ratios will assess whether the magma viscosity could have been low enough to produce these features via flow processes; or whether expansion of the pluton and tilting of planar primary magmatic layers, prior to solidification, could be responsible.

Spreading Depolarizations of Cerebral Cortex After Brain Injury: Mechanism of Injury Progression and Relevance to Military Neurotrauma

DTIC Science & Technology

2006-11-01

sustained penetrating brain injury (PBI). Emergency craniotomies are performed to treat these severe injuries in theater, sometimes on a daily...after craniotomy surgery. ECoG recordings were made subsequently for 1-10 days. CSD was identified by rapidly developing depression of ECoG amplitude...treat patients with moderate-to-severe TBI provides the opportunity to monitor for CSD by ECoG recordings. In these cases, craniotomy is performed as

Biodegradable Core-shell Dual-Metal-Organic-Frameworks Nanotheranostic Agent for Multiple Imaging Guided Combination Cancer Therapy

PubMed Central

Wang, Dongdong; Zhou, Jiajia; Shi, Ruohong; Wu, Huihui; Chen, Ruhui; Duan, Beichen; Xia, Guoliang; Xu, Pengping; Wang, Hui; Zhou, Shu; Wang, Chengming; Wang, Haibao; Guo, Zhen; Chen, Qianwang

2017-01-01

Metal-organic-frameworks (MOFs) possess high porosity, large surface area, and tunable functionality are promising candidates for synchronous diagnosis and therapy in cancer treatment. Although large number of MOFs has been discovered, conventional MOF-based nanoplatforms are mainly limited to the sole MOF source with sole functionality. In this study, surfactant modified Prussian blue (PB) core coated by compact ZIF-8 shell (core-shell dual-MOFs, CSD-MOFs) has been reported through a versatile stepwise approach. With Prussian blue as core, CSD-MOFs are able to serve as both magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) agents. We show that CSD-MOFs crystals loading the anticancer drug doxorubicin (DOX) are efficient pH and near-infrared (NIR) dual-stimuli responsive drug delivery vehicles. After the degradation of ZIF-8, simultaneous NIR irradiation to the inner PB MOFs continuously generate heat that kill cancer cells. Their efficacy on HeLa cancer cell lines is higher compared with the respective single treatment modality, achieving synergistic chemo-thermal therapy efficacy. In vivo results indicate that the anti-tumor efficacy of CSD-MOFs@DOX+NIR was 7.16 and 5.07 times enhanced compared to single chemo-therapy and single thermal-therapy respectively. Our strategy opens new possibilities to construct multifunctional theranostic systems through integration of two different MOFs. PMID:29158848

Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability.

PubMed

Onoue, Satomi; Takahashi, Haruki; Kawabata, Yohei; Seto, Yoshiki; Hatanaka, Junya; Timmermann, Barbara; Yamada, Shizuo

2010-04-01

Considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders, however, the therapeutic potential of curcumin could often be limited by its poor solubility, bioavailability, and photostability. To overcome these drawbacks, efficacious formulations of curcumin, including nanocrystal solid dispersion (CSD-Cur), amorphous solid dispersion (ASD-Cur), and nanoemulsion (NE-Cur), were designed with the aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the prepared formulations were characterized by scanning/transmission electron microscope for morphological analysis, laser diffraction, and dynamic light scattering for particle size analysis, and polarized light microscope, powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. In dissolution tests, all curcumin formulations exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin. Significant improvement in pharmacokinetic behavior was observed in the newly developed formulations, as evidenced by 12- (ASD-Cur), 16- (CSD-Cur), and 9-fold (NE-Cur) increase of oral bioavailability. Upon photochemical characterization, curcumin was found to be photoreactive and photodegradable in the solution state, possibly via type 2 photochemical reaction, whereas high photochemical stability was seen in the solid formulations, especially CSD-Cur. On the basis of these observations, taken together with dissolution and pharmacokinetic behaviors, CSD strategy would be efficacious to enhance bioavailability of curcumin with high photochemical stability. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Responsible conduct of research in communication sciences and disorders: faculty and student perceptions.

PubMed

Minifie, Fred D; Robey, Randall R; Horner, Jennifer; Ingham, Janis C; Lansing, Charissa; McCartney, James H; Alldredge, Elham-Eid; Slater, Sarah C; Moss, Sharon E

2011-02-01

Two Web-based surveys (Surveys I and II) were used to assess perceptions of faculty and students in Communication Sciences and Disorders (CSD) regarding the responsible conduct of research (RCR). Survey questions addressed 9 RCR domains thought important to the responsible conduct of research: (a) human subjects protections; (b) research involving animals; (c) publication practices and responsible authorship; (d) mentor/trainee responsibilities; (e) collaborative science; (f) peer review; (g) data acquisition, management, sharing, and ownership; (h) conflicts of interest; and (i) research misconduct. Respondents rated each of 37 topics for importance and for sufficiency of instructional coverage. Respondents to Survey I were 137 faculty members from 68 (26%) of the 261 graduate programs in CSD. By comparison, 237 students from 39 (15%) programs responded to Survey II. Data about the importance and sufficiency of coverage of each of the 37 items were transformed into z scores to reveal relative ratings among the 37 topics. Data presentations were grouped for topics in each of the 9 RCR domains. Ratings indicated the relatively high importance assigned among the 37 topics by CSD faculty and students. Sufficiency of coverage of those same topics received lower ratings. The results of these surveys support the notion that students in CSD perceive that they are receiving information about RCR. The data pertaining to sufficiency of coverage provide a basis for improving instruction in this important aspect of research education.

Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG.

PubMed

Hauk, O; Keil, A; Elbert, T; Müller, M M

2002-01-30

We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred.

Growth and characterization of zinc oxide and PZT films for micromachined acoustic wave devices

NASA Astrophysics Data System (ADS)

Yoon, Sang Hoon

The ability to detect the presence of low concentrations of harmful substances, such as biomolecular agents, warfare agents, and pathogen cells, in our environment and food chain would greatly advance our safety, provide more sensitive tools for medical diagnostics, and protect against terrorism. Acoustic wave (AW) devices have been widely studied for such applications due to several attractive properties, such as rapid response, reliability, portability, ease of use, and low cost. The principle of these sensors is based on a fundamental feature of the acoustic wave that is generated and detected by a piezoelectric material. The performance of the device, therefore, greatly depends on the properties of piezoelectric thin film. The required properties include a high piezoelectric coefficient and high electromechanical coefficients. The surface roughness and the mechanical properties, such as Young's modulus and hardness, are also factors that can affect the wave propagation of the device. Since the film properties are influenced by the structure of the material, understanding thin film structure is very important for the design of high-performance piezoelectric MEMS devices for biosensor applications. In this research, two piezoelectric thin film materials were fabricated and investigated. ZnO films were fabricated by CSD (Chemical Solution Deposition) and sputtering, and PZT films were fabricated by CSD only. The process parameters for solution derived ZnO and PZT films, such as the substrate type, the effect of the chelating agent, and heat treatment, were studied to find the relationship between process parameters and thin film structure. In the case of the sputtered ZnO films, the process gas types and their ratio, heat treatment in situ, and post deposition were investigated. The key results of systematic experiments show that the combined influence of chemical modifiers and substrates in chemical solution deposition have an effect on the crystallographic orientation of the films, which is explained by the phase transformation that occurs from amorphous pyrolized film to crystalline film. Sputtered ZnO films do not show a strong dependence on the parameters, possibly indicating a reduced energy barrier for the growth of ZnO film due to plasma energy. Based on an understanding of the relationship between process and thin film structure, the growth mechanism of CSD ZnO is proposed. The devices are fabricated on 4-inch silicon wafers by a microelectronic fabrication method. The fabrication procedure and issues relating to device fabrication are discussed.

Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

PubMed

Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

2016-03-30

The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy.

Arterial baroreflex control of muscle blood flow at the onset of voluntary locomotion in mice

PubMed Central

Masuki, Shizue; Nose, Hiroshi

2003-01-01

To assess the role of arterial baroreflex control in muscle blood flow (MBF) and voluntary locomotion, mean arterial pressure (MAP), MBF, and electromyograms (EMGs) were measured in freely moving mice before (CNT) and after blocking the afferent or efferent pathway of arterial baroreflexes, carotid sinus denervation (CSD), or intraperitoneal administration of phentolamine (BLK), respectively. MAP was measured through a catheter placed in the femoral artery. MBF was measured with a needle-type laser-Doppler flowmeter and recorded through a low-pass filter with an edge frequency of 0.1 Hz. The frequency and duration of locomotion were judged from EMG recordings in the hindlimb. These probes were implanted at least 2 days before the measurements. Muscle vascular conductance (MVC = MBF/MAP) in all groups started to rise within 1 s after the onset of locomotion, but the increasing rate in CSD and BLK was significantly higher than in CNT for the first 9 s (P < 0.001). MAP in CSD and BLK significantly decreased below the baseline within 1 s and this was highly correlated with the increase in MVC for the first 9 s (R2 = 0.842, P < 0.001), whereas MAP in CNT increased significantly 8 s after the onset of locomotion. Although the total period of movement in a free-moving state for 60 min was not significantly different between CNT and CSD (P > 0.1), the frequency of movement with a short duration of 0.1–0.4 min was higher in CSD than in CNT (P < 0.001), which was highly correlated with the reduction in MAP accompanying each period of movement (R2 = 0.883, P < 0.01). These results suggest that arterial baroreflexes suppress vasodilatation in contracting muscle to maintain MAP at the onset of voluntary locomotion, and are necessary to continue a given duration of locomotion in mice. PMID:12937292

GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

NASA Technical Reports Server (NTRS)

Cross, James H., II

1990-01-01

The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

Somatostatin receptor scintigraphy in patients with cat-scratch disease.

PubMed

Krause, R; Piswanger-Soelkner, C; Lipp, R W; Daxböck, F; Schnedl, W J; Hoier, S; Reisinger, E C

2006-01-01

Somatostatin receptor scintigraphy images various neoplastic, granulomatous, and auto-immune diseases. Cat-scratch disease in an infectious granulomatous disease usually affecting the lymphnodes. It is not known whether cat-scratch disease provides positive somatostatin receptor scintigrams. Twelve patients with lymphadenitis and suspected cat-scratch disease were investigated by immunofluorescence antibody testing and somatostatin receptor scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella henselae specific PCR was then performed. Eleven of 12 patients showed IgG antibodies against B. henselae. SRS showed positive scintigraphic results in 6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS demonstrated positive scintigrams in all patients with a positive PCR. In one patient with suspected CSD SRS was negative as well as antibody testing. Somatostatin receptor scintigraphy correlated with positive Bartonella henselae specific PCR tests and positive Bartonella henselae specific antibody tests in patients with CSD.

Cat-scratch disease presenting as a solitary splenic abscess in an elderly man.

PubMed

Nakamura, Momoko; Kurimoto, Mio; Kato, Takehiro; Kunieda, Takeshige

2015-03-24

Patients with cat-scratch disease (CSD), which is caused by Bartonella henselae, typically present with local lymphadenopathy with a brief period of fever and general symptoms. Most cases are self-limiting and usually afflict children and young adults. Although rare, CSD can lead to serious complications, especially in immunocompromised patients. These rare complications often require intensive treatment. We describe the case of a 79-year-old man who presented with general malaise and a high fever. The physical examination findings were unremarkable. Of note, the lymph nodes were not enlarged. An abdominal CT scan with intravenous contrast revealed a solitary splenic abscess and no lymphadenopathy. The initial antibiotic treatment was ineffective and a splenectomy was indicated. A history of contact with cats raised the possibility of CSD, which was confirmed by a positive serology test result for B henselae. Antibiotic treatment with azithromycin successfully treated the splenic abscess and splenectomy was avoided. 2015 BMJ Publishing Group Ltd.

Chronic subjective dizziness versus conversion disorder: discussion of clinical findings and rehabilitation.

PubMed

Honaker, Julie A; Gilbert, Jane M; Staab, Jeffrey P

2010-06-01

Audiologists frequently encounter patients who complain of chronic dizziness or imbalance, in the absence of active vestibular or neurological deficits. Knowledge about conditions that cause this clinical presentation will allow audiologists to make important contributions to accurate diagnosis and effective management of these patients. This article reviews 2 such conditions, chronic subjective dizziness (CSD) and conversion disorder. A case of CSD and another of conversion disorder are presented, with a literature review of their clinical presentations, key diagnostic features, and treatment strategies. The role of the audiologist in assessing patients with these conditions and facilitating appropriate treatment referrals is discussed. The audiologist is in a key position to identify individuals with CSD and conversion disorder, 2 conditions that can be effectively managed if properly recognized. The authors demonstrate an effective team approach program that includes the audiologist's contribution to differential diagnosis, education of patients and other clinicians about these conditions, and development of recommendations for neurological, psychiatric, otologic, and physical therapy referrals.

Introducing uncertainty analysis of nucleation and crystal growth models in Process Analytical Technology (PAT) system design of crystallization processes.

PubMed

Samad, Noor Asma Fazli Abdul; Sin, Gürkan; Gernaey, Krist V; Gani, Rafiqul

2013-11-01

This paper presents the application of uncertainty and sensitivity analysis as part of a systematic model-based process monitoring and control (PAT) system design framework for crystallization processes. For the uncertainty analysis, the Monte Carlo procedure is used to propagate input uncertainty, while for sensitivity analysis, global methods including the standardized regression coefficients (SRC) and Morris screening are used to identify the most significant parameters. The potassium dihydrogen phosphate (KDP) crystallization process is used as a case study, both in open-loop and closed-loop operation. In the uncertainty analysis, the impact on the predicted output of uncertain parameters related to the nucleation and the crystal growth model has been investigated for both a one- and two-dimensional crystal size distribution (CSD). The open-loop results show that the input uncertainties lead to significant uncertainties on the CSD, with appearance of a secondary peak due to secondary nucleation for both cases. The sensitivity analysis indicated that the most important parameters affecting the CSDs are nucleation order and growth order constants. In the proposed PAT system design (closed-loop), the target CSD variability was successfully reduced compared to the open-loop case, also when considering uncertainty in nucleation and crystal growth model parameters. The latter forms a strong indication of the robustness of the proposed PAT system design in achieving the target CSD and encourages its transfer to full-scale implementation. Copyright © 2013 Elsevier B.V. All rights reserved.

Extracting functional components of neural dynamics with Independent Component Analysis and inverse Current Source Density.

PubMed

Lęski, Szymon; Kublik, Ewa; Swiejkowski, Daniel A; Wróbel, Andrzej; Wójcik, Daniel K

2010-12-01

Local field potentials have good temporal resolution but are blurred due to the slow spatial decay of the electric field. For simultaneous recordings on regular grids one can reconstruct efficiently the current sources (CSD) using the inverse Current Source Density method (iCSD). It is possible to decompose the resultant spatiotemporal information about the current dynamics into functional components using Independent Component Analysis (ICA). We show on test data modeling recordings of evoked potentials on a grid of 4 × 5 × 7 points that meaningful results are obtained with spatial ICA decomposition of reconstructed CSD. The components obtained through decomposition of CSD are better defined and allow easier physiological interpretation than the results of similar analysis of corresponding evoked potentials in the thalamus. We show that spatiotemporal ICA decompositions can perform better for certain types of sources but it does not seem to be the case for the experimental data studied. Having found the appropriate approach to decomposing neural dynamics into functional components we use the technique to study the somatosensory evoked potentials recorded on a grid spanning a large part of the forebrain. We discuss two example components associated with the first waves of activation of the somatosensory thalamus. We show that the proposed method brings up new, more detailed information on the time and spatial location of specific activity conveyed through various parts of the somatosensory thalamus in the rat.

Three-dimensional Hadamard-encoded proton spectroscopic imaging in the human brain using time-cascaded pulses at 3 Tesla.

PubMed

Cohen, Ouri; Tal, Assaf; Gonen, Oded

2014-10-01

To reduce the specific-absorption-rate (SAR) and chemical shift displacement (CSD) of three-dimensional (3D) Hadamard spectroscopic imaging (HSI) and maintain its point spread function (PSF) benefits. A 3D hybrid of 2D longitudinal, 1D transverse HSI (L-HSI, T-HSI) sequence is introduced and demonstrated in a phantom and the human brain at 3 Tesla (T). Instead of superimposing each of the selective Hadamard radiofrequency (RF) pulses with its N single-slice components, they are cascaded in time, allowing N-fold stronger gradients, reducing the CSD. A spatially refocusing 180° RF pulse following the T-HSI encoding block provides variable, arbitrary echo time (TE) to eliminate undesirable short T2 species' signals, e.g., lipids. The sequence yields 10-15% better signal-to-noise ratio (SNR) and 8-16% less signal bleed than 3D chemical shift imaging of equal repetition time, spatial resolution and grid size. The 13 ± 6, 22 ± 7, 24 ± 8, and 31 ± 14 in vivo SNRs for myo-inositol, choline, creatine, and N-acetylaspartate were obtained in 21 min from 1 cm(3) voxels at TE ≈ 20 ms. Maximum CSD was 0.3 mm/ppm in each direction. The new hybrid HSI sequence offers a better localized PSF at reduced CSD and SAR at 3T. The short and variable TE permits acquisition of short T2 and J-coupled metabolites with higher SNR. Copyright © 2013 Wiley Periodicals, Inc.

[The meaning of medical intervention and religious faith for the elderly cancer patient].

PubMed

Teixeira, Jorge Juarez Vieira; Lefèvre, Fernando

2008-01-01

This study aimed at identifying the meaning medical intervention and religious faith have for the elderly patient with cancer. A descriptive and qualitative investigation was developed between January 9 and March 28, 2001 in the Hospital do Servidor Público Estadual--Francisco Morato de Oliveira/IAMSPE (Hospital for State Public Servants). The studied sample was not randomized and consisted of 20 elderly men and women with cancer. The data were collected in semi-structured interviews and organized and analyzed using the Collective Subject Discourse method, applying three methodological illustrations: the Central Idea, Key Expressions and the Collective Subject Discourse (CSD). The main central ideas of the discourse material were: 1. Nothing to complain about. I think it is very good and they are on the right track; 2. No. For now, I'm doing everything the doctors say; 3. I've already participated, but not currently; 4. I don't participate in religious activity; 5. Invigoration, hope and balance. Religious faith is everything! 6. It remains the same; however, it changed the way to be. The CSD shows that the adopted medical intervention gave the elderly renewed hope and that religious faith is a key instrument for facing the disease.

Atmospheric aerosols size distribution properties in winter and pre-monsoon over western Indian Thar Desert location

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

Panwar, Chhagan, E-mail: chhaganpanwar@gmail.com; Vyas, B. M.

The first ever experimental results over Indian Thar Desert region concerning to height integrated aerosols size distribution function in particles size ranging between 0.09 to 2 µm such as, aerosols columnar size distribution (CSD), effective radius (R{sub eff}), integrated content of total aerosols (N{sub t}), columnar content of accumulation and coarse size aerosols particles concentration (N{sub a}) (size < 0.5 µm) and (N{sub c}) (size between 0.5 to 2 µm) have been described specifically during winter (a stable weather condition and intense anthropogenic pollution activity period) and pre-monsoon (intense dust storms of natural mineral aerosols as well as unstable atmospheric weather condition period)more » at Jaisalmer (26.90°N, 69.90°E, 220 m above surface level (asl)) located in central Thar desert vicinity of western Indian site. The CSD and various derived other aerosols size parameters are retrieved from their average spectral characteristics of Aerosol Optical Thickness (AOT) from UV to Infrared wavelength spectrum measured from Multi-Wavelength solar Radiometer (MWR). The natures of CSD are, in general, bio-modal character, instead of uniformly distributed character and power law distributions. The observed primary peaks in CSD plots are seen around about 10{sup 13} m{sup 2} μm{sup −1} at radius range 0.09-0.20 µm during both the seasons. But, in winter months, secondary peaks of relatively lower CSD values of 10{sup 10} to 10{sup 11} m{sup 2}/μm{sup −1} occur within a lower radius size range 0.4 to 0.6 µm. In contrast to this, while in dust dominated and hot season, the dominated secondary maxima of the higher CSD of about 10{sup 12} m{sup 2}μm{sup −3} is found of bigger aerosols size particles in a rage of 0.6 to 1.0 µm which is clearly demonstrating the characteristics of higher aerosols laden of bigger size aerosols in summer months relative to their prevailed lower aerosols loading of smaller size aerosols particles (0.4 to 0.6 µm) in cold months. Several other interesting features of changing nature of monthly spectral AOT, R{sub eff}, N{sub t}, N{sub a} and N{sub C} (particles/m{sup 2}) have been discussed in detail in this paper.« less

Large critical current densities and pinning forces in CSD-grown superconducting GdBa2Cu3O7-x -BaHfO3 nanocomposite films

NASA Astrophysics Data System (ADS)

Cayado, Pablo; Erbe, Manuela; Kauffmann-Weiss, Sandra; Bühler, Carl; Jung, Alexandra; Hänisch, Jens; Holzapfel, Bernhard

2017-09-01

GdBa2Cu3O7-x -BaHfO3 (GdBCO-BHO) nanocomposite (NC) films containing 12 mol% BHO nanoparticles were prepared by chemical solution deposition (CSD) following the TFA route on SrTiO3 (STO) single crystals and buffered metallic tapes supplied by two different companies: Deutsche Nanoschicht GmbH and SuperOx. We optimized the preparation of our GdBCO-BHO solutions with acetylacetone making the film synthesis very robust and reproducible, and obtained 220 nm films with excellent superconducting properties. We show the structural, morphological and superconducting properties of the films after a careful optimization of the processing parameters (growth temperature, oxygen partial pressure and heating ramp). The films reach critical temperatures (T c) of ˜94 K, self-field critical current densities (J c) of >7 MA cm- 2 and maximum pinning force densities (F p) of ˜16 GN m- 3 at 77 K on STO and T c of ˜94.5 K and J c > 1.5 MA cm- 2 on buffered metallic tapes. The transport properties under applied magnetic fields are significantly improved with respect to the pristine GdBCO films. The GdBCO-BHO NC films on STO present epitaxial c-axis orientation with excellent out-of-plane and in-plane texture. The films are, in general, very dense with a low amount of pores and only superficial indentations. On the other hand, we present, for the first time, a systematic study of CSD-grown GdBCO-BHO NC films on buffered metallic tapes. We have used the optimized growth conditions for STO as a reference and identified some limitations on the film synthesis that should be overcome for further improvement of the films’ superconducting properties.

Test-retest reliability of computer-based video analysis of general movements in healthy term-born infants.

PubMed

Valle, Susanne Collier; Støen, Ragnhild; Sæther, Rannei; Jensenius, Alexander Refsum; Adde, Lars

2015-10-01

A computer-based video analysis has recently been presented for quantitative assessment of general movements (GMs). This method's test-retest reliability, however, has not yet been evaluated. The aim of the current study was to evaluate the test-retest reliability of computer-based video analysis of GMs, and to explore the association between computer-based video analysis and the temporal organization of fidgety movements (FMs). Test-retest reliability study. 75 healthy, term-born infants were recorded twice the same day during the FMs period using a standardized video set-up. The computer-based movement variables "quantity of motion mean" (Qmean), "quantity of motion standard deviation" (QSD) and "centroid of motion standard deviation" (CSD) were analyzed, reflecting the amount of motion and the variability of the spatial center of motion of the infant, respectively. In addition, the association between the variable CSD and the temporal organization of FMs was explored. Intraclass correlation coefficients (ICC 1.1 and ICC 3.1) were calculated to assess test-retest reliability. The ICC values for the variables CSD, Qmean and QSD were 0.80, 0.80 and 0.86 for ICC (1.1), respectively; and 0.80, 0.86 and 0.90 for ICC (3.1), respectively. There were significantly lower CSD values in the recordings with continual FMs compared to the recordings with intermittent FMs (p<0.05). This study showed high test-retest reliability of computer-based video analysis of GMs, and a significant association between our computer-based video analysis and the temporal organization of FMs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Crystallization kinetics of olivine-phyric shergottites

NASA Astrophysics Data System (ADS)

Ennis, Megan E.; McSween, Harry Y.

2014-08-01

Crystal size distribution (CSD) and spatial distribution pattern (SDP) analyses are applied to the early crystallizing phases, olivine and pyroxene, in olivine-phyric shergottites (Elephant moraine [EET] 79001A, Dar al Gani [DaG] 476, and dhofar [Dho] 019) from each sampling locality inferred from Mars ejection ages. Trace element zonation patterns (P and Cr) in olivine are also used to characterize the crystallization history of these Martian basalts. Previously reported 2-D CSDs for these meteorites are re-evaluated using a newer stereographically corrected methodology. Kinks in the olivine CSD plots suggest several populations that crystallized under different conditions. CSDs for pyroxene in DaG 476 and EET 79001A reveal single populations that grew under steady-state conditions; pyroxenes in Dho 019 were too intergrown for CSD analysis. Magma chamber residence times of several days for small grains to several months for olivine megacrysts are calculated using the CSD slopes and growth rates inferred from previous experimental data. Phosphorus imaging in olivines in DaG 476 and Dho 019 indicate rapid growth of skeletal, sector-zoned, or patchy cores, probably in response to delayed nucleation, followed by slow growth, and finally rapid dendritic growth with back-filling to form oscillatory zoning in rims. SPD analyses indicate that olivine and pyroxene crystals grew or accumulated in clusters rather than as randomly distributed grains. These data reveal complex solidification histories for Martian basalts, and are generally consistent with the formation at depth of olivine megacryst cores, which were entrained in ascending magmas that crystallized pyroxenes, small olivines, and oscillatory rims on megacrysts.

Neural Mechanisms of Context Effects on Face Recognition: Automatic Binding and Context Shift Decrements

PubMed Central

Hayes, Scott M.; Baena, Elsa; Truong, Trong-Kha; Cabeza, Roberto

2011-01-01

Although people do not normally try to remember associations between faces and physical contexts, these associations are established automatically, as indicated by the difficulty of recognizing familiar faces in different contexts (“butcher-on-the-bus” phenomenon). The present functional MRI (fMRI) study investigated the automatic binding of faces and scenes. In the Face-Face (F-F) condition, faces were presented alone during both encoding and retrieval, whereas in the Face/Scene-Face (FS-F) condition, they were presented overlaid on scenes during encoding but alone during retrieval (context change). Although participants were instructed to focus only on the faces during both encoding and retrieval, recognition performance was worse in the FS-F than the F-F condition (“context shift decrement”—CSD), confirming automatic face-scene binding during encoding. This binding was mediated by the hippocampus as indicated by greater subsequent memory effects (remembered > forgotten) in this region for the FS-F than the F-F condition. Scene memory was mediated by the right parahippocampal cortex, which was reactivated during successful retrieval when the faces were associated with a scene during encoding (FS-F condition). Analyses using the CSD as a regressor yielded a clear hemispheric asymmetry in medial temporal lobe activity during encoding: left hippocampal and parahippocampal activity was associated with a smaller CSD, indicating more flexible memory representations immune to context changes, whereas right hippocampal/rhinal activity was associated with a larger CSD, indicating less flexible representations sensitive to context change. Taken together, the results clarify the neural mechanisms of context effects on face recognition. PMID:19925208

Enhanced performance of sulfur-infiltrated bimodal mesoporous carbon foam by chemical solution deposition as cathode materials for lithium sulfur batteries

NASA Astrophysics Data System (ADS)

Jeong, Tae-Gyung; Chun, Jinyong; Cho, Byung-Won; Lee, Jinwoo; Kim, Yong-Tae

2017-02-01

The porous carbon matrix is widely recognized to be a promising sulfur reservoir to improve the cycle life by suppressing the polysulfide dissolution in lithium sulfur batteries (LSB). Herein, we synthesized mesocellular carbon foam (MSUF-C) with bimodal mesopore (4 and 30 nm) and large pore volume (1.72 cm2/g) using MSUF silica as a template and employed it as both the sulfur reservoir and the conductive agent in the sulfur cathode. Sulfur was uniformly infiltrated into MSUF-C pores by a chemical solution deposition method (MSUF-C/S CSD) and the amount of sulfur loading was achieved as high as 73% thanks to the large pore volume with the CSD approach. MSUF-C/S CSD showed a high capacity (889 mAh/g after 100 cycles at 0.2 C), an improved rate capability (879 mAh/g at 1C and 420 mAh/g at 2C), and a good capacity retention with a fade rate of 0.16% per cycle over 100 cycles.

Enhanced performance of sulfur-infiltrated bimodal mesoporous carbon foam by chemical solution deposition as cathode materials for lithium sulfur batteries

PubMed Central

Jeong, Tae-Gyung; Chun, Jinyong; Cho, Byung-Won; Lee, Jinwoo; Kim, Yong-Tae

2017-01-01

The porous carbon matrix is widely recognized to be a promising sulfur reservoir to improve the cycle life by suppressing the polysulfide dissolution in lithium sulfur batteries (LSB). Herein, we synthesized mesocellular carbon foam (MSUF-C) with bimodal mesopore (4 and 30 nm) and large pore volume (1.72 cm2/g) using MSUF silica as a template and employed it as both the sulfur reservoir and the conductive agent in the sulfur cathode. Sulfur was uniformly infiltrated into MSUF-C pores by a chemical solution deposition method (MSUF-C/S CSD) and the amount of sulfur loading was achieved as high as 73% thanks to the large pore volume with the CSD approach. MSUF-C/S CSD showed a high capacity (889 mAh/g after 100 cycles at 0.2 C), an improved rate capability (879 mAh/g at 1C and 420 mAh/g at 2C), and a good capacity retention with a fade rate of 0.16% per cycle over 100 cycles. PMID:28165041

Unmanned Aircraft System (UAS) Delegation of Separation in NextGen Airspace

NASA Technical Reports Server (NTRS)

Kenny, Caitlin A.; Shively, Robert J.; Jordan, Kevin

2014-01-01

The purpose of this study was to determine the feasibility of unmanned aircraft systems (UAS) performing delegated separation in the national airspace system (NAS). Delegated separation is the transfer of responsibility for maintaining separation between aircraft or vehicles from air navigation service providers to the relevant pilot or flight operator. The effects of delegated separation and traffic display information level were collected through performance, workload, and situation awareness measures. The results of this study show benefits related to the use of conflict detection alerts being shown on the UAS operator's cockpit situation display (CSD), and to the use of full delegation. Overall, changing the level of separation responsibility and adding conflict detection alerts on the CSD was not found to have an adverse effect on performance as shown by the low amounts of losses of separation. The use of conflict detection alerts on the CSD and full delegation responsibilities given to the UAS operator were found to create significantly reduced workload, significantly increased situation awareness and significantly easier communications between the UAS operator and air traffic controller without significantly increasing the amount of losses of separation.

Cerebrospinal Fluid Biomarkers of Alzheimer's Disease Correlate With Electroencephalography Parameters Assessed by Exact Low-Resolution Electromagnetic Tomography (eLORETA).

PubMed

Hata, Masahiro; Tanaka, Toshihisa; Kazui, Hiroaki; Ishii, Ryouhei; Canuet, Leonides; Pascual-Marqui, Roberto D; Aoki, Yasunori; Ikeda, Shunichiro; Sato, Shunsuke; Suzuki, Yukiko; Kanemoto, Hideki; Yoshiyama, Kenji; Iwase, Masao

2017-09-01

Recently, cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease (AD) have garnered a lot of clinical attention. To explore neurophysiological traits of AD and parameters for its clinical diagnosis, we examined the association between CSF biomarkers and electroencephalography (EEG) parameters in 14 probable AD patients. Using exact low-resolution electromagnetic tomography (eLORETA), artifact-free 40-sesond EEG data were estimated with current source density (CSD) and lagged phase synchronization (LPS) as the EEG parameters. Correlations between CSF biomarkers and the EEG parameters were assessed. Patients with AD showed significant negative correlation between CSF beta-amyloid (Aβ)-42 concentration and the logarithms of CSD over the right temporal area in the theta band. Total tau concentration was negatively correlated with the LPS between the left frontal eye field and the right auditory area in the alpha-2 band in patients with AD. Our study results suggest that AD biomarkers, in particular CSF Aβ42 and total tau concentrations are associated with the EEG parameters CSD and LPS, respectively. Our results could yield more insights into the complicated pathology of AD.

Mitsubishi thermal imager using the 512 x 512 PtSi focal plane arrays

NASA Astrophysics Data System (ADS)

Fujino, Shotaro; Miyoshi, Tetsuo; Yokoh, Masataka; Kitahara, Teruyoshi

1990-01-01

MITSUBISHI THERMAL IMAGER model IR-5120A is high resolution and high sensitivity infrared television imaging system. It was exhibited in SPIE'S 1988 Technical Symposium on OPTICS, ELECTRO-OPTICS, and SENSORS, held at April 1988 Orlando, and acquired interest of many attendants of the symposium for it's high performance. The detector is a Platinium Silicide Charge Sweep Device (CSD) array containing more than 260,000 individual pixels manufactured by Mitsubishi Electric Co. The IR-5120A consists of a Camera Head. containing the CSD, a stirling cycle cooler and support electronics, and a Camera Control Unit containing the pixel fixed pattern noise corrector, video controllor, cooler driver and support power supplies. The stirling cycle cooler built into the Camera Head is used for keeping CSD temperature of approx. 80K with the features such as light weight, long life of more than 2000 hours and low acoustical noise. This paper describes an improved Thermal Imager, with more light weight, compact size and higher performance, and it's design philosophy, characteristics and field image.

Chitin synthase III: synthetic lethal mutants and "stress related" chitin synthesis that bypasses the CSD3/CHS6 localization pathway.

PubMed

Osmond, B C; Specht, C A; Robbins, P W

1999-09-28

We screened Saccharomyces strains for mutants that are synthetically lethal with deletion of the major chitin synthase gene CHS3. In addition to finding, not surprisingly, that mutations in major cell wall-related genes such as FKS1 (glucan synthase) and mutations in any of the Golgi glycosylation complex genes (MNN9 family) are lethal in combination with chs3Delta, we found that a mutation in Srv2p, a bifunctional regulatory gene, is notably lethal in the chs3 deletion. In extending studies of fks1-chitin synthase 3 interactions, we made the surprising discovery that deletion of CSD3/CHS6, a gene normally required for Chs3p delivery and activity in vivo, was not lethal with fks1 and, in fact, that lack of Csd3p/Chs6p did not decrease the high level of stress-related chitin made in the fks1 mutant. This finding suggests that "stress response" chitin synthesis proceeds through an alternate Chs3p targeting pathway.

Chitin synthase III: Synthetic lethal mutants and “stress related” chitin synthesis that bypasses the CSD3/CHS6 localization pathway

PubMed Central

Osmond, Barbara C.; Specht, Charles A.; Robbins, Phillips W.

1999-01-01

We screened Saccharomyces strains for mutants that are synthetically lethal with deletion of the major chitin synthase gene CHS3. In addition to finding, not surprisingly, that mutations in major cell wall-related genes such as FKS1 (glucan synthase) and mutations in any of the Golgi glycosylation complex genes (MNN9 family) are lethal in combination with chs3Δ, we found that a mutation in Srv2p, a bifunctional regulatory gene, is notably lethal in the chs3 deletion. In extending studies of fks1-chitin synthase 3 interactions, we made the surprising discovery that deletion of CSD3/CHS6, a gene normally required for Chs3p delivery and activity in vivo, was not lethal with fks1 and, in fact, that lack of Csd3p/Chs6p did not decrease the high level of stress-related chitin made in the fks1 mutant. This finding suggests that “stress response” chitin synthesis proceeds through an alternate Chs3p targeting pathway. PMID:10500155

Unmanned aircraft system (UAS) delegation of separation in NextGen airspace

NASA Astrophysics Data System (ADS)

Kenny, Caitlin A.

The purpose of this thesis was to determine the feasibility of unmanned aircraft systems (UAS) performing delegated separation in the national airspace system (NAS). Delegated separation is the transfer of responsibility for maintaining separation between aircraft or vehicles from air navigation service providers to the relevant pilot or flight operator. The effects of delegated separation and traffic display information level were collected through performance, workload, and situation awareness measures. The results of this study showed benefits related to the use of conflict detection alerts being shown on the UAS operator's cockpit situation display (CSD) and to the use of full delegation. Overall, changing the level of separation responsibility and adding conflict detection alerts on the CSD were not found to have an adverse effect on performance as shown by the low amounts of losses of separation. The use of conflict detection alerts on the CSD and full delegation responsibilities given to the UAS operator were found to create significantly reduced workload, significantly increased situation awareness and significantly easier communications between the UAS operator and air traffic controller without significantly increasing the amount of losses of separation.

Mechanisms of migraine aura revealed by functional MRI in human visual cortex

PubMed Central

Hadjikhani, Nouchine; Sanchez del Rio, Margarita; Wu, Ona; Schwartz, Denis; Bakker, Dick; Fischl, Bruce; Kwong, Kenneth K.; Cutrer, F. Michael; Rosen, Bruce R.; Tootell, Roger B. H.; Sorensen, A. Gregory; Moskowitz, Michael A.

2001-01-01

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex. PMID:11287655

Genetic sex determination and extinction.

PubMed

Hedrick, Philip W; Gadau, Jürgen; Page, Robert E

2006-02-01

Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

Cat-scratch disease. Subtle vertebral bone marrow abnormalities demonstrated by MR imaging and radionuclide bone scan.

PubMed

Wilson, J D; Castillo, M

1995-01-01

Cat-scratch disease (CSD) is a benign, self-limited cause of lymphadenitis occurring mainly in children and young adults. Its etiology is a delicate, small gram-negative pleomorphic bacillus. Less common manifestations of CSD are seen in 5% of patients and include Parinaud's oculoglandular syndrome (with enlargement of the preauricular nodes), parotid gland enlargement, encephalitis, radiculopathy, pneumonitis, erythema nodosum, thrombocytopenia, and lytic bone lesions. We describe a patient in whom magnetic resonance imaging initially detected subtle vertebral bone marrow abnormalities that correlated with the site of abnormality on a subsequent radionuclide bone scan.

Budgetary Impact of Telotristat Ethyl, a Novel Treatment for Patients with Carcinoid Syndrome Diarrhea: A US Health Plan Perspective.

PubMed

Joish, Vijay N; Frech, Feride; Lapuerta, Pablo

2017-12-01

Telotristat ethyl (TE) was recently approved for carcinoid syndrome diarrhea (CSD) in patients not adequately controlled with somatostatin analog long-acting release (SSA LAR) therapy alone. A budget impact model was developed to determine the short-term affordability of reimbursing TE in a US health plan. A budget impact model compared health care costs when CSD is managed per current treatment patterns (SSA LAR, reference drug scenario) versus when TE is incorporated in the treatment algorithm (SSA LAR + TE, new drug scenario). Prevalence of CSD, proportion of patients not adequately controlled on SSA LAR, monthly treatment costs (pharmacy and medical), and treatment efficacy were derived from the literature. In the reference drug scenario, an escalated monthly dose of SSA LAR therapy of 40 mg was assumed to treat patients with CSD not adequately controlled on the labeled dose of SSA LAR. In the new drug scenario, TE was added to the maximum labeled monthly dose of SSA LAR therapy of 30 mg. The incremental budget impact was calculated based on an assumed TE market uptake of 28%, 42%, and 55% during Years 1, 2, and 3, respectively. One-way sensitivity analyses were conducted to test model assumptions. A hypothetical health plan of 1 million members was estimated to have 42 prevalent CSD patients of whom 17 would be inadequately controlled on SSA LAR therapy. The monthly medical cost per patient not adequately controlled on SSA LAR in addition to pharmacotherapy was estimated to be $3946 based on the literature. Based on the observed treatment response in a clinical trial of 20% and 44% for the base case reference and new drug scenarios, total per patient per month costs were estimated to be $7563 and $11,205, respectively. Total annual costs in the new drug scenario were estimated to be $2.3 to $2.5 million during the first 3 years. The overall incremental annual costs were estimated to be $154,000 in Year 1, $231,000 in Year 2, and $302,000 in Year 3. This translated to an incremental per patient per month cost of $0.013, $0.019, and $0.025 for Years 1, 2, and 3. These results remained robust in 1-way sensitivity analyses. The availability of TE for patients not adequately controlled on SSA LAR therapy provides a novel treatment option for CSD. This model showed that providing access to this first-in-class oral agent would have a minimal budget impact to a US health plan. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

5-Arylidene derivatives of Meldrum's acid: Synthesis, structural characterization using single crystal and powder crystal X-ray diffraction, and electronic properties

NASA Astrophysics Data System (ADS)

Dey, Tanusri; Ghosh, Soumen; Ghosh, Somnath; Mukherjee, Alok Kumar

2015-07-01

Four 5-arylidene derivatives of Meldrum's acid, 5-(4-chlorobenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (2), 5-(3-hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (3), 5-(3,4-dimethoxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (4) and 5-(2,4-dimethoxy benzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (5) have been synthesized and their crystal structures have been determined using single crystal X-ray diffractometry for 2, 4 and 5 and X-ray powder diffraction for 3. The nature of intermolecular interactions in 2-5 has been analyzed through Hirshfeld surfaces and 2D fingerprint plots. The DFT optimized molecular geometries in 2-5 agree closely with those obtained from the crystallographic studies. The crystal packing in 2-5 exhibits an interplay of Osbnd H⋯O, Csbnd H⋯O, Csbnd H⋯Cl and Csbnd H⋯π (arene) hydrogen bonds and π⋯π interactions, which assemble molecules into three-dimensional architecture in 2, 3 and 5 and two-dimensional framework in 4. The Hirshfeld surface analyses of 2-5, Meldrum's acid (1) and a few related 5-arylidene derivatives of Meldrum's acid retrieved from the Cambridge Structural Database (CSD) indicate that about 85% of the Hirshfeld surface area (72% in 2 where H⋯Cl contribution is about 13%) in this class of compounds are due to H⋯H, O⋯H and C⋯H contacts. The HOMO-LUMO energy gap (>2.2 eV) in 2-5 indicates a significant degree of internal charge transfer within the molecule.

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

PubMed

de Almeida Rabello Oliveira, Marcela; da Rocha Ataíde, Terezinha; de Oliveira, Suzana Lima; de Melo Lucena, Ana Luíza; de Lira, Carla Emmanuela Pereira Rodrigues; Soares, Anderson Acioli; de Almeida, Clarissa Beatriz Santos; Ximenes-da-Silva, Adriana

2008-03-21

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study.

PubMed

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W; Christensen, Karl; Olesen, Jes

2009-08-01

Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. In this randomised, double-blind, placebo-controlled crossover trial, 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months. Randomisation was by computer-generated list. Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura, migraine without aura, or other type of headache. Primary endpoints were a reduction in aura attacks with or without headache and a reduction in migraine headache days with or without an aura. Analysis was per protocol. This trial is registered, number NCT00332007. 39 patients were included in the study, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly different between placebo and tonabersat groups (3.0 days in each group; p=0.09). Tonabersat was well tolerated but overall had more side-effects than placebo. Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its known inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. Minster Pharmaceuticals; Lundbeck Foundation.

The effect of scene context on episodic object recognition: parahippocampal cortex mediates memory encoding and retrieval success.

PubMed

Hayes, Scott M; Nadel, Lynn; Ryan, Lee

2007-01-01

Previous research has investigated intentional retrieval of contextual information and contextual influences on object identification and word recognition, yet few studies have investigated context effects in episodic memory for objects. To address this issue, unique objects embedded in a visually rich scene or on a white background were presented to participants. At test, objects were presented either in the original scene or on a white background. A series of behavioral studies with young adults demonstrated a context shift decrement (CSD)-decreased recognition performance when context is changed between encoding and retrieval. The CSD was not attenuated by encoding or retrieval manipulations, suggesting that binding of object and context may be automatic. A final experiment explored the neural correlates of the CSD, using functional Magnetic Resonance Imaging. Parahippocampal cortex (PHC) activation (right greater than left) during incidental encoding was associated with subsequent memory of objects in the context shift condition. Greater activity in right PHC was also observed during successful recognition of objects previously presented in a scene. Finally, a subset of regions activated during scene encoding, such as bilateral PHC, was reactivated when the object was presented on a white background at retrieval. Although participants were not required to intentionally retrieve contextual information, the results suggest that PHC may reinstate visual context to mediate successful episodic memory retrieval. The CSD is attributed to automatic and obligatory binding of object and context. The results suggest that PHC is important not only for processing of scene information, but also plays a role in successful episodic memory encoding and retrieval. These findings are consistent with the view that spatial information is stored in the hippocampal complex, one of the central tenets of Multiple Trace Theory. (c) 2007 Wiley-Liss, Inc.

Effects of sertraline on brain current source of the high beta frequency band: analysis of electroencephalography during audiovisual erotic stimulation in males with premature ejaculation.

PubMed

Kwon, O Y; Kam, S C; Choi, J H; Do, J M; Hyun, J S

2011-01-01

To identify the effects of sertraline, a selective serotonin reuptake inhibitor, for the treatment of premature ejaculation (PE), changes in brain current-source density (CSD) of the high beta frequency band (22-30 Hz) induced by sertraline administration were investigated during audiovisual erotic stimulation. Eleven patients with PE (36.9±7.8 yrs) and 11 male volunteers (24.2±1.9 years) were enrolled. Scalp electroencephalography (EEG) was conducted twice: once before sertraline administration and then again 4 h after the administration of 50 mg sertraline. Statistical non-parametric maps were obtained using the EEG segments to detect the current-density differences in the high beta frequency bands (beta-3, 22-30 Hz) between the EEGs before and after sertraline administration in the patient group and between the patient group and controls after the administration of sertraline during the erotic video sessions. Comparing between before and after sertraline administration in the patients with PE, the CSD of the high beta frequency band at 4 h after sertraline administration increased significantly in both superior frontal gyri and the right medial frontal gyrus (P<0.01). The CSD of the beta-3 band of the patients with PE were less activated significantly in the middle and superior temporal gyrus, lingual and fusiform gyrus, inferior occipital gyrus and cuneus of the right cerebral hemisphere compared with the normal volunteers 4 h after sertraline administration (P<0.01). In conclusion, sertraline administration increased the CSD in both the superior frontal and right middle temporal gyrus in patients with PE. The results suggest that the increased neural activity in these particular cerebral regions after sertraline administration may be associated with inhibitory effects on ejaculation in patients with PE.

Material properties of CorCap passive cardiac support device.

PubMed

Chitsaz, Sam; Wenk, Jonathan F; Ge, Liang; Wisneski, Andrew; Mookhoek, Aart; Ratcliffe, Mark B; Guccione, Julius M; Tseng, Elaine E

2013-01-01

Myocardial function deteriorates during ventricular remodeling in patients with congestive heart failure (HF). Ventricular restraint therapy using a cardiac support device (CSD) is designed to reduce the amount of stress inside the dilated ventricles, which in turn halts remodeling. However, as an open mesh surrounding the heart, it is unknown what the mechanical properties of the CSD are in different fiber orientations. Composite specimens of CorCap (Acorn Cardiovascular, Inc, St. Paul, MN) CSD fabric and silicone were constructed in different fiber orientations and tested on a custom-built biaxial stretcher. Silicone controls were made and stretched to detect the parameters of the matrix. CSD coefficients were calculated using the composite and silicone matrix stress-strain data. Stiffness in different fiber orientations was determined. Silicone specimens exerted a linear behavior, with stiffness of 2.57 MPa. For the composites with 1 fiber set aligned with respect to the stretch axes, stiffness in the direction of the aligned fiber set was higher than that in the cross-fiber direction (14.39 MPa versus 5.66 MPa), indicating greater compliance in the cross-fiber direction. When the orientation of the fiber sets in the composite were matched to the expected clinical orientation of the implanted CorCap, the stiffness in the circumferential axis (with respect to the heart) was greater than in the longitudinal axis (10.55 MPa versus 9.70 MPa). The mechanical properties of the CorCap demonstrate directionality with greater stiffness circumferentially than longitudinally. Implantation of the CorCap clinically should take into account the directionality of the biomechanics to optimize ventricular restraint. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of low-level laser therapy on bone healing of critical-size defects treated with bovine bone graft.

PubMed

Bosco, Alvaro Francisco; Faleiros, Paula Lazilha; Carmona, Luana Rodrigues; Garcia, Valdir Gouveia; Theodoro, Letícia Helena; de Araujo, Nathália Januario; Nagata, Maria José Hitomi; de Almeida, Juliano Milanezi

2016-10-01

To histomorphometrically analyze the effect of low-level laser therapy (LLLT) on bone formation process in surgically created critical-size defects (CSDs) treated with bovine bone graft (BBG) and its influence over particles' resorption of BBG. A 10-mm diameter CSD was surgically created in the calvaria of 64 male rats, which were distributed into 4 experimental groups: the C group (control), only blood clot; the LLLT group, LLLT (GaAlAs, 660nm) and blood clot; the BBG group, CSD filled with BBG; the BBG/LLLT group, LLLT and CSD filled with BBG. Animals were euthanized at either 30 or 60days post-operation. A histological analysis was performed. Additionally, the percentage of newly formed bone area (NFBA) and remaining particles areas (RPA) of BBG were histometrically evaluated and data statistically analyzed. The LLLT (5.82±2.05; 7.34±1.01) group presented significantly greater NFBA when compared to the C group (1.61±0.30; 5.59±0.94) at 30 and 60days post-operation (p<0.05). The BBG/LLLT group (7.39±1.45; 9.44±2.36) presented significantly greater NFBA than the BBG group (3.85±1.56; 8.02±0.63) at 30 and 60days postoperation (p<0.05). There was no significant difference in the mean percentage of implanted material RPA between the BBG and the BBG/LLLT groups. LLLT can improve bone formation process in CSD filled or not with BBG in rat calvaria, but it is not able to accelerate particles resorption of this material in the interior of bone defect. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care.

PubMed

García-Iranzo, Emma M; Rodríguez-Lucena, Francisco J; Matoses-Chirivella, Carmen; García-Monsalve, Ana; Murcia-López, Ana Cristina; Navarro-Ruiz, Andrés

2017-07-01

The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

PubMed

Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

2015-03-01

Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches. Copyright © 2015 Elsevier Inc. All rights reserved.

Polymorphism in R-tamsulosin (an alpha blocker): The unexpected manifestation of a sulfonamide⋯o-diethoxybenzene heterosynthon

NASA Astrophysics Data System (ADS)

Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, Krishnan

2014-12-01

A two point Nsbnd H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P21, C2, and P21 space groups respectively with two molecules in the asymmetric unit (Z‧ = 2), whereas, form III of freebase crystallize in the orthorhombic P212121 space group with Z‧ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯o-diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring sulfonamide homo and heterosynthons.

Characterization of non-classical Csbnd Br⋯π interactions in (E)-1,3-dibromo-5-(2-(ferrocenyl)vinyl)benzene and related derivatives of ferrocene

NASA Astrophysics Data System (ADS)

Shukla, Rahul; Panini, Piyush; McAdam, C. John; Robinson, Brian H.; Simpson, Jim; Tagg, Tei; Chopra, Deepak

2017-03-01

Amongst the halogens, the involvement of bromine atoms in various types of intermolecular interactions is comparatively the least studied. In this manuscript, we report the formation of Csbnd Br⋯π interactions, with the π-rings being the cyclopentadienyl (Cp) rings of a ferrocene molecule in a newly synthesized compound (E)-1,3-dibromo-5-(2-(ferrocenyl)vinyl)benzene. We have also performed a detailed quantitative analysis on Csbnd Br⋯π interactions observed in the synthesized molecule and in several related molecules found in the Cambridge Structure Database (CSD) showing the presence of these interactions. A topological analysis based upon QTAIM theory and electrostatic potential ESP mapped on the Hirshfeld surface of these molecules confirm that these interactions are better described as "halogen bonds" wherein the electropositive region (σ-hole) on the Br-atom interacts with the electronegative region over the Cp-ring of the ferrocene. Further, the electronegative region on the bromine atom (perpendicular to the Csbnd Br bond) was observed to be involved in the formation of highly directional Csbnd H⋯Br interactions with the ∠Csbnd Br⋯H close to 90°. Thus the bromine atom is acting as both a "halogen bond donor" and "hydrogen bond acceptor" in the crystal packing with the two interactions being mutually orthogonal.

Estimated critical conditions for UO[sub 2]F[sub 2]--H[sub 2]O systems in fully water-reflected spherical geometry

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

Jordan, W.C.; Turner, J.C.

1992-12-01

The purpose of this report is to document reference calculations performed using the SCALE-4.0 code system to determine the critical parameters of UO[sub 2]F[sub 2]-H[sub 2]O spheres. The calculations are an extension of those documented in ORNL/CSD/TM-284. Specifically, the data for low-enriched UO[sub 2]F[sub 2]-H[sub 2]O spheres have been extended to highly enriched uranium. These calculations, together with those reported in ORNL/CSD/TM-284, provide a consistent set of critical parameters (k[sub [infinity

[Bartonella henselae vertebral osteomyelitis: report of a case].

PubMed

Juan Zepeda, T; Jorge Morales, S; Hugo Letelier, A; Luis Delpiano, M

2016-01-01

Cat scratch disease (CSD) is caused by Bartonella henselae, with unknown prevalence and incidence in the Chilean paediatric population. Regional lymphadenopathy is the most common presentation, while atypical forms constitute a diagnostic challenge. To report a case of CSD with osteomyelitis and present guidelines regarding treatment. An eight year-old patient, with prolonged febrile illness, back pain and neck stiffness. Laboratory studies highlight positive IgG for Bartonella henselae. The abdominal ultrasound showed splenic micro-abscesses, and the MRI showing vertebral lesions suggestive of osteomyelitis. The diagnosis of atypical forms requires a high rate of suspicion, as in this case, in which the patient manifested the musculoskeletal symptoms simultaneously with the febrile syndrome, which led us to study possible complications of the disease. Current knowledge of the treatment of atypical or complicated CSD is derived from the observation of case studies, rather than randomized trials. It is suggested that antibiotic therapy is analysed individually, with the help of a specialist. The importance of high clinical suspicion are emphasised and discussed, as well presenting some treatment options based on the evidence from the current literature. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Computational model of cerebral blood flow redistribution during cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.

2016-04-01

In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.

Improving crystal size distribution by internal seeding combined cooling/antisolvent crystallization with a cooling/heating cycle

NASA Astrophysics Data System (ADS)

Lenka, Maheswata; Sarkar, Debasis

2018-03-01

This work investigates the effect of internal seeding and an initial cooling/heating cycle on the final crystal size distribution (CSD) during a combined cooling/antisolvent crystallization of L-asparagine monohydrate from it's aqueous solution using isopropyl-alcohol as antisolvent. Internal seeds were generated by one-pot addition of various amounts of antisolvent to the crystallizer. It was then followed by a cooling/heating cycle to dissolve the fines produced and thus obtain a suitable initial seed. A combined cooling/antisolvent crystallization was then followed by employing a linear cooling profile with simultaneous addition of antisolvent with a constant mass flow rate to promote the growth of the internally generated seeds. The amount of initial antisolvent influences the characteristics of the internal seeds generated and the effect of initial amount of antisolvent on the final CSD is investigated. It was found that the introduction of a single cooling/heating cycle significantly improves the reproducibility of final CSD as well as the mean size. Overall, the study indicates that the application of internal seeding with a single cooling/heating cycle for fines dissolution is an effective technique to tailor crystal size distribution.

CERVICAL SPINE SIGNS AND SYMPTOMS: PERPETUATING RATHER THAN PREDISPOSING FACTORS FOR TEMPOROMANDIBULAR DISORDERS IN WOMEN

PubMed Central

Bevilaqua-Grossi, Débora; Chaves, Thaís Cristina; de Oliveira, Anamaria Siriani

2007-01-01

Aim: The purpose of this study was to assess in a sample of female community cases the relationship between the increase of percentage of cervical signs and symptoms and the severity of temporomandibular disorders (TMD) and vice-versa. Material and Methods: One hundred women (aged 18-26 years) clinically diagnosed with TMD signs and symptoms and cervical spine disorders were randomly selected from a sample of college students. Results: 43% of the volunteers demonstrated the same severity for TMD and cervical spine disorders (CSD). The increase in TMD signs and symptoms was accompanied by increase in CSD severity, except for pain during palpation of posterior temporal muscle, more frequently observed in the severe CSD group. However, increase in pain during cervical extension, sounds during cervical lateral flexion, and tenderness to palpation of upper fibers of trapezius and suboccipital muscles were observed in association with the progression of TMD severity. Conclusion: The increase in cervical symptomatology seems to accompany TMD severity; nonetheless, the inverse was not verified. Such results suggest that cervical spine signs and symptoms could be better recognized as perpetuating rather than predisposing factors for TMD. PMID:19089141

Effect of gap detection threshold on consistency of speech in children with speech sound disorder.

PubMed

Sayyahi, Fateme; Soleymani, Zahra; Akbari, Mohammad; Bijankhan, Mahmood; Dolatshahi, Behrooz

2017-02-01

The present study examined the relationship between gap detection threshold and speech error consistency in children with speech sound disorder. The participants were children five to six years of age who were categorized into three groups of typical speech, consistent speech disorder (CSD) and inconsistent speech disorder (ISD).The phonetic gap detection threshold test was used for this study, which is a valid test comprised six syllables with inter-stimulus intervals between 20-300ms. The participants were asked to listen to the recorded stimuli three times and indicate whether they heard one or two sounds. There was no significant difference between the typical and CSD groups (p=0.55), but there were significant differences in performance between the ISD and CSD groups and the ISD and typical groups (p=0.00). The ISD group discriminated between speech sounds at a higher threshold. Children with inconsistent speech errors could not distinguish speech sounds during time-limited phonetic discrimination. It is suggested that inconsistency in speech is a representation of inconsistency in auditory perception, which causes by high gap detection threshold. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic incompatibility drives mate choice in a parasitic wasp.

PubMed

Thiel, Andra; Weeda, Anne C; de Boer, Jetske G; Hoffmeister, Thomas S

2013-07-30

Allelic incompatibility between individuals of the same species should select for mate choice based on the genetic make-up of both partners at loci that influence offspring fitness. As a consequence, mate choice may be an important driver of allelic diversity. A complementary sex determination (CSD) system is responsible for intraspecific allelic incompatibility in many species of ants, bees, and wasps. CSD may thus favour disassortative mating and in this, resembles the MHC of the vertebrate immune system, or the self-incompatibility (SI) system of higher plants. Here we show that in the monogamous parasitic wasp Bracon brevicornis (Wesmael), females are able to reject partners with incompatible alleles. Forcing females to accept initially rejected partners resulted in sex ratio distortion and partial infertility of offspring. CSD-disassortative mating occurred independent of kin recognition and inbreeding avoidance in our experiment. The fitness consequences of mate choice are directly observable, not influenced by environmental effects, and more severe than in comparable systems (SI or MHC), on individuals as well as at the population level. Our results thus demonstrate the strong potential of female mate choice for maintaining high offspring fitness in this species.

Operation of the solvent-refined-coal pilot plant, Wilsonville, Alabama. Annual technical report, January-December 1980

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

Lewis, H.E.

1981-08-01

The plant was in operation for the equivalent of 247 days, an on-stream factor of 67.7%. Kentucky 9 coals from the Lafayette, Dotiki and Fies mines were processed. During 1980, the operating conditions and equipment were adjusted to evaluate potential process improvements. These experiments produced significant results in the following areas: Operating V103 High Pressure Separator in the hot mode; varying T102 Vacuum Column operating temperature; adding light SRC (LSRC), a product of the third stage of the Critical Solvent Deashing (CSD) unit, to the process solvent; investigating the effects of the chlorine content of the feed coal on corrosionmore » in the process vessels; evaluating the effects of adding sodium carbonate on corrosion rates; operating under conditions of low severity; i.e., low reactor temperature and long residence time; and testing an alternate CSD deashing solvent. A series of simulation runs investigating the design operating conditions for a planned 6000 ton per day SRC-I demonstation plant were also completed. Numerous improvements were made in the CSD processing area, and the components for a hydrotreating unit were installed.« less

Depression among people with type 2 diabetes mellitus, US National Health and Nutrition Examination Survey (NHANES), 2005-2012.

PubMed

Wang, Yiting; Lopez, Janice M S; Bolge, Susan C; Zhu, Vivienne J; Stang, Paul E

2016-04-05

Depression in people with diabetes can result in increased risk for diabetes-related complications. The prevalence of depression has been estimated to be 17.6 % in people with type 2 diabetes mellitus (T2DM), based on studies published between 1980 and 2005. There is a lack of more recent estimates of depression prevalence among the US general T2DM population. The present study used the US National Health and Nutrition Examination Survey (NHANES) 2005-2012 data to provide an updated, population-based estimate for the prevalence of depression in people with T2DM. NHANES is a cross-sectional survey of a nationally representative sample of the civilian, non-institutionalized US population. Starting from 2005, the Patient Health Questionnaire (PHQ-9) was included to measure signs and symptoms of depression. We defined PHQ-9 total scores ≥ 10 as clinically relevant depression (CRD), and ≥ 15 as clinically significant depression (CSD). Self-reported current antidepressant use was also combined to estimate overall burden of depression. Predictors of CRD and CSD were investigated using survey logistic regression models. A total of 2182 participants with T2DM were identified. The overall prevalence of CRD and CSD among people with T2DM is 10.6 % (95 % confidence interval (CI) 8.9-12.2 %), and 4.2 % (95 % CI 3.4-5.1 %), respectively. The combined burden of depressive symptoms and antidepressants may be as high as 25.4 % (95 % CI 23.0-27.9 %). Significant predictors of CRD include age (younger than 65), sex (women), income (lower than 130 % of poverty level), education (below college), smoking (current or former smoker), body mass index (≥30 kg/m(2)), sleep problems, hospitalization in the past year, and total cholesterol (≥200 mg/dl). Significant predictors of CSD also include physical activity (below guideline) and cardiovascular diseases. The prevalence of CRD and CSD among people with T2DM in the US may be lower than in earlier studies, however, the burden of depression remains high. Further research with longitudinal follow-up for depression in people with T2DM is needed to understand real world effectiveness of depression management.

New developments in crystallography: exploring its technology, methods and scope in the molecular biosciences.

PubMed

Helliwell, John R

2017-08-31

Since the Protein Data Bank (PDB) was founded in 1971, there are now over 120,000 depositions, the majority of which are from X-ray crystallography and 90% of those made use of synchrotron beamlines. At the Cambridge Structure Database (CSD), founded in 1965, there are more than 800,000 'small molecule' crystal structure depositions and a very large number of those are relevant in the biosciences as ligands or cofactors. The technology for crystal structure analysis is still developing rapidly both at synchrotrons and in home labs. Determination of the details of the hydrogen atoms in biological macromolecules is well served using neutrons as probe. Large multi-macromolecular complexes cause major challenges to crystallization; electrons as probes offer unique advantages here. Methods developments naturally accompany technology change, mainly incremental but some, such as the tuneability, intensity and collimation of synchrotron radiation, have effected radical changes in capability of biological crystallography. In the past few years, the X-ray laser has taken X-ray crystallography measurement times into the femtosecond range. In terms of applications many new discoveries have been made in the molecular biosciences. The scope of crystallographic techniques is indeed very wide. As examples, new insights into chemical catalysis of enzymes and relating ligand bound structures to thermodynamics have been gained but predictive power is seen as not yet achieved. Metal complexes are also an emerging theme for biomedicine applications. Our studies of coloration of live and cooked lobsters proved to be an unexpected favourite with the public and schoolchildren. More generally, public understanding of the biosciences and crystallography's role within the field have been greatly enhanced by the United Nations International Year of Crystallography coordinated by the International Union of Crystallography. This topical review describes each of these areas along with illustrative results to document the scope of each methodology. © 2017 The Author(s).

chs-4, a class IV chitin synthase gene from Neurospora crassa.

PubMed

Din, A B; Specht, C A; Robbins, P W; Yarden, O

1996-02-05

In Saccharomyces cerevisiae, most of the cellular chitin is produced by chitin synthase III, which requires the product encoded by the CSD2/CAL1/DIT101/KT12 gene. We have identified, isolated and structurally characterized as CSD2/CAL1/DIT101/KT12 homologue in the filamentous ascomycete Neurospora crassa and have used a "reverse genetics" approach to determine its role in vivo. The yeast gene was used as a heterologous probe for the isolation of a N. crassa gene(designated chs-4) encoding a polypeptide belonging to a class of chitin synthases which we have designated class IV. The predicted polypeptide encoded by this gene is highly similar to those of S. cerevisiae and Candida albicans. N. crassa strains in which chs-4 had been inactivated by the Repeat-Induced point mutation (RIP) process grew and developed in a normal manner under standard growth conditions. However, when grown in the presence of sorbose (a carbon source which induces morphological changes accompanied by elevated chitin content), chitin levels in the chs-4RIP strain were significantly lower than those observed in the wild type. We suggest that CHS4 may serve as an auxiliary enzyme in N. crassa and that, in contrast to yeasts, it is possible that filamentous fungi may have more than one class IV chitin synthase.

Contagious parthenogenesis, automixis, and a sex determination meltdown.

PubMed

Engelstädter, Jan; Sandrock, Christoph; Vorburger, Christoph

2011-02-01

Because of the twofold cost of sex, genes conferring asexual reproduction are expected to spread rapidly in sexual populations. However, in reality this simple prediction is often confounded by several complications observed in natural systems. Motivated by recent findings in the Cape honey bee and in the parasitoid wasp Lysiphlebus fabarum, we explore through mathematical models the spread of a recessive, parthenogenesis inducing allele in a haplodiploid population. The focus of these models is on the intricate interactions between the mode of parthenogenesis induction through automixis and complementary sex determination (CSD) systems. These interactions may result in asexual production of diploid male offspring and the spread of the parthenogenesis-inducing allele through these males. We demonstrate that if parthenogenetic females produce a substantial proportion of male offspring, this may prevent the parthenogenesis-inducing allele from spreading. However, this effect is weakened if these diploid males are at least partially fertile. We also predict a degradation of multilocus CSD systems during the spread of parthenogenesis, following which only a single polymorphic CSD locus is maintained. Finally, based on empirical parameter estimates from L. fabarum we predict that male production in parthenogens is unlikely to prevent the eventual loss of sexual reproduction in this system. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Striate cortical contribution to the transcorneal electrically evoked response of the visual system.

PubMed

Shimazu, K; Miyake, Y; Fukatsu, Y; Watanabe, S

1996-01-01

Analyses of current-source-density (CSD) and multiple unit activity (MUA) in area 17 of the cat were performed to determine the sources of the cortical transcorneal electrically evoked response. Cortical field potential, CSD and MUA profiles were obtained with multi-electrodes. CSD findings include: current sinks (inward cell membrane current) within 20 ms latency, in layers 4 and 6 of the striate cortex; current sinks corresponding to N3 (negative component of the EER; latency, 35 ms) in layer 4 and lower layer 3 with current sources (outward cell membrane current) for N3 in the supragranular layers; current sinks with latency over 40 ms in the supragranular layers. In the layers 4 and 6, simultaneous MUA was seen. When the stimulus frequency was increased or with dual stimulation, the N3 current sinks were decreased. This indicates that N1 (latency, 9 ms) and N2 (latency, 20 ms) reflect near-field potentials in layers 4 and 6, generated by geniculocortical afferents, and that N3 is a post- and polysynaptic component. It is also suggested that dipoles composed of cell bodies and the apical dendrites of pyramidal cells of layer 3, generated by satellite cells in layer 4, play a major role in generating N3.

Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes

PubMed Central

Carrie, Chris; Giraud, Estelle; Duncan, Owen; Xu, Lin; Wang, Yan; Huang, Shaobai; Clifton, Rachel; Murcha, Monika; Filipovska, Aleksandra; Rackham, Oliver; Vrielink, Alice; Whelan, James

2010-01-01

The disulfide relay system of the mitochondrial intermembrane space has been extensively characterized in Saccharomyces cerevisiae. It contains two essential components, Mia40 and Erv1. The genome of Arabidopsis thaliana contains a single gene for each of these components. Although insertional inactivation of Erv1 leads to a lethal phenotype, inactivation of Mia40 results in no detectable deleterious phenotype. A. thaliana Mia40 is targeted to and accumulates in mitochondria and peroxisomes. Inactivation of Mia40 results in an alteration of several proteins in mitochondria, an absence of copper/zinc superoxide dismutase (CSD1), the chaperone for superoxide dismutase (Ccs1) that inserts copper into CSD1, and a decrease in capacity and amount of complex I. In peroxisomes the absence of Mia40 leads to an absence of CSD3 and a decrease in abnormal inflorescence meristem 1 (Aim1), a β-oxidation pathway enzyme. Inactivation of Mia40 leads to an alteration of the transcriptome of A. thaliana, with genes encoding peroxisomal proteins, redox functions, and biotic stress significantly changing in abundance. Thus, the mechanistic operation of the mitochondrial disulfide relay system is different in A. thaliana compared with other systems, and Mia40 has taken on new roles in peroxisomes and mitochondria. PMID:20829360

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis.

PubMed

Kim, Minah; Cho, Kang Ik Kevin; Yoon, Youngwoo Bryan; Lee, Tae Young; Kwon, Jun Soo

2017-02-01

Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Preventive effects of Chlorella on skeletal muscle atrophy in muscle-specific mitochondrial aldehyde dehydrogenase 2 activity-deficient mice.

PubMed

Nakashima, Yuya; Ohsawa, Ikuroh; Nishimaki, Kiyomi; Kumamoto, Shoichiro; Maruyama, Isao; Suzuki, Yoshihiko; Ohta, Shigeo

2014-10-11

Oxidative stress is involved in age-related muscle atrophy, such as sarcopenia. Since Chlorella, a unicellular green alga, contains various antioxidant substances, we used a mouse model of enhanced oxidative stress to investigate whether Chlorella could prevent muscle atrophy. Aldehyde dehydrogenase 2 (ALDH2) is an anti-oxidative enzyme that detoxifies reactive aldehydes derived from lipid peroxides such as 4-hydroxy-2-nonenal (4-HNE). We therefore used transgenic mice expressing a dominant-negative form of ALDH2 (ALDH2*2 Tg mice) to selectively decrease ALDH2 activity in the muscles. To evaluate the effect of Chlorella, the mice were fed a Chlorella-supplemented diet (CSD) for 6 months. ALDH2*2 Tg mice exhibited small body size, muscle atrophy, decreased fat content, osteopenia, and kyphosis, accompanied by increased muscular 4-HNE levels. The CSD helped in recovery of body weight, enhanced oxidative stress, and increased levels of a muscle impairment marker, creatine phosphokinase (CPK) induced by ALDH2*2. Furthermore, histological and histochemical analyses revealed that the consumption of the CSD improved skeletal muscle atrophy and the activity of the mitochondrial cytochrome c oxidase. This study suggests that long-term consumption of Chlorella has the potential to prevent age-related muscle atrophy.

Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

PubMed

Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

2016-12-01

Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

PubMed

Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

2018-03-01

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Validation study in four health-care databases: upper gastrointestinal bleeding misclassification affects precision but not magnitude of drug-related upper gastrointestinal bleeding risk.

PubMed

Valkhoff, Vera E; Coloma, Preciosa M; Masclee, Gwen M C; Gini, Rosa; Innocenti, Francesco; Lapi, Francesco; Molokhia, Mariam; Mosseveld, Mees; Nielsson, Malene Schou; Schuemie, Martijn; Thiessard, Frantz; van der Lei, Johan; Sturkenboom, Miriam C J M; Trifirò, Gianluca

2014-08-01

To evaluate the accuracy of disease codes and free text in identifying upper gastrointestinal bleeding (UGIB) from electronic health-care records (EHRs). We conducted a validation study in four European electronic health-care record (EHR) databases such as Integrated Primary Care Information (IPCI), Health Search/CSD Patient Database (HSD), ARS, and Aarhus, in which we identified UGIB cases using free text or disease codes: (1) International Classification of Disease (ICD)-9 (HSD, ARS); (2) ICD-10 (Aarhus); and (3) International Classification of Primary Care (ICPC) (IPCI). From each database, we randomly selected and manually reviewed 200 cases to calculate positive predictive values (PPVs). We employed different case definitions to assess the effect of outcome misclassification on estimation of risk of drug-related UGIB. PPV was 22% [95% confidence interval (CI): 16, 28] and 21% (95% CI: 16, 28) in IPCI for free text and ICPC codes, respectively. PPV was 91% (95% CI: 86, 95) for ICD-9 codes and 47% (95% CI: 35, 59) for free text in HSD. PPV for ICD-9 codes in ARS was 72% (95% CI: 65, 78) and 77% (95% CI: 69, 83) for ICD-10 codes (Aarhus). More specific definitions did not have significant impact on risk estimation of drug-related UGIB, except for wider CIs. ICD-9-CM and ICD-10 disease codes have good PPV in identifying UGIB from EHR; less granular terminology (ICPC) may require additional strategies. Use of more specific UGIB definitions affects precision, but not magnitude, of risk estimates. Copyright © 2014 Elsevier Inc. All rights reserved.

Toward understanding life under subzero conditions: the significance of exploring psychrophilic "cold-shock" proteins.

PubMed

Kuhn, Emanuele

2012-11-01

Understanding the behavior of proteins under freezing conditions is vital for detecting and locating extraterrestrial life in cold environments, such as those found on Mars and the icy moons of Jupiter and Saturn. This review highlights the importance of studying psychrophilic "cold-shock" proteins, a topic that has yet to be explored. A strategy for analyzing the psychrophilic RNA helicase protein CsdA (Psyc_1082) from Psychrobacter arcticus 273-4 as a key protein for life under freezing temperatures is proposed. The experimental model presented here was developed based on previous data from investigations of Escherichia coli, P. arcticus 273-4, and RNA helicases. P. arcticus 273-4 is considered a model for life in freezing environments. It is capable of growing in temperatures as cold as -10°C by using physiological strategies to survive not only in freezing temperatures but also under low-water-activity and limited-nutrient-availability conditions. The analyses of its genome, transcriptome, and proteome revealed specific adaptations that allow it to inhabit freezing environments by adopting a slow metabolic strategy rather than a cellular dormancy state. During growth at subzero temperatures, P. arcticus 273-4 genes related to energy metabolism and carbon substrate incorporation are downregulated, and genes for maintenance of membranes, cell walls, and nucleic acid motion are upregulated. At -6°C, P. arcticus 273-4 does not upregulate the expression of either RNA or protein chaperones; however, it upregulates the expression of its cold-shock induced DEAD-box RNA helicase protein A (CsdA - Psyc_1082). CsdA - Psyc_1082 was investigated as a key helper protein for sustaining life in subzero conditions. Proving CsdA - Psyc_1082 to be functional as a key protein for life under freezing temperatures may extend the known minimum growth temperature of a mesophilic cell and provide key information about the mechanisms that underlie cold-induced biological systems in icy worlds.

Lymphadenitis associated with cat-scratch disease simulating a neoplasm: Imaging findings with histopathological associations.

PubMed

Chen, Ying; Fu, Yan-Biao; Xu, Xiu-Fang; Pan, Yao; Lu, Chen-Ying; Zhu, Xiu-Liang; Li, Qing-Hai; Yu, Ri-Sheng

2018-01-01

The lymphadenitis associated with cat-scratch disease (CSD) is often confused with neoplasms by a number of radiologists and clinicians, and consequently, unnecessary invasive procedures or surgeries are performed. In the present study, the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) findings of 10 patients (6 men and 4 women) with clinically and pathologically confirmed lymphadenitis associated with CSD were retrospectively analyzed (CT in 3 patients, MRI in 6 patients, and CT and MRI in 1 patient) at The Second Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) between January 2007 and November 2014. As a result, 17 enlarged lymph nodes were identified in 10 cases. The 5 nodes identified by CT scan exhibited relatively inhomogeneous isodensity to muscle, with patchy low density in the center. All 14 nodes identified by MRI scan exhibited homogeneous or heterogeneous isointensity to muscle or slightly increased intensity compared with that of muscle on T1-weighted images (T1WI), and homogeneous or heterogeneous hyperintensity on fat-suppressed T2WI. Following enhancement, all 17 enlarged lymph nodes associated with CSD demonstrated the following 3 different enhancement patterns: Moderate homogeneous enhancement (n=8), which was associated with histologically identified early disease stage; marked heterogeneous enhancement with no enhancement of the necrotic areas (n=4), and heterogeneous enhancement with progressively 'spoke-wheel-like' (defined as radiating enhancement from the center) enhancement of the patchy low-density area (n=1), which was associated with histologically identified intermediate disease stage; and astral low-density/hypointensity with marked enhancement (n=2) or a 'rose flower' sign (n=2), which was associated with histologically identified late disease stage. We hypothesized that the CT and MRI results of lymphadenitis in CSD may be associated with the pathological features. It may be suggested that the diagnosis of CSD may be formed when considering the characteristic CT and MRI features of astral low-density/hypointensity with marked enhancement or a 'rose flower' sign (defined as marginal petaloid enhancement) in the late disease stage, or the MRI results of homogeneous, moderate enhancement in the early disease stage, or the CT/MRI data of heterogeneous enhancement with non-enhancing area in the center in the intermediate disease stage, in solitary or multiple enlarged lymph nodes associated with general subcutaneous edema in the vicinity of the nodes on CT/MRI and with a history of cat exposure.

Vaginal Repair of Cesarean Section Scar Diverticula that Resulted in Improved Postoperative Menstruation.

PubMed

Zhou, Jieru; Yao, Min; Wang, Husheng; Tan, Weilin; Chen, Pin; Wang, Xipeng

2016-01-01

Owing to the increase in cesarean sections (C-sections) worldwide, long-term complications such as postmenstrual spotting, chronic pelvic pain, and C-section scar ectopic pregnancies have created a new medical era of gynecologic disease. A new type of vaginal repair is evaluated to repair C-section diverticulum (CSD) and rebuild the muscular layer to improve symptoms of abnormal uterine bleeding and decrease the risk of uterine rupture. Retrospective cohort study (Canadian Task Force classification II-2). University hospital. A total of 121 patients with CSD diagnoses by transvaginal ultrasound (TVU) presented with postmenstrual spotting between June 2012 and March 2015. All patients had undergone at least 1 C-section delivery and had no history of postmenstrual spotting before undergoing C-section. Vaginal excision and suture of CSD. The mean duration of menstruation was 14.87 ± 3.46 days preoperatively and decreased to 8.22 ± 2.73 days at 1 month after surgery, 8.89 ± 2.67 days at 3 months after surgery, and 9.02 ± 2.47 days at 6 months after surgery (p < .01). The length, width, depth, and thickness of the remaining muscular layer (TRM) at 1 month, 3 months, and 6 months assessed by TVU also improved significantly after surgery (p < .05). However, postoperative menstruation and imaging data did not differ markedly between 3 months and 6 months, suggesting that follow-up at 3 months represents an adequate endpoint for evaluating the effectiveness of surgery. At 6 months, 80.3% of patients (94 of 117) reached ≤10 days of menstruation. Further study revealed that a TRM at 6 months of ≥8.5 mm measured by TVU (relative risk [RR], 6.418; 95% confidence interval [CI], 1.478-28.443) and an interval between CS and vaginal repair of ≤2.5 years (RR, 12.0; 95% CI, 1.541- 93.454) were good prognostic factors associated with surgery. Vaginal repair of CSD improved the symptoms of postmenstrual spotting and anatomically corrected the scars. An interval between C-section and a surgery of ≤2.5 years was optimal for vaginal repair, and a TRM at 6 months of ≥8.5 mm represented the standard healing of CSD. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

An assessment of calcite crystal growth mechanisms based on crystal size distributions

USGS Publications Warehouse

Kile, D.E.; Eberl, D.D.; Hoch, A.R.; Reddy, M.M.

2000-01-01

Calcite crystal growth experiments were undertaken to test a recently proposed model that relates crystal growth mechanisms to the shapes of crystal size distributions (CSDs). According to this approach, CSDs for minerals have three basic shapes: (1) asymptotic, which is related to a crystal growth mechanism having constant-rate nucleation accompanied by surface-controlled growth; (2) lognormal, which results from decaying-rate nucleation accompanied by surface-controlled growth; and (3) a theoretical, universal, steady-state curve attributed to Ostwald ripening. In addition, there is a fourth crystal growth mechanism that does not have a specific CSD shape, but which preserves the relative shapes of previously formed CSDs. This mechanism is attributed to supply-controlled growth. All three shapes were produced experimentally in the calcite growth experiments by modifying nucleation conditions and solution concentrations. The asymptotic CSD formed when additional reactants were added stepwise to the surface of solutions that were supersaturated with respect to calcite (initial Ω = 20, where Ω = 1 represents saturation), thereby leading to the continuous nucleation and growth of calcite crystals. Lognormal CSDs resulted when reactants were added continuously below the solution surface, via a submerged tube, to similarly supersaturated solutions (initial Ω = 22 to 41), thereby leading to a single nucleation event followed by surface-controlled growth. The Ostwald CSD resulted when concentrated reactants were rapidly mixed, leading initially to high levels of supersaturation (Ω >100), and to the formation and subsequent dissolution of very small nuclei, thereby yielding CSDs having small crystal size variances. The three CSD shapes likely were produced early in the crystallization process, in the nanometer crystal size range, and preserved during subsequent growth. Preservation of the relative shapes of the CSDs indicates that a supply-controlled growth mechanism was established and maintained during the constant-composition experiments. CSDs having shapes intermediate between lognormal and Ostwald also were generated by varying the initial levels of supersaturation (initial Ω = 28.2 to 69.2) in rapidly mixed solutions. Lognormal CSDs were observed for natural calcite crystals that are found in septarian concretions occurring in southeastern Colorado. Based on the model described above, these CSDs indicate initial growth by surface control, followed by supply-controlled growth. Thus, CSDs may be used to deduce crystal growth mechanisms from which geologic conditions early in the growth history of a mineral can be inferred. Conversely, CSD shape can be predicted during industrial crystallization by applying the appropriate conditions for a particular growth mechanism.

Mineralogy of Iron Microbial Mats from Loihi Seamount

PubMed Central

Toner, Brandy M.; Berquó, Thelma S.; Michel, F. Marc; Sorensen, Jeffry V.; Templeton, Alexis S.; Edwards, Katrina J.

2011-01-01

Extensive mats of Fe oxyhydroxides and associated Fe-oxidizing microbial organisms form in diverse geochemical settings – freshwater seeps to deep-sea vents – where ever opposing Fe(II)-oxygen gradients prevail. The mineralogy, reactivity, and structural transformations of Fe oxyhydroxides precipitated from submarine hydrothermal fluids within microbial mats remains elusive in active and fossil systems. In response, a study of Fe microbial mat formation at the Loihi Seamount was conducted to describe the physical and chemical characteristics of Fe-phases using extended X-ray absorption fine structure spectroscopy, powder X-ray diffraction, synchrotron radiation X-ray total scattering, low-temperature magnetic measurements, and Mössbauer spectroscopy. Particle sizes of 3.5–4.6 nm were estimated from magnetism data, and coherent scattering domain (CSD) sizes as small as 1.6 nm are indicated by pair distribution function (PDF) analysis. Disorder in the nanostructured Fe-bearing phases results in limited intermediate-range structural order: less than that of standard two-line ferrihydrite (Fh), except for the Pohaku site. The short-range ordered natural Fh (FhSRO) phases were stable at 4°C in the presence of oxygen for at least 1 year and during 400°C treatment. The observed stability of the FhSRO is consistent with magnetic observations that point to non-interacting nanoparticles. PDF analyses of total scattering data provide further evidence for FhSRO particles with a poorly ordered silica coating. The presence of coated particles explains the small CSD for the mat minerals, as well as the stability of the minerals over time and against heating. The mineral properties observed here provide a starting point from which progressively older and more extensively altered Fe deposits may be examined, with the ultimate goal of improved interpretation of past biogeochemical conditions and diagenetic processes. PMID:22485113

THF water hydrate crystallization: an experimental investigation

NASA Astrophysics Data System (ADS)

Devarakonda, Surya; Groysman, Alexander; Myerson, Allan S.

1999-08-01

Supersaturated solutions of THF-water hydrate system were experimentally studied before and during crystallization, to examine the system's behavior in the metastable zone and observe any anomalies suggesting cluster formation. Nucleation induction time measurements, with and without additives, were performed to screen potential growth inhibitors. Shifts in the onset points of crystallization for water and THF-water mixtures with additives were measured using differential scanning calorimetry (DSC). Aspartame was among one of the few successfully screened inhibitors. Preliminary on-line crystal size distribution (CSD) measurements were performed on this system to monitor the crystal size during crystallization. The CSD data was also used to compute the hydrate crystal growth rates, which were found to be in the order of 145 μm/h.

Chemical structure and dynamics: Annual report 1996

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

Colson, S.D.; McDowell, R.S.

1997-03-01

The Chemical Structure and Dynamics (CS&D) program is a major component of the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) developed by Pacific Northwest National Laboratory (PNNL) to provide a state-of-the-art collaborative facility for studies of chemical structure and dynamics. We respond to the need for a fundamental, molecular-level understanding of chemistry at a wide variety of environmentally important interfaces by (1) extending the experimental characterization and theoretical description of chemical reactions to encompass the effects of condensed media and interfaces; (2) developing a multidisciplinary capability for describing interfacial chemical processes within which the new knowledge generated can bemore » brought to bear on complex phenomena in environmental chemistry and in nuclear waste processing and storage; and (3) developing state-of-the-art analytical methods for characterizing waste tanks and pollutant distributions, and for detecting and monitoring trace atmospheric species.« less

Chemicals and Structural Foams to Neutralize or Defeat Anti-Personnel Mines

DTIC Science & Technology

1990-10-01

first-level goals in LD. This shows the basic approach used for this analysis. I OVERALL GOALi Select Best Foam System II Best Foam Product Best Delivery...pouring back and forth three times would have three steps for that part of the process, plus any other motions, such as pulling off the lid, and...i B-II I I I I I I :’½ j> I I I I 3 Typical Tilt-Rod AP Mine I I I I I I Typical Pull Firing Pin Device H I I I I I I I iPrsu -SniiePatcCsdMn I i

An Assessment of the State-of-the-art in Multidisciplinary Aeromechanical Analyses

NASA Technical Reports Server (NTRS)

Datta, Anubhav; Johnson, Wayne

2008-01-01

This paper presents a survey of the current state-of-the-art in multidisciplinary aeromechanical analyses which integrate advanced Computational Structural Dynamics (CSD) and Computational Fluid Dynamics (CFD) methods. The application areas to be surveyed include fixed wing aircraft, turbomachinery, and rotary wing aircraft. The objective of the authors in the present paper, together with a companion paper on requirements, is to lay out a path for a High Performance Computing (HPC) based next generation comprehensive rotorcraft analysis. From this survey of the key technologies in other application areas it is possible to identify the critical technology gaps that stem from unique rotorcraft requirements.

Carotid Intima-Media Thickness Is Increased In Patients With Treated Mucopolysaccharidoses Types I and II, And Correlates With Arterial Stiffness

PubMed Central

Wang, Raymond Y.; Braunlin, Elizabeth A.; Rudser, Kyle D.; Dengel, Donald R.; Metzig, Andrea M.; Covault, Kelly K.; Polgreen, Lynda E.; Shapiro, Elsa; Steinberger, Julia; Kelly, Aaron S.

2013-01-01

Background Treatments for mucopolysaccharidoses (MPS) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives To determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery compliance (cCSC), distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56 ± 0.05 mm) compared to controls (0.44 ± 0.04 mm; adjusted p < 0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14 ± 0.09 mm2/mmHg versus 0.16 ± 0.05 mm2/mmHg; adjusted p = 0.019), and higher cIEM (1362 ± 877 mmHg versus 942 ± 396 mmHg; adjusted p < 0.001). cCSD in MPS patients was lower than control (29.7 ± 16.4% versus 32.0 ± 8.2%) but was not statistically; p = 0.12. Among MPS patients, cCSD showed a significant association with cIMT (p = 0.047), while the association between cIEM and cIMT approached significance (p = 0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients. PMID:24268528

Generator localization by current source density (CSD): Implications of volume conduction and field closure at intracranial and scalp resolutions

PubMed Central

Tenke, Craig E.; Kayser, Jürgen

2012-01-01

The topographic ambiguity and reference-dependency that has plagued EEG/ERP research throughout its history are largely attributable to volume conduction, which may be concisely described by a vector form of Ohm’s Law. This biophysical relationship is common to popular algorithms that infer neuronal generators via inverse solutions. It may be further simplified as Poisson’s source equation, which identifies underlying current generators from estimates of the second spatial derivative of the field potential (Laplacian transformation). Intracranial current source density (CSD) studies have dissected the “cortical dipole” into intracortical sources and sinks, corresponding to physiologically-meaningful patterns of neuronal activity at a sublaminar resolution, much of which is locally cancelled (i.e., closed field). By virtue of the macroscopic scale of the scalp-recorded EEG, a surface Laplacian reflects the radial projections of these underlying currents, representing a unique, unambiguous measure of neuronal activity at scalp. Although the surface Laplacian requires minimal assumptions compared to complex, model-sensitive inverses, the resulting waveform topographies faithfully summarize and simplify essential constraints that must be placed on putative generators of a scalp potential topography, even if they arise from deep or partially-closed fields. CSD methods thereby provide a global empirical and biophysical context for generator localization, spanning scales from intracortical to scalp recordings. PMID:22796039

Thin Versus Thick Description: Analyzing Representations of People and Their Life Worlds in the Literature of Communication Sciences and Disorders.

PubMed

Hengst, Julie A; Devanga, Suma; Mosier, Hillary

2015-11-01

Evidence-based practice relies on clinicians to translate research evidence for individual clients. This study, the initial phase of a broader research project, examines the textual resources of such translations by analyzing how people with acquired cognitive-communication disorders (ACCD) and their life worlds have been represented in Communication Sciences and Disorders (CSD) research articles. Using textual analysis, we completed a categorical analysis of 6,059 articles published between 1936 and 2012, coding for genre, population, and any evidence of thick representations of people and their life worlds, and a discourse analysis of representations used in 56 ACCD research articles, identifying thin and thick representations in 4 domains (derived from the International Classification of Functioning, Disability, and Health) and across article sections. The categorical analysis identified a higher percentage of ACCD articles with some evidence of thick representation (30%) compared with all CSD articles (12%) sampled. However, discourse analysis of ACCD research articles found that thick representations were quite limited; 34/56 articles had thin representational profiles, 19/56 had mixed profiles, and 3/56 had thick profiles. These findings document the dominance of thin representations in the CSD literature, which we suggest makes translational work more difficult. How clinicians translate such evidence will be addressed in the next research phase, an interview study of speech-language pathologists.

Role of magnetic resonance imaging and scintigraphy in the diagnosis and follow-up of osteomyelitis in cat-scratch disease.

PubMed

Rozmanic, Vojko; Banac, Srdjan; Miletic, Damir; Manestar, Koraljka; Kamber, Silvija; Paparic, Sime

2007-01-01

Cat-scratch disease (CSD) is a self-limiting infectious disease characterised with lymphadenopathy in a patient with a history of cat contact. Cases of bone involvement in patients with CSD are rare. We reported a case of 11-year-old boy with prolonged intermittent fever, inguinal lymphadenopathy and osteomyelitis. He had a history of exposure to kittens. The physical examination revealed a febrile boy without an apparent site of infection except an enlarged inguinal lymph node. Its histopathology demonstrated granulomatous lesion with no presence of acid-fast bacilli. Serum titers for Bartonella henselae were positive. Multiple bone lesions were detected by skeletal scintigraphy. Magnetic resonance imaging (MRI) confirmed and characterised osteolytic masses. The oral combination of azithromycin and rifampicin were given for 6 weeks with a good clinical response. At follow-up, the boy was without symptoms or signs of the disease. Successive MRI controls showed gradual regression of the bone lesions together with significant decrease of acute-phase reactants. In conclusion, CSD should be considered in the differential diagnosis of osteomyelitis. MRI is more reliable for the characterisation, evaluation of soft-tissue extension and follow-up of the bone lesions than scintigraphy. However, the later method permits an overview of the multiple osseous lesions. Therefore, standard MRI equipment may not exclude bone scintigraphy. Both methods are required until whole-body MRI units become routine.

Flowage differentiation in an andesitic dyke of the Motru Dyke Swarm (Southern Carpathians, Romania) inferred from AMS, CSD and geochemistry

NASA Astrophysics Data System (ADS)

Nkono, Collin; Féménias, Olivier; Diot, Hervé; Berza, Tudor; Demaiffe, Daniel

2006-06-01

Two dykes of different thickness (5.5 m for TJ31 and 23 m for TJ34) from the late Pan-African calc-alkaline Motru Dyke Swarm (S. Carpathians, Romania) have been studied by electron microprobe (mineral chemistry), crystal size distribution (CSD), anisotropy of magnetic susceptibility (AMS) and whole-rock geochemistry. All the physical and chemical variations observed across the dyke's width point to concordant results and show that the variations of both modal abundance and size of the amphibole and biotite microphenocrysts inside the dykes (deduced from the classical CSD measurements) are the result of a mechanical segregation of suspended crystals during magmatic transport. Despite a pene-contemporaneous regional tectonic, the flow-induced differentiation in the thicker dyke is characterized by the concentration of pre-existing Ti-rich pargasite-tschermakite, clinopyroxene and plagioclase crystals in the core of the dyke and of the extracted differentiated liquid near the walls. This mechanical differentiation induces a chemical differentiation with a basaltic andesite composition for the core of the dyke whereas the margins are andesitic. Thus the chilled margins appear as a slightly more evolved liquid with a Newtonian behaviour when compared to the average composition of the dyke. The localization of the liquid on both sides of the dyke has certainly facilitated the ascent of the central part of the dyke that behaved as a Binghamian mush.

Pattern visual evoked potentials in eyes with disc swelling due to cat scratch disease-associated neuroretinitis.

PubMed

Chai, Yuzhu; Yamamoto, Shuichi; Hirayama, Atsuko; Yotsukura, Jiro; Yamazaki, Hiroko

2005-01-01

To evaluate optic nerve function by pattern visual evoked potentials (VEPs) in eyes with optic disc swelling due to neuroretinitis associated with cat scratch disease (CSD). Four eyes of four patients with marked optic disc swelling resembling optic neuritis but diagnosed serologically as CSD received systemic steroid treatment. VEPs elicited by black and white checkerboard stimuli created on a TV monitor were recorded before the treatment. The visual acuity (VA) in the affected eyes was decreased to 20/50 in two eyes and finger counting in two eyes at their initial visits. Ophthalmoscopic examination revealed neuroretinitis characterized by severe optic disc swelling, chorioretinal exudates, and macular edema in all eyes. Anti-Bartonella henselae serum antibody was markedly elevated in all patients confirming the diagnosis of CSD. The P100 of the transient VEPs was only mildly reduced without a delay in the implicit times in three eyes and only slightly delayed in the other eye. The steady-state VEPs were mildly reduced in two eyes and phase-reversed in other two eyes. The VA fully recovered after systemic steroid treatment in all patients. Although all examined patients showed marked swelling of the optic disc and visual decrease, the pattern VEPs were not affected as severely as in idiopathic optic neuritis. However, the degree of change of the pattern VEPs varied among patients.

Implementation of a WAP-based telemedicine system for patient monitoring.

PubMed

Hung, Kevin; Zhang, Yuan-Ting

2003-06-01

Many parties have already demonstrated telemedicine applications that use cellular phones and the Internet. A current trend in telecommunication is the convergence of wireless communication and computer network technologies, and the emergence of wireless application protocol (WAP) devices is an example. Since WAP will also be a common feature found in future mobile communication devices, it is worthwhile to investigate its use in telemedicine. This paper describes the implementation and experiences with a WAP-based telemedicine system for patient-monitoring that has been developed in our laboratory. It utilizes WAP devices as mobile access terminals for general inquiry and patient-monitoring services. Authorized users can browse the patients' general data, monitored blood pressure (BP), and electrocardiogram (ECG) on WAP devices in store-and-forward mode. The applications, written in wireless markup language (WML), WMLScript, and Perl, resided in a content server. A MySQL relational database system was set up to store the BP readings, ECG data, patient records, clinic and hospital information, and doctors' appointments with patients. A wireless ECG subsystem was built for recording ambulatory ECG in an indoor environment and for storing ECG data into the database. For testing, a WAP phone compliant with WAP 1.1 was used at GSM 1800 MHz by circuit-switched data (CSD) to connect to the content server through a WAP gateway, which was provided by a mobile phone service provider in Hong Kong. Data were successfully retrieved from the database and displayed on the WAP phone. The system shows how WAP can be feasible in remote patient-monitoring and patient data retrieval.

Estimated critical conditions for UO{sub 2}F{sub 2}--H{sub 2}O systems in fully water-reflected spherical geometry

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

Jordan, W.C.; Turner, J.C.

1992-12-01

The purpose of this report is to document reference calculations performed using the SCALE-4.0 code system to determine the critical parameters of UO{sub 2}F{sub 2}-H{sub 2}O spheres. The calculations are an extension of those documented in ORNL/CSD/TM-284. Specifically, the data for low-enriched UO{sub 2}F{sub 2}-H{sub 2}O spheres have been extended to highly enriched uranium. These calculations, together with those reported in ORNL/CSD/TM-284, provide a consistent set of critical parameters (k{sub {infinity}}, volume, mass, mass of water) for UO{sub 2}F{sub 2} and water over the full range of enrichment and moderation ratio.

A graphically oriented specification language for automatic code generation. GRASP/Ada: A Graphical Representation of Algorithms, Structure, and Processes for Ada, phase 1

NASA Technical Reports Server (NTRS)

Cross, James H., II; Morrison, Kelly I.; May, Charles H., Jr.; Waddel, Kathryn C.

1989-01-01

The first phase of a three-phase effort to develop a new graphically oriented specification language which will facilitate the reverse engineering of Ada source code into graphical representations (GRs) as well as the automatic generation of Ada source code is described. A simplified view of the three phases of Graphical Representations for Algorithms, Structure, and Processes for Ada (GRASP/Ada) with respect to three basic classes of GRs is presented. Phase 1 concentrated on the derivation of an algorithmic diagram, the control structure diagram (CSD) (CRO88a) from Ada source code or Ada PDL. Phase 2 includes the generation of architectural and system level diagrams such as structure charts and data flow diagrams and should result in a requirements specification for a graphically oriented language able to support automatic code generation. Phase 3 will concentrate on the development of a prototype to demonstrate the feasibility of this new specification language.

Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

PubMed Central

2013-01-01

Background Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. Methods Serial (3–5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine. Results HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD). Conclusions In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy. Trial registration ClinicalTrials.Gov NCT00715481 PMID:23829205

Socioeconomic risk factors for cholera in different transmission settings: An analysis of the data of a cluster randomized trial in Bangladesh.

PubMed

Saha, Amit; Hayen, Andrew; Ali, Mohammad; Rosewell, Alexander; Clemens, John D; Raina MacIntyre, C; Qadri, Firdausi

2017-09-05

Cholera remains a threat globally, and socioeconomic factors play an important role in transmission of the disease. We assessed socioeconomic risk factors for cholera in vaccinated and non-vaccinated communities to understand whether the socioeconomic risk factors differ by transmission patterns for cholera. We used data from a cluster randomized control trial conducted in Dhaka, Bangladesh. There were 90 geographic clusters; 30 in each of the three arms of the study: vaccine (VAC), vaccine plus behavioural change (VBC), and non-intervention. The data were analysed for the three populations: (1) vaccinees in the vaccinated communities (VAC and VBC arms), (2) non-vaccinated individuals in the vaccinated communities and (3) all individuals in the non-vaccinated communities (non-intervention arm). A generalized estimating equation with logit link function was used to evaluate the risk factors for cholera among these different populations adjusting for household level correlation in the data. A total of 528 cholera and 226 cholera with severe dehydration (CSD) in 268,896 persons were observed during the two-year follow-up. For population 1, the cholera risk was not associated with any socioeconomic factors; however CSD was less likely to occur among individuals living in a household having ≤4 members (aOR=0.55, 95% CI=0.32-0.96). Among population 2, younger participants and individuals reporting diarrhoea during registration were more likely to have cholera. Females and individuals reporting diarrhoea during registration were at increased risk of CSD. Among population 3, individuals living in a household without a concrete floor, in an area with high population density, closer to the study hospital, or not treating drinking water were at significantly higher risk for both cholera and CSD. The profile of socioeconomic factors associated with cholera varies by individuals' vaccination status as well as the transmission setting. In a vaccinated community where transmission would be expected to be lower, socioeconomic factors may not increase the risk of the disease. Copyright © 2017. Published by Elsevier Ltd.

Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life.

PubMed

Wampach, Linda; Heintz-Buschart, Anna; Hogan, Angela; Muller, Emilie E L; Narayanasamy, Shaman; Laczny, Cedric C; Hugerth, Luisa W; Bindl, Lutz; Bottu, Jean; Andersson, Anders F; de Beaufort, Carine; Wilmes, Paul

2017-01-01

Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus , and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides . Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.

Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life

PubMed Central

Wampach, Linda; Heintz-Buschart, Anna; Hogan, Angela; Muller, Emilie E. L.; Narayanasamy, Shaman; Laczny, Cedric C.; Hugerth, Luisa W.; Bindl, Lutz; Bottu, Jean; Andersson, Anders F.; de Beaufort, Carine; Wilmes, Paul

2017-01-01

Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract. PMID:28512451

CrystalMoM: a tool for modeling the evolution of Crystals Size Distributions in magmas with the Method of Moments

NASA Astrophysics Data System (ADS)

Colucci, Simone; de'Michieli Vitturi, Mattia; Landi, Patrizia

2016-04-01

It is well known that nucleation and growth of crystals play a fundamental role in controlling magma ascent dynamics and eruptive behavior. Size- and shape-distribution of crystal populations can affect mixture viscosity, causing, potentially, transitions between effusive and explosive eruptions. Furthermore, volcanic samples are usually characterized in terms of Crystal Size Distribution (CSD), which provide a valuable insight into the physical processes that led to the observed distributions. For example, a large average size can be representative of a slow magma ascent, and a bimodal CSD may indicate two events of nucleation, determined by two degassing events within the conduit. The Method of Moments (MoM), well established in the field of chemical engineering, represents a mesoscopic modeling approach that rigorously tracks the polydispersity by considering the evolution in time and space of integral parameters characterizing the distribution, the moments, by solving their transport differential-integral equations. One important advantage of this approach is that the moments of the distribution correspond to quantities that have meaningful physical interpretations and are directly measurable in natural eruptive products, as well as in experimental samples. For example, when the CSD is defined by the number of particles of size D per unit volume of the magmatic mixture, the zeroth moment gives the total number of crystals, the third moment gives the crystal volume fraction in the magmatic mixture and ratios between successive moments provide different ways to evaluate average crystal length. Tracking these quantities, instead of volume fraction only, will allow using, for example, more accurate viscosity models in numerical code for magma ascent. Here we adopted, for the first time, a quadrature based method of moments to track the temporal evolution of CSD in a magmatic mixture and we verified and calibrated the model again experimental data. We also show how the equations and the tool developed can be integrated in a magma ascent numerical model, with application to eruptive events occurred at Stromboli volcano (Italy).

NOAA Stratospheric Ozone Webpage

Science.gov Websites

Stratospheric Ozone Banner Home Data Science NOAA in Action In the Press FAQ NOAA Homepage In the Action In the Press FAQ Earth System Research Laboratory - CSD Homepage Earth System Research Laboratory

A Systems Approach to Scaffold Communication Skills Development

PubMed Central

Er, Nelson L.

2008-01-01

Objectives To implement a communication skills development (CSD) system and evaluate its effectiveness in a clinical communications course. Design Students conducted baseline interviews and wrote SOAP notes, and based on faculty, patient, self- and peer assessments, set goals for improvement of their communication skills. Students participated in various activities to scaffold their learning, several of which took place in a web-based environment to enhance access and function for both students and faculty members. Quantitative and qualitative analyses were performed. Assessment Students' communication skills improved as evidenced by assessment scores. Student and faculty comments offered additional evidence of the effectiveness of standardized patient interviews, learning strategies, and assessment methods. Conclusion The CSD system effectively integrated various types of learning activities and feedback processes. The use of scaffolding strategies appeared to enhance the development of students' communication skills. PMID:18483601

Electrical properties of solution processed highly transparent ZnO TFT with organic gate dielectric

NASA Astrophysics Data System (ADS)

Pandya, Nirav C.; Joshi, Nikhil G.; Trivedi, U. N.; Joshi, U. S.

2013-02-01

All oxide thin film transistors (TFT) with zinc oxide active layer were fabricated by chemical solution deposition (CSD) using aqueous solutions on glass substrate. Thin film transistors (TFTs) with amorphous zinc oxide as channel layers and poly-vinyl alcohol as dielectric layers were fabricated at low temperatures by chemical solution deposition (CSD). Atomic force microscopy (AFM) confirmed nano grain size with fairly smooth surface topography. Very small leakage currents were achieved in the transfer curves, while soft saturation was observed in the output current voltage (I-V) characteristics of the device. Optical transmission of better than 87% in the visible region was estimated, which is better than the organic gate insulator based ZnO TFTs reported so far. Our results offer lot of promise to TFT based display and optoelectronics.

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues.

PubMed

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

PubMed Central

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

Background The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. PMID:28053504

Effusive silicic volcanism in the Paraná Magmatic Province, South Brazil: Physico-chemical conditions of storage and eruption and considerations on the rheological behavior during emplacement

NASA Astrophysics Data System (ADS)

Polo, L. A.; Giordano, D.; Janasi, V. A.; Guimarães, L. F.

2018-04-01

Expressive occurrences of effusive deposits were identified in silicic units from the Paraná Magmatic Province outcropping in a key area in south Brazil where three units with different compositions occur (Caxias do Sul dacites, CSd, Barros Cassal andesites to dacites, BCs, and Santa Maria rhyolites, SMr). Textural and chemical characteristics of phenocrysts, microphenocrysts and microlites suggest that crystallization started in a shallow magma chamber and continued during ascent to the surface. These magmas had an unique character (e.g., very high temperatures 1000 °C and low H2O contents 1-2 wt%), and formed several types of deposits that are clearly indicative of locally fed lava flows and had physical properties consistent with this mode of eruption (e.g., viscosities as low as 104.2 Pa·s at ca. 1000 °C for the CSd). The very low estimated H2O contents are a consequence of their petrogenesis (i.e., fractionation from tholeiitic basalts plus assimilation of crustal melts from water-poor granitic sources), and was probably a key factor influencing the non-explosive nature of these deposits. The comparatively higher viscosity calculated for the Santa Maria rhyolite (> 1-2 orders of magnitude greater than CSd) would make it a better candidate to generate expressive pyroclastic deposits, but this might be offset by its remarkably low H2O contents (≤ 1 wt%) and low discharge ratios.

Signatures of selection among sex-determining alleles of the honey bee.

PubMed

Hasselmann, Martin; Beye, Martin

2004-04-06

Patterns of DNA polymorphisms are a primary tool for dissecting signatures of selection; however, the underlying selective forces are poorly understood for most genes. A classical example of diversifying selection is the complementary sex-determining locus that is found in the very large insect order Hymenoptera (bees, wasps, ants, and sawflies). The gene responsible for sex determination, the complementary sex determiner (csd), has been most recently identified in the honey bee. Females are heterozygous at this locus. Males result when there is only one functional allele present, as a result of either homozygosity (fertilized eggs) or, more commonly, hemizygosity (unfertilized eggs). The homozygotes, diploid males, do not reproduce and have zero fitness, which implies positive selection in favor of rare alleles. Large differences in csd cDNA sequences within and between four populations were found that fall into two major groups, types I and II. Type I consists of several allelic lineages that were maintained over an extended period, an indication of balancing selection. Diversifying selection has operated on several confined parts of the protein, as shown by an excess of nonsynonymous differences. Elevated sequence differences indicate another selected part near a repeat region. These findings have general implications about the understanding of both the function of the multiallelic mechanism and the adaptive processes on the level of nucleotide sequences. Moreover, the first csd sequence data are a notable basis for the avoidance of diploid males in bee selection programs by allele-assisted breeding.

Synaptic activation patterns of the perirhinal-entorhinal inter-connections.

PubMed

de Villers-Sidani, E; Tahvildari, B; Alonso, A

2004-01-01

Ample neuropsychological evidence supports the role of rhinal cortices in memory. The perirhinal cortex (PRC) represents one of the main conduits for the bi-directional flow of information between the entorhinal-hippocampal network and the cortical mantle, a process essential in memory formation. However, despite anatomical evidence for a robust reciprocal connectivity between the perirhinal and entorhinal cortices, neurophysiological understanding of this circuitry is lacking. We now present the results of a series of electrophysiological experiments in rats that demonstrate robust synaptic activation patterns of the perirhinal-entorhinal inter-connections. First, using silicon multi-electrode arrays placed under visual guidance in vivo we performed current source density (CSD) analysis of lateral entorhinal cortex (LEC) responses to PRC stimulation, which demonstrated a current sink in layers II-III of the LEC with a latency consistent with monosynaptic activation. To further substantiate and extend this conclusion, we developed a PRC-LEC slice preparation where CSD analysis also revealed a current sink in superficial LEC layers in response to PRC stimulation. Importantly, intracellular recording of superficial LEC layer neurons confirmed that they receive a major monosynaptic excitatory input from the PRC. Finally, CSD analysis of the LEC to PRC projection in vivo also allowed us to document robust feedback synaptic activation of PRC neurons to deep LEC layer activation. We conclude that a clear bidirectional pattern of synaptic interactions exists between the PRC and LEC that would support a dynamic flow of information subserving memory function in the temporal lobe.

Inverse current source density method in two dimensions: inferring neural activation from multielectrode recordings.

PubMed

Łęski, Szymon; Pettersen, Klas H; Tunstall, Beth; Einevoll, Gaute T; Gigg, John; Wójcik, Daniel K

2011-12-01

The recent development of large multielectrode recording arrays has made it affordable for an increasing number of laboratories to record from multiple brain regions simultaneously. The development of analytical tools for array data, however, lags behind these technological advances in hardware. In this paper, we present a method based on forward modeling for estimating current source density from electrophysiological signals recorded on a two-dimensional grid using multi-electrode rectangular arrays. This new method, which we call two-dimensional inverse Current Source Density (iCSD 2D), is based upon and extends our previous one- and three-dimensional techniques. We test several variants of our method, both on surrogate data generated from a collection of Gaussian sources, and on model data from a population of layer 5 neocortical pyramidal neurons. We also apply the method to experimental data from the rat subiculum. The main advantages of the proposed method are the explicit specification of its assumptions, the possibility to include system-specific information as it becomes available, the ability to estimate CSD at the grid boundaries, and lower reconstruction errors when compared to the traditional approach. These features make iCSD 2D a substantial improvement over the approaches used so far and a powerful new tool for the analysis of multielectrode array data. We also provide a free GUI-based MATLAB toolbox to analyze and visualize our test data as well as user datasets.

EPA's Role in the United Nations Economic and Social Council

EPA Pesticide Factsheets

The United Nations Economic and Social Council (ECOSOC) considers the world’s economic, social, and environmental challenges. ECOSOC is composed of subsidiary bodies, including the recently concluded Commission on Sustainable Development (CSD).

Estimating the safety benefits of context sensitive solutions.

DOT National Transportation Integrated Search

2011-11-01

Context Sensitive Solutions (CSS), also commonly known by the original name Context Sensitive Design : (CSD), is an alternative approach to the conventional transportation-oriented decision-making and design : processes. The CSS approach can be used ...

Three dimensional, numerical analysis of an elasto hydrodynamic lubrication using fluid structure interaction (FSI) approach

NASA Astrophysics Data System (ADS)

Hanoca, P.; Ramakrishna, H. V.

2018-03-01

This work is related to develop a methodology to model and simulate the TEHD using the sequential application of CFD and CSD. The FSI analyses are carried out using ANSYS Workbench. In this analysis steady state, 3D Navier-Stoke equations along with energy equation are solved. Liquid properties are introduced where the viscosity and density are the function of pressure and temperature. The cavitation phenomenon is adopted in the analysis. Numerical analysis has been carried at different speeds and surfaces temperatures. During the analysis, it was found that as speed increases, hydrodynamic pressures will also increases. The pressure profile obtained from the Roelands equation is more sensitive to the temperature as compared to the Barus equation. The stress distributions specify the significant positions in the bearing structure. The developed method is capable of giving latest approaching into the physics of elasto hydrodynamic lubrication.

Initial Aerodynamic and Acoustic Study of an Active Twist Rotor Using a Loosely Coupled CFD/CSD Method

NASA Technical Reports Server (NTRS)

Boyd, David D. Jr.

2009-01-01

Preliminary aerodynamic and performance predictions for an active twist rotor for a HART-II type of configuration are performed using a computational fluid dynamics (CFD) code, OVERFLOW2, and a computational structural dynamics (CSD) code, CAMRAD -II. These codes are loosely coupled to compute a consistent set of aerodynamics and elastic blade motions. Resultant aerodynamic and blade motion data are then used in the Ffowcs-Williams Hawkins solver, PSU-WOPWOP, to compute noise on an observer plane under the rotor. Active twist of the rotor blade is achieved in CAMRAD-II by application of a periodic torsional moment couple (of equal and opposite sign) at the blade root and tip at a specified frequency and amplitude. To provide confidence in these particular active twist predictions for which no measured data is available, the rotor system geometry and computational set up examined here are identical to that used in a previous successful Higher Harmonic Control (HHC) computational study. For a single frequency equal to three times the blade passage frequency (3P), active twist is applied across a range of control phase angles at two different amplitudes. Predicted results indicate that there are control phase angles where the maximum mid-frequency noise level and the 4P non -rotating hub vibrations can be reduced, potentially, both at the same time. However, these calculated reductions are predicted to come with a performance penalty in the form of a reduction in rotor lift-to-drag ratio due to an increase in rotor profile power.

Doped ZrO2 for future lead free piezoelectric devices

NASA Astrophysics Data System (ADS)

Starschich, S.; Böttger, U.

2018-01-01

The ferroelectric and piezoelectric properties of doped ZrO2 prepared by chemical solution deposition (CSD) are investigated. Doping with different elements such as Mg, In, La, and Y leads to a stabilization of the constricted hysteresis. As shown in a previous work, for the constricted hysteresis of ZrO2, the piezoelectric response is significantly larger compared to ZrO2 with a normal hysteresis. The Mg doped ZrO2 shows a strong temperature and cycle stability. For the piezoelectric properties, a magnesium concentration of 7% shows the largest piezoelectric response with a piezoelectric coefficient of >10 pm/V, as well as the best cycle stability. Due to thicker films, which can be realized by the CSD technique, the shown doped ZrO2 films are a promising candidate for energy related applications such as piezoelectric energy harvesting as well as for microelectromechanical systems.

Excitation functions for (d,x) reactions on (133)Cs up to Ed=40MeV.

PubMed

Tárkányi, F; Ditrói, F; Takács, S; Hermanne, A; Baba, M; Ignatyuk, A V

2016-04-01

In the frame of a systematic study of excitation functions of deuteron induced reactions the excitation functions of the (133)Cs(d,x)(133m,133mg,131mg)Ba,(134,)(132)Cs and (12)(9m)Xe nuclear reactions were measured up to 40MeV deuteron energies by using the stacked foil irradiation technique and γ-ray spectroscopy of activated samples. The results were compared with calculations performed with the theoretical nuclear reaction codes ALICE-IPPE-D, EMPIRE II-D and TALYS calculation listed in the TENDL-2014 library. A moderate agreement was obtained. Based on the integral yields deduced from our measured cross sections, production of (131)Cs via the (133)Cs(d,4n)(131)Ba→(131)Cs reaction and (133)Ba via (133)Cs(d,2n) reactions is discussed in comparison with other charged particle production routes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-shivering thermogenesis during prostaglandin E1 fever in rats: role of the cerebral cortex.

PubMed

Monda, M; Amaro, S; De Luca, B

1994-07-18

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E1 (PGE1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc) and oxygen (O2) consumption were monitored during the fever from PGE1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, TIBAT, Tc and O2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE1-induced febrile response.

Quantification of mid and late evoked sinks in laminar current source density profiles of columns in the primary auditory cortex

PubMed Central

Schaefer, Markus K.; Hechavarría, Julio C.; Kössl, Manfred

2015-01-01

Current source density (CSD) analysis assesses spatiotemporal synaptic activations at somatic and/or dendritic levels in the form of depolarizing current sinks. Whereas many studies have focused on the short (<50 ms) latency sinks, associated with thalamocortical projections, sinks with longer latencies have received less attention. Here, we analyzed laminar CSD patterns for the first 600 ms after stimulus onset in the primary auditory cortex of Mongolian gerbils. By applying an algorithm for contour calculation, three distinct mid and four late evoked sinks were identified in layers I, III, Va, VIa, and VIb. Our results further showed that the patterns of intracortical information-flow remained qualitatively similar for low and for high sound pressure level stimuli at the characteristic frequency (CF) as well as for stimuli ± 1 octave from CF. There were, however, differences associated with the strength, vertical extent, onset latency, and duration of the sinks for the four stimulation paradigms used. Stimuli one octave above the most sensitive frequency evoked a new, and quite reliable, sink in layer Va whereas low level stimulation led to the disappearance of the layer VIb sink. These data indicate the presence of input sources specifically activated in response to level and/or frequency parameters. Furthermore, spectral integration above vs. below the CF of neurons is asymmetric as illustrated by CSD profiles. These results are important because synaptic feedback associated with mid and late sinks—beginning at 50 ms post stimulus latency—is likely crucial for response modulation resulting from higher order processes like memory, learning or cognitive control. PMID:26557058

The short legs of great apes: evidence for aggressive behavior in australopiths.

PubMed

Carrier, David R

2007-03-01

Early hominins, australopiths, were similar to most large primates in having relatively short hindlimbs for their body size. The short legs of large primates are thought to represent specialization for vertical climbing and quadrupedal stability on branches. Although this may be true, there are reasons to suspect that the evolution of short legs may also represent specialization for physical aggression. Fighting in apes is a behavior in which short legs are expected to improve performance by lowering the center of mass during bipedal stance and by increasing the leverage through which muscle forces can be applied to the ground. Among anthropoid primates, body size sexual dimorphism (SSD) and canine height sexual dimorphism (CSD) are strongly correlated with levels of male-male competition, allowing SSD and CSD to be used as indices of male-male aggression. Here I show that the evolution of hindlimb length in apes is inversely correlated with the evolution of SSD (R(2)= 0.683, P-value = 0.006) and the evolution of CSD (R(2)= 0.630, P-value = 0.013). In contrast, a significant correlation was not observed for the relationship between the evolution of hindlimb and forelimb lengths. These observations are consistent with the suggestion that selection for fighting performance has maintained relatively short hindlimbs in species of Hominoidea with high levels of male-male competition. Although australopiths were highly derived for striding bipedalism when traveling on the ground, they retained short legs compared to those of Homo for over two million years, approximately 100,000 generations. Their short legs may be indicative of persistent selection for high levels of aggression.

Indicators of environmental contamination by heavy metals in leaves of Taraxacum officinale in two zones of the metropolitan area of Mexico City.

PubMed

Gómez-Arroyo, Sandra; Barba-García, Arisbel; Arenas-Huertero, Francisco; Cortés-Eslava, Josefina; de la Mora, Michel Grutter; García-Martínez, Rocío

2018-02-01

The present study was designed to detect the effect of heavy metals in two zones of the Metropolitan Area of Mexico City (MAMC), the Centro de Ciencias de la Atmósfera (CCA), and the Altzomoni station in the Iztaccíhuatl-Popocatépetl National Park. Taraxacum officinale was selected as the indicator organism of responses to atmospheric contamination by heavy metals. Determinations of heavy metals were performed, and total mRNA was extracted to quantify the expression of microRNA398 (miR398), superoxide dismutase 2 (CSD2), and the amounts of free radicals using the bromide of 3-(4,5-dimethylthiazole-2-ilo)-2,5-diphenyltetrazole (MTT) salts reduction assay. Results from the Altzomoni station showed high concentrations of five heavy metals, especially Aluminum, while three heavy metals were identified in the CCA-UNAM zone, most importantly, Vanadium, both in the dry season; miR398 expression presented subtle changes but was greater in the leaves from the stations with higher concentrations of heavy metals. Observations included a significant expression of CSD2, mainly in the dry season in both study zones, where levels were significant with respect to controls (p < 0.05). Reduced MTT was also higher in the dry season than in the rainy season (p < 0.05). In conclusion, the increase in heavy metals on the leaves of Taraxacum officinale induces increased expression of the CSD2 gene and reduced MTT; thus, they can be used as indicators for biomonitoring heavy metal concentrations.

Stress modulation of the memory retrograde-enhancing effects of the awakening drug modafinil in mice.

PubMed

Béracochéa, Daniel; Liscia, Pierrette; Tronche, Christophe; Chauveau, Frédéric; Jouanin, Jean-Claude; Piérard, Christophe

2008-01-01

This study investigated the dose-effect relationship of modafinil administration on contextual memory processes, in parallel with the measurements of plasma corticosterone levels in acutely stressed mice. Memory was first evaluated in normal (nonstressed) mice either in contextual (CSD) or spatial (SSD) tasks. Thus, C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board. The discriminations occurred on either distinct (CSD) or identical (SSD) floors (internal contextual cues). All mice received a vehicle intraperitoneal injection before learning and were injected 24 h later (20 min before the test session) either with vehicle or modafinil. Results showed that modafinil-treated mice behaved similarly as vehicles in the spatial SSD task, whereas in contrast, memory of the first-learned discrimination (D1) in the CSD task was enhanced by a 32- but not a 16-mg/kg modafinil dose. Hence, we studied the effect of a pretest acute stress (electric footshocks) specifically on D1 performance in modafinil-treated subjects. Immediately after behavioral testing, blood was sampled to measure plasma corticosterone levels. Results showed that: (1) stress significantly improved performance in vehicles, (2) stress decreased the efficiency threshold of modafinil, as performance was enhanced at the low dose (16 mg/kg), whereas this enhancement was obtained for the high dose (32 mg/kg) under nonstress conditions, (3) the performance was impaired at the high (32 mg/kg) dose, and (4) modafinil significantly reduced the magnitude of the stress-induced corticosterone secretion, mainly at the dose of 32 mg/kg.

Comparison of 3 airway access techniques during suspected spine injury management in American football.

PubMed

Toler, Julianne D; Petschauer, Meredith A; Mihalik, Jason P; Oyama, Sakiko; Halverson, S Doug; Guskiewicz, Kevin M

2010-03-01

To determine how head movement and time to access airway were affected by 3 emergency airway access techniques used in American football. Prospective counterbalanced design. University research laboratory. Eighteen certified athletic trainers (ATCs) and 18 noncertified students (NCSs). Each participant performed 1 trial of each of the 3 after airway access techniques: quick release mechanism (QRM), cordless screwdriver (CSD), and pocket mask insertion (PMI). Time to task completion in seconds, head movement in each plane (sagittal, frontal, and transverse), maximum head movement in each plane, helmet movement in each plane, and maximum helmet movement in each plane. We observed a significant difference between all 3 techniques with respect to time required to achieve airway access (F(2,68) = 263.88; P < 0.001). The PMI allowed for the quickest access followed by the QRM and CSD techniques, respectively. The PMI technique also resulted in significantly less head movement (F(2,68) = 9.06; P = 0.001) and less maximum head movement (F(2,68) = 13.84; P < 0.001) in the frontal plane compared with the QRM and CSD techniques. The PMI technique should be used to gain rapid airway access when managing a football athlete experiencing respiratory arrest in the presence of a suspected cervical spine injury. In the event the athlete does not present with respiratory arrest, the facemask may be removed carefully with a pocket mask ready. Medical professionals must be familiar with differences in equipment and the effects these may have on the management of the spine-injured athlete.

Ambient temperature enhanced freezing tolerance of Chrysanthemum dichrum CdICE1 Arabidopsis via miR398.

PubMed

Chen, Yu; Jiang, Jiafu; Song, Aiping; Chen, Sumei; Shan, Hong; Luo, Huolin; Gu, Chunsun; Sun, Jing; Zhu, Lu; Fang, Weimin; Chen, Fadi

2013-12-19

ICE (Inducer of CBF Expression) family genes play an important role in the regulation of cold tolerance pathways. In an earlier study, we isolated the gene CdICE1 from Chrysanthemum dichrum and demonstrated that freezing tolerance was enhanced by CdICE1 overexpression. Therefore, we sought to determine the mechanism by which ICE1 family genes participate in freezing tolerance. Using EMSA (Electrophoretic Mobility Shift Assay) and yeast one-hybrid assays, we confirmed that CdICE1 binds specifically to the MYC element in the CdDREBa promoter and activates transcription. In addition, overexpression of CdICE1 enhanced Arabidopsis freezing tolerance after transition from 23°C to 4°C or 16°C. We found that after acclimation to 4°C, CdICE1, like Arabidopsis AtICE1, promoted expression of CBFs (CRT/DRE Binding Factor) and their genes downstream involved in freezing tolerance, including COR15a (Cold-Regulated 15a), COR6.6, and RD29a (Responsive to Dessication 29a). Interestingly, we observed that CdICE1-overexpressing plants experienced significant reduction in miR398. In addition, its target genes CSD1 (Copper/zinc Superoxide Dismutase 1) and CSD2 showed inducible expression under acclimation at 16°C, indicating that the miR398-CSD pathway was involved in the induction of freezing tolerance. Our data indicate that CdICE1-mediated freezing tolerance occurs via different pathways, involving either CBF or miR398, under acclimation at two different temperatures.

Ambient temperature enhanced freezing tolerance of Chrysanthemum dichrum CdICE1 Arabidopsis via miR398

PubMed Central

2013-01-01

Background ICE (Inducer of CBF Expression) family genes play an important role in the regulation of cold tolerance pathways. In an earlier study, we isolated the gene CdICE1 from Chrysanthemum dichrum and demonstrated that freezing tolerance was enhanced by CdICE1 overexpression. Therefore, we sought to determine the mechanism by which ICE1 family genes participate in freezing tolerance. Results Using EMSA (Electrophoretic Mobility Shift Assay) and yeast one-hybrid assays, we confirmed that CdICE1 binds specifically to the MYC element in the CdDREBa promoter and activates transcription. In addition, overexpression of CdICE1 enhanced Arabidopsis freezing tolerance after transition from 23°C to 4°C or 16°C. We found that after acclimation to 4°C, CdICE1, like Arabidopsis AtICE1, promoted expression of CBFs (CRT/DRE Binding Factor) and their genes downstream involved in freezing tolerance, including COR15a (Cold-Regulated 15a), COR6.6, and RD29a (Responsive to Dessication 29a). Interestingly, we observed that CdICE1-overexpressing plants experienced significant reduction in miR398. In addition, its target genes CSD1 (Copper/zinc Superoxide Dismutase 1) and CSD2 showed inducible expression under acclimation at 16°C, indicating that the miR398-CSD pathway was involved in the induction of freezing tolerance. Conclusions Our data indicate that CdICE1-mediated freezing tolerance occurs via different pathways, involving either CBF or miR398, under acclimation at two different temperatures. PMID:24350981

Infant and toddlers' feeding practices and obesity amongst low-income families in Mexico.

PubMed

Jimenez-Cruz, Arturo; Bacardi-Gascon, Montserrat; Pichardo-Osuna, Alexandra; Mandujano-Trujillo, Zally; Castillo-Ruiz, Octelina

2010-01-01

The aim of this study was to determine the risk factors of childhood obesity among infants and toddlers from low-income families from three cities in Mexico. This is a cross-sectional study of mothers and their infants and toddlers attending a vaccination centre at three primary care clinics in Tijuana, Tuxtla, and Reynosa. Anthropometric measurements of the mothers and children were conducted at the clinic and a questionnaire was administered to the mother. Eight-hundred and ten mothers and their 5 to 24 months old infants participated in the study. Average age for the mothers was 24 (21-28) years, and 57% of them were either overweight or obese. The children's average age was 12.7 (5-24) months. Overall overweight prevalence in this sample was 11% and obesity 8%, these increased with age, from 3% for overweight and 6 % for obesity before 6 months, to 13 and 10% between 12 to 24 months respectively. Thirty-five percent of infants were breastfed>or=6 month and 92% were introduced to other solid foods before 6 months. Introduction of high-fat content snacks (HFS) and carbonated and non-carbonated sweetened (CSD) drinks starts before 6 months and more than sixty percent of the children between 12 to 24 months of age were eating HFS and CSD sweetened drinks at least once a week. Consumption of snacks and CSD sweetened drinks (>or=1 week) was associated with being overweight and obese (crude), OR, 1.82; 95% CI=1.24-2.65 (p=0.002). These results suggest that preventive programs should be initiated during pregnancy and continued.

Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources.

PubMed

Bradley, Allison; Yao, Jun; Dewald, Jules; Richter, Claus-Peter

2016-01-01

Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG). Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized. EEG data were generated by simulating multiple cortical sources (2-4) with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD) algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity) and Recall (percentage of the simulated sources reconstructed) of each of the CSD algorithms were calculated. While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms.

Spatiotemporal variations in CO2 flux in a fringing reef simulated using a novel carbonate system dynamics model

NASA Astrophysics Data System (ADS)

Watanabe, A.; Yamamoto, T.; Nadaoka, K.; Maeda, Y.; Miyajima, T.; Tanaka, Y.; Blanco, A. C.

2013-03-01

A carbonate system dynamics (CSD) model was developed in a fringing reef on the east coast of Ishigaki Island, southwest Japan, by incorporating organic and inorganic carbon fluxes (photosynthesis and calcification), air-sea gas exchanges, and benthic cover of coral and seagrass into a three-dimensional hydrodynamic model. The CSD model could reproduce temporal variations in dissolved inorganic carbon (DIC) and total alkalinity in coral zones, but not in seagrass meadows. The poor reproduction in seagrass meadows can be attributed to significant contributions of submarine groundwater discharge as well as misclassification of remotely sensed megabenthos in this area. In comparison with offshore areas, the reef acted as a CO2 sink during the observation period when it was averaged over 24 h. The CSD model also indicated large spatiotemporal differences in the carbon dioxide (CO2) sink/source, possibly related to hydrodynamic features such as effective offshore seawater exchange and neap/spring tidal variation. This suggests that the data obtained from a single point observation may lead to misinterpretation of the overall trend and thus should be carefully considered. The model analysis also showed that the advective flux of DIC from neighboring grids is several times greater than local biological flux of DIC and is three orders of magnitude greater than the air-sea gas flux at the coral zone. Sensitivity tests in which coral or seagrass covers were altered revealed that the CO2 sink potential was much more sensitive to changes in coral cover than seagrass cover.

Behavior in the open field predicts the number of KCl-induced cortical spreading depressions in rats.

PubMed

Bogdanov, Volodymyr Borysovych; Bogdanova, Olena Viktorivna; Koulchitsky, Stanislav Vladimirovich; Chauvel, Virginie; Multon, Sylvie; Makarchuk, Mykola Yukhymovych; Brennan, Kevin Christopher; Renshaw, Perry Franklin; Schoenen, Jean

2013-01-01

Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility to CSD and anxiety we used the open field test in male Sprague-Dawley rats chronically treated with the preventive anti-migraine drugs valproate or riboflavin. Animals avoiding the central area of the open field chamber and those with less exploratory activity (i.e. rearing) were considered more anxious. After 4 weeks of treatment CSDs were elicited by application of 1M KCl over the occipital cortex and the number of CSDs occurring over a 2h period was compared to the previously assessed open field behavior. Higher anxiety-like behavior was significantly correlated with a higher frequency of KCl-induced CSDs. In saline-treated animals, fewer rearings were found in animals with more frequent CSDs (R=-1.00). The duration of ambulatory episodes in the open field center correlated negatively with number of CSDs in the valproate group (R=-0.83; p<0.005) and in riboflavin treated group (R=-0.69; p<0.05) as well as total time spent in the open field center in both groups (R=-0.75; p<0.05 and R=-0.58; p<0.1 respectively). These results suggest that anxiety symptoms are associated with susceptibility to CSD and might explain why it can be an aggravating factor in migraine with aura. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources

PubMed Central

Bradley, Allison; Yao, Jun; Dewald, Jules; Richter, Claus-Peter

2016-01-01

Background Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG). Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized. Methods EEG data were generated by simulating multiple cortical sources (2–4) with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD) algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity) and Recall (percentage of the simulated sources reconstructed) of each of the CSD algorithms were calculated. Results While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms. PMID:26809000

Alternative approximation concepts for space frame synthesis

NASA Technical Reports Server (NTRS)

Lust, R. V.; Schmit, L. A.

1985-01-01

A structural synthesis methodology for the minimum mass design of 3-dimensionall frame-truss structures under multiple static loading conditions and subject to limits on displacements, rotations, stresses, local buckling, and element cross-sectional dimensions is presented. A variety of approximation concept options are employed to yield near optimum designs after no more than 10 structural analyses. Available options include: (A) formulation of the nonlinear mathematcal programming problem in either reciprocal section property (RSP) or cross-sectional dimension (CSD) space; (B) two alternative approximate problem structures in each design space; and (C) three distinct assumptions about element end-force variations. Fixed element, design element linking, and temporary constraint deletion features are also included. The solution of each approximate problem, in either its primal or dual form, is obtained using CONMIN, a feasible directions program. The frame-truss synthesis methodology is implemented in the COMPASS computer program and is used to solve a variety of problems. These problems were chosen so that, in addition to exercising the various approximation concepts options, the results could be compared with previously published work.

Direct CFD Predictions of Low Frequency Sounds Generated by Helicopter Main Rotors

NASA Technical Reports Server (NTRS)

Sim, Ben W.; Potsdam, Mark; Conner, Dave; Watts, Michael E.

2010-01-01

This proposed paper will highlight the application of a CSD/CFD methodology currently inuse by the US Army Aerfolightdynamics Directorate (AFDD) to assess the feasibility and fidelity of directly predicting low frequency sounds of helicopter rotors.

Integrated Aeromechanics with Three-Dimensional Solid-Multibody Structures

NASA Technical Reports Server (NTRS)

Datta, Anubhav; Johnson, Wayne

2014-01-01

A full three-dimensional finite element-multibody structural dynamic solver is coupled to a three-dimensional Reynolds-averaged Navier-Stokes solver for the prediction of integrated aeromechanical stresses and strains on a rotor blade in forward flight. The objective is to lay the foundations of all major pieces of an integrated three-dimensional rotor dynamic analysis - from model construction to aeromechanical solution to stress/strain calculation. The primary focus is on the aeromechanical solution. Two types of three-dimensional CFD/CSD interfaces are constructed for this purpose with an emphasis on resolving errors from geometry mis-match so that initial-stage approximate structural geometries can also be effectively analyzed. A three-dimensional structural model is constructed as an approximation to a UH-60A-like fully articulated rotor. The aerodynamic model is identical to the UH-60A rotor. For preliminary validation measurements from a UH-60A high speed flight is used where CFD coupling is essential to capture the advancing side tip transonic effects. The key conclusion is that an integrated aeromechanical analysis is indeed possible with three-dimensional structural dynamics but requires a careful description of its geometry and discretization of its parts.

ONSITE ENGINEERING REPORT FOR SOLIDIFICATION/ STABILIZATION TREATMENT TESTING OF CONTAMINATED SOILS

EPA Science Inventory

The EPA's Office of Solid Waste and Emergency Response (OSWER) is currently developing land disposal restrictions (LDRs) for contaminated soil and debris (CS&D). The Office of Research and Development, through its Risk Reduction Engineering Laboratory (RREL), is providing support...

Synaptic release and extracellular actions of Zn2+ limit propagation of spreading depression and related events in vitro and in vivo

PubMed Central

Aiba, Isamu; Carlson, Andrew P.; Sheline, Christian T.

2012-01-01

Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn2+ is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn2+ accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn2+ concentrations with exogenous ZnCl2 reduced SD propagation rates. Selective chelation of endogenous Zn2+ (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn2+ derived from synaptic vesicles. Thus, in tissues where synaptic Zn2+ release was absent [knockout (KO) of vesicular Zn2+ transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn2+ in these tissues. The role of synaptic Zn2+ was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn2+ can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn2+ on SD may counteract to some extent the neurotoxic effects of intracellular Zn2+ accumulation in acute brain injury models. PMID:22131381

Synaptic release and extracellular actions of Zn2+ limit propagation of spreading depression and related events in vitro and in vivo.

PubMed

Aiba, Isamu; Carlson, Andrew P; Sheline, Christian T; Shuttleworth, C William

2012-02-01

Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn(2+) is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn(2+) accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn(2+) concentrations with exogenous ZnCl(2) reduced SD propagation rates. Selective chelation of endogenous Zn(2+) (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn(2+) derived from synaptic vesicles. Thus, in tissues where synaptic Zn(2+) release was absent [knockout (KO) of vesicular Zn(2+) transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn(2+) in these tissues. The role of synaptic Zn(2+) was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn(2+) can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn(2+) on SD may counteract to some extent the neurotoxic effects of intracellular Zn(2+) accumulation in acute brain injury models.

Cat-scratch disease: ocular manifestations and treatment outcome.

PubMed

Habot-Wilner, Zohar; Trivizki, Omer; Goldstein, Michaella; Kesler, Anat; Shulman, Shiri; Horowitz, Josepha; Amer, Radgonde; David, Ran; Ben-Arie-Weintrob, Yael; Bakshi, Erez; Almog, Yehoshua; Sartani, Gil; Vishnevskia-Dai, Vicktoria; Kramer, Michal; Bar, Asaf; Kehat, Rinat; Ephros, Moshe; Giladi, Michael

2018-03-05

To characterize cat-scratch disease (CSD) ocular manifestations and visual outcome and evaluate the effect of systemic antibiotics and corticosteroids on final visual acuity (VA). Multicentre retrospective cohort study. Medical records of 86 patients with ocular disease (107 eyes) of 3222 patients identified in a national CSD surveillance study were reviewed. Mean age was 35.1 ± 14.2 years. Median follow-up was 20 weeks (range 1-806 weeks). Of 94/107 (88%) eyes with swollen disc, 60 (64%) had neuroretinitis at presentation, 14 (15%) developed neuroretinitis during follow-up, and 20 (21%) were diagnosed with inflammatory disc oedema. Optic nerve head lesion, uveitis, optic neuropathy and retinal vessel occlusion were found in 43 (40%), 38 (36%), 34 (33%) and 8 (7%) eyes, respectively. Good VA (better than 20/40), moderate vision loss (20/40-20/200) and severe vision loss (worse than 20/200) were found in 26/79 (33%), 35/79 (44%) and 18/79 (23%) eyes at baseline and in 63/79 (80%), 11/79 (14%) and 5/79 (6%) eyes at final follow-up, respectively (p < 0.001). Significant VA improvement (defined as improvement of ≥3 Snellen lines at final follow-up compared to baseline) occurred in 12/24 (50%) eyes treated with antibiotics compared with 14/16 (88%) eyes treated with antibiotics and corticosteroids (p = 0.02). Multivariate logistic regression was suggestive of the same association (odds ratio 7.0; 95% CI 1.3-37.7; p = 0.024). Optic nerve head lesion is a common and unique manifestation of ocular CSD. Most patients improved and had final good VA. Combined antibiotics and corticosteroid treatment was associated with a better visual outcome. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators.

PubMed

Brankack, J; Stewart, M; Fox, S E

1993-07-02

Single-electrode depth profiles of the hippocampal EEG were made in urethane-anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC'-CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta-related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated.

Intracortical circuits amplify sound-evoked activity in primary auditory cortex following systemic injection of salicylate in the rat

PubMed Central

Chrostowski, Michael; Salvi, Richard J.; Allman, Brian L.

2012-01-01

A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and possibly hyperacusis in humans and other animals. Salicylate has well-established effects on cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical enhancement of the sound-evoked field potential at the level of the primary auditory cortex (A1). Previous electrophysiologic studies have begun to characterize changes in thalamorecipient layers of A1; however, A1 is a complex neural circuit with recurrent intracortical connections. To describe the effects of acute systemic salicylate treatment on both thalamic and intracortical sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally characterized by a large, short-latency, monosynaptic, thalamically driven sink in granular layers followed by a lower amplitude, longer latency, polysynaptic, intracortically driven sink in supragranular layers. Following systemic administration of salicylate, there was a near doubling of both granular and supragranular sink amplitudes at higher sound levels. The supragranular sink amplitude input/output function changed from becoming asymptotic at approximately 50 dB to sharply nonasymptotic, often dominating the granular sink amplitude at higher sound levels. The supragranular sink also exhibited a significant decrease in peak latency, reflecting an acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit (MU) activity was altered by salicylate; the normally onset/sustained MU response type was transformed into a primarily onset response type in granular and infragranular layers. The results from CSD analysis indicate that salicylate significantly enhances sound-driven response via intracortical circuits. PMID:22496535

Modelling headache and migraine and its pharmacological manipulation

PubMed Central

Erdener, S E; Dalkara, T

2014-01-01

Similarities between laboratory animals and humans in anatomy and physiology of the cephalic nociceptive pathways have allowed scientists to create successful models that have significantly contributed to our understanding of headache. They have also been instrumental in the development of novel anti-migraine drugs different from classical pain killers. Nevertheless, modelling the mechanisms underlying primary headache disorders like migraine has been challenging due to limitations in testing the postulated hypotheses in humans. Recent developments in imaging techniques have begun to fill this translational gap. The unambiguous demonstration of cortical spreading depolarization (CSD) during migraine aura in patients has reawakened interest in studying CSD in animals as a noxious brain event that can activate the trigeminovascular system. CSD-based models, including transgenics and optogenetics, may more realistically simulate pain generation in migraine, which is thought to originate within the brain. The realization that behavioural correlates of headache and migrainous symptoms like photophobia can be assessed quantitatively in laboratory animals, has created an opportunity to directly study the headache in intact animals without the confounding effects of anaesthetics. Headache and migraine-like episodes induced by administration of glyceryltrinitrate and CGRP to humans and parallel behavioural and biological changes observed in rodents create interesting possibilities for translational research. Not unexpectedly, species differences and model-specific observations have also led to controversies as well as disappointments in clinical trials, which, in return, has helped us improve the models and advance our understanding of headache. Here, we review commonly used headache and migraine models with an emphasis on recent developments. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24611635

Hemifield-dependent N1 and event-related theta/delta oscillations: An unbiased comparison of surface Laplacian and common EEG reference choices

PubMed Central

Kayser, Jürgen; Tenke, Craig E.

2015-01-01

Surface Laplacian methodology has been used to reduce the impact of volume conduction and arbitrary choice of EEG recording reference for the analysis of surface potentials. However, the empirical implications of employing these different transformations to the same EEG data remain obscure. This study directly compared the statistical effects of four commonly-used (nose, linked mastoids, average) or recommended (reference electrode standardization technique [REST]) references and their spherical spline current source density (CSD) transformation for a large data set stemming from a well-understood experimental manipulation. ERPs (72 sites) recorded from 130 individuals during a visual half-field paradigm with highly-controlled emotional stimuli were characterized by mid-parietooccipital N1 (125 ms peak latency) and event-related synchronization (ERS) of theta/delta (160 ms), which were most robust over the contralateral hemisphere. All five data transformations were rescaled to the same covariance and submitted to a single temporal or time-frequency PCA (Varimax) to yield simplified estimates of N1 or theta/delta ERS. Unbiased nonparametric permutation tests revealed that these hemifield-dependent asymmetries were by far most focal and prominent for CSD data, despite all transformations showing maximum effects at mid-parietooccipital sites. Employing smaller subsamples (signal-to-noise) or window-based ERP/ERS amplitudes did not affect these comparisons. Furthermore, correlations between N1 and theta/delta ERS at these sites were strongest for CSD and weakest for nose-referenced data. Contrary to the common notion that the spatial high pass filter properties of a surface Laplacian reduce important contributions of neuronal generators to the EEG signal, the present findings demonstrate that instead volume conduction inherent in surface potentials weakens the representation of neuronal activation patterns at scalp that directly reflect regional brain activity. PMID:25562833

Beverage intake and obesity in early childhood: evidence form primary health care clients in Northwest Argentina.

PubMed

Alderete, E; Bejarano, I; Rodríguez, A

2015-12-07

Sugar sweetened beverages (SSB) are thought to play an important role in weight gain. We examined the relationship between the intake of caloric and noncaloric beverages (SSB and water) and the nutritional status of children. In 2014, we randomly selected 16 public health clinics in four cities of Northwest Argentina and conducted a survey among mothers of children 0-6 years of age. Children's beverage intake was ascertained by 24-h dietary recall provided by the mothers. Children's weight and height measures were obtained from clinic's registries. We calculated the body mass index using the International Obesity Task Force standards. The analysis included 562 children 25 months to 6 years of age with normal or above normal nutritional status. Children's beverage consumption was as follows, water 81.8%, carbonated soft drinks (CSD) 49.7%, coffee/tea/cocoa 44.0%, artificial fruit drinks 35.6%, flavored water 17.9%, natural fruit juice 14.5%. In multivariate logistic regression models the likelihood of being obese v. being overweight or having normal weight doubled with an intake of one to five glasses of CSD (OR=2.2) and increased by more than three-fold with an intake of more than five glasses (OR=3.5). Drinking more than five glasses of water decreased the likelihood of being obese by less than half (OR=0.3). The percentage of children drinking more than five glasses of other beverages was low (3.3-0.9%) and regression models did not yield significant results. The study contributed evidence for reducing children's CSD intake and for promoting water consumption, together with the implementation of comprehensive regulatory public health policies.

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

PubMed

Lee, Kang-Gon; Lee, Kang-Sik; Kang, Yu-Jeoung; Hwang, Jong-Hyun; Lee, Se-Hwan; Park, Sang-Hyug; Park, Yongdoo; Cho, Young-Sam; Lee, Bu-Kyu

2018-05-01

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins.

PubMed Central

Li, W W; Hsiung, Y; Wong, V; Galvin, K; Zhou, Y; Shi, Y; Lee, A S

1997-01-01

The highly conserved grp78 core promoter element plays an important role in the induction of grp78 under diverse stress signals. Previous studies have established a functional region in the 3' half of the core (stress-inducible change region [SICR]) which exhibits stress-inducible changes in stressed nuclei. The human transcription factor YY1 is shown to bind the SICR and transactivate the core element under stress conditions. Here we report that expression library screening with the core element has identified two new core binding proteins, YB-1 and dbpA. Both proteins belong to the Y-box family of proteins characterized by an evolutionarily conserved DNA binding motif, the cold shock domain (CSD). In contrast to YY1, which binds only double-stranded SICR, the Y-box/CSD proteins much prefer the lower strand of the SICR. The Y-box proteins can repress the inducibility of the grp78 core element mediated by treatment of cells with A23187, thapsigargin, and tunicamycin. In gel shift assays, YY1 binding to the core element is inhibited by either YB-1 or dbpA. A yeast interaction trap screen using LexA-YY1 as a bait and a HeLa cell cDNA-acid patch fusion library identified YB-1 as a YY1-interacting protein. In cotransfection experiments, the Y-box proteins antagonize the YY1-mediated enhancement of transcription directed by the grp78 core in stressed cells. Thus, the CSD proteins may be part of the stress signal transduction mechanism in the mammalian system. PMID:8972186

Frequent Hemodialysis Schedules Are Associated with Reduced Levels of Dialysis-induced Cardiac Injury (Myocardial Stunning)

PubMed Central

Jefferies, Helen J.; Virk, Bhupinder; Schiller, Brigitte; Moran, John

2011-01-01

Summary Background and objectives Recurrent hemodialysis (HD)-induced ischemic cardiac injury (myocardial stunning) is common and associated with high ultrafiltration (UF) requirements, intradialytic hypotension, long-term loss of systolic function, increased likelihood of cardiovascular events, and death. More frequent HD regimens are associated with lower UF requirements and improved hemodynamic tolerability, improved cardiovascular outcomes, and reduced mortality compared with conventional thrice-weekly HD. This study investigated the hypothesis that modification of UF volume and rate with more frequent HD therapies would abrogate dialysis-induced myocardial stunning. Design, settings, participants, & measurements A cross-sectional study of 46 patients established on hemodialysis >3 months compared four groups receiving the current range of quotidian therapies: conventional thrice-weekly HD (CHD3); more-frequent HD five to six times/week in a center (CSD) and at home (HSD); and home nocturnal HD (HN). Serial echocardiography quantitatively assessed regional systolic function to identify intradialytic left ventricular regional wall motion abnormalities (RWMAs). Cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and inflammatory markers were quantified. Results More frequent HD regimens were associated with lower UF volumes and rates compared with CHD3. Intradialytic fall in systolic BP was reduced in CSD and HSD groups and abolished in HN group. Mean RWMAs per patient reduced with increasing dialysis intensity (CHD3 > CSD > HSD > HN). Home-based groups demonstrated lower high-sensitivity C-reative protein levels, with trends to lower cTnT and NT-proBNP levels in the more frequent groups. Conclusions Frequent HD regimes are associated with less dialysis-induced myocardial stunning compared with conventional HD. This may contribute to improved outcomes associated with frequent HD therapies. PMID:21597028

A single-molecule diode

NASA Astrophysics Data System (ADS)

Elbing, Mark; Ochs, Rolf; Koentopp, Max; Fischer, Matthias; von Hänisch, Carsten; Weigend, Florian; Evers, Ferdinand; Weber, Heiko B.; Mayor, Marcel

2005-06-01

We have designed and synthesized a molecular rod that consists of two weakly coupled electronic π -systems with mutually shifted energy levels. The asymmetry thus implied manifests itself in a current-voltage characteristic with pronounced dependence on the sign of the bias voltage, which makes the molecule a prototype for a molecular diode. The individual molecules were immobilized by sulfur-gold bonds between both electrodes of a mechanically controlled break junction, and their electronic transport properties have been investigated. The results indeed show diode-like current-voltage characteristics. In contrast to that, control experiments with symmetric molecular rods consisting of two identical π -systems did not show significant asymmetries in the transport properties. To investigate the underlying transport mechanism, phenomenological arguments are combined with calculations based on density functional theory. The theoretical analysis suggests that the bias dependence of the polarizability of the molecule feeds back into the current leading to an asymmetric shape of the current-voltage characteristics, similar to the phenomena in a semiconductor diode. Author contributions: F.E., H.B.W., and M.M. designed research; M.E., R.O., M.K., M.F., F.E., H.B.W., and M.M. performed research; M.E., R.O., M.K., M.F., C.v.H., F.W., F.E., H.B.W., and M.M. contributed new reagents/analytic tools; M.E., R.O., M.K., C.v.H., F.E., H.B.W., and M.M. analyzed data; and F.E., H.B.W., and M.M. wrote the paper.This paper was submitted directly (Track II) to the PNAS office.Abbreviations: A, acceptor; D, donor; MCB, mechanically controlled break junction.Data deposition: The atomic coordinates have been deposited in the Cambridge Structural Database, Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, United Kingdom (CSD reference no. 241632).

Influence of Pb and La contents on the lattice configuration of La-substituted Pb(Zr,Ti)O3 films fabricated by CSD method.

PubMed

Shima, Hiromi; Nishida, Ken; Funakubo, Hiroshi; Iijima, Takashi; Katoda, Takashi; Naganuma, Hiroshi; Okamura, Soichiro

2009-04-01

The influence of Pb and La contents on the lattice configuration in La-substituted Pb(Zr0(.65),Ti0(.35))O3 (La- PZT) films was systematically investigated. La-PZT films with various La and Pb contents were fabricated on Pt/Ti/SiO(2)/Si substrates by chemical solution deposition (CSD). In the La- PZT films with a Pb content ratio of 125% relative to a stoichiometric value, La ions were substituted for not only A-site ions but also B-site ions at La contents greater than 3 mol%. La substitution for B-site seems to cause larger reduction of the unit cell size. In addition, we found that in the La-PZT films with a La content of 3 mol%, the Pb content of 116 mol% (120% relative to a stoichiometric value) was optimum from the viewpoint of site occupancy. This indicates that excess Pb prevented the A-site substitution of La ions.

A novel electrochemical biosensor for ultrasensitive and specific detection of DNA based on molecular beacon mediated circular strand displacement and rolling circle amplification.

PubMed

Cheng, Wei; Zhang, Wei; Yan, Yurong; Shen, Bo; Zhu, Dan; Lei, Pinhua; Ding, Shijia

2014-12-15

A novel electrochemical biosensing strategy was developed for ultrasensitive and specific detection of target DNA using a cascade signal amplification based on molecular beacon (MB) mediated circular strand displacement (CSD), rolling circle amplification (RCA), biotin-strepavidin system, and enzymatic amplification. The target DNA hybridized with the loop portion of MB probe immobilized on the gold electrode and triggered the CSD, leading to multiple biotin-tagged DNA duplex. Furthermore, via biotin-streptavidin interaction, the RCA was implemented, producing long massive tandem-repeat DNA sequences for binding numerous biotinylated detection probes. This enabled an ultrasensitive electrochemical readout by further employing the streptavidin-alkaline phosphatase. The proposed biosensor showed very high sensitivity and selectivity with a dynamic response range from 1 fM to 100 pM. The proposed strategy could have the potential for applying in clinical molecular diagnostics and environmental monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

Coupled CFD/CSD Analysis of an Active-Twist Rotor in a Wind Tunnel with Experimental Validation

NASA Technical Reports Server (NTRS)

Massey, Steven J.; Kreshock, Andrew R.; Sekula, Martin K.

2015-01-01

An unsteady Reynolds averaged Navier-Stokes analysis loosely coupled with a comprehensive rotorcraft code is presented for a second-generation active-twist rotor. High fidelity Navier-Stokes results for three configurations: an isolated rotor, a rotor with fuselage, and a rotor with fuselage mounted in a wind tunnel, are compared to lifting-line theory based comprehensive rotorcraft code calculations and wind tunnel data. Results indicate that CFD/CSD predictions of flapwise bending moments are in good agreement with wind tunnel measurements for configurations with a fuselage, and that modeling the wind tunnel environment does not significantly enhance computed results. Actuated rotor results for the rotor with fuselage configuration are also validated for predictions of vibratory blade loads and fixed-system vibratory loads. Varying levels of agreement with wind tunnel measurements are observed for blade vibratory loads, depending on the load component (flap, lag, or torsion) and the harmonic being examined. Predicted trends in fixed-system vibratory loads are in good agreement with wind tunnel measurements.

Draft Tube Baffle (DTB) crystallizers: A study of stationary and dynamically behaving Crystal Size Distributions (CSD)

NASA Astrophysics Data System (ADS)

Deleer, B. G. M.

1981-11-01

Based on population balance, CSD behavior as a function of geometrical and operating variables was studied, using a crystallizer. A potash alum-water system, involving a separation technique which uses surface active agents and an apolar, organic liquid to separate potash alum crystals from mother liquid under the influence of gravity was used to check experimental findings against literature data. Results show action of annular settling spaces is strongly influenced by fluid velocities perpendicular to those directed upwards. The well-mixed volume decreases with increasing crystallizer size until a minimum effective volume is reached. As supersaturation is constant throughout the crystallizer volume under stationary operating conditions, the annular settling space behaves like a growth chamber for crystals in its volume. Swirl in the lower part of the annular volume introduces significant back mixing. Crystals within this space either grow and return to the well-mixed part, or withdraw from the annular volume permanently.

The posterior semantic asymmetry (PSA): An early brain electrical signature of semantic activation from written words.

PubMed

Koppehele-Gossel, Judith; Schnuerch, Robert; Gibbons, Henning

2018-06-06

This study replicates and extends the findings of Koppehele-Gossel, Schnuerch, and Gibbons (2016) of a posterior semantic asymmetry (PSA) in event-related brain potentials (ERPs), which closely tracks the time course and degree of semantic activation from single visual words. This negativity peaked 300 ms after word onset, was derived by subtracting right- from left-side activity, and was larger in a semantic task compared to two non-semantic control tasks. The validity of the PSA in reflecting the effort to activate word meaning was again attested by a negative correlation between the meaning-specific PSA increase and verbal intelligence, even after controlling for nonverbal intelligence. Extending prior work, current source density (CSD) transformation was used. CSD results were consistent with a left temporo-parietal cortical origin of the PSA. Moreover, no PSA was found for pictorial material, suggesting that the component reflects early semantic processing specific to verbal stimuli. Copyright © 2018 Elsevier Inc. All rights reserved.

Elastic instability of the nano-structured state as an intrinsic probe to study the early formation stages of sol gel derived (Pb1-xCax)TiO3 thin films

NASA Astrophysics Data System (ADS)

Bretos, I.; Ricote, J.; Jiménez-Riobóo, R. J.; Pardo, L.; Calzada, M. L.

2007-12-01

A novel method to investigate the early formation stages of polycrystalline (Pb1-xCax)TiO3 (PCT) perovskite films by means of traditional Brillouin and micro-Brillouin spectroscopy (BS, mBS) is described in the present work. The films were prepared by chemical solution deposition (CSD) onto oxidized (100)Si substrates and treated at temperatures between 350 650 °C by rapid thermal processing (RTP). The elastic instability observed by Brillouin spectroscopy at the nano-structured state of the PCT films was used here to determine their crystallization temperatures. Coexistence of different nanocrystalline phases (e.g., pyrochlore, perovskite) in the films could also be detected by this technique. The reliability of these results is demonstrated by complementary information obtained by X-ray diffraction (XRD) and scanning force microscopy (SFM). The effects of the annealing temperature and of the Ca2+ content on the crystallization process of these films are also discussed.

Investigation on the forced response of a radial turbine under aerodynamic excitations

NASA Astrophysics Data System (ADS)

Ma, Chaochen; Huang, Zhi; Qi, Mingxu

2016-04-01

Rotor blades in a radial turbine with nozzle guide vanes typically experience harmonic aerodynamic excitations due to the rotor stator interaction. Dynamic stresses induced by the harmonic excitations can result in high cycle fatigue (HCF) of the blades. A reliable prediction method for forced response issue is essential to avoid the HCF problem. In this work, the forced response mechanisms were investigated based on a fluid structure interaction (FSI) method. Aerodynamic excitations were obtained by three-dimensional unsteady computational fluid dynamics (CFD) simulation with phase shifted periodic boundary conditions. The first two harmonic pressures were determined as the primary components of the excitation and applied to finite element (FE) model to conduct the computational structural dynamics (CSD) simulation. The computed results from the harmonic forced response analysis show good agreement with the predictions of Singh's advanced frequency evaluation (SAFE) diagram. Moreover, the mode superposition method used in FE simulation offers an efficient way to provide quantitative assessments of mode response levels and resonant strength.

Aliasing of the Schumann resonance background signal by sprite-associated Q-bursts

NASA Astrophysics Data System (ADS)

Guha, Anirban; Williams, Earle; Boldi, Robert; Sátori, Gabriella; Nagy, Tamás; Bór, József; Montanyà, Joan; Ortega, Pascal

2017-12-01

The Earth's naturally occurring Schumann resonances (SR) are composed of a quasi-continuous background component and a larger-amplitude, short-duration transient component, otherwise called 'Q-burst' (Ogawa et al., 1967). Sprites in the mesosphere are also known to accompany the energetic positive ground flashes that launch the Q-bursts (Boccippio et al., 1995). Spectra of the background Schumann Resonances (SR) require a natural stabilization period of ∼10-12 min for the three conspicuous modal parameters to be derived from Lorentzian fitting. Before the spectra are computed and the fitting process is initiated, the raw time series data need to be properly filtered for local cultural noise, narrow band interference as well as for large transients in the form of global Q-bursts. Mushtak and Williams (2009) describe an effective technique called Isolated Lorentzian (I-LOR), in which, the contributions from local cultural and various other noises are minimized to a great extent. An automated technique based on median filtering of time series data has been developed. These special lightning flashes are known to have greater contribution in the ELF range (below 1 kHz) compared to general negative CG strikes (Huang et al., 1999; Cummer et al., 2006). The global distributions of these Q-bursts have been studied by Huang et al. (1999) Rhode Island, USA by wave impedance methods from single station ELF measurements at Rhode Island, USA and from Japan Hobara et al. (2006). The present work aims to demonstrate the effect of Q-bursts on SR background spectra using GPS time-stamped observation of TLEs. It is observed that the Q-bursts selected for the present work do alias the background spectra over a 5-s period, though the amplitudes of these Q-bursts are far below the background threshold of 16 Core Standard Deviation (CSD) so that they do not strongly alias the background spectra of 10-12 min duration. The examination of one exceptional Q-burst shows that appreciable spectral aliasing can occur even when 12-min spectral integrations are considered. The statistical result shows that for a 12-min spectrum, events above 16 CSD are capable of producing significant frequency aliasing of the modal frequencies, although the intensity aliasing might have a negligible effect unless the events are exceptionally large (∼200 CSD). The spectral CSD methodology may be used to extract the time of arrival of the Q-burst transients. This methodology may be combined with a hyperbolic ranging, thus becoming an effective tool to detect TLEs globally with a modest number of networked observational stations.

Surface defects on the Gd{sub 2}Zr{sub 2}O{sub 7} oxide films grown on textured NiW technical substrates by chemical solution method

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

Zhao, Y., E-mail: yuezhao@sjtu.edu.cn

2017-02-15

Epitaxial growth of oxide thin films has attracted much interest because of their broad applications in various fields. In this study, we investigated the microstructure of textured Gd{sub 2}Zr{sub 2}O{sub 7} films grown on (001)〈100〉 orientated NiW alloy substrates by a chemical solution deposition (CSD) method. The aging effect of precursor solution on defect formation was thoroughly investigated. A slight difference was observed between the as-obtained and aged precursor solutions with respect to the phase purity and global texture of films prepared using these solutions. However, the surface morphologies are different, i.e., some regular-shaped regions (mainly hexagonal or dodecagonal) weremore » observed on the film prepared using the as-obtained precursor, whereas the film prepared using the aged precursor exhibits a homogeneous structure. Electron backscatter diffraction and scanning electron microscopy analyses showed that the Gd{sub 2}Zr{sub 2}O{sub 7} grains present within the regular-shaped regions are polycrystalline, whereas those present in the surrounding are epitaxial. Some polycrystalline regions ranging from several micrometers to several tens of micrometers grew across the NiW grain boundaries underneath. To understand this phenomenon, the properties of the precursors and corresponding xerogel were studied by Fourier transform infrared spectroscopy and coupled thermogravimetry/differential thermal analysis. The results showed that both the solutions mainly contain small Gd−Zr−O clusters obtained by the reaction of zirconium acetylacetonate with propionic acid during the precursor synthesis. The regular-shaped regions were probably formed by large Gd−Zr−O frameworks with a metastable structure in the solution with limited aging time. This study demonstrates the importance of the precise control of chemical reaction path to enhance the stability and homogeneity of the precursors of the CSD route. - Highlights: •We investigate microstructure of Gd{sub 2}Zr{sub 2}O{sub 7} films grown by a chemical solution route. •The aging effect of precursor solution on formation of surface defect was thoroughly studied. •Gd−Zr−O clusters are present in the precursor solutions.« less

77 FR 73669 - Response to Comments Received for the “The Menlo Report: Ethical Principles Guiding Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... Technology Research'' (``The Menlo Report'') for the Department of Homeland Security (DHS), Science and Technology, Cyber Security Division (CSD), Protected Repository for the Defense of Infrastructure Against Cyber Threats (PREDICT) Project AGENCY: Science and Technology Directorate, DHS. ACTION: Response...

Developments and Validations of Fully Coupled CFD and Practical Vortex Transport Method for High-Fidelity Wake Modeling in Fixed and Rotary Wing Applications

NASA Technical Reports Server (NTRS)

Anusonti-Inthra, Phuriwat

2010-01-01

A novel Computational Fluid Dynamics (CFD) coupling framework using a conventional Reynolds-Averaged Navier-Stokes (BANS) solver to resolve the near-body flow field and a Particle-based Vorticity Transport Method (PVTM) to predict the evolution of the far field wake is developed, refined, and evaluated for fixed and rotary wing cases. For the rotary wing case, the RANS/PVTM modules are loosely coupled to a Computational Structural Dynamics (CSD) module that provides blade motion and vehicle trim information. The PVTM module is refined by the addition of vortex diffusion, stretching, and reorientation models as well as an efficient memory model. Results from the coupled framework are compared with several experimental data sets (a fixed-wing wind tunnel test and a rotary-wing hover test).

Towards a complete Δ(27) × SO(10) GUT of flavour

NASA Astrophysics Data System (ADS)

Björkeroth, Fredrik

2017-09-01

We propose a renormalisable model based on Δ(27) family symmetry with an SO(10) grand unified theory (GUT) leading to a novel form of spontaneous geometrical CP violation. The symmetries are broken close to the GUT breaking scale to yield the minimal supersymmetric standard model with standard R-parity. Low-scale Yukawa structure is dictated by the coupling of matter to Δ(27) antitriplets \\bar φ whose vacuum expectation values are aligned in the CSD3 directions by the superpotential. Light physical Majorana neutrinos masses emerge from the seesaw mechanism within SO(10). The model predicts a normal neutrino mass hierarchy with the best-fit lightest neutrino mass m 1 ∼ 0.3 meV, CP-violating oscillation phase δl ≈ 280° and the remaining neutrino parameters all within 1σ of their best-fit experimental values.

Numerical simulation and validation of helicopter blade-vortex interaction using coupled CFD/CSD and three levels of aerodynamic modeling

NASA Astrophysics Data System (ADS)

Amiraux, Mathieu

Rotorcraft Blade-Vortex Interaction (BVI) remains one of the most challenging flow phenomenon to simulate numerically. Over the past decade, the HART-II rotor test and its extensive experimental dataset has been a major database for validation of CFD codes. Its strong BVI signature, with high levels of intrusive noise and vibrations, makes it a difficult test for computational methods. The main challenge is to accurately capture and preserve the vortices which interact with the rotor, while predicting correct blade deformations and loading. This doctoral dissertation presents the application of a coupled CFD/CSD methodology to the problem of helicopter BVI and compares three levels of fidelity for aerodynamic modeling: a hybrid lifting-line/free-wake (wake coupling) method, with modified compressible unsteady model; a hybrid URANS/free-wake method; and a URANS-based wake capturing method, using multiple overset meshes to capture the entire flow field. To further increase numerical correlation, three helicopter fuselage models are implemented in the framework. The first is a high resolution 3D GPU panel code; the second is an immersed boundary based method, with 3D elliptic grid adaption; the last one uses a body-fitted, curvilinear fuselage mesh. The main contribution of this work is the implementation and systematic comparison of multiple numerical methods to perform BVI modeling. The trade-offs between solution accuracy and computational cost are highlighted for the different approaches. Various improvements have been made to each code to enhance physical fidelity, while advanced technologies, such as GPU computing, have been employed to increase efficiency. The resulting numerical setup covers all aspects of the simulation creating a truly multi-fidelity and multi-physics framework. Overall, the wake capturing approach showed the best BVI phasing correlation and good blade deflection predictions, with slightly under-predicted aerodynamic loading magnitudes. However, it proved to be much more expensive than the other two methods. Wake coupling with RANS solver had very good loading magnitude predictions, and therefore good acoustic intensities, with acceptable computational cost. The lifting-line based technique often had over-predicted aerodynamic levels, due to the degree of empiricism of the model, but its very short run-times, thanks to GPU technology, makes it a very attractive approach.

Engaging in Critical Social Dialogue with Socially Diverse Undergraduate Teacher Candidates at a California State University

ERIC Educational Resources Information Center

Chavez-Reyes, Christina

2012-01-01

"Critical social dialogue" (CSD) is the process of problem posing, facilitating personal stories through silence and multimodal assignments, and positioning them for students to re-examine and re-evaluate their understanding of systems of social difference, the beginnings of a multicultural and social justice intellectual frame for…

CloudStackProjectsNContributions

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

Nielsen, Roy

2017-07-12

Collection of applications and cloud templates. Project currently based on www.packer.io for automation, www.github.com/boxcutter templates and the www.github.com/csd-dev-tools/ClockworkVMs application for wrapping both of the above for easy creation of virtual systems. Will in future also contain cloud templates tuned for various services, applications and purposes.

An Evidence-Based Practice Model across the Academic and Clinical Settings

ERIC Educational Resources Information Center

Wolter, Julie A.; Corbin-Lewis, Kim; Self, Trisha; Elsweiler, Anne

2011-01-01

This tutorial is designed to provide academic communication sciences and disorders (CSD) programs, at both the undergraduate and graduate levels, with a comprehensive instructional model on evidence-based practice (EBP). The model was designed to help students view EBP as an ongoing process needed in all clinical decision making. The three facets…

Service-oriented Reasoning Architecture for Resource-Task Assignment in Sensor Networks

DTIC Science & Technology

2011-04-01

www.csd.abdn.ac.uk/research/ita/sam/downloads/ontology/ISTAR.owl Sensing Resource Platform Sensors SR4 Nimrod MR2 LDRFCamera, SARCamera, TVCamera SR5 WASP...resources in the theatre. This is because according to the knowledge available to the ISTAR reasoner service, a ‘ Nimrod ’ could perform high altitude

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie.

PubMed

De Risio, Luisa; Lewis, Tom; Freeman, Julia; de Stefani, Alberta; Matiasek, Lara; Blott, Sarah

2011-06-01

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Physically based DC lifetime model for lead zirconate titanate films

NASA Astrophysics Data System (ADS)

Garten, Lauren M.; Hagiwara, Manabu; Ko, Song Won; Trolier-McKinstry, Susan

2017-09-01

Accurate lifetime predictions for Pb(Zr0.52Ti0.48)O3 thin films are critical for a number of applications, but current reliability models are not consistent with the resistance degradation mechanisms in lead zirconate titanate. In this work, the reliability and lifetime of chemical solution deposited (CSD) and sputtered Pb(Zr0.52Ti0.48)O3 thin films are characterized using highly accelerated lifetime testing (HALT) and leakage current-voltage (I-V) measurements. Temperature dependent HALT results and impedance spectroscopy show activation energies of approximately 1.2 eV for the CSD films and 0.6 eV for the sputtered films. The voltage dependent HALT results are consistent with previous reports, but do not clearly indicate what causes device failure. To understand more about the underlying physical mechanisms leading to degradation, the I-V data are fit to known conduction mechanisms, with Schottky emission having the best-fit and realistic extracted material parameters. Using the Schottky emission equation as a base, a unique model is developed to predict the lifetime under highly accelerated testing conditions based on the physical mechanisms of degradation.

A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607).

PubMed

Kalinsky, Kevin; Lee, Sandra; Rubin, Krista M; Lawrence, Donald P; Iafrarte, Anthony J; Borger, Darell R; Margolin, Kim A; Leitao, Mario M; Tarhini, Ahmad A; Koon, Henry B; Pecora, Andrew L; Jaslowski, Anthony J; Cohen, Gary I; Kuzel, Timothy M; Lao, Christopher D; Kirkwood, John M

2017-07-15

KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 L576P . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. Patients received 70 mg of oral dasatinib twice daily. The primary objective for this 2-stage phase 2 trial was response rate. Stage I was open to KIT+ and wild-type KIT (KIT-) mucosal, acral, and CSD melanoma (n = 57). Stage II accrued only KIT+ tumors (n = 30). To enrich the trial for KIT+ tumors, vulvovaginal melanoma was added, and CSD melanoma was removed from eligibility. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. From May 2009 to December 2010, the first stage enrolled 57 patients. Among the evaluable patients, 3 of 51 (5.9%) achieved a partial response: all were KIT-. Stage II closed early because of slow accrual (November 2011 to December 2015). In stage II, 4 of 22 evaluable patients (18.2%) had a partial response; the median duration was 4.2 months. The median PFS was 2.1 months (n = 73; 95% confidence interval [CI], 1.5-2.9 months). The median OS was 7.5 months (95% CI, 6.0-11.9 months). In exploratory analyses, no differences were seen in PFS or OS with the KIT status or subtype. Dasatinib was discontinued because of adverse events in 9 of 75 patients (12%). The dasatinib response rate among KIT+ melanoma patients was low. In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Cancer 2017;123:2688-97. © 2017 American Cancer Society. © 2017 American Cancer Society.

Quantitation Error in 1H MRS Caused by B1 Inhomogeneity and Chemical Shift Displacement.

PubMed

Watanabe, Hidehiro; Takaya, Nobuhiro

2017-11-08

The quantitation accuracy in proton magnetic resonance spectroscopy ( 1 H MRS) improves at higher B 0 field. However, a larger chemical shift displacement (CSD) and stronger B 1 inhomogeneity exist. In this work, we evaluate the quantitation accuracy for the spectra of metabolite mixtures in phantom experiments at 4.7T. We demonstrate a position-dependent error in quantitation and propose a correction method by measuring water signals. All experiments were conducted on a whole-body 4.7T magnetic resonance (MR) system with a quadrature volume coil for transmission and reception. We arranged three bottles filled with metabolite solutions of N-acetyl aspartate (NAA) and creatine (Cr) in a vertical row inside a cylindrical phantom filled with water. Peak areas of three singlets of NAA and Cr were measured on three 1 H spectra at three volume of interests (VOIs) inside three bottles. We also measured a series of water spectra with a shifted carrier frequency and measured a reception sensitivity map. The ratios of NAA and Cr at 3.92 ppm to Cr at 3.01 ppm differed amongst the three VOIs in peak area, which leads to a position-dependent error. The nature of slope depicting the relationship between peak areas and the shifted values of frequency was like that between the reception sensitivities and displacement at every VOI. CSD and inhomogeneity of reception sensitivity cause amplitude modulation along the direction of chemical shift on the spectra, resulting in a quantitation error. This error may be more significant at higher B 0 field where CSD and B 1 inhomogeneity are more severe. This error may also occur in reception using a surface coil having inhomogeneous B 1 . Since this type of error is around a few percent, the data should be analyzed with greater attention while discussing small differences in the studies of 1 H MRS.

Causal effects on child language development: A review of studies in communication sciences and disorders.

PubMed

Rogers, Clare R; Nulty, Karissa L; Betancourt, Mariana Aparicio; DeThorne, Laura S

2015-01-01

We reviewed recent studies published across key journals within the field of communication sciences and disorders (CSD) to survey what causal influences on child language development were being considered. Specifically, we reviewed a total of 2921 abstracts published within the following journals between 2003 and 2013: Language, Speech, and Hearing Services in Schools (LSHSS); American Journal of Speech-Language Pathology (AJSLP); Journal of Speech, Language, and Hearing Research (JSLHR); Journal of Communication Disorders (JCD); and the International Journal of Language and Communication Disorders (IJLCD). Of the 346 eligible articles that addressed causal factors on child language development across the five journals, 11% were categorized as Genetic (37/346), 83% (287/346) were categorized as Environmental, and 6% (22/346) were categorized as Mixed. The bulk of studies addressing environmental influences focused on therapist intervention (154/296=52%), family/caregiver linguistic input (65/296=22%), or family/caregiver qualities (39/296=13%). A more in-depth review of all eligible studies published in 2013 (n=34) revealed that family/caregiver qualities served as the most commonly controlled environmental factor (e.g., SES) and only 3 studies explicitly noted the possibility of gene-environment interplay. This review highlighted the need to expand the research base for the field of CSD to include a broader range of environmental influences on child language development (e.g., diet, toxin exposure, stress) and to consider more directly the complex and dynamic interplay between genetic and environmental effects. Readers will be able to highlight causal factors on child language development that have been studied over the past decade in CSD and recognize additional influences worthy of consideration. In addition, readers will become familiar with basic tenets of developmental systems theory, including the complex interplay between genetic and environmental factors that shapes child development. Copyright © 2015 Elsevier Inc. All rights reserved.

HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes

PubMed Central

Penno, Giuseppe; Solini, Anna; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Laviola, Luigi; Nicolucci, Antonio; Pugliese, Giuseppe

2013-01-01

OBJECTIVE To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS Serial (3–5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications. PMID:23491522

SMOKE: Characterization of Smoke Particulate for Spacecraft Fire Detection

NASA Technical Reports Server (NTRS)

Urban, D. L.; Mulholland, G.; Yuan, Z. G.; Yang, J.; Cleary, T.

2001-01-01

'Smoke' is a flight definition investigation whose purpose is to characterize the smoke particulate from microgravity smoke sources to enable improved design of future space-craft smoke detectors. In the earliest missions (Mercury, Gemini and Apollo), the crew quarters were so cramped that it was considered reasonable that the astronauts would rapidly detect any fire. The Skylab module, however, included approximately 30 UV-sensing fire detectors. The Space Shuttle Orbiter has nine particle-ionization smoke detectors in the mid-deck and flight deck. The detectors for the US segments of the International Space Station (ISS) are laser-diode, forward-scattering, smoke detectors. Current plans for the ISS call for two detectors in the open area of the module, and detectors in racks that have cooling air-flow. Due to the complete absence of microgravity data, all three of these detector systems were designed based upon 1-g test data and experience. As planned mission durations and complexity increase and the volume of spacecraft increases, the need for and importance of effective, crew-independent, fire detection will grow significantly, necessitating more research into microgravity fire phenomena. In 1997 the Comparative Soot Diagnostics Experiment (CSD) flew in the Orbiter Middeck as a Glovebox payload. The CSD experiment was designed to produce small quantities of smoke from several sources to obtain particulate samples and to determine the response of the ISS and Orbiter smoke detectors to these sources. Marked differences in the performance of the detectors compared to their behavior in 1-g were observed. In extreme cases, the detector used in the orbiter was completely blind to easily visible smoke from sources that were readily detected in 1-g. It is hypothesized but as yet unverified that this performance difference was due to enhanced growth of liquid smoke droplets in low-g. These CSD results clearly demonstrate that spacecraft smoke detector design cannot be based on 1-g experience.

miR398 and miR395 are involved in response to SO2 stress in Arabidopsis thaliana.

PubMed

Li, Lihong; Yi, Huilan; Xue, Meizhao; Yi, Min

2017-11-01

Sulfur dioxide (SO 2 ) is a common air pollutant that has adverse effects on plants. MicroRNAs (miRNAs) are small noncoding RNA that play critical roles in plant development and stress response. In this study, we found that two miRNAs, miR398 and miR395, were differentially expressed in Arabidopsis shoots under SO 2 stress. The expression of miR398 was down-regulated, and the transcript levels of its target genes, Cu/Zn superoxide dismutases (CSD1 and CSD2), were increased during SO 2 exposure. The activity of superoxide dismutase (SOD), one of the major antioxidant enzymes, was enhanced with the increase in the CSD transcript level, suggesting an important role of miR398 in response to SO 2 -induced oxidative stress. Meanwhile, the expression of miR395 was increased, and the transcript levels of its target genes, ATP sulfurylases (APS3 and APS4) and a low-affinity sulfate transporter (SULTR2;1), were decreased in Arabidopsis shoots, showing that miR395 played important roles in the regulation of sulfate assimilation and translocation during SO 2 exposure. The content of glutathione (GSH), an important sulfur-containing antioxidant, was enhanced with the changes in sulfur metabolism in Arabidopsis shoots under SO 2 stress. These results showed that both miR398 and miR395 were involved in protecting plants from oxidative damage during SO 2 exposure. Many stress-responsive cis-elements were found in the promoter regions of MIR398 and MIR395, suggesting that these miRNAs might respond to various environmental conditions, including SO 2 stress. Overall, our study provides an insight into the regulatory roles of miRNAs in response to SO 2 stress in plants, and highlights the molecular mechanisms of plant adaptation to environmental stress.

Isotropic non-white matter partial volume effects in constrained spherical deconvolution.

PubMed

Roine, Timo; Jeurissen, Ben; Perrone, Daniele; Aelterman, Jan; Leemans, Alexander; Philips, Wilfried; Sijbers, Jan

2014-01-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DW signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM-GM interface is especially important. We suggest acquiring data with high diffusion-weighting 2500-3000 s/mm(2), reasonable SNR (~30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.

Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition.

PubMed

Claudino, M A; Priviero, F B M; Camargo, E A; Teixeira, C E; De Nucci, G; Antunes, E; Zanesco, A

2007-01-01

The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min. L-NAME treatment (2 and 10 mg/rat/day) started after 4 weeks of prior physical conditioning and lasted 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil and BAY 41-2272. The effect of electrical field stimulation (EFS) on the relaxations responses of CC was evaluated. Run training prevented the arterial hypertension induced by L-NAME treatment (LN-SD: 135+/-2 and 141+/-2 mm Hg for both doses of L-NAME) compared to LN-SD groups (154+/-1 and 175+/-2 mm Hg, for 2 and 10 mg of L-NAME, respectively). Run training produced an increase in the maximal responses (E(max)) of CC for ACh (C-SD: 47+/-3; C-TR: 52+/-1; and LN-TR: 53+/-3%) and SNP (C-SD: 89+/-1; C-TR: 98+/-1; and LN-TR: 95+/-1%). Both potency and E(max) for ACh were reduced in a dose of 10 mg of L-NAME, and run training restored the reduction of E(max) for ACh. No changes were found for BAY 41-2271 and sildenafil. Relaxing responses to EFS was reduced by L-NAME treatment that was restored by prior physical conditioning. In conclusion, our study shows a beneficial effect of prior physical conditioning on the impaired CC relaxing responses in rats made hypertensive by chronic NO blockade.

Investigation of non-corrin cobalt(II)-containing sites in protein structures of the Protein Data Bank.

PubMed

Abriata, Luciano Andres

2013-04-01

Protein X-ray structures with non-corrin cobalt(II)-containing sites, either natural or substituting another native ion, were downloaded from the Protein Data Bank and explored to (i) describe which amino acids are involved in their first ligand shells and (ii) analyze cobalt(II)-donor bond lengths in comparison with previously reported target distances, CSD data and EXAFS data. The set of amino acids involved in Co(II) binding is similar to that observed for catalytic Zn(II) sites, i.e. with a large fraction of carboxylate O atoms from aspartate and glutamate and aromatic N atoms from histidine. The computed Co(II)-donor bond lengths were found to depend strongly on structure resolution, an artifact previously detected for other metal-donor distances. Small corrections are suggested for the target bond lengths to the aromatic N atoms of histidines and the O atoms of water and hydroxide. The available target distance for cysteine (Scys) is confirmed; those for backbone O and other donors remain uncertain and should be handled with caution in refinement and modeling protocols. Finally, a relationship between both Co(II)-O bond lengths in bidentate carboxylates is quantified.

Mechanisms of Lin28-Mediated miRNA and mRNA Regulation—A Structural and Functional Perspective

PubMed Central

Mayr, Florian; Heinemann, Udo

2013-01-01

Lin28 is an essential RNA-binding protein that is ubiquitously expressed in embryonic stem cells. Its physiological function has been linked to the regulation of differentiation, development, and oncogenesis as well as glucose metabolism. Lin28 mediates these pleiotropic functions by inhibiting let-7 miRNA biogenesis and by modulating the translation of target mRNAs. Both activities strongly depend on Lin28’s RNA-binding domains (RBDs), an N-terminal cold-shock domain (CSD) and a C-terminal Zn-knuckle domain (ZKD). Recent biochemical and structural studies revealed the mechanisms of how Lin28 controls let-7 biogenesis. Lin28 binds to the terminal loop of pri- and pre-let-7 miRNA and represses their processing by Drosha and Dicer. Several biochemical and structural studies showed that the specificity of this interaction is mainly mediated by the ZKD with a conserved GGAGA or GGAGA-like motif. Further RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq) studies confirmed this binding motif and uncovered a large number of new mRNA binding sites. Here we review exciting recent progress in our understanding of how Lin28 binds structurally diverse RNAs and fulfills its pleiotropic functions. PMID:23939427

Responsible Conduct of Research in Communication Sciences and Disorders: Faculty and Student Perceptions

ERIC Educational Resources Information Center

Minifie, Fred D.; Robey, Randall R.; Horner, Jennifer; Ingham, Janis C.; Lansing, Charissa; McCartney, James H.; Alldredge, Elham-Eid; Slater, Sarah C.; Moss, Sharon E.

2011-01-01

Purpose: Two Web-based surveys (Surveys I and II) were used to assess perceptions of faculty and students in Communication Sciences and Disorders (CSD) regarding the responsible conduct of research (RCR). Method: Survey questions addressed 9 RCR domains thought important to the responsible conduct of research: (a) human subjects protections; (b)…

Establishing a Pedagogical Framework for the Multicultural Course in Communication Sciences and Disorders

ERIC Educational Resources Information Center

Horton-Ikard, RaMonda; Munoz, Maria L.; Thomas-Tate, Shurita; Keller-Bell, Yolanda

2009-01-01

Purpose: To provide an overview of a model for teaching a foundational course in multicultural (MC) issues and to demonstrate how it can be modified for use in communication sciences and disorders (CSD) by integrating 3 primary dimensions of cultural competence: awareness, knowledge, and skills. Method: This tutorial begins by establishing the…

Chugach School District: A Personalized, Performance-Based System. Insights from the Field. CompetencyWorks Report

ERIC Educational Resources Information Center

Sturgis, Chris

2016-01-01

This paper explores how an Alaskan school district shifted from a traditional K-12 education system to a personalized, performance-based system, embedded in the culture of the community, which led to increased student achievement. Chugach School District (CSD) first implemented competency education over twenty years ago, paving the way in…

UAV Data Exchange Test Bed for At-Sea and Ashore Information Systems

DTIC Science & Technology

2014-12-02

29 3.2 Visualization using NASA World Wind . . . . . . . . . . . . . . . . . . . . . . . . 30 3.3 Visualization using Quantum GIS...Data Server and the Global Positioning Warehouse 37 4.1 Naval Position Repository Installation . . . . . . . . . . . . . . . . . . . . . . . . . 37 4.2...4.4 Data Exchange between CSD and NPR . . . . . . . . . . . . . . . . . . . . . . . . 41 5 Maritime Tactical Command and Control 43 5.1 Global Command

Teaching CSD Graduate Students to Think Critically, Apply Evidence, and Write Professionally

ERIC Educational Resources Information Center

Grillo, Elizabeth U.; Koenig, Mareile A.; Gunter, Cheryl D.; Kim, Sojung

2015-01-01

The purpose of this study was to assess the effectiveness of teaching modules designed to enhance the use of critical thinking (CT), evidence-based practice (EBP), and professional writing (PW) skills by graduate students in communication sciences and disorders. Three single-session teaching modules were developed to highlight key features of CT,…

76 FR 81517 - Submission for Review and Comment: “The Menlo Report: Ethical Principles Guiding Information and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

...'' (``Menlo Report'') for the Department of Homeland Security (DHS), Science and Technology, Cyber Security Division (CSD), Protected Repository for the Defense of Infrastructure Against Cyber Threats (PREDICT... be found at: http://www.cyber.st.dhs.gov/wp-content/uploads/2011/12/MenloPrinciplesCORE-20110915-r560...

Comparative Soot Diagnostics: Preliminary Results

NASA Technical Reports Server (NTRS)

Urban, David L.; Griffin, DeVon W.; Gard, Melissa Y.

1997-01-01

The motivation for the Comparative Soot Diagnostics (CSD) experiment lies in the broad practical importance of understanding combustion generated particulate. Depending upon the circumstances, particulate matter can affect the durability and performance of combustion equipment, can be a pollutant, can be used to detect fires and, in the form of soot, can be the dominant source of radiant energy from flames. The nonbuoyant structure of most flames of practical interest makes understanding of soot processes in low gravity flames important to our ability to predict fire behavior on earth. These studies also have direct applications to fire safety in human-crew spacecraft, since smoke is the indicator used for automated detection in current spacecraft. In the earliest missions (Mercury, Gemini and Apollo), the crew quarters were so cramped that it was considered reasonable that the astronauts would rapidly detect any fire. The Skylab module, however, included approximately 20 UV-sensing fire detectors. The Space Shuttle has 9 particle-ionization smoke detectors in the mid-deck and flight deck and Spacelab has six additional particle-ionization smoke detectors. The designated detectors for the ISS are laser-diode, forward-scattering, smoke or particulate detectors. Current plans for the ISS call for two detectors in the open area of the module, and detectors in racks that have both cooling air flow and electrical power. Due to the complete absence of data concerning the nature of particulate and radiant emission from incipient and fully developed low-g fires, all three of these detector systems were designed based upon l-g test data and experience. As planned mission durations and complexity increase and the volume of spacecraft increases, the need for and importance of effective, crew-independent, fire detection grows significantly. To provide this level of protection, more knowledge is needed concerning low-gravity fire phenomena and, in particular, how they might be detected and suppressed. Prior to CSD, no combustion-generated particulate samples had been collected near the flame zone for well-developed microgravity flames. All of the extant data either came from drop tower tests and therefore only corresponded to the early stages of a fire or were collected far from the flame zone. The fuel sources in the drop tower tests were restricted to laminar gas-jet diffusion flames and very rapidly overheated wire insulation. The gas-jet tests indicated, through thermophoretic sampling, (2) that soot primaries and aggregates (groups of primary particles) in low-gravity may be significantly larger than those in normal gravity (1-g). This raises new scientific questions about soot processes as well as practical issues for particulate size sensitivity and detection alarm threshold levels used in on-orbit smoke detectors. Preliminary tests in the 2.2 second drop tower suggest that particulate generated by overheated wire insulation may be larger in low-g than in 1-g. Transmission Electron Microscope (TEM) grids downstream of the fire region in the Wire Insulation Flammability experiment as well as visual observation of long string-like aggregates, further confirm this suggestion. The combined impact of these limited results and theoretical predictions is that, as opposed to extrapolation from l-g data, direct knowledge of low-g combustion particulate is needed for more confident design of smoke detectors for spacecraft. This paper describes the operation and preliminary results of the CSD, a project conceived and developed at NASA Lewis Research Center. The CSD flight experiment was conducted in the Middeck Glovebox Facility (MGBX) on USMP-3. The project is support by NASA Headquarters Microgravity Science and Applications Division and Code Q. The results presented here are from the microgravity portion of the experiment, including the temporal response of the detectors and average sizes of the primary and aggregate particles captured on the thermophoretic probes.

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

PubMed Central

Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

2016-01-01

Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations. PMID:28101455

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development.

PubMed

Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

2016-12-01

Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

The bright future of unconventional σ/π-hole interactions.

PubMed

Bauzá, Antonio; Mooibroek, Tiddo J; Frontera, Antonio

2015-08-24

Non-covalent interactions play a crucial role in (supramolecular) chemistry and much of biology. Supramolecular forces can indeed determine the structure and function of a host-guest system. Many sensors, for example, rely on reversible bonding with the analyte. Natural machineries also often have a significant non-covalent component (e.g. protein folding, recognition) and rational interference in such 'living' devices can have pharmacological implications. For the rational design/tweaking of supramolecular systems it is helpful to know what supramolecular synthons are available and to understand the forces that make these synthons stick to one another. In this review we focus on σ-hole and π-hole interactions. A σ- or π-hole can be seen as positive electrostatic potential on unpopulated σ* or π(() *()) orbitals, which are thus capable of interacting with some electron dense region. A σ-hole is typically located along the vector of a covalent bond such as XH or XHlg (X=any atom, Hlg=halogen), which are respectively known as hydrogen and halogen bond donors. Only recently it has become clear that σ-holes can also be found along a covalent bond with chalcogen (XCh), pnictogen (XPn) and tetrel (XTr) atoms. Interactions with these synthons are named chalcogen, pnigtogen and tetrel interactions. A π-hole is typically located perpendicular to the molecular framework of diatomic π-systems such as carbonyls, or conjugated π-systems such as hexafluorobenzene. Anion-π and lone-pair-π interactions are examples of named π-hole interactions between conjugated π-systems and anions or lone-pair electrons respectively. While the above nomenclature indicates the distinct chemical identity of the supramolecular synthon acting as Lewis acid, it is worth stressing that the underlying physics is very similar. This implies that interactions that are now not so well-established might turn out to be equally useful as conventional hydrogen and halogen bonds. In summary, we describe the physical nature of σ- and π-hole interactions, present a selection of inquiries that utilise σ- and π-holes, and give an overview of analyses of structural databases (CSD/PDB) that demonstrate how prevalent these interactions already are in solid-state structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Defense of Japan

DTIC Science & Technology

2018-01-03

national elections. The party majority gives Abe the potential to formally amend Article 9 of the Japanese constitution to authorize the Japanese Self ...Pacific. Japanese Constitution; Article 9; The United States and Japan Bi-lateral defense treaty; Collective Self Defense; Pacifism; Japanese Self ...involvement in collective self -defense (CSD). Factors leading up to this decision are a rapidly evolving strategic and political environment in

An Office Automation Needs Assessment Model

DTIC Science & Technology

1985-08-01

TRACKING FORM . . . 74 I. CSD OFFICE SYSTEMS ANALYSIS WORKSHEETS . . . 75 J. AMO EVALUATIONS OF PROPOSED MODEL ...... 113 FOOTNOTES...as to "who should plan for office automated systems," a checklist of attributes should be evaluated , including: experience, expertise, availability of...with experience, differs with respect to breadth of knowledge in numerous areas. In evaluating in-house vs. outside resources, the Hospital Commander

An Exploratory Analysis of the Navy Personnel Support Delivery Model

DTIC Science & Technology

2017-09-01

technology-competent generation. Our efforts are focused on providing a quantitative effort to understanding past trends in Personnel Support Detachment (PSD... quantitative effort to understanding past trends in Personnel Support Detachment (PSD) and Customer Service Desk (CSD) transactions that may aid manpower...56 xiv THIS PAGE INTENTIONALLY LEFT BLANK xv LIST OF TABLES Table 1. Final Dataset Column Names and Descriptions

Culture, Polymerase Chain Reaction and Restriction Fragment Length Polymorphism Studies in Bartonella bacilliformis

DTIC Science & Technology

1998-09-22

within the BA lesions ofHIV-infected patients that appeared similar to the CSD bacillus. ReIman et aI. provided the first infotmation on the genus of the...1993. 31(7): 1730-1734. 21. ReIman DA. Bacillary angiomatosis and Rochalimaea species. Curro CUn. Top. Infect. Dis. pp. 205-219. MElliODS and MATERIALS

On geological interpretations of crystal size distributions: Constant vs. proportionate growth

USGS Publications Warehouse

Eberl, D.D.; Kile, D.E.; Drits, V.A.

2002-01-01

Geological interpretations of crystal size distributions (CSDs) depend on understanding the crystal growth laws that generated the distributions. Most descriptions of crystal growth, including a population-balance modeling equation that is widely used in petrology, assume that crystal growth rates at any particular time are identical for all crystals, and, therefore, independent of crystal size. This type of growth under constant conditions can be modeled by adding a constant length to the diameter of each crystal for each time step. This growth equation is unlikely to be correct for most mineral systems because it neither generates nor maintains the shapes of lognormal CSDs, which are among the most common types of CSDs observed in rocks. In an alternative approach, size-dependent (proportionate) growth is modeled approximately by multiplying the size of each crystal by a factor, an operation that maintains CSD shape and variance, and which is in accord with calcite growth experiments. The latter growth law can be obtained during supply controlled growth using a modified version of the Law of Proportionate Effect (LPE), an equation that simulates the reaction path followed by a CSD shape as mean size increases.

Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice

PubMed Central

Bates, EA; Nikai, T; Brennan, KC; Fu, Y-H; Charles, AC; Basbaum, AI; Ptáček, LJ; Ahn, AH

2016-01-01

The association between the clinical use of nitroglycerin (NTG) and headache has led to the examination of NTG as a model trigger for migraine and related headache disorders, both in humans and laboratory animals. In this study in mice, we hypothesized that NTG could trigger behavioural and physiological responses that resemble a common manifestation of migraine in humans. We report that animals exhibit a dose-dependent and prolonged NTG-induced thermal and mechanical allodynia, starting 30–60 min after intraperitoneal injection of NTG at 5–10 mg/kg. NTG administration also induced Fos expression, an anatomical marker of neuronal activity in neurons of the trigeminal nucleus caudalis and cervical spinal cord dorsal horn, suggesting that enhanced nociceptive processing within the spinal cord contributes to the increased nociceptive behaviour. Moreover, sumatriptan, a drug with relative specificity for migraine, alleviated the NTG-induced allodynia. We also tested whether NTG reduces the threshold for cortical spreading depression (CSD), an event considered to be the physiological substrate of the migraine aura. We found that the threshold of CSD was unaffected by NTG, suggesting that NTG stimulates migraine mechanisms that are independent of the regulation of cortical excitability. PMID:19489890

Sparsity-based image monitoring of crystal size distribution during crystallization

NASA Astrophysics Data System (ADS)

Liu, Tao; Huo, Yan; Ma, Cai Y.; Wang, Xue Z.

2017-07-01

To facilitate monitoring crystal size distribution (CSD) during a crystallization process by using an in-situ imaging system, a sparsity-based image analysis method is proposed for real-time implementation. To cope with image degradation arising from in-situ measurement subject to particle motion, solution turbulence, and uneven illumination background in the crystallizer, sparse representation of a real-time captured crystal image is developed based on using an in-situ image dictionary established in advance, such that the noise components in the captured image can be efficiently removed. Subsequently, the edges of a crystal shape in a captured image are determined in terms of the salience information defined from the denoised crystal images. These edges are used to derive a blur kernel for reconstruction of a denoised image. A non-blind deconvolution algorithm is given for the real-time reconstruction. Consequently, image segmentation can be easily performed for evaluation of CSD. The crystal image dictionary and blur kernels are timely updated in terms of the imaging conditions to improve the restoration efficiency. An experimental study on the cooling crystallization of α-type L-glutamic acid (LGA) is shown to demonstrate the effectiveness and merit of the proposed method.

[New opportunities of magnetic-resonance imaging: an algorithm of CSD-HARDI tractography in reconstruction of the brainstem reticular formation fibers].

PubMed

Aleksandrova, E V; Batalov, A I; Pogosbekyan, E L; Zakharova, N E; Fadeeva, L M; Kravchuk, A D; Pronin, I N; Potapov, A A

2018-01-01

The study purpose was to develop a technique for intravital visualization of the brainstem reticular formation fibers in healthy volunteers using magnetic resonance imaging (MRI). The study included 21 subjects (13 males and 8 females) aged 21 to 62 years. The study was performed on a magnetic resonance imaging scanner with a magnetic field strength of 3 T in T1, T2, T2-FLAIR, DWI, and SWI modes. A CSD-HARDI algorithm was used to identify thin intersecting fibers of the reticular formatio. We developed a technique for reconstructing the reticular formation pathways, tested it in healthy volunteers, and obtained standard quantitative indicators (fractional anisotropy (FA), apparent diffusion coefficient (ACD), fiber length and density, and axial and radial diffusion). We performed a comparative analysis of these indicators in males and females. There was no difference between these groups and between indicators for the right and left brainstem. Our findings will enable comparative analysis of examination results in patients with brain pathology accompanied by brainstem injury, which may help predict the outcome. This work was supported by a grant of the Russian Foundation for Basic Research (#16-04-01472).

Enhancing weak transient signals in SEVIRI false color imagery: Application to dust source detection in southern Africa

NASA Astrophysics Data System (ADS)

Murray, J. E.; Brindley, H. E.; Bryant, R. G.; Russell, J. E.; Jenkins, K. F.; Washington, R.

2016-09-01

A method is described to significantly enhance the signature of dust events using observations from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI). The approach involves the derivation of a composite clear-sky signal for selected channels on an individual time step and pixel basis. These composite signals are subtracted from each observation in the relevant channels to enhance weak transient signals associated with either (a) low levels of dust emission or (b) dust emissions with high salt or low quartz content. Different channel combinations, of the differenced data from the steps above, are then rendered in false color imagery for the purpose of improved identification of dust source locations and activity. We have applied this clear-sky difference (CSD) algorithm over three (globally significant) source regions in southern Africa: the Makgadikgadi Basin, Etosha Pan, and the Namibian and western South African coast. Case study analyses indicate three notable advantages associated with the CSD approach over established image rendering methods: (i) an improved ability to detect dust plumes, (ii) the observation of source activation earlier in the diurnal cycle, and (iii) an improved ability to resolve and pinpoint dust plume source locations.

Comorbidity of internal derangement of the temporomandibular joint and silent dysfunction of the cervical spine.

PubMed

Stiesch-Scholz, M; Fink, M; Tschernitschek, H

2003-04-01

The aim of this evaluation was to examine correlations between internal derangement of the temporomandibular joint (TMJ) and cervical spine disorder (CSD). A prospective controlled clinical study was carried out. Thirty patients with signs and symptoms of internal derangement but without any subjective neck problems and 30 age- and gender-matched control subjects without signs and symptoms of internal derangement were examined. The investigation of the temporomandibular system was carried out using a 'Craniomandibular Index'. Afterwards an examiner-blinded manual medical investigation of the craniocervical system was performed. This included muscle palpation of the cervical spine and shoulder girdle as well as passive movement tests of the cervical spine, to detect restrictions in the range of movement as well as segmental intervertebral dysfunction. The internal derangement of the TMJ was significantly associated with 'silent' CSD (t-test, P < 0.05). Patients with raised muscle tenderness of the temporomandibular system exhibited significantly more often pain on pressure of the neck muscles than patients without muscle tenderness of the temporomandibular system (t-test, P < 0.05). As a result of the present study, for patients with internal derangement of the TMJ an additional examination of the craniocervical system should be recommended.

What Can Crystal Size Distributions and Olivine Compositions Tell Us About Magma Solidification Processes in Kilauea Iki Lava Lake, Hawaii?

NASA Astrophysics Data System (ADS)

Vinet, N.; Higgins, M. D.

2009-12-01

Lava lakes offer the opportunity to investigate magma solidification and can be considered as a proxy for small magma chambers or layered intrusions. Here we present data from Kilauea Iki Lava Lake, which formed during the near-summit 1959 picritic eruption of Kilauea Volcano, Hawaii. Microprobe geochemical analyses and crystal size distributions (CSDs) of olivine were determined from three eruption scoria samples, and 34 drill core samples taken from 1967 to 1988. The data provide valuable information on the dynamics and timescales of the intra-lake solidification processes, along with origin of, and temporal constraints on, the distinct olivine populations. Based on their core and rim forsterite (Fo) content, three distinct olivine populations were distinguished: (1) a high-Fo population (Fo85-88); (2) an intermediate-Fo population (Fo77-81); and (3) a low-Fo population (Fo72-76). Groups 1 and 2 both have deformed and undeformed crystals indicating that they formed partly within Kilauea plumbing system before the eruption. The second group seems to be associated with the ‘vertical olivine-rich bodies’ (VORBs) of Helz (1980). These structures raise magma from the lower part of the lake; hence they may have a contrasting composition maintained from the initial filling of the lake. The third population may be the result of rejuvenation within the lake during its cooling. Although the shape of the olivine CSDs is fairly uniform, we note significant variations that allow the recognition and quantification of multiple solidification processes. Our data display evidence of minor accumulation occurring by settling modified by convection currents. The concave-up curvature of at least half of the CSDs is strong evidence for mixing of magmas or crystal populations. The turndown at smallest sizes of the CSD, particularly present for samples at the edge of the lake, is thought to be the result of coarsening. Our CSD and crystal chemistry data suggest that the early populations and their related magmas underwent several solidification processes at depth, such as minor growth, coarsening, aggregation and deformation, plus settling and mixing maybe, no matter the order of appearance. The CSD analysis also yields estimates of the crystal residence time for different olivine populations, which are not necessarily the same as those defined using the olivine composition. For a growth rate of 10-9 mm/s, the range of residence times is 2-30 years. The CSDs can be segmented into three main groups: (a) a minor 2-4 yr-old population of smaller, rejuvenated crystals; (b) a dominant 10-18 yr-old population of intermediate-sized crystals; and (c) a 20-30 yr-old population of larger, coarsened, and often deformed crystals. Although the focus is here on volcanic rocks, our work gives a new perspective on the solidification of basic magma that can gain valuable insights into the overall understanding of mafic layered intrusions. References: Helz (1980), Bull. Volc. 43 (4): 675-701

Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review.

PubMed

Ciofi-Silva, Caroline Lopes; Hansen, Lisbeth Lima; Almeida, Alda Graciele Claudio Dos Santos; Kawagoe, Julia Yaeko; Padoveze, Maria Clara; Graziano, Kazuko Uchikawa

2016-09-01

to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed. analisar as evidências científicas sobre aerossóis gerados durante atividades de limpeza dos produtos para saúde no Centro de Material e Esterilização (CME) e o impacto da pressão negativa do ar ambiente na área de limpeza para controle da dispersão de aerossóis para áreas adjacentes. para essa revisão sistemática de literatura foram realizadas: busca de diretrizes, manuais ou normas técnicas nacionais e internacionais indicadas por especialistas; busca no portal e bases de dados PUBMED, SCOPUS, Cinahl e Web of Science; e busca manual de artigos científicos. Os cinco documentos técnicos analisados preconizam que na área de limpeza do CME haja diferencial negativo de pressão do ar ambiente, porém não foram encontrados artigos científicos sobre o impacto dessa intervenção. Os quatro artigos incluídos trataram dos aerossóis formados após uso de lavadora ultrassônica (aumento da contaminação principalmente durante o uso) e do jato de água pressurizado (formação de aerossóis menores que 5µm). Em um estudo foram avaliados aerossóis formados a partir de torneira de água quente contaminada com Legionella pneumophila. há evidências sobre formação de aerossóis durante atividades de limpeza em CME. Estudos sobre doenças ocupacionais de origem respiratória dos trabalhadores que atuam em CME devem ser realizados. examinar la evidencia científica sobre los aerosoles generados durante las actividades de limpieza de productos de salud en el Centro de Materiales y Esterilización (CME) y el impacto de la presión negativa del aire ambiente en la zona de limpieza para controlar la dispersión de aerosoles a las zonas adyacentes. para esta revisión sistemática de literatura se llevaron a cabo: búsqueda de directrices, manuales o normas técnicas nacionales e internacionales impartidas por expertos; búsqueda en las bases de datos PUBMED, SCOPUS, Cinahl y Web of Science; y búsqueda manual de artículos científicos. Los cinco documentos técnicos analizados recomiendan que el área de limpieza del CME tenga un diferencial negativo de presión en el aire ambiente, aunque no se han encontrado artículos científicos sobre el impacto de esta intervención. Los cuatro artículos incluidos fueron sobre los aerosoles formados después del uso de la lavadora ultrasónica (aumento de la contaminación, especialmente durante el uso) y chorro de agua a presión (formación de aerosoles menores a 5µm). De esta forma, en un solo estudio se evaluaron los aerosoles formados a partir de un grifo de agua caliente contaminada con Legionella pneumophila. hay evidencia de formación de aerosoles durante las actividades de limpieza en CME. Sin embargo, es necesario realizar estudios sobre las enfermedades profesionales de origen respiratorio de los trabajadores que trabajan en CME.

Regenerative Medicine for Battlefield Injuries

DTIC Science & Technology

2013-10-01

across a critical size defect (CSD) in the fibula, using the axolotl , Abystoma mexicanum as a model system. The scope of the research is to...successful because they initiated the whole cascade of events required for cartilage development. These results indicate that the axolotl fibula can be used...TERMS Regeneration across a critical size defect in axolotl fibula, efficacy of growth factor combinations 16. SECURITY CLASSIFICATION OF: 17

Chemical Propulsion Information Agency Bulletin, Volume 24, No. 2

DTIC Science & Technology

1998-03-01

NASA in 1960 (CTPB), or hydroxyl-terminated polybutadiene ( HTPB ). Repre- and 1961. Subsequently, UT-CSD developed and produced the 5- sentative data...March 1998 Page 5 Polybutadienes Dominate... continued from page 5 Although Aerojet reportedly investigated HTPB propellants in been the Titan IV...Vehicle (EELV) range, HTPBs were viewed as serious contenders for tactical adopting all-liquid propulsion designs, the application of HTPB systems by

Computer Aided Process Planning of Machined Metal Parts

DTIC Science & Technology

1984-09-01

the manufac- turer to accentuate the positive to assist marketing . Machine usage costs and facility loadings are frequently critical. For example...Variant systems currently on the market include Multiplan (TM of OIR, Inc.), CY-Miplan (TM of Computervision), PICAPP (TM of PICAPP, Inc.) and CSD...Multiproduct, Multistage Manufacturing Systems, Journal of Engineering for Industry, ASME, August 1977. Hitomi, K. and I. Ham, Product Mix and Machine Loading

Fluid-structure interaction analysis and lifetime estimation of a natural gas pipeline centrifugal compressor under near-choke and near-surge conditions

NASA Astrophysics Data System (ADS)

Ju, Yaping; Liu, Hui; Yao, Ziyun; Xing, Peng; Zhang, Chuhua

2015-11-01

Up to present, there have been no studies concerning the application of fluid-structure interaction (FSI) analysis to the lifetime estimation of multi-stage centrifugal compressors under dangerous unsteady aerodynamic excitations. In this paper, computational fluid dynamics (CFD) simulations of a three-stage natural gas pipeline centrifugal compressor are performed under near-choke and near-surge conditions, and the unsteady aerodynamic pressure acting on impeller blades are obtained. Then computational structural dynamics (CSD) analysis is conducted through a one-way coupling FSI model to predict alternating stresses in impeller blades. Finally, the compressor lifetime is estimated using the nominal stress approach. The FSI results show that the impellers of latter stages suffer larger fluctuation stresses but smaller mean stresses than those at preceding stages under near-choke and near-surge conditions. The most dangerous position in the compressor is found to be located near the leading edge of the last-stage impeller blade. Compressor lifetime estimation shows that the investigated compressor can run up to 102.7 h under the near-choke condition and 200.2 h under the near-surge condition. This study is expected to provide a scientific guidance for the operation safety of natural gas pipeline centrifugal compressors.

Reward processing deficits and impulsivity in high-risk offspring of alcoholics: A study of event-related potentials during a monetary gambling task.

PubMed

Kamarajan, Chella; Pandey, Ashwini K; Chorlian, David B; Manz, Niklas; Stimus, Arthur T; Bauer, Lance O; Hesselbrock, Victor M; Schuckit, Marc A; Kuperman, Samuel; Kramer, John; Porjesz, Bernice

2015-11-01

Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. The goal of the present study is to elucidate reward processing deficits, externalizing disorders, and impulsivity as elicited by electrophysiological, clinical and behavioral measures in subjects at high risk for alcoholism from families densely affected by alcoholism in the context of brain maturation across age groups and gender. Event-related potentials (ERPs) and current source density (CSD) during a monetary gambling task (MGT) were measured in 12-25 year old offspring (N=1864) of families in the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective study; the high risk (HR, N=1569) subjects were from families densely affected with alcoholism and the low risk (LR, N=295) subjects were from community families. Externalizing disorders and impulsivity scores were also compared between LR and HR groups. HR offspring from older (16-25 years) male and younger (12-15 years) female subgroups showed lower P3 amplitude than LR subjects. The amplitude decrement was most prominent in HR males during the loss condition. Overall, P3 amplitude increase at anterior sites and decrease at posterior areas were seen in older compared to younger subjects, suggesting frontalization during brain maturation. The HR subgroups also exhibited hypofrontality manifested as weaker CSD activity during both loss and gain conditions at frontal regions. Further, the HR subjects had higher impulsivity scores and increased prevalence of externalizing disorders. P3 amplitudes during the gain condition were negatively correlated with impulsivity scores. Older male and younger female HR offspring, compared to their LR counterparts, manifested reward processing deficits as indexed by lower P3 amplitude and weaker CSD activity, along with higher prevalence of externalizing disorders and higher impulsivity scores. Reward related P3 is a valuable measure reflecting neurocognitive dysfunction in subjects at risk for alcoholism, as well as to characterize reward processing and brain maturation across gender and age group. Copyright © 2015 Elsevier B.V. All rights reserved.

XRD measurement of mean crystallite thickness of illite and illite/smectite: Reappraisal of the Kubler index and the Scherrer equation

USGS Publications Warehouse

Drits, Victor A.; Środoń, Jan; Eberl, D.D.

1997-01-01

The standard form of the Scherrer equation, which has been used to calculate the mean thickness of the coherent scattering domain (CSD) of illite crystals from X-ray diffraction (XRD) full width data at half maximum (FWHM) intensity, employs a constant, Ksh, of 0.89. Use of this constant is unjustified, even if swelling has no effect on peak broadening, because this constant is valid only if all CSDs have a single thickness. For different thickness distributions, the Scherrer “constant” has very different values.Analysis of fundamental particle thickness data (transmission electron microscopy, TEM) for samples of authigenic illite and illite/smectite from diagenetically altered pyroclastics and filamentous illites from sandstones reveals a unique family of lognormal thickness distributions for these clays. Experimental relations between the distributions' lognormal parameters and mean thicknesses are established. These relations then are used to calculate the mean thickness of CSDs for illitic samples from XRD FWHM, or from integral XRD peak widths (integrated intensity/maximum intensity).For mixed-layer illite/smectite, the measured thickness of the CSD corresponds to the mean thickness of the mixed-layer crystal. Using this measurement, the mean thickness of the fundamental particles that compose the mixed-layer crystals can be calculated after XRD determination of percent smectitic interlayers. The effect of mixed layering (swelling) on XRD peak width for these samples is eliminated by using the 003 reflection for glycolated samples, and the 001, 002 or 003 reflection for dehydrated, K-saturated samples. If this technique is applied to the 001 reflection of air-dried samples (Kubler index measurement), mean CSD thicknesses are underestimated due to the mixed-layering effect.The technique was calibrated using NEW MOD©-simulated XRD profiles of illite, and then tested on well-characterized illite and illite/smectite samples. The XRD measurements are in good agreement with estimates of the mean thickness of fundamental particles obtained both from TEM measurements and from fixed cations content, up to a mean value of 20 layers. Correction for instrumental broadening under the conditions employed here is unnecessary for this range of thicknesses.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide.

PubMed

Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

2011-07-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

PubMed Central

2011-01-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors. PMID:21722364

Microstructure of calcite deformed by high-pressure torsion: An X-ray line profile study

NASA Astrophysics Data System (ADS)

Schuster, Roman; Schafler, Erhard; Schell, Norbert; Kunz, Martin; Abart, Rainer

2017-11-01

Calcite aggregates were deformed to high strain using high-pressure torsion and applying confining pressures of 1-6 GPa and temperatures between room temperature and 450 °C. The run products were characterized by X-ray diffraction, and key microstructural parameters were extracted employing X-ray line profile analysis. The dominant slip system was determined as r { 10 1 bar 4 } ⟨ 2 bar 021 ⟩ with edge dislocation character. The resulting dislocation density and the size of the coherently scattering domains (CSD) exhibit a systematic dependence on the P-T conditions of deformation. While high pressure generally impedes recovery through reducing point defect mobility, the picture is complicated by pressure-induced phase transformations in the CaCO3 system. Transition from the calcite stability field to those of the high-pressure polymorphs CaCO3-II, CaCO3-III and CaCO3-IIIb leads to a change of the microstructural evolution with deformation. At 450 °C and pressures within the calcite stability field, dislocation densities and CSD sizes saturate at shear strains exceeding 10 in agreement with earlier studies at lower pressures. In the stability field of CaCO3-II, the dislocation density exhibits a more complex behavior. Furthermore, at a given strain and strain rate, the dislocation density increases and the CSD size decreases with increasing pressure within the stability fields of either calcite or of the high-pressure polymorphs. There is, however, a jump from high dislocation densities and small CSDs in the upper pressure region of the calcite stability field to lower dislocation densities and larger CSDs in the low-pressure region of the CaCO3-II stability field. This jump is more pronounced at higher temperatures and less so at room temperature. The pressure influence on the deformation-induced evolution of dislocation densities implies that pressure variations may change the rheology of carbonate rocks. In particular, a weakening is expected to occur at the transition from the calcite to the CaCO3-II stability field, if aragonite does not form.

GlycomeDB – integration of open-access carbohydrate structure databases

PubMed Central

Ranzinger, René; Herget, Stephan; Wetter, Thomas; von der Lieth, Claus-Wilhelm

2008-01-01

Background Although carbohydrates are the third major class of biological macromolecules, after proteins and DNA, there is neither a comprehensive database for carbohydrate structures nor an established universal structure encoding scheme for computational purposes. Funding for further development of the Complex Carbohydrate Structure Database (CCSD or CarbBank) ceased in 1997, and since then several initiatives have developed independent databases with partially overlapping foci. For each database, different encoding schemes for residues and sequence topology were designed. Therefore, it is virtually impossible to obtain an overview of all deposited structures or to compare the contents of the various databases. Results We have implemented procedures which download the structures contained in the seven major databases, e.g. GLYCOSCIENCES.de, the Consortium for Functional Glycomics (CFG), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Bacterial Carbohydrate Structure Database (BCSDB). We have created a new database called GlycomeDB, containing all structures, their taxonomic annotations and references (IDs) for the original databases. More than 100000 datasets were imported, resulting in more than 33000 unique sequences now encoded in GlycomeDB using the universal format GlycoCT. Inconsistencies were found in all public databases, which were discussed and corrected in multiple feedback rounds with the responsible curators. Conclusion GlycomeDB is a new, publicly available database for carbohydrate sequences with a unified, all-encompassing structure encoding format and NCBI taxonomic referencing. The database is updated weekly and can be downloaded free of charge. The JAVA application GlycoUpdateDB is also available for establishing and updating a local installation of GlycomeDB. With the advent of GlycomeDB, the distributed islands of knowledge in glycomics are now bridged to form a single resource. PMID:18803830

ProBiS-database: precalculated binding site similarities and local pairwise alignments of PDB structures.

PubMed

Konc, Janez; Cesnik, Tomo; Konc, Joanna Trykowska; Penca, Matej; Janežič, Dušanka

2012-02-27

ProBiS-Database is a searchable repository of precalculated local structural alignments in proteins detected by the ProBiS algorithm in the Protein Data Bank. Identification of functionally important binding regions of the protein is facilitated by structural similarity scores mapped to the query protein structure. PDB structures that have been aligned with a query protein may be rapidly retrieved from the ProBiS-Database, which is thus able to generate hypotheses concerning the roles of uncharacterized proteins. Presented with uncharacterized protein structure, ProBiS-Database can discern relationships between such a query protein and other better known proteins in the PDB. Fast access and a user-friendly graphical interface promote easy exploration of this database of over 420 million local structural alignments. The ProBiS-Database is updated weekly and is freely available online at http://probis.cmm.ki.si/database.

Design of efficient circularly symmetric two-dimensional variable digital FIR filters.

PubMed

Bindima, Thayyil; Elias, Elizabeth

2016-05-01

Circularly symmetric two-dimensional (2D) finite impulse response (FIR) filters find extensive use in image and medical applications, especially for isotropic filtering. Moreover, the design and implementation of 2D digital filters with variable fractional delay and variable magnitude responses without redesigning the filter has become a crucial topic of interest due to its significance in low-cost applications. Recently the design using fixed word length coefficients has gained importance due to the replacement of multipliers by shifters and adders, which reduces the hardware complexity. Among the various approaches to 2D design, transforming a one-dimensional (1D) filter to 2D by transformation, is reported to be an efficient technique. In this paper, 1D variable digital filters (VDFs) with tunable cut-off frequencies are designed using Farrow structure based interpolation approach, and the sub-filter coefficients in the Farrow structure are made multiplier-less using canonic signed digit (CSD) representation. The resulting performance degradation in the filters is overcome by using artificial bee colony (ABC) optimization. Finally, the optimized 1D VDFs are mapped to 2D using generalized McClellan transformation resulting in low complexity, circularly symmetric 2D VDFs with real-time tunability.

Design of efficient circularly symmetric two-dimensional variable digital FIR filters

PubMed Central

Bindima, Thayyil; Elias, Elizabeth

2016-01-01

Circularly symmetric two-dimensional (2D) finite impulse response (FIR) filters find extensive use in image and medical applications, especially for isotropic filtering. Moreover, the design and implementation of 2D digital filters with variable fractional delay and variable magnitude responses without redesigning the filter has become a crucial topic of interest due to its significance in low-cost applications. Recently the design using fixed word length coefficients has gained importance due to the replacement of multipliers by shifters and adders, which reduces the hardware complexity. Among the various approaches to 2D design, transforming a one-dimensional (1D) filter to 2D by transformation, is reported to be an efficient technique. In this paper, 1D variable digital filters (VDFs) with tunable cut-off frequencies are designed using Farrow structure based interpolation approach, and the sub-filter coefficients in the Farrow structure are made multiplier-less using canonic signed digit (CSD) representation. The resulting performance degradation in the filters is overcome by using artificial bee colony (ABC) optimization. Finally, the optimized 1D VDFs are mapped to 2D using generalized McClellan transformation resulting in low complexity, circularly symmetric 2D VDFs with real-time tunability. PMID:27222739

Construction of crystal structure prototype database: methods and applications.

PubMed

Su, Chuanxun; Lv, Jian; Li, Quan; Wang, Hui; Zhang, Lijun; Wang, Yanchao; Ma, Yanming

2017-04-26

Crystal structure prototype data have become a useful source of information for materials discovery in the fields of crystallography, chemistry, physics, and materials science. This work reports the development of a robust and efficient method for assessing the similarity of structures on the basis of their interatomic distances. Using this method, we proposed a simple and unambiguous definition of crystal structure prototype based on hierarchical clustering theory, and constructed the crystal structure prototype database (CSPD) by filtering the known crystallographic structures in a database. With similar method, a program structure prototype analysis package (SPAP) was developed to remove similar structures in CALYPSO prediction results and extract predicted low energy structures for a separate theoretical structure database. A series of statistics describing the distribution of crystal structure prototypes in the CSPD was compiled to provide an important insight for structure prediction and high-throughput calculations. Illustrative examples of the application of the proposed database are given, including the generation of initial structures for structure prediction and determination of the prototype structure in databases. These examples demonstrate the CSPD to be a generally applicable and useful tool for materials discovery.

Construction of crystal structure prototype database: methods and applications

NASA Astrophysics Data System (ADS)

Su, Chuanxun; Lv, Jian; Li, Quan; Wang, Hui; Zhang, Lijun; Wang, Yanchao; Ma, Yanming

2017-04-01

Crystal structure prototype data have become a useful source of information for materials discovery in the fields of crystallography, chemistry, physics, and materials science. This work reports the development of a robust and efficient method for assessing the similarity of structures on the basis of their interatomic distances. Using this method, we proposed a simple and unambiguous definition of crystal structure prototype based on hierarchical clustering theory, and constructed the crystal structure prototype database (CSPD) by filtering the known crystallographic structures in a database. With similar method, a program structure prototype analysis package (SPAP) was developed to remove similar structures in CALYPSO prediction results and extract predicted low energy structures for a separate theoretical structure database. A series of statistics describing the distribution of crystal structure prototypes in the CSPD was compiled to provide an important insight for structure prediction and high-throughput calculations. Illustrative examples of the application of the proposed database are given, including the generation of initial structures for structure prediction and determination of the prototype structure in databases. These examples demonstrate the CSPD to be a generally applicable and useful tool for materials discovery.

Structural Ceramics Database

National Institute of Standards and Technology Data Gateway

SRD 30 NIST Structural Ceramics Database (Web, free access)   The NIST Structural Ceramics Database (WebSCD) provides evaluated materials property data for a wide range of advanced ceramics known variously as structural ceramics, engineering ceramics, and fine ceramics.

AAPG-CSD geologic provinces code map

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

Meyer, R.F.; Wallace, L.G.; Wagner, F.J. Jr.

1991-10-01

This article provides the history of a revised geologic map which was drawn based on both surface geology and petroleum occurrence. The map includes offshore maps for California and the Gulf Coast of Texas and Louisiana. For onshore sites it provides geologic province boundaries which were drawn along county boundaries to approximate their position relative to oil and gas production. The offshore sites are drawn based on the universal transverse Mercator system.

Five-Year Research and Development Plan, Fiscal Years 2008-2013

DTIC Science & Technology

2008-08-01

protect our interior 1.l.1 Deploy a mix of infrastructure, technology, and personnel on the Southwest border to ensure all illegal activity along...requirements into a systems model. FY 2009: • Review the System of Systems model and ensure it correctly addresses SBI requirements. FY 2010... on a ship). This security architecture provides the framework within which DHS will incorporate their near-term CSD and future container security

Lidar - ESRL WindCube 200s, Arlington Airport - Raw Data

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

Choukulkar, Aditya

The available "readme" file introduces the basics of the Doppler lidar data and offers a detailed description of the variables present in the data files. If you have any further questions about the data and its interpretation, contact either Alan Brewer () or Aditya Choukulkar (). It is highly recommended to discuss any planned use of the data with NOAA-CSD scientists. For more information, refer to the attached readme.

Lidar - ESRL WindCube 200s, Arlington Airport - Processed Data

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

Choukulkar, Aditya

The available "readme" file introduces the basics of the Doppler lidar data and offers a detailed description of the variables present in the data files. If you have any further questions about the data and its interpretation, contact either Alan Brewer () or Aditya Choukulkar (). It is highly recommended to discuss any planned use of the data with NOAA-CSD scientists. For more information, refer to the attached readme.

Social defeat interacts with Disc1 mutations in the mouse to affect behavior.

PubMed

Haque, F Nipa; Lipina, Tatiana V; Roder, John C; Wong, Albert H C

2012-08-01

DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene-environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia. We hypothesized that gene-environment interactions would affect behavior in a mutant Disc1 mouse model. We examined the effect of chronic social defeat (CSD) as an environmental stressor in two lines of mice carrying different Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and the social interaction task for sociability and social novelty (SSN). We found that Disc1-L100P +/- and wild-type mice have similar anxiety responses to CSD, while Q31L +/- mice had a very different response. We also found evidence of significant gene-environment interactions in the OF, EPM and SSN. Copyright © 2012 Elsevier B.V. All rights reserved.

Geologic distributions of US oil and gas

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

Not Available

1992-07-31

This publication presents nonproprietary field size distributions that encompass most domestic oil and gas fields at year-end 1989. These data are organized by geologic provinces as defined by the American Association of Petroleum Geologists` Committee on Statistics of Drilling (AAPG/CSD), by regional geographic aggregates of the AAPG/CSD provinces, and Nationally. The report also provides partial volumetric distributions of petroleum liquid and natural gas ultimate recoveries for three macro-geologic variables: principal lithology of the reservoir rock, principal trapping condition and geologic age of the reservoir rock, The former two variables are presented Nationally and by geographic region, in more detail thanmore » has heretofore been available. The latter variable is provided Nationally at the same level of detail previously available. Eighteen tables and 66 figures present original data on domestic oil and gas occurrence. Unfortunately, volumetric data inadequacy dictated exclusion of Appalachian region oil and gas fields from the study. All other areas of the United States known to be productive of crude oil or natural gas through year-end 1989, onshore and offshore, were included. It should be noted that none of the results and conclusions would be expected to substantively differ had data for the Appalachian region been available for inclusion in the study.« less

Geologic distributions of US oil and gas

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

Not Available

1992-07-31

This publication presents nonproprietary field size distributions that encompass most domestic oil and gas fields at year-end 1989. These data are organized by geologic provinces as defined by the American Association of Petroleum Geologists' Committee on Statistics of Drilling (AAPG/CSD), by regional geographic aggregates of the AAPG/CSD provinces, and Nationally. The report also provides partial volumetric distributions of petroleum liquid and natural gas ultimate recoveries for three macro-geologic variables: principal lithology of the reservoir rock, principal trapping condition and geologic age of the reservoir rock, The former two variables are presented Nationally and by geographic region, in more detail thanmore » has heretofore been available. The latter variable is provided Nationally at the same level of detail previously available. Eighteen tables and 66 figures present original data on domestic oil and gas occurrence. Unfortunately, volumetric data inadequacy dictated exclusion of Appalachian region oil and gas fields from the study. All other areas of the United States known to be productive of crude oil or natural gas through year-end 1989, onshore and offshore, were included. It should be noted that none of the results and conclusions would be expected to substantively differ had data for the Appalachian region been available for inclusion in the study.« less

Investigation of the operating conditions to morphology evolution of β-L-glutamic acid during seeded cooling crystallization

NASA Astrophysics Data System (ADS)

Zhang, Fangkun; Liu, Tao; Huo, Yan; Guan, Runduo; Wang, Xue Z.

2017-07-01

In this paper the effects of operating conditions including cooling rate, initial supersaturation, and seeding temperature were investigated on the morphology evolution of β-L-glutamic acid (β-LGA) during seeded cooling crystallization. Based on the results of in-situ image acquisition of the crystal morphology evolution during the crystallization process, it was found that the crystal products tend to be plate-like or short rod-like under a slow cooling rate, low initial supersaturation, and low seeding temperature. In the opposite, the operating conditions of a faster cooling rate, higher initial supersaturation, and higher seeding temperature tend to produce long rod-like or needle-like crystals, and meanwhile, the length and width of crystal products will be increased together with a wider crystal size distribution (CSD). The aspect ratio of crystals, defined by the crystal length over width measured from in-situ or sample images, was taken as a shape index to analyze the crystal morphologies. Based on comparative analysis of the experimental results, guidelines on these operating conditions were given for obtaining the desired crystal shapes, along with the strategies for obtaining a narrower CSD for better product quality. Experimental verifications were performed to illustrate the proposed guidelines on the operating conditions for seeded cooling crystallization of LGA solution.

Biological Assessment of a Calcium Silicate Incorporated Hydroxyapatite-Gelatin Nanocomposite: A Comparison to Decellularized Bone Matrix

PubMed Central

Lee, Dong Joon; Padilla, Ricardo; Zhang, He; Hu, Wei-Shou; Ko, Ching-Chang

2014-01-01

Our laboratory utilized biomimicry to develop a synthetic bone scaffold based on hydroxyapatite-gelatin-calcium silicate (HGCS). Here, we evaluated the potential of HGCS scaffold in bone formation in vivo using the rat calvarial critical-sized defect (CSD). Twelve Sprague-Dawley rats were randomized to four groups: control (defect only), decellularized bone matrix (DECBM), and HGCS with and without multipotent adult progenitor cells (MAPCs). DECBM was prepared by removing all the cells using SDS and NH4OH. After 12 weeks, the CSD specimens were harvested to evaluate radiographical, histological, and histomorphometrical outcomes. The in vitro osteogenic effects of the materials were studied by focal adhesion, MTS, and alizarin red. Micro-CT analysis indicated that the DECBM and the HGCS scaffold groups developed greater radiopaque areas than the other groups. Bone regeneration, assessed using histological analysis and fluorochrome labeling, was the highest in the HGCS scaffold seeded with MAPCs. The DECBM group showed limited osteoinductivity, causing a gap between the implant and host tissue. The group grafted with HGCS+MAPCs resulting in twice as much new bone formation seems to indicate a role for effective bone regeneration. In conclusion, the novel HGCS scaffold could improve bone regeneration and is a promising carrier for stem cell-mediated bone regeneration. PMID:25054149

Orientation control of barium titanate films using metal oxide nanosheet layer

NASA Astrophysics Data System (ADS)

Uchida, Hiroshi; Oi, Tomotake; Noguchi, Keito; Moki, Shota; Kim, Jin Woon; Shima, Hiromi; Nishida, Ken; Kiguchi, Takanori; Akama, Akihiko; Konno, Toyohiko J.; Funakubo, Hiroshi

2016-10-01

In the present work, we aim to achieve the preferred crystal orientation of chemical solution deposition (CSD)-derived BaTiO3 films on ubiquitous Si wafers with the assistance of Ca2Nb3O10 nanosheet (ns-CN) template layers. The ns-CN on platinized Si (Pt/Si) substrates aligned the BaTiO3(100) plane to the substrate surface, because of the favorable lattice matching of the ns-CN (001) plane. The CSD process in air required a high crystallization temperature of 900 °C for the preferred crystal orientation of BaTiO3(100) because of the BaCO3 byproduct generated during the combustion reaction of the precursor gel. The processing in vacuum to remove CO2 species enhanced the crystal orientation even at the crystallization temperature of 800 °C, although it can generate oxygen vacancies (\\text{V}\\text{O}{} \\bullet \\bullet ) that cause distorted polarization behavior under an applied field higher than approximately 150 kV/cm. The relative dielectric constant (εr) of the (100)-oriented BaTiO3 film on the ns-CN-supported Pt/Si substrate (ns-CN/Pt/Si) was generally larger than that of the randomly oriented film on Pt/Si, depending on the degree of crystal orientation.

A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque.

PubMed

Schroeder, C E; Mehta, A D; Givre, S J

1998-01-01

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal-ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.

sec-Butylpropylacetamide (SPD) has antimigraine properties

PubMed Central

Kaufmann, Dan; Bates, Emily A; Yagen, Boris; Bialer, Meir; Saunders, Gerald H; Wilcox, Karen; White, H Steve; Brennan, KC

2016-01-01

Background Though migraine is disabling and affects 12%–15% of the population, there are few drugs that have been developed specifically for migraine prevention. Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile. sec-Butylpropylacetamide (SPD) is a novel VPA derivative, designed to be more potent and tolerable than VPA, that has shown efficacy in animal seizure and pain models. Methods We evaluated SPD’s antimigraine potential in the cortical spreading depression (CSD) and nitroglycerin (NTG) models of migraine. To evaluate SPD’s mechanism of action, we performed whole-cell recordings on cultured cortical neurons and neuroblastoma cells. Results In the CSD model, the SPD-treated group showed a significantly lower median number of CSDs compared to controls. In the NTG-induced mechanical allodynia model, SPD dose-dependently reduced mechanical sensitivity compared to controls. SPD showed both a significant potentiation of GABA-mediated currents and a smaller but significant decrease in NMDA currents in cultured cortical neurons. Kainic acid-evoked currents and voltage-dependent sodium channel currents were not changed by SPD. Conclusions These results demonstrate SPD’s potential as a promising novel antimigraine compound, and suggest a GABAergic mechanism of action. PMID:26568161

Comparative measurements of piezoelectric coefficient of PZT films by Berlincourt, interferometer, and vibrometer methods.

PubMed

Huang, Zhaorong; Zhang, Qi; Corkovic, Silvana; Dorey, Robert; Whatmore, Roger W

2006-12-01

Chemical solution deposition (CSD) techniques were used to prepare lead zirconate (Zr) titanate (Ti) (PZT) thin films with Zr/Ti ratios of 30/70 and 52/48. Usually CSD processing is restricted to making crack-free, single-layer films of 70-nm thick, but modifications to the sol-gel process have permitted the fabrication of dense, crack-free, single layers up to 200 to 300 nm thick, which can be built-up into layers up to 3-microm thick. Thicker PZT films (> 2-microm single layer) can be produced by using a composite sol-gel/ceramic process. Knowledge of the electroactive properties of these materials is essential for modeling and design of novel micro-electromechanical systems (MEMS) devices, but accurate measurement of these properties is by no means straightforward. A novel, double-beam, common-path laser interferometer has been developed to measure the longitudinal (d33) piezoelectric coefficient in films; the results were compared with the values obtained by Berlin-court and laser scanning vibrometer methods. It was found that, for thin-film samples, the d(33,f) values obtained from the Berlincourt method are usually larger: than those obtained from the interferometer and the vibrometer methods; the reasons for this are discussed.

A novel surfactant-free lipid-based formulation for improving oral bioavailability of loratadine using colloidal silicon dioxide as emulsifier and solid carrier.

PubMed

Huang, Ri; Tan, Yonggang; Shen, Lao; Wang, Tao; Quan, Dongqin

2018-05-08

The purpose of this study was to develop an innovative surfactant-free lipid-based formulation (LF) for improving oral bioavailability of loratadine based on using solid particles colloidal silicon dioxide (CSD) as emulsifier and solid carrier. Loratadine was dissolved in oil solution with the aid of co-solvent and LF were prepared by a simple adsorption and milling technique. The LF Powder was evaluated in terms of angle of repose and X-ray powder diffraction. After dispersing and emulsifying in water, the particle size and morphology were also characterized. In vitro dissolution and pharmacokinetic behavior in vivo were also studied. Orthogonal design indicated that the amount of CSD in formulations had a major and significant influence on emulsification. The optimal formulation showed LF with good flowability and without crystallization or deposition of loratadine in it. After dispersing in water, an emulsion with mean droplet size of 1.2μm was obtained. Although the dissolution of drug from LF was slower in vitro in acidic aqueous solution, pharmacokinetic studies in vivo showed that the bioavailability of loratadine increased 2.49-fold by CF compared to commercial tablet. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

mTM-align: a server for fast protein structure database search and multiple protein structure alignment.

PubMed

Dong, Runze; Pan, Shuo; Peng, Zhenling; Zhang, Yang; Yang, Jianyi

2018-05-21

With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop algorithms for efficient protein structure comparisons. In this article, we present the mTM-align server, which consists of two closely related modules: one for structure database search and the other for multiple structure alignment. The database search is speeded up based on a heuristic algorithm and a hierarchical organization of the structures in the database. The multiple structure alignment is performed using the recently developed algorithm mTM-align. Benchmark tests demonstrate that our algorithms outperform other peering methods for both modules, in terms of speed and accuracy. One of the unique features for the server is the interplay between database search and multiple structure alignment. The server provides service not only for performing fast database search, but also for making accurate multiple structure alignment with the structures found by the search. For the database search, it takes about 2-5 min for a structure of a medium size (∼300 residues). For the multiple structure alignment, it takes a few seconds for ∼10 structures of medium sizes. The server is freely available at: http://yanglab.nankai.edu.cn/mTM-align/.

Comprehensive analysis of the N-glycan biosynthetic pathway using bioinformatics to generate UniCorn: A theoretical N-glycan structure database.

PubMed

Akune, Yukie; Lin, Chi-Hung; Abrahams, Jodie L; Zhang, Jingyu; Packer, Nicolle H; Aoki-Kinoshita, Kiyoko F; Campbell, Matthew P

2016-08-05

Glycan structures attached to proteins are comprised of diverse monosaccharide sequences and linkages that are produced from precursor nucleotide-sugars by a series of glycosyltransferases. Databases of these structures are an essential resource for the interpretation of analytical data and the development of bioinformatics tools. However, with no template to predict what structures are possible the human glycan structure databases are incomplete and rely heavily on the curation of published, experimentally determined, glycan structure data. In this work, a library of 45 human glycosyltransferases was used to generate a theoretical database of N-glycan structures comprised of 15 or less monosaccharide residues. Enzyme specificities were sourced from major online databases including Kyoto Encyclopedia of Genes and Genomes (KEGG) Glycan, Consortium for Functional Glycomics (CFG), Carbohydrate-Active enZymes (CAZy), GlycoGene DataBase (GGDB) and BRENDA. Based on the known activities, more than 1.1 million theoretical structures and 4.7 million synthetic reactions were generated and stored in our database called UniCorn. Furthermore, we analyzed the differences between the predicted glycan structures in UniCorn and those contained in UniCarbKB (www.unicarbkb.org), a database which stores experimentally described glycan structures reported in the literature, and demonstrate that UniCorn can be used to aid in the assignment of ambiguous structures whilst also serving as a discovery database. Copyright © 2016 Elsevier Ltd. All rights reserved.

URS DataBase: universe of RNA structures and their motifs.

PubMed

Baulin, Eugene; Yacovlev, Victor; Khachko, Denis; Spirin, Sergei; Roytberg, Mikhail

2016-01-01

The Universe of RNA Structures DataBase (URSDB) stores information obtained from all RNA-containing PDB entries (2935 entries in October 2015). The content of the database is updated regularly. The database consists of 51 tables containing indexed data on various elements of the RNA structures. The database provides a web interface allowing user to select a subset of structures with desired features and to obtain various statistical data for a selected subset of structures or for all structures. In particular, one can easily obtain statistics on geometric parameters of base pairs, on structural motifs (stems, loops, etc.) or on different types of pseudoknots. The user can also view and get information on an individual structure or its selected parts, e.g. RNA-protein hydrogen bonds. URSDB employs a new original definition of loops in RNA structures. That definition fits both pseudoknot-free and pseudoknotted secondary structures and coincides with the classical definition in case of pseudoknot-free structures. To our knowledge, URSDB is the first database supporting searches based on topological classification of pseudoknots and on extended loop classification.Database URL: http://server3.lpm.org.ru/urs/. © The Author(s) 2016. Published by Oxford University Press.

URS DataBase: universe of RNA structures and their motifs

PubMed Central

Baulin, Eugene; Yacovlev, Victor; Khachko, Denis; Spirin, Sergei; Roytberg, Mikhail

2016-01-01

The Universe of RNA Structures DataBase (URSDB) stores information obtained from all RNA-containing PDB entries (2935 entries in October 2015). The content of the database is updated regularly. The database consists of 51 tables containing indexed data on various elements of the RNA structures. The database provides a web interface allowing user to select a subset of structures with desired features and to obtain various statistical data for a selected subset of structures or for all structures. In particular, one can easily obtain statistics on geometric parameters of base pairs, on structural motifs (stems, loops, etc.) or on different types of pseudoknots. The user can also view and get information on an individual structure or its selected parts, e.g. RNA–protein hydrogen bonds. URSDB employs a new original definition of loops in RNA structures. That definition fits both pseudoknot-free and pseudoknotted secondary structures and coincides with the classical definition in case of pseudoknot-free structures. To our knowledge, URSDB is the first database supporting searches based on topological classification of pseudoknots and on extended loop classification. Database URL: http://server3.lpm.org.ru/urs/ PMID:27242032

PuReD-MCL: a graph-based PubMed document clustering methodology.

PubMed

Theodosiou, T; Darzentas, N; Angelis, L; Ouzounis, C A

2008-09-01

Biomedical literature is the principal repository of biomedical knowledge, with PubMed being the most complete database collecting, organizing and analyzing such textual knowledge. There are numerous efforts that attempt to exploit this information by using text mining and machine learning techniques. We developed a novel approach, called PuReD-MCL (Pubmed Related Documents-MCL), which is based on the graph clustering algorithm MCL and relevant resources from PubMed. PuReD-MCL avoids using natural language processing (NLP) techniques directly; instead, it takes advantage of existing resources, available from PubMed. PuReD-MCL then clusters documents efficiently using the MCL graph clustering algorithm, which is based on graph flow simulation. This process allows users to analyse the results by highlighting important clues, and finally to visualize the clusters and all relevant information using an interactive graph layout algorithm, for instance BioLayout Express 3D. The methodology was applied to two different datasets, previously used for the validation of the document clustering tool TextQuest. The first dataset involves the organisms Escherichia coli and yeast, whereas the second is related to Drosophila development. PuReD-MCL successfully reproduces the annotated results obtained from TextQuest, while at the same time provides additional insights into the clusters and the corresponding documents. Source code in perl and R are available from http://tartara.csd.auth.gr/~theodos/

A case study for a digital seabed database: Bohai Sea engineering geology database

NASA Astrophysics Data System (ADS)

Tianyun, Su; Shikui, Zhai; Baohua, Liu; Ruicai, Liang; Yanpeng, Zheng; Yong, Wang

2006-07-01

This paper discusses the designing plan of ORACLE-based Bohai Sea engineering geology database structure from requisition analysis, conceptual structure analysis, logical structure analysis, physical structure analysis and security designing. In the study, we used the object-oriented Unified Modeling Language (UML) to model the conceptual structure of the database and used the powerful function of data management which the object-oriented and relational database ORACLE provides to organize and manage the storage space and improve its security performance. By this means, the database can provide rapid and highly effective performance in data storage, maintenance and query to satisfy the application requisition of the Bohai Sea Oilfield Paradigm Area Information System.

A contour-based shape descriptor for biomedical image classification and retrieval

NASA Astrophysics Data System (ADS)

You, Daekeun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.

2013-12-01

Contours, object blobs, and specific feature points are utilized to represent object shapes and extract shape descriptors that can then be used for object detection or image classification. In this research we develop a shape descriptor for biomedical image type (or, modality) classification. We adapt a feature extraction method used in optical character recognition (OCR) for character shape representation, and apply various image preprocessing methods to successfully adapt the method to our application. The proposed shape descriptor is applied to radiology images (e.g., MRI, CT, ultrasound, X-ray, etc.) to assess its usefulness for modality classification. In our experiment we compare our method with other visual descriptors such as CEDD, CLD, Tamura, and PHOG that extract color, texture, or shape information from images. The proposed method achieved the highest classification accuracy of 74.1% among all other individual descriptors in the test, and when combined with CSD (color structure descriptor) showed better performance (78.9%) than using the shape descriptor alone.

The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

PubMed Central

Milardi, Demetrio; Cacciola, Alberto; Calamuneri, Alessandro; Ghilardi, Maria F.; Caminiti, Fabrizia; Cascio, Filippo; Andronaco, Veronica; Anastasi, Giuseppe; Mormina, Enricomaria; Arrigo, Alessandro; Bruschetta, Daniele; Quartarone, Angelo

2017-01-01

Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders. PMID:28443000

Performance optimization of spectral amplitude coding OCDMA system using new enhanced multi diagonal code

NASA Astrophysics Data System (ADS)

Imtiaz, Waqas A.; Ilyas, M.; Khan, Yousaf

2016-11-01

This paper propose a new code to optimize the performance of spectral amplitude coding-optical code division multiple access (SAC-OCDMA) system. The unique two-matrix structure of the proposed enhanced multi diagonal (EMD) code and effective correlation properties, between intended and interfering subscribers, significantly elevates the performance of SAC-OCDMA system by negating multiple access interference (MAI) and associated phase induce intensity noise (PIIN). Performance of SAC-OCDMA system based on the proposed code is thoroughly analyzed for two detection techniques through analytic and simulation analysis by referring to bit error rate (BER), signal to noise ratio (SNR) and eye patterns at the receiving end. It is shown that EMD code while using SDD technique provides high transmission capacity, reduces the receiver complexity, and provides better performance as compared to complementary subtraction detection (CSD) technique. Furthermore, analysis shows that, for a minimum acceptable BER of 10-9 , the proposed system supports 64 subscribers at data rates of up to 2 Gbps for both up-down link transmission.

Inorganic Crystal Structure Database (ICSD)

National Institute of Standards and Technology Data Gateway

SRD 84 FIZ/NIST Inorganic Crystal Structure Database (ICSD) (PC database for purchase)   The Inorganic Crystal Structure Database (ICSD) is produced cooperatively by the Fachinformationszentrum Karlsruhe(FIZ) and the National Institute of Standards and Technology (NIST). The ICSD is a comprehensive collection of crystal structure data of inorganic compounds containing more than 140,000 entries and covering the literature from 1915 to the present.

Enhancing weak transient signals in SEVIRI false colour imagery: application to dust source detection in southern Africa

NASA Astrophysics Data System (ADS)

Murray, Jon E.; Brindley, Helen E.; Bryant, Robert G.; Russell, Jacqui E.; Jenkins, Katherine F.

2013-04-01

Understanding the processes governing the availability and entrainment of mineral dust into the atmosphere requires dust sources to be identified and the evolution of dust events to be monitored. To achieve this aim a wide range of approaches have been developed utilising observations from a variety of different satellite sensors. Global maps of source regions and their relative strengths have been derived from instruments in low Earth orbit (e.g. Total Ozone Monitoring Spectrometer (TOMS) (Prospero et al., 2002), MODerate resolution Imaging Spectrometer (MODIS) (Ginoux et al., 2012)). Instruments such as MODIS can also be used to improve precise source location (Baddock et al., 2009) but the information available is restricted to the satellite overpass times which may not be coincident with active dust emission from the source. Hence, at a regional scale, some of the more successful approaches used to characterise the activity of different sources use high temporal resolution data available from instruments in geostationary orbit. For example, the widely used red-green-blue (RGB) dust scheme developed by Lensky and Rosenfeld (2008) (hereafter LR2008) makes use of observations from selected thermal channels of the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) in a false colour rendering scheme in which dust appears pink. This scheme has provided the basis for numerous studies of north African dust sources and factors governing their activation (e.g. Schepanski et al., 2007, 2009, 2012). However, the LR2008 imagery can fail to identify dust events due to the effects of atmospheric moisture, variations in dust layer height and optical properties, and surface conditions (Brindley et al., 2012). Here we introduce a new method designed to circumvent some of these issues and enhance the signature of dust events using observations from SEVIRI. The approach involves the derivation of a composite clear-sky signal for selected channels on an individual time-step and pixel basis. These composite signals are subtracted from each observation in the relevant channels to enhance weak transient signals associated with low levels of dust emission. Different channel combinations are then rendered in false colour imagery to better identify dust source locations and activity. We have applied this new clear-sky difference (CSD) algorithm over three key source regions in southern Africa: the Makgadikgadi Basin, Etosha Pan, and the Namibian and western South African coast. Case studies indicate that advantages associated with the CSD approach include an improved ability to detect dust and distinguish multiple sources, the observation of source activation earlier in the diurnal cycle, and an improved ability to pinpoint dust source locations. These advantages are confirmed by a survey of four-years of data, comparing the results obtained using the CSD technique with those derived from LR2008 dust imagery. On average the new algorithm more than doubles the number of dust events identified, with the greatest improvement for the Makgadigkadi Basin and coastal regions. We anticipate exploiting this new activation record derived using the CSD approach to better understand the surface and meteorological conditions controlling dust uplift and subsequent atmospheric transport.

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

PubMed

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

Role of Caveolin-1 in Prostate Cancer Angiogenesis

DTIC Science & Technology

2008-12-01

CSD deleted rcav-1 protein (Δrcav- 1), treated EC and prostate cancer cells with different concentrations of FITC- Δrcav-1 over 1-6 h, and examined the...Months 7-24) 4. Biological function end points. (Months 25-36) We are currently investigating different siRNA transfection protocols to find...activities through auto regulatory, Akt-mediated maintanence of mRNA stabilities of cancer promoting growth factors. In preparation 6. Tahir SA

Dissecting the Roles of Brain Injury and Combat-Related Stress in Post-Traumatic Headache

DTIC Science & Technology

2015-10-01

were the major goals of the project? Post-traumatic headache (PTH) is an epidemic in our military personnel. It is a chronic, migraine -like...and affective processing that lead to PTH. Cortical spreading depression (CSD) is the physiological correlate of the migraine aura, but it also...paradigm. NTG infusion triggers migraine without aura in human migraineurs and reduced mechanical allodynia threshold in rodents. This enables 11

Mona Bronson, et al., Plaintiffs, vs. Board of Education of the City School District of the City of Cincinnati, et al., Defendants. Case No. C-1-74-205.

ERIC Educational Resources Information Center

Rice, Walter Herbert

In this decision, Judge W. H. Rice finds the Cincinnati (Ohio) School District (CSD) in compliance with some provisions of a school desegregation consent decree from June 22, 1984, and not in compliance with others. The original decision was historic in allowing the school district charged with promoting or allowing unconstitutional segregation to…

Representative shuttle evaporative heat sink

NASA Technical Reports Server (NTRS)

Hixon, C. W.

1978-01-01

The design, fabrication, and testing of a representative shuttle evaporative heat sink (RSEHS) system which vaporizes an expendable fluid to provide cooling for the shuttle heat transport fluid loop is reported. The optimized RSEHS minimum weight design meets or exceeds the shuttle flash evaporator system requirements. A cold trap which cryo-pumps flash evaporator exhaust water from the CSD vacuum chamber test facility to prevent water contamination of the chamber pumping equipment is also described.

The 2014 Nucleic Acids Research Database Issue and an updated NAR online Molecular Biology Database Collection.

PubMed

Fernández-Suárez, Xosé M; Rigden, Daniel J; Galperin, Michael Y

2014-01-01

The 2014 Nucleic Acids Research Database Issue includes descriptions of 58 new molecular biology databases and recent updates to 123 databases previously featured in NAR or other journals. For convenience, the issue is now divided into eight sections that reflect major subject categories. Among the highlights of this issue are six databases of the transcription factor binding sites in various organisms and updates on such popular databases as CAZy, Database of Genomic Variants (DGV), dbGaP, DrugBank, KEGG, miRBase, Pfam, Reactome, SEED, TCDB and UniProt. There is a strong block of structural databases, which includes, among others, the new RNA Bricks database, updates on PDBe, PDBsum, ArchDB, Gene3D, ModBase, Nucleic Acid Database and the recently revived iPfam database. An update on the NCBI's MMDB describes VAST+, an improved tool for protein structure comparison. Two articles highlight the development of the Structural Classification of Proteins (SCOP) database: one describes SCOPe, which automates assignment of new structures to the existing SCOP hierarchy; the other one describes the first version of SCOP2, with its more flexible approach to classifying protein structures. This issue also includes a collection of articles on bacterial taxonomy and metagenomics, which includes updates on the List of Prokaryotic Names with Standing in Nomenclature (LPSN), Ribosomal Database Project (RDP), the Silva/LTP project and several new metagenomics resources. The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been expanded to 1552 databases. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/).

Etiology of three recent diseases of citrus in São Paulo State: sudden death, variegated chlorosis and huanglongbing.

PubMed

Bové, Joseph Marie; Ayres, Antonio Juliano

2007-01-01

The state of São Paulo (SSP) is the first sweet orange growing region in the world. Yet, the SSP citrus industry has been, and still is, under constant attack from various diseases. In the 1940s, tristeza-quick decline (T-QD) was responsible for the death of 9 million trees in SSP. The causal agent was a new virus, citrus tristeza virus (CTV). The virus was efficiently spread by aphid vectors, and killed most of the trees grafted on sour orange rootstock. Control of the disease resided in replacing sour orange by alternative rootstocks giving tolerant combinations with scions such as sweet orange. Because of its drought resistance, Rangpur lime became the favourite alternative rootstock, and, by 1995, 85% of the SSP sweet orange trees were grafted on this rootstock. Therefore, when in 1999, many trees grafted on Rangpur lime started to decline and suddenly died, the spectre of T-QD seemed to hang over SSP again. By 2003, the total number of dead or affected trees was estimated to be over one million. The new disease, citrus sudden death (CSD), resembles T-QD in several aspects. The two diseases have almost the same symptoms, they spread in time and space in a manner strikingly similar, and the pathological anatomy of the bark at the bud union is alike. Transmission of the CSD agent by graft-inoculation has been obtained with budwood inoculum taken not only on CSD-affected trees (grafted on Rangpur lime), but also on symptomless trees (grafted on Cleopatra mandarin) from the same citrus block. This result shows that symptomless trees on Cleopatra mandarin are tolerant to the CSD agent. Trees on rootstocks such as Sunki mandarin or Swingle citrumelo are also tolerant. Thus, in the CSD-affected region, control consists in replacing Rangpur lime with compatible rootstocks, or in approach-grafting compatible rootstock seedlings to the scions of trees on Rangpur lime (inarching). More than 5 million trees have been inarched in this way. A new disease of sweet orange, citrus variegated chlorosis (CVC), was observed in 1987 in the Triangulo Mineiro of Minas Gerais State and the northern and north-eastern parts of SSP. By 2000, the disease affected already 34% of the 200 million sweet orange trees in SSP. By 2005, the percentage had increased to 43%, and CVC was present in all citrus growing regions of Brazil. Electron microscopy showed that xylem-limited bacteria were present in all symptomatic sweet orange leaves and fruit tissues tested, but not in similar materials from healthy, symptomless trees. Bacteria were consistently cultured from twigs of CVC-affected sweet orange trees but not from twigs of healthy trees. Serological analyses showed the CVC bacterium to be a strain of Xylella fastidiosa. The disease could be reproduced and Koch's postulates fulfilled, by mechanically inoculating a pure culture of X. fastidiosa isolate 8.1.b into sweet orange seedlings. The genome of a CVC strain of X. fastidiosa was sequenced in SSP in the frame of a project supported by FAPESP and Fundecitrus. X. fastidiosa is the first plant pathogenic bacterium, the genome of which has been sequenced. Until recently, America was free of huanglongbing (HLB), but in March 2004 and August 2005, symptoms of the disease were recognized, respectively in the State of São Paulo (SSP) and in Florida, USA. HLB was known in China since 1870 and in South Africa since 1928. Because of its destructiveness and its rapid spread by efficient psyllid insect-vectors, HLB is probably the most serious citrus disease. HLB is caused by a phloem sieve tube-restricted Gram negative bacterium, not yet available in culture. In the 1990s, the bacterium was characterized by molecular techniques as a member of the alpha proteobacteria designated Candidatus Liberibacter africanus for the disease in Africa, and Candidatus Liberibacter asiaticus for HLB in Asia. In SSP, Ca. L. asiaticus is also present, but most of the trees are infected with a new species, Candidatus Liberibacter americanus.

MMDB: Entrez’s 3D-structure database

PubMed Central

Wang, Yanli; Anderson, John B.; Chen, Jie; Geer, Lewis Y.; He, Siqian; Hurwitz, David I.; Liebert, Cynthia A.; Madej, Thomas; Marchler, Gabriele H.; Marchler-Bauer, Aron; Panchenko, Anna R.; Shoemaker, Benjamin A.; Song, James S.; Thiessen, Paul A.; Yamashita, Roxanne A.; Bryant, Stephen H.

2002-01-01

Three-dimensional structures are now known within many protein families and it is quite likely, in searching a sequence database, that one will encounter a homolog with known structure. The goal of Entrez’s 3D-structure database is to make this information, and the functional annotation it can provide, easily accessible to molecular biologists. To this end Entrez’s search engine provides three powerful features. (i) Sequence and structure neighbors; one may select all sequences similar to one of interest, for example, and link to any known 3D structures. (ii) Links between databases; one may search by term matching in MEDLINE, for example, and link to 3D structures reported in these articles. (iii) Sequence and structure visualization; identifying a homolog with known structure, one may view molecular-graphic and alignment displays, to infer approximate 3D structure. In this article we focus on two features of Entrez’s Molecular Modeling Database (MMDB) not described previously: links from individual biopolymer chains within 3D structures to a systematic taxonomy of organisms represented in molecular databases, and links from individual chains (and compact 3D domains within them) to structure neighbors, other chains (and 3D domains) with similar 3D structure. MMDB may be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure. PMID:11752307

HIV Structural Database

National Institute of Standards and Technology Data Gateway

SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention

PubMed Central

Kayser, Jürgen; Tenke, Craig E.; Abraham, Karen S.; Alschuler, Daniel M.; Alvarenga, Jorge E.; Skipper, Jamie; Warner, Virginia; Bruder, Gerard E.; Weissman, Myrna M.

2016-01-01

Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100-200 ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly-controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72-channel ERPs recorded from 152 individuals (age 13-68 years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212 ms peak latency), P3 source (385 ms) and a late centroparietal source (630 ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSD-PCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli. PMID:27263509

Neural hyperactivity in the amygdala induced by chronic treatment of rats with analgesics may elucidate the mechanisms underlying psychiatric comorbidities associated with medication-overuse headache.

PubMed

Wanasuntronwong, Aree; Jansri, Ukkrit; Srikiatkhachorn, Anan

2017-01-03

Patients with medication-overuse headache suffer not only from chronic headache, but often from psychiatric comorbidities, such as anxiety and depression. The mechanisms underlying these comorbidities are unclear, but the amygdala is likely to be involved in their pathogenesis. To investigate the mechanisms underlying the comorbidities we used elevated plus maze and open field tests to assess anxiety-like behavior in rats chronically treated with analgesics. We measured the electrical properties of neurons in the amygdala, and examined the cortical spreading depression (CSD)-evoked expression of Fos in the trigeminal nucleus caudalis (TNC) and amygdala of rats chronically treated with analgesics. CSD, an analog of aura, evokes Fos expression in the TNC of rodents suggesting trigeminal nociception, considered to be a model of migraine. Increased anxiety-like behavior was seen both in elevated plus maze and open field tests in a model of medication overuse produced in male rats by chronic treatment with aspirin or acetaminophen. The time spent in the open arms of the maze by aspirin- or acetaminophen-treated rats (53 ± 36.1 and 37 ± 29.5 s, respectively) was significantly shorter than that spent by saline-treated vehicle control rats (138 ± 22.6 s, P < 0.001). Chronic treatment with the analgesics increased the excitability of neurons in the central nucleus of the amygdala as indicated by their more negative threshold for action potential generation (-54.6 ± 5.01 mV for aspirin-treated, -55.2 ± 0.97 mV for acetaminophen-treated, and -31.50 ± 5.34 mV for saline-treated rats, P < 0.001). Chronic treatment with analgesics increased the CSD-evoked expression of Fos in the TNC and amygdala [18 ± 10.2 Fos-immunoreactive (IR) neurons per slide in the amygdala of rats treated with aspirin, 11 ± 5.4 IR neurons per slide in rats treated with acetaminophen, and 4 ± 3.7 IR neurons per slide in saline-treated control rats, P < 0.001]. Chronic treatment with analgesics can increase the excitability of neurons in the amygdala, which could underlie the anxiety seen in patients with medication-overuse headache.

Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex.

PubMed

Haegens, Saskia; Barczak, Annamaria; Musacchia, Gabriella; Lipton, Michael L; Mehta, Ashesh D; Lakatos, Peter; Schroeder, Charles E

2015-10-21

The functional significance of the α rhythm is widely debated. It has been proposed that α reflects sensory inhibition and/or a temporal sampling or "parsing" mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate α rhythms and whether the generation of α is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed α current generators in the supragranular, granular, and infragranular layers. MUA phase-locked to local current source/sink configurations confirmed that α rhythms index local neuronal excitability fluctuations. CSD-defined α generators were strongest in the supragranular layers, whereas LFP α power was greatest in the infragranular layers, consistent with some of the previous reports. The discrepancy between LFP and CSD findings appears to be attributable to contamination of the infragranular LFP signal by activity that is volume-conducted from the stronger supragranular α generators. The presence of α generators across cortical depth in V1, S1, and A1 suggests the involvement of α in feedforward as well as feedback processes and is consistent with the view that α rhythms, perhaps in addition to a role in sensory inhibition, may parse sensory input streams in a way that facilitates communication across cortical areas. The α rhythm is thought to reflect sensory inhibition and/or a temporal parsing mechanism. Here, we address two outstanding issues: (1) whether α is a general mechanism across sensory systems and (2) which cortical layers generate α oscillations. Using intracranial recordings from macaque V1, S1, and A1, we show α band activity with a similar spectral and laminar profile in each of these sensory areas. Furthermore, α generators were present in each of the cortical layers, with a strong source in superficial layers. We argue that previous findings, locating α generators exclusively in the deeper layers, were biased because of use of less locally specific local field potential measurements. The laminar distribution of α band activity appears more complex than generally assumed. Copyright © 2015 the authors 0270-6474/15/3514341-12$15.00/0.

Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex

PubMed Central

Barczak, Annamaria; Musacchia, Gabriella; Lipton, Michael L.; Mehta, Ashesh D.; Lakatos, Peter; Schroeder, Charles E.

2015-01-01

The functional significance of the α rhythm is widely debated. It has been proposed that α reflects sensory inhibition and/or a temporal sampling or “parsing” mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate α rhythms and whether the generation of α is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed α current generators in the supragranular, granular, and infragranular layers. MUA phase-locked to local current source/sink configurations confirmed that α rhythms index local neuronal excitability fluctuations. CSD-defined α generators were strongest in the supragranular layers, whereas LFP α power was greatest in the infragranular layers, consistent with some of the previous reports. The discrepancy between LFP and CSD findings appears to be attributable to contamination of the infragranular LFP signal by activity that is volume-conducted from the stronger supragranular α generators. The presence of α generators across cortical depth in V1, S1, and A1 suggests the involvement of α in feedforward as well as feedback processes and is consistent with the view that α rhythms, perhaps in addition to a role in sensory inhibition, may parse sensory input streams in a way that facilitates communication across cortical areas. SIGNIFICANCE STATEMENT The α rhythm is thought to reflect sensory inhibition and/or a temporal parsing mechanism. Here, we address two outstanding issues: (1) whether α is a general mechanism across sensory systems and (2) which cortical layers generate α oscillations. Using intracranial recordings from macaque V1, S1, and A1, we show α band activity with a similar spectral and laminar profile in each of these sensory areas. Furthermore, α generators were present in each of the cortical layers, with a strong source in superficial layers. We argue that previous findings, locating α generators exclusively in the deeper layers, were biased because of use of less locally specific local field potential measurements. The laminar distribution of α band activity appears more complex than generally assumed. PMID:26490871

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.

PubMed

Kajikawa, Yoshinao; Smiley, John F; Schroeder, Charles E

2017-10-18

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. Copyright © 2017 the authors 0270-6474/17/3710139-15$15.00/0.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

PubMed Central

Smiley, John F.; Schroeder, Charles E.

2017-01-01

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed “local” (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. PMID:28924008

EEG current source density and the phenomenology of the default network.

PubMed

Cannon, Rex L; Baldwin, Debora R

2012-10-01

In recent years, there has been an increasing line of research dedicated to the investigation of the default mode network (DMN) of the brain and resting state networks. However, the mental activity of the DMN has not been rigorously assessed to date. The specific aims of the current study were 2-fold: First, we sought to determine whether the current source density (CSD) levels in the DMN would correspond to other neuroimaging techniques. Second, we sought to understand the subjective mental activity of the DMN during baseline recordings. This study was conducted with 63 nonclinical participants, 34 female and 29 males with a mean age of 19.2 years (standard deviation = 2.0). The participants were recorded in 8 conditions. First, 4-minute eyes-closed baseline (ECB) and eyes-opened baseline (EOB) were obtained. The participants then completed 3 assessment instruments and 3 image conditions while the electroencephalography (EEG) was continuously recorded. Participants completed subjective reports for baselines and image conditions. These were rated by 3 independent raters and compared for reliability using a random effects model with an absolute agreement definition. The mean CSD between all conditions differed significantly, in many but not all regions of interest in the DMN. Interestingly, as suggested by other studies, the DMN appears preferential to self-relevant, self-specific, or self-perceptive processes. The reliability analyses show α for interrater agreement for ECB at .95 and EOB at .96. The subjective reports obtained from the participants regarding the mental activities employed during baseline recordings correspond to attentional and self-regulatory processes, which may also implicate the resting state or DMN as playing a direct role in the maintenance of a complex behavior (eg, being still, attending, and self-regulating). Thus, attention and self-regulation constitute the phenomenology of the resting state (DMN) in this study. The results also demonstrate that EEG CSD is a useful method to examine the DMN during concept-specific tasks to elucidate the neural activity associated with these concepts. Standardized low-resolution electromagnetic tomography (sLORETA) can localize to 5 mm(3), which is comparable to the findings in functional magnetic resonance imaging (fMRI). However, sLORETA can provide data about the difference in activity between groups, individuals, or populations which in many cases fMRI cannot provide.

Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention.

PubMed

Kayser, Jürgen; Tenke, Craig E; Abraham, Karen S; Alschuler, Daniel M; Alvarenga, Jorge E; Skipper, Jamie; Warner, Virginia; Bruder, Gerard E; Weissman, Myrna M

2016-11-15

Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100-200ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72-channel ERPs recorded from 152 individuals (ages 13-68years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212ms peak latency), P3 source (385ms) and a late centroparietal source (630ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSD-PCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.

Inclusion of brown midrib dwarf pearl millet silage in the diet of lactating dairy cows.

PubMed

Harper, M T; Melgar, A; Oh, J; Nedelkov, K; Sanchez, G; Roth, G W; Hristov, A N

2018-06-01

Brown midrib brachytic dwarf pearl millet (Pennisetum glaucum) forage harvested at the flag leaf visible stage and subsequently ensiled was investigated as a partial replacement of corn silage in the diet of high-producing dairy cows. Seventeen lactating Holstein cows were fed 2 diets in a crossover design experiment with 2 periods of 28 d each. Both diets had forage:concentrate ratios of 60:40. The control diet (CSD) was based on corn silage and alfalfa haylage, and in the treatment diet, 20% of the corn silage dry matter (corresponding to 10% of the dietary dry matter) was replaced with pearl millet silage (PMD). The effects of partial substitution of corn silage with pearl millet silage on dry matter intake, milk yield, milk components, fatty acid profile, apparent total-tract digestibility of nutrients, N utilization, and enteric methane emissions were analyzed. The pearl millet silage was higher in crude protein and neutral detergent fiber and lower in lignin and starch than the corn silage. Diet did not affect dry matter intake or energy-corrected milk yield, which averaged 46.7 ± 1.92 kg/d. The PMD treatment tended to increase milk fat concentration, had no effect on milk fat yield, and increased milk urea N. Concentrations and yields of milk protein and lactose were not affected by diet. Apparent total-tract digestibility of dry matter decreased from 66.5% in CSD to 64.5% in PMD. Similarly, organic matter and crude protein digestibility was decreased by PMD, whereas neutral- and acid-detergent fiber digestibility was increased. Total milk trans fatty acid concentration was decreased by PMD, with a particular decrease in trans-10 18:1. Urinary urea and fecal N excretion increased with PMD compared with CSD. Milk N efficiency decreased with PMD. Carbon dioxide emission was not different between the diets, but PMD increased enteric methane emission from 396 to 454 g/d and increased methane yield and intensity. Substituting corn silage with brown midrib dwarf pearl millet silage at 10% of the diet dry matter supported high milk production in dairy cows. When planning on farm forage production strategies, brown midrib dwarf pearl millet should be considered as a viable fiber source. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An affinity-structure database of helix-turn-helix: DNA complexes with a universal coordinate system.

PubMed

AlQuraishi, Mohammed; Tang, Shengdong; Xia, Xide

2015-11-19

Molecular interactions between proteins and DNA molecules underlie many cellular processes, including transcriptional regulation, chromosome replication, and nucleosome positioning. Computational analyses of protein-DNA interactions rely on experimental data characterizing known protein-DNA interactions structurally and biochemically. While many databases exist that contain either structural or biochemical data, few integrate these two data sources in a unified fashion. Such integration is becoming increasingly critical with the rapid growth of structural and biochemical data, and the emergence of algorithms that rely on the synthesis of multiple data types to derive computational models of molecular interactions. We have developed an integrated affinity-structure database in which the experimental and quantitative DNA binding affinities of helix-turn-helix proteins are mapped onto the crystal structures of the corresponding protein-DNA complexes. This database provides access to: (i) protein-DNA structures, (ii) quantitative summaries of protein-DNA binding affinities using position weight matrices, and (iii) raw experimental data of protein-DNA binding instances. Critically, this database establishes a correspondence between experimental structural data and quantitative binding affinity data at the single basepair level. Furthermore, we present a novel alignment algorithm that structurally aligns the protein-DNA complexes in the database and creates a unified residue-level coordinate system for comparing the physico-chemical environments at the interface between complexes. Using this unified coordinate system, we compute the statistics of atomic interactions at the protein-DNA interface of helix-turn-helix proteins. We provide an interactive website for visualization, querying, and analyzing this database, and a downloadable version to facilitate programmatic analysis. This database will facilitate the analysis of protein-DNA interactions and the development of programmatic computational methods that capitalize on integration of structural and biochemical datasets. The database can be accessed at http://ProteinDNA.hms.harvard.edu.

Tautomerism in chemical information management systems

NASA Astrophysics Data System (ADS)

Warr, Wendy A.

2010-06-01

Tautomerism has an impact on many of the processes in chemical information management systems including novelty checking during registration into chemical structure databases; storage of structures; exact and substructure searching in chemical structure databases; and depiction of structures retrieved by a search. The approaches taken by 27 different software vendors and database producers are compared. It is hoped that this comparison will act as a discussion document that could ultimately improve databases and software for researchers in the future.

Columba: an integrated database of proteins, structures, and annotations.

PubMed

Trissl, Silke; Rother, Kristian; Müller, Heiko; Steinke, Thomas; Koch, Ina; Preissner, Robert; Frömmel, Cornelius; Leser, Ulf

2005-03-31

Structural and functional research often requires the computation of sets of protein structures based on certain properties of the proteins, such as sequence features, fold classification, or functional annotation. Compiling such sets using current web resources is tedious because the necessary data are spread over many different databases. To facilitate this task, we have created COLUMBA, an integrated database of annotations of protein structures. COLUMBA currently integrates twelve different databases, including PDB, KEGG, Swiss-Prot, CATH, SCOP, the Gene Ontology, and ENZYME. The database can be searched using either keyword search or data source-specific web forms. Users can thus quickly select and download PDB entries that, for instance, participate in a particular pathway, are classified as containing a certain CATH architecture, are annotated as having a certain molecular function in the Gene Ontology, and whose structures have a resolution under a defined threshold. The results of queries are provided in both machine-readable extensible markup language and human-readable format. The structures themselves can be viewed interactively on the web. The COLUMBA database facilitates the creation of protein structure data sets for many structure-based studies. It allows to combine queries on a number of structure-related databases not covered by other projects at present. Thus, information on both many and few protein structures can be used efficiently. The web interface for COLUMBA is available at http://www.columba-db.de.