Time-Domain Receiver Function Deconvolution using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Moreira, L. P.

2017-12-01

Receiver Functions (RF) are well know method for crust modelling using passive seismological signals. Many different techniques were developed to calculate the RF traces, applying the deconvolution calculation to radial and vertical seismogram components. A popular method used a spectral division of both components, which requires human intervention to apply the Water Level procedure to avoid instabilities from division by small numbers. One of most used method is an iterative procedure to estimate the RF peaks and applying the convolution with vertical component seismogram, comparing the result with the radial component. This method is suitable for automatic processing, however several RF traces are invalid due to peak estimation failure.In this work it is proposed a deconvolution algorithm using Genetic Algorithm (GA) to estimate the RF peaks. This method is entirely processed in the time domain, avoiding the time-to-frequency calculations (and vice-versa), and totally suitable for automatic processing. Estimated peaks can be used to generate RF traces in a seismogram format for visualization. The RF trace quality is similar for high magnitude events, although there are less failures for RF calculation of smaller events, increasing the overall performance for high number of events per station.

Structure and functional analysis of LptC, a conserved membrane protein involved in the lipopolysaccharide export pathway in Escherichia coli.

PubMed

Tran, An X; Dong, Changjiang; Whitfield, Chris

2010-10-22

LptC is a conserved bitopic inner membrane protein from Escherichia coli involved in the export of lipopolysaccharide from its site of synthesis in the cytoplasmic membrane to the outer membrane. LptC forms a complex with the ATP-binding cassette transporter, LptBFG, which is thought to facilitate the extraction of lipopolysaccharide from the inner membrane and release it into a translocation pathway that includes the putative periplasmic chaperone LptA. Cysteine modification experiments established that the catalytic domain of LptC is oriented toward the periplasm. The structure of the periplasmic domain is described at a resolution of 2.2-Å from x-ray crystallographic data. The periplasmic domain of LptC consists of a twisted boat structure with two β-sheets in apposition to each other. The β-sheets contain seven and eight antiparallel β-strands, respectively. This structure bears a high degree of resemblance to the crystal structure of LptA. Like LptA, LptC binds lipopolysaccharide in vitro. In vitro, LptA can displace lipopolysaccharide from LptC (but not vice versa), consistent with their locations and their proposed placement in a unidirectional export pathway.

The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

PubMed Central

Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

2009-01-01

The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

Interaction between mating-type proteins from the homothallic fungus Sordaria macrospora.

PubMed

Jacobsen, Sabine; Wittig, Michael; Pöggeler, Stefanie

2002-06-01

Mating-type genes control sexual development in ascomycetes. Little is known about their function in homothallic species, which are self-fertile and do not require a mating partner for sexual reproduction. The function of mating-type genes in the homothallic fungus Sordaria macrospora was assayed using a yeast system in order to find properties typical of eukaryotic transcription factors. We were able to demonstrate that the mating-type proteins SMTA-1 and SMTa-1 have domains capable of activating transcription of yeast reporter genes. Two-hybrid analysis for heterodimerization and homodimerization revealed the ability of SMTA-1 to interact with SMTa-1 and vice versa. These two proteins are encoded by different mating types in the related heterothallic species Neurospora crassa. The interaction between SMTA-1 and SMTa-1 was defined by experiments with truncated versions of SMTA-1 and in vitro by means of protein cross-linking. Moreover, we gained evidence for homodimerization of SMTA-1. Possible functions of mating-type proteins in the homothallic ascomycete S. macrospora are discussed.

Sequence Exchange between Homologous NB-LRR Genes Converts Virus Resistance into Nematode Resistance, and Vice Versa1[OPEN

PubMed Central

Koropacka, Kamila; Roosien, Jan; Dees, Robert; Overmars, Hein; van Schaik, Casper; Pomp, Rikus; Bouwman, Liesbeth; Helder, Johannes; Bakker, Jaap; Smant, Geert

2017-01-01

Plants have evolved a limited repertoire of NB-LRR disease resistance (R) genes to protect themselves against myriad pathogens. This limitation is thought to be counterbalanced by the rapid evolution of NB-LRR proteins, as only a few sequence changes have been shown to be sufficient to alter resistance specificities toward novel strains of a pathogen. However, little is known about the flexibility of NB-LRR R genes to switch resistance specificities between phylogenetically unrelated pathogens. To investigate this, we created domain swaps between the close homologs Gpa2 and Rx1, which confer resistance in potato (Solanum tuberosum) to the cyst nematode Globodera pallida and Potato virus X, respectively. The genetic fusion of the CC-NB-ARC of Gpa2 with the LRR of Rx1 (Gpa2CN/Rx1L) results in autoactivity, but lowering the protein levels restored its specific activation response, including extreme resistance to Potato virus X in potato shoots. The reciprocal chimera (Rx1CN/Gpa2L) shows a loss-of-function phenotype, but exchange of the first three LRRs of Gpa2 by the corresponding region of Rx1 was sufficient to regain a wild-type resistance response to G. pallida in the roots. These data demonstrate that exchanging the recognition moiety in the LRR is sufficient to convert extreme virus resistance in the leaves into mild nematode resistance in the roots, and vice versa. In addition, we show that the CC-NB-ARC can operate independently of the recognition specificities defined by the LRR domain, either aboveground or belowground. These data show the versatility of NB-LRR genes to generate resistance to unrelated pathogens with completely different lifestyles and routes of invasion. PMID:28747428

Sequence Exchange between Homologous NB-LRR Genes Converts Virus Resistance into Nematode Resistance, and Vice Versa.

PubMed

Slootweg, Erik; Koropacka, Kamila; Roosien, Jan; Dees, Robert; Overmars, Hein; Lankhorst, Rene Klein; van Schaik, Casper; Pomp, Rikus; Bouwman, Liesbeth; Helder, Johannes; Schots, Arjen; Bakker, Jaap; Smant, Geert; Goverse, Aska

2017-09-01

Plants have evolved a limited repertoire of NB-LRR disease resistance ( R ) genes to protect themselves against myriad pathogens. This limitation is thought to be counterbalanced by the rapid evolution of NB-LRR proteins, as only a few sequence changes have been shown to be sufficient to alter resistance specificities toward novel strains of a pathogen. However, little is known about the flexibility of NB-LRR R genes to switch resistance specificities between phylogenetically unrelated pathogens. To investigate this, we created domain swaps between the close homologs Gpa2 and Rx1 , which confer resistance in potato ( Solanum tuberosum ) to the cyst nematode Globodera pallida and Potato virus X , respectively. The genetic fusion of the CC-NB-ARC of Gpa2 with the LRR of Rx1 (Gpa2 CN /Rx1 L ) results in autoactivity, but lowering the protein levels restored its specific activation response, including extreme resistance to Potato virus X in potato shoots. The reciprocal chimera (Rx1 CN /Gpa2 L ) shows a loss-of-function phenotype, but exchange of the first three LRRs of Gpa2 by the corresponding region of Rx1 was sufficient to regain a wild-type resistance response to G. pallida in the roots. These data demonstrate that exchanging the recognition moiety in the LRR is sufficient to convert extreme virus resistance in the leaves into mild nematode resistance in the roots, and vice versa. In addition, we show that the CC-NB-ARC can operate independently of the recognition specificities defined by the LRR domain, either aboveground or belowground. These data show the versatility of NB-LRR genes to generate resistance to unrelated pathogens with completely different lifestyles and routes of invasion. © 2017 American Society of Plant Biologists. All Rights Reserved.

MAPPING THE PROJECTIONS OF CHILD VARIABLES UPON A SPECIAL PARENT BEHAVIOR MODEL AND VICE VERSA.

ERIC Educational Resources Information Center

LAUTERBACH, CARL G.; SCHAEFER, EARL S.

SPHERICAL MODELS OF PARENT BEHAVIOR AND OF SELF-REPORTED PERSONALITY ADJUSTMENT WERE CONSTRUCTED IN AN ATTEMPT TO EXAMINE INTERRELATIONSHIPS OF THE VARIABLES OF THOSE DOMAINS. THE THREE MAJOR DIMENSIONS OF PARENT BEHAVIOR ARE DESCRIBED AND EMPLOYED--(1) ACCEPTANCE VS. REJECTION, (2) PSYCHOLOGICAL CONTROL, AND (3) LAX VS. FIRM CONTROL. THE THREE…

Leveraging a National Opportunity to Create a New Model for Civic Engagement

ERIC Educational Resources Information Center

Rodriguez-Farrar, Hanna; Finley, Ashley

2017-01-01

The presidential and vice-presidential debates organized by the Commission on Presidential Debates have been among the most-viewed television programs in history. But much has changed since the debates were first televised in 1960. Information channels that were once the domain of traditional media (i.e., television and print journalism) are being…

Making Connections among Multiple Graphical Representations of Fractions: Sense-Making Competencies Enhance Perceptual Fluency, but Not Vice Versa

ERIC Educational Resources Information Center

Rau, Martina A.; Aleven, Vincent; Rummel, Nikol

2017-01-01

Prior research shows that representational competencies that enable students to use graphical representations to reason and solve tasks is key to learning in many science, technology, engineering, and mathematics domains. We focus on two types of representational competencies: (1) "sense making" of connections by verbally explaining how…

The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

PubMed Central

Dingemans, Jozef; Poudyal, Bandita

2018-01-01

ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two distinct pathways leading to biofilm formation and biofilm drug tolerance are under the control of two sets of amino acid residues located within the HmsP sensory domain of SagS. The respective amino acids are likely part of ligand binding interaction sites. Thus, our findings have the potential not only to enable the manipulation of SagS function but also to enable research of biofilm drug tolerance in a manner independent of biofilm formation (and vice versa). Moreover, the manipulation of SagS function represents a promising target/avenue open for biofilm control. PMID:29848761

Effects of local thermodynamics and of stellar mass ratio on accretion disc stability in close binaries

NASA Astrophysics Data System (ADS)

Lanzafame, G.

2009-08-01

Inflow kinematics at the inner Lagrangian point L1, gas compressibility, and physical turbulent viscosity play a fundamental role on accretion disc dynamics and structure in a close binary (CB). Physical viscosity supports the accretion disc development inside the primary gravitational potential well, developing the gas radial transport, converting mechanical energy into heat. The Stellar-Mass-Ratio (SMR) between the compact primary and the secondary star (M1/M2) is also effective, not only in the location of the inner Lagrangian point, but also in the angular kinematics of the mass transfer and in the geometry of the gravitational potential wells. In this work we pay attention in particular to the role of the SMR, evaluating boundaries, separating theoretical domains in compressibility-viscosity graphs where physical conditions allow a well-bound disc development, as a function of mass transfer kinematic conditions. In such domains, the lower is the gas compressibility (the higher the polytropic index γ), the higher is the physical viscosity (α) requested. In this work, we show how the boundaries of such domains vary as a function of M1/M2. Conclusions as far as dwarf novae outbursts are concerned, induced by mass transfer rate variations, are also reported. The smaller M1/M2, the shorter the duration of the active-to-quiet and vice-versa transitional phases. Time-scales are of the order of outburst duration of SU Uma, OY Car, Z Cha and SS Cyg-like objects. Moreover, conclusions as far as active-quiet-active phenomena in a CB, according to viscous-thermal instabilities, in accordance to such domains, are also reported.

A Computational Analysis of Mental Image Generation: Evidence from Functional Dissociations in Split-Brain Patients.

DTIC Science & Technology

1984-08-20

neuropsychological data on the apraxias and the visual agnosias imply that motor and visual memories can be separately spared or destroyed after brain...agraphia Imagery dissociations 53 and (vice versa), and visual object agnosia without apraxia (and vice versa). We next asked him to *draw the letters in

Influence of Kohn singularity on the occurrence scattering time in degenerate quantum collisional plasmas

NASA Astrophysics Data System (ADS)

Lee, Myoung-Jae; Jung, Young-Dae

2017-10-01

The influence of Kohn singularity on the occurrence scattering time for the electron-ion interaction is investigated in degenerate quantum collisional plasmas. The first-order eikonal analysis is used to obtain the scattering amplitude and the occurrence scattering time. The result shows that the Friedel oscillation due to the Kohn singularity suppresses the advance phenomena of occurrence scattering time in both forward and backward scattering domains. It is shown that the increase of plasmon energy would reduce the time advance for both forward and backward scattering domains. However, the increase of Fermi energy would enhance the phenomena of time advance. It is also found that the time advance with high collision frequency is larger than that with low collision frequency for the forward scattering domain and vice versa for the backward scattering domain. We have shown that the time advance is stronger in general for the forward scattering domain than that for the backward scattering domain.

Conservation and variability in the structure and function of the Cas5d endoribonuclease in the CRISPR-mediated microbial immune system.

PubMed

Koo, Yoon; Ka, Donghyun; Kim, Eun-Jin; Suh, Nayoung; Bae, Euiyoung

2013-10-23

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form an RNA-mediated microbial immune system against invading foreign genetic elements. Cas5 proteins constitute one of the most prevalent Cas protein families in CRISPR-Cas systems and are predicted to have RNA recognition motif (RRM) domains. Cas5d is a subtype I-C-specific Cas5 protein that can be divided into two distinct subgroups, one of which has extra C-terminal residues while the other contains a longer insertion in the middle of its N-terminal RRM domain. Here, we report crystal structures of Cas5d from Streptococcus pyogenes and Xanthomonas oryzae, which respectively represent the two Cas5d subgroups. Despite a common domain architecture consisting of an N-terminal RRM domain and a C-terminal β-sheet domain, the structural differences between the two Cas5d proteins are highlighted by the presence of a unique extended helical region protruding from the N-terminal RRM domain of X. oryzae Cas5d. We also demonstrate that Cas5d proteins possess not only specific endoribonuclease activity for CRISPR RNAs but also nonspecific double-stranded DNA binding affinity. These findings suggest that Cas5d may play multiple roles in CRISPR-mediated immunity. Furthermore, the specific RNA processing was also observed between S. pyogenes Cas5d protein and X. oryzae CRISPR RNA and vice versa. This cross-species activity of Cas5d provides a special opportunity for elucidating conserved features of the CRISPR RNA processing event. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modeling the Combined Terrorist-Narcotics Trafficker Threat to National Security

DTIC Science & Technology

2012-05-01

views expressed in this article are those of the authors and do not reflect the official policy or position of the National Defense University...Mason University. Dr. Woodcock was Chief Scientist , Vice President, and Director of the Advanced Mathematics Program, BAE SYSTEMS-Portal Solutions...this relationship. In some cases, both organizations need the same facilitators: improve financial gains, expand geographical domains, provide common

Presidential Leadership in Institutional Advancement: From the Perspective of the President and Vice President of Institutional Advancement

ERIC Educational Resources Information Center

Sturgis, Rhonda

2006-01-01

Since the establishment of higher education systems in the US the position of college and university president has evolved. In regards to fund-raising this position has changed dramatically with the creation of the vice president of institutional advancement. Over time these two positions have expanded the fund-raising function into a team effort.…

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

PubMed Central

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I; Lindahl, Erik; Elinder, Fredrik

2016-01-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions – a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. PMID:27278891

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

NASA Astrophysics Data System (ADS)

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I.; Lindahl, Erik; Elinder, Fredrik

2016-06-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.

The HAMP Signal Relay Domain Adopts Multiple Conformational States through Collective Piston and Tilt Motions

PubMed Central

Zhu, Lizhe; Bolhuis, Peter G.; Vreede, Jocelyne

2013-01-01

The HAMP domain is a linker region in prokaryotic sensor proteins and relays input signals to the transmitter domain and vice versa. Functional as a dimer, the structure of HAMP shows a parallel coiled-coil motif comprising four helices. To date, it is unclear how HAMP can relay signals from one domain to another, although several models exist. In this work, we use molecular simulation to test the hypothesis that HAMP adopts different conformations, one of which represents an active, signal-relaying configuration, and another an inactive, resting state. We first performed molecular dynamics simulation on the prototype HAMP domain Af1503 from Archaeoglobus fulgidus. We explored its conformational space by taking the structure of the A291F mutant disabling HAMP activity as a starting point. These simulations revealed additional conformational states that differ in the tilt angles between the helices as well as the relative piston shifts of the helices relative to each other. By enhancing the sampling in a metadynamics set up, we investigated three mechanistic models for HAMP signal transduction. Our results indicate that HAMP can access additional conformational states characterized by piston motion. Furthermore, the piston motion of the N-terminal helix of one monomer is directly correlated with the opposite piston motion of the C-terminal helix of the other monomer. The change in piston motion is accompanied by a change in tilt angle between the monomers, thus revealing that HAMP exhibits a collective motion, i.e. a combination of changes in tilt angles and a piston-like displacement. Our results provide insights into the conformational changes that underlie the signaling mechanism involving HAMP. PMID:23468603

Enhancing and reducing chirality by opposite circularly-polarized light irradiation on crystalline chiral domains consisting of nonchiral photoresponsive W-shaped liquid crystal molecules.

PubMed

Choi, Suk-Won; Takezoe, Hideo

2016-09-28

We found possible chirality enhancement and reduction in chiral domains formed by photoresponsive W-shaped molecules by irradiation with circularly polarized light (CPL). The W-shaped molecules exhibit a unique smectic phase with spontaneously segregated chiral domains, although the molecules are nonchiral. The chirality control was generated in the crystalline phase, which shows chiral segregation as in the upper smectic phase, and the result appeared to be as follows: for a certain chiral domain, right-CPL stimuli enhanced the chirality, while left-CPL stimuli reduced the chirality, and vice versa for another chiral domain. Interestingly, no domain-size change could be observed after CPL irradiation, suggesting some changes in the causes of chirality. In this way, the present system can recognize the handedness of the applied chiral stimuli. In other words, the present material can be used as a sensitive chiral-stimuli-recognizing material and should find invaluable applications, including in chiroptical switches, sensors, and memories as well as in chiral recognition.

Aggregation of population‐based genetic variation over protein domain homologues and its potential use in genetic diagnostics

PubMed Central

Wiel, Laurens; Venselaar, Hanka; Veltman, Joris A.; Vriend, Gert

2017-01-01

Abstract Whole exomes of patients with a genetic disorder are nowadays routinely sequenced but interpretation of the identified genetic variants remains a major challenge. The increased availability of population‐based human genetic variation has given rise to measures of genetic tolerance that have been used, for example, to predict disease‐causing genes in neurodevelopmental disorders. Here, we investigated whether combining variant information from homologous protein domains can improve variant interpretation. For this purpose, we developed a framework that maps population variation and known pathogenic mutations onto 2,750 “meta‐domains.” These meta‐domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta‐domains high‐frequency population variation re‐occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa. The use of these meta‐domains can improve the interpretation of genetic variation. PMID:28815929

Non-intentional but not automatic: reduction of word- and arrow-based compatibility effects by sound distractors in the same categorical domain.

PubMed

Miles, James D; Proctor, Robert W

2009-10-01

In the current study, we show that the non-intentional processing of visually presented words and symbols can be attenuated by sounds. Importantly, this attenuation is dependent on the similarity in categorical domain between the sounds and words or symbols. Participants performed a task in which left or right responses were made contingent on the color of a centrally presented target that was either a location word (LEFT or RIGHT) or a left or right arrow. Responses were faster when they were on the side congruent with the word or arrow. This bias was reduced for location words by a neutral spoken word and for arrows by a tone series, but not vice versa. We suggest that words and symbols are processed with minimal attentional requirements until they are categorized into specific knowledge domains, but then become sensitive to other information within the same domain regardless of the similarity between modalities.

29 CFR 452.19 - Executive functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Executive functions. 452.19 Section 452.19 Labor... DISCLOSURE ACT OF 1959 Coverage of Election Provisions § 452.19 Executive functions. The definitional phrase “a person authorized to perform the functions of president, vice president, secretary, treasurer, or...

Why Finance Should Care about Ecology.

PubMed

Scholtens, Bert

2017-07-01

Finance ignores ecosystems, which has resulted in a growing list of environmental and social problems. In this article, the importance of ecology for finance is assessed. We suggest The piece also suggests that the financial intermediation perspective can align finance and ecology for the benefit of society. This requires that financial institutions account for information about the impact of finance on the environment and vice versa, and that they are held accountable by their supervisors in this domain. Copyright © 2017 Elsevier Ltd. All rights reserved.

29 CFR 404.1 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... from insurance and endowment contracts, capital gains, discharge of indebtedness, share of partnership... person authorized to perform the functions of president, vice president, secretary, treasurer, or other executive functions of a labor organization, and any member of its executive board or similar governing body...

29 CFR 404.1 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... from insurance and endowment contracts, capital gains, discharge of indebtedness, share of partnership... person authorized to perform the functions of president, vice president, secretary, treasurer, or other executive functions of a labor organization, and any member of its executive board or similar governing body...

29 CFR 404.1 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... from insurance and endowment contracts, capital gains, discharge of indebtedness, share of partnership... person authorized to perform the functions of president, vice president, secretary, treasurer, or other executive functions of a labor organization, and any member of its executive board or similar governing body...

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

Novascone, Stephen Rhead; Peterson, John William

Abstract This report documents the progress of simulating pore migration in ceramic (UO 2 and mixed oxide or MOX) fuel using BISON. The porosity field is treated as a function of space and time whose evolution is governed by a custom convection-diffusion-reaction equation (described here) which is coupled to the heat transfer equation via the temperature field. The porosity is initialized to a constant value at every point in the domain, and as the temperature (and its gradient) are increased by application of a heat source, the pores move up the thermal gradient and accumulate at the center of themore » fuel in a time-frame that is consistent with observations from experiments. There is an inverse dependence of the fuel’s thermal conductivity on porosity (increasing porosity decreases thermal conductivity, and vice-versa) which is also accounted for, allowing the porosity equation to couple back into the heat transfer equation. Results from an example simulation are shown to demonstrate the new capability.« less

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.

PubMed

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2017-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo . However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa , which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo .

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics

PubMed Central

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2018-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo. However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa, which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo. PMID:29375551

Linking Executive Function and Peer Problems from Early Childhood Through Middle Adolescence.

PubMed

Holmes, Christopher J; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2016-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children's Behavior Questionnaire and Child Behavior Checklist and child's performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and afterschool caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa.

Linking Executive Function and Peer Problems from Early Childhood through Middle Adolescence

PubMed Central

Holmes, Christopher J.; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2015-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1,164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children’s Behavior Questionnaire and Child Behavior Checklist and child’s performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and after school caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa. PMID:26096194

76 FR 17974 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

...\\ Historically, the Vice Chairman's primary function was to facilitate communication between the Exchange and its... proposes to amend its Bylaws to eliminate its Audit Committee because its functions are duplicative of the functions performed by the Audit Committee of its parent company, CBOE Holdings, Inc. (``CBOE Holdings...

Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains*

PubMed Central

Kienast, Yvonne; Jucknischke, Ute; Scheiblich, Stefan; Thier, Martina; de Wouters, Mariana; Haas, Alexander; Lehmann, Christian; Brand, Verena; Bernicke, Dirk; Honold, Konrad; Lorenz, Stefan

2016-01-01

By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-β family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9·pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants. PMID:26677222

Adaptation of interoperability standards for cross domain usage

NASA Astrophysics Data System (ADS)

Essendorfer, B.; Kerth, Christian; Zaschke, Christian

2017-05-01

As globalization affects most aspects of modern life, challenges of quick and flexible data sharing apply to many different domains. To protect a nation's security for example, one has to look well beyond borders and understand economical, ecological, cultural as well as historical influences. Most of the time information is produced and stored digitally and one of the biggest challenges is to receive relevant readable information applicable to a specific problem out of a large data stock at the right time. These challenges to enable data sharing across national, organizational and systems borders are known to other domains (e.g., ecology or medicine) as well. Solutions like specific standards have been worked on for the specific problems. The question is: what can the different domains learn from each other and do we have solutions when we need to interlink the information produced in these domains? A known problem is to make civil security data available to the military domain and vice versa in collaborative operations. But what happens if an environmental crisis leads to the need to quickly cooperate with civil or military security in order to save lives? How can we achieve interoperability in such complex scenarios? The paper introduces an approach to adapt standards from one domain to another and lines out problems that have to be overcome and limitations that may apply.

Psychosis Is Mutable over Time: A Longitudinal Psychopathology Study.

PubMed

Wigand, Moritz E; Lang, Fabian U; Müller-Stierlin, Annabel S; Reichhardt, Lea; Trif, Silvana; Schulze, Thomas G; Strik, Werner; Becker, Thomas; Jäger, Markus

2018-03-14

A neurobiologically informed, system-specific psychopathological approach has been suggested for use in schizophrenia. However, to our knowledge, such an approach has not been used to prospectively describe the course of schizophrenia. We assessed psychopathology in a well-described sample of 100 patients with schizophrenia or schizoaffective disorder with the Bern Psychopathology Scale (BPS) at 6-month intervals for up to 18 months. The BPS groups symptoms into the 3 domains language, affectivity and motor behaviour; each domain is rated as being normal, inhibited or disinhibited. In addition, we collected qualitative psychopathological data in the form of case reports. Forty-eight patients completed at least 2 assessments over the course of at least 1 year. Of these, 16 patients (33.3%) showed a bipolar course pattern (i.e., a switch from inhibited to disinhibited or vice versa) in 1 domain and 6 patients (12.5%) in more than 1 domain. Shifts from 1 dominant domain to another were seen frequently (n = 20, 41.7%), but shifts between 1 dominant domain and a combination of dominant domains were more common (n = 33, 68.8%). The course of schizophrenia is heterogeneous and shows frequent changes in psychopathology. This should be taken into account in the communication with patients and in the research on underlying illness mechanisms and treatment. A major limitation of this study is the small sample size. © 2018 S. Karger AG, Basel.

Ecologically rational choice and the structure of the environment.

PubMed

Pleskac, Timothy J; Hertwig, Ralph

2014-10-01

In life, risk is reward and vice versa. Unfortunately, the big rewards people desire are relatively unlikely to occur. This relationship between risk and reward or probabilities and payoffs seems obvious to the financial community and to laypeople alike. Yet theories of decision making have largely ignored it. We conducted an ecological analysis of life's gambles, ranging from the domains of roulette and life insurance to scientific publications and artificial insemination. Across all domains, payoffs and probabilities proved intimately tied, with payoff magnitudes signaling their probabilities. In some cases, the constraints of the market result in these two core elements of choice being related via a power function; in other cases, other factors such as social norms appear to produce the inverse relationship between risks and rewards. We offer evidence that decision makers exploit this relationship in the form of a heuristic--the risk-reward heuristic--to infer the probability of a payoff during decisions under uncertainty. We demonstrate how the heuristic can help explain observed ambiguity aversion. We further show how this ecological relationship can inform other aspects of decision making, particularly the approach of using monetary lotteries to study choice under risk and uncertainty. Taken together, these findings suggest that theories of decision making need to model not only the decision process but also the environment to which the process is adapted.

76 FR 7610 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-10

...). Historically, the Vice Chairman's primary functions were to take a lead role in facilitating communication... limited role, focused solely on CBOE. Under its charter, the primary functions of the CBOE Audit Committee... management will perform these functions. Section 2.3 of the Bylaws is proposed to be amended to delete the...

Crossover from attractive to repulsive Casimir forces and vice versa.

PubMed

Schmidt, Felix M; Diehl, H W

2008-09-05

Systems described by an O(n) symmetrical varphi;{4} Hamiltonian are considered in a d-dimensional film geometry at their bulk critical points. The critical Casimir forces between the film's boundary planes B_{j}, j=1,2, are investigated as functions of film thickness L for generic symmetry-preserving boundary conditions partial differential_{n}phi=c[over composite function]_{j}phi. The L-dependent part of the reduced excess free energy per cross-sectional area takes the scaling form f_{res} approximately D(c_{1}L;{Phi/nu},c_{2}L;{Phi/nu})/L;{d-1} when d<4, where c_{i} are scaling fields associated with the variables c[over composite function]_{i} and Phi is a surface crossover exponent. Explicit two-loop renormalization group results for the function D(c_{1},c_{2}) at d=4- dimensions are presented. These show that (i) the Casimir force can have either sign, depending on c_{1} and c_{2}, and (ii) for appropriate choices of the enhancements c[over composite function]_{j}, crossovers from attraction to repulsion and vice versa occur as L increases.

49 CFR 1011.3 - The Chairman, Vice Chairman, and Board Member.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the executive head of the Board and has general responsibilities for: (i) The overall management and functioning of the Board; (ii) The formulation of plans and policies designed to assure the effective... the Board exercises the executive and administrative functions of the Board, including: (i) The...

AgRISTARS: Yield model development/soil moisture. Interface control document

NASA Technical Reports Server (NTRS)

1980-01-01

The interactions and support functions required between the crop Yield Model Development (YMD) Project and Soil Moisture (SM) Project are defined. The requirements for YMD support of SM and vice-versa are outlined. Specific tasks in support of these interfaces are defined for development of support functions.

Integrating Development, Alumni Relations, and Marketing for Fundraising Success

ERIC Educational Resources Information Center

Stevick, Thomas R.

2010-01-01

At many institutions, the vice president of institutional advancement oversees the functions of development, alumni relations, and marketing and communications. University leaders expect these functions to be integrated and to work hand-in-hand to advance the institution's mission, particularly in the area of private donations. The reality is that…

A framework for discrete stochastic simulation on 3D moving boundary domains

DOE PAGES

Drawert, Brian; Hellander, Stefan; Trogdon, Michael; ...

2016-11-14

We have developed a method for modeling spatial stochastic biochemical reactions in complex, three-dimensional, and time-dependent domains using the reaction-diffusion master equation formalism. In particular, we look to address the fully coupled problems that arise in systems biology where the shape and mechanical properties of a cell are determined by the state of the biochemistry and vice versa. To validate our method and characterize the error involved, we compare our results for a carefully constructed test problem to those of a microscale implementation. Finally, we demonstrate the effectiveness of our method by simulating a model of polarization and shmoo formationmore » during the mating of yeast. The method is generally applicable to problems in systems biology where biochemistry and mechanics are coupled, and spatial stochastic effects are critical.« less

Toward a psychology of human-animal relations.

PubMed

Amiot, Catherine E; Bastian, Brock

2015-01-01

Nonhuman animals are ubiquitous to human life, and permeate a diversity of social contexts by providing humans with food and clothing, serving as participants in research, improving healing, and offering entertainment, leisure, and companionship. Despite the impact that animals have on human lives and vice versa, the field of psychology has barely touched upon the topic of human-animal relations as an important domain of human activity. We review the current state of research on human-animal relations, showing how this body of work has implications for a diverse range of psychological themes including evolutionary processes, development, normative factors, gender and individual differences, health and therapy, and intergroup relations. Our aim is to highlight human-animal relations as a domain of human life that merits theoretical and empirical attention from psychology as a discipline. PsycINFO Database Record (c) 2015 APA, all rights reserved.

77 FR 25207 - Sunshine Act Meetings; National Science Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... Gravity Wave Observatory (LIGO) Thursday, May 3, 2012 Committee on Strategy and Budget (CSB) Open Session... Election for NSB Chairman and Vice Chairman NSF Personnel Strategic Alignment of Budget and Functions...

News in Brief

NASA Astrophysics Data System (ADS)

2012-12-01

Vice President Shen Wenqing Meets with Ecuadorian Guests For the First Time a Chinese Researcher Gives the Plenary Lecture at the International Symposium on Combustion Vice President Shen Wenqing Meets with NSERC Executive Vice-President Vice President Sun Jiaguang Meets with CONICYT President Ten-Year Anniversary Workshop of NSFC-IIASA Young Scientists Summer Program Held in Beijing Vice President Shen Wenqing Meets Guest from K.T. Li Foundation The 6th ASIAHORCs General Meeting in Beijing President Chen Yiyu Meets with DFG Delegation Vice President Shen Yan Visited International Organizations in Italy and France Vice President Wang Jie Meets with CEO of Academy of Malaysia

Upper crustal structure of Alabama from regional magnetic and gravity data: Using geology to interpret geophysics, and vice versa

USGS Publications Warehouse

Steltenpohl, Mark G.; Horton, J. Wright; Hatcher, Robert D.; Zietz, Isidore; Daniels, David L.; Higgins, Michael W.

2013-01-01

Aeromagnetic and gravity data sets obtained for Alabama (United States) have been digitally merged and filtered to enhance upper-crustal anomalies. Beneath the Appalachian Basin in northwestern Alabama, broad deep-crustal anomalies of the continental interior include the Grenville front and New York–Alabama lineament (dextral fault). Toward the east and south, high-angle discordance between the northeast-trending Appalachians and the east-west–trending wedge of overlapping Mesozoic and Cenozoic Gulf Coastal Plain sediments reveals how bedrock geophysical signatures progressively change with deeper burial. High-frequency magnetic anomalies in the Appalachian deformed domain (ADD) correspond to amphibolites and mylonites outlining terranes, while broader, lower-amplitude domains include Paleozoic intrusive bodies and Grenville basement gneiss. Fundamental ADD structures (e.g., the Alexander City, Towaliga, and Goat Rock–Bartletts Ferry faults) can be traced southward beneath the Gulf Coastal Plain to the suture with Gondwanan crust of the Suwannee terrane. Within the ADD, there is clear magnetic distinction between Laurentian crust and the strongly linear, high-frequency magnetic highs of peri-Gondwanan (Carolina-Uchee) arc terranes. The contact (Central Piedmont suture) corresponds to surface exposures of the Bartletts Ferry fault. ADD magnetic and gravity signatures are truncated by the east-west–trending Altamaha magnetic low associated with the Suwannee suture. Arcuate northeast-trending magnetic linears of the Suwannee terrane reflect internal structure and Mesozoic failed-rift trends. Geophysical data can be used to make inferences on surface and subsurface geology and vice versa, which has applicability anywhere that bedrock is exposed or concealed beneath essentially non-magnetic sedimentary cover.

Unconscious Imagination and the Mental Imagery Debate

PubMed Central

Brogaard, Berit; Gatzia, Dimitria Electra

2017-01-01

Traditionally, philosophers have appealed to the phenomenological similarity between visual experience and visual imagery to support the hypothesis that there is significant overlap between the perceptual and imaginative domains. The current evidence, however, is inconclusive: while evidence from transcranial brain stimulation seems to support this conclusion, neurophysiological evidence from brain lesion studies (e.g., from patients with brain lesions resulting in a loss of mental imagery but not a corresponding loss of perception and vice versa) indicates that there are functional and anatomical dissociations between mental imagery and perception. Assuming that the mental imagery and perception do not overlap, at least, to the extent traditionally assumed, then the question arises as to what exactly mental imagery is and whether it parallels perception by proceeding via several functionally distinct mechanisms. In this review, we argue that even though there may not be a shared mechanism underlying vision for perception and conscious imagery, there is an overlap between the mechanisms underlying vision for action and unconscious visual imagery. On the basis of these findings, we propose a modification of Kosslyn’s model of imagery that accommodates unconscious imagination and explore possible explanations of the quasi-pictorial phenomenology of conscious visual imagery in light of the fact that its underlying neural substrates and mechanisms typically are distinct from those of visual experience. PMID:28588527

Religion and mental health

PubMed Central

Behere, Prakash B.; Das, Anweshak; Yadav, Richa; Behere, Aniruddh P.

2013-01-01

In this chapter, the relation between religion and mental health and vice versa has been described. From primitive times different religions have different beliefs and systems of worshipping. Every religion with their belief system has implications on mental health and illness. We described how Hindu system of beliefs and rituals may have an effect in causation of various mental illnesses. It is also described how religion can help an individual to sustain one's life in various domains. The relationship between different religion and symptomatology is described. The impact and outcome of religion on mental health have been highlighted. PMID:23858253

The 3-D numerical study of airflow in the compressor/combustor prediffuser and dump diffuser of an industrial gas turbine

NASA Technical Reports Server (NTRS)

Agrawal, Ajay K.; Yang, Tah-Teh

1993-01-01

This paper describes the 3D computations of a flow field in the compressor/combustor diffusers of an industrial gas turbine. The geometry considered includes components such as the combustor support strut, the transition piece and the impingement sleeve with discrete cooling air holes on its surface. Because the geometry was complex and 3D, the airflow path was divided into two computational domains sharing an interface region. The body-fitted grid was generated independently in each of the two domains. The governing equations for incompressible Navier-Stokes equations were solved using the finite volume approach. The results show that the flow in the prediffuser is strongly coupled with the flow in the dump diffuser and vice versa. The computations also revealed that the flow in the dump diffuser is highly nonuniform.

Performance analysis of FET microwave devices by use of extended spectral-element time-domain method

NASA Astrophysics Data System (ADS)

Sheng, Yijun; Xu, Kan; Wang, Daoxiang; Chen, Rushan

2013-05-01

The extended spectral-element time-domain (SETD) method is employed to analyse field effect transistor (FET) microwave devices. In order to impose the contribution of the FET microwave devices into the electromagnetic simulation, the SETD method is extended by introducing a lumped current term into the vector Helmholtz equation. The change of currents on each lumped component can be expressed by the change of voltage via corresponding models of equivalent circuit. The electric fields around the lumped component must be influenced by the change of voltage on each lumped component, and vice versa. So a global coupling about the EM-circuit can be built directly. The fully explicit solving scheme is maintained in this extended SETD method and the CPU time can be saved spontaneously. Three practical FET microwave devices are analysed in this article. The numerical results demonstrate the ability and accuracy of this method.

40 CFR 122.22 - Signatories to permit applications and reports (applicable to State programs, see § 123.25).

Code of Federal Regulations, 2010 CFR

2010-07-01

... including having the explicit or implicit duty of making major capital investment recommendations, and..., secretary, treasurer, or vice-president of the corporation in charge of a principal business function, or any other person who perfoms similar policy- or decision-making functions for the corporation, or (ii...

40 CFR 122.22 - Signatories to permit applications and reports (applicable to State programs, see § 123.25).

Code of Federal Regulations, 2011 CFR

2011-07-01

... including having the explicit or implicit duty of making major capital investment recommendations, and..., secretary, treasurer, or vice-president of the corporation in charge of a principal business function, or any other person who perfoms similar policy- or decision-making functions for the corporation, or (ii...

Compositional clustering in task structure learning

PubMed Central

Frank, Michael J.

2018-01-01

Humans are remarkably adept at generalizing knowledge between experiences in a way that can be difficult for computers. Often, this entails generalizing constituent pieces of experiences that do not fully overlap, but nonetheless share useful similarities with, previously acquired knowledge. However, it is often unclear how knowledge gained in one context should generalize to another. Previous computational models and data suggest that rather than learning about each individual context, humans build latent abstract structures and learn to link these structures to arbitrary contexts, facilitating generalization. In these models, task structures that are more popular across contexts are more likely to be revisited in new contexts. However, these models can only re-use policies as a whole and are unable to transfer knowledge about the transition structure of the environment even if only the goal has changed (or vice-versa). This contrasts with ecological settings, where some aspects of task structure, such as the transition function, will be shared between context separately from other aspects, such as the reward function. Here, we develop a novel non-parametric Bayesian agent that forms independent latent clusters for transition and reward functions, affording separable transfer of their constituent parts across contexts. We show that the relative performance of this agent compared to an agent that jointly clusters reward and transition functions depends environmental task statistics: the mutual information between transition and reward functions and the stochasticity of the observations. We formalize our analysis through an information theoretic account of the priors, and propose a meta learning agent that dynamically arbitrates between strategies across task domains to optimize a statistical tradeoff. PMID:29672581

Cooperative roles of fish protein kinase containing Z-DNA binding domains and double-stranded RNA-dependent protein kinase in interferon-mediated antiviral response.

PubMed

Liu, Ting-Kai; Zhang, Yi-Bing; Liu, Ying; Sun, Fan; Gui, Jian-Fang

2011-12-01

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) inhibits protein synthesis by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). In fish species, in addition to PKR, there exists a PKR-like protein kinase containing Z-DNA binding domains (PKZ). However, the antiviral role of fish PKZ and the functional relationship between fish PKZ and PKR remain unknown. Here we confirmed the coexpression of fish PKZ and PKR proteins in Carassius auratus blastula embryonic (CAB) cells and identified them as two typical interferon (IFN)-inducible eIF2α kinases, both of which displayed an ability to inhibit virus replication. Strikingly, fish IFN or all kinds of IFN stimuli activated PKZ and PKR to phosphorylated eIF2α. Overexpression of both fish kinases together conferred much more significant inhibition of virus replication than overexpression of either protein, whereas morpholino knockdown of both made fish cells more vulnerable to virus infection than knockdown of either. The antiviral ability of fish PKZ was weaker than fish PKR, which correlated with its lower ability to phosphorylate eIF2α than PKR. Moreover, the independent association of fish PKZ or PKR reveals that each of them formed homodimers and that fish PKZ phosphorylated eIF2α independently on fish PKR and vice versa. These results suggest that fish PKZ and PKR play a nonredundant but cooperative role in IFN antiviral response.

Animal NLRs provide structural insights into plant NLR function.

PubMed

Bentham, Adam; Burdett, Hayden; Anderson, Peter A; Williams, Simon J; Kobe, Bostjan

2017-03-01

The plant immune system employs intracellular NLRs (nucleotide binding [NB], leucine-rich repeat [LRR]/nucleotide-binding oligomerization domain [NOD]-like receptors) to detect effector proteins secreted into the plant cell by potential pathogens. Activated plant NLRs trigger a range of immune responses, collectively known as the hypersensitive response (HR), which culminates in death of the infected cell. Plant NLRs show structural and functional resemblance to animal NLRs involved in inflammatory and innate immune responses. Therefore, knowledge of the activation and regulation of animal NLRs can help us understand the mechanism of action of plant NLRs, and vice versa. This review provides an overview of the innate immune pathways in plants and animals, focusing on the available structural and biochemical information available for both plant and animal NLRs. We highlight the gap in knowledge between the animal and plant systems, in particular the lack of structural information for plant NLRs, with crystal structures only available for the N-terminal domains of plant NLRs and an integrated decoy domain, in contrast to the more complete structures available for animal NLRs. We assess the similarities and differences between plant and animal NLRs, and use the structural information on the animal NLR pair NAIP/NLRC4 to derive a plausible model for plant NLR activation. Signalling by cooperative assembly formation (SCAF) appears to operate in most innate immunity pathways, including plant and animal NLRs. Our proposed model of plant NLR activation includes three key steps: (1) initially, the NLR exists in an inactive auto-inhibited state; (2) a combination of binding by activating elicitor and ATP leads to a structural rearrangement of the NLR; and (3) signalling occurs through cooperative assembly of the resistosome. Further studies, structural and biochemical in particular, will be required to provide additional evidence for the different features of this model and shed light on the many existing variations, e.g. helper NLRs and NLRs containing integrated decoys. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Structure-property relations in sputter deposited epitaxial (1-x)Pb(Mg1/3Nb2/3)O3- xPbTiO3 thin films

NASA Astrophysics Data System (ADS)

Frederick, Joshua C.

Lead-based ferroelectric materials are of significant technological importance for sensing and actuation due to their high piezoelectric performance (i.e., the ability to convert an electrical signal to mechanical displacement, and vice versa). Traditionally, bulk ceramic or single crystals materials have filled these roles; however, emerging technologies stand to benefit by incorporating thin films to achieve miniaturization while maintaining high efficiency and sensitivity. Currently, chemical systems that have been well characterized in bulk form (e.g. Pb(Mg1/3Nb2/3)O3- xPbTiO3, or PMN-xPT) require further study to optimize both the chemistry and structure for deployment in thin film devices. Furthermore, the effect of internal electric fields is more significant at the length scales of thin films, resulting in self biases that require compensation to reveal their intrinsic dielectric response. To this end, the structure-property relations of epitaxial PMN-xPT films sputter deposited on a variety of substrates were investigated. Attention was paid to how the structure (i.e., strain state, crystal structure, domain configuration, and defects) gave rise to the ferroelectric, dielectric, and piezoelectric response. Three-dimensional visualization of the dielectric response as a simultaneous function of electric field and temperature revealed the true phase transition of the films, which was found to correspond to the strain state and defect concentration. A lead-buffered anneal process was implemented to enhance the ferroelectric and dielectric response of the films without altering their stoichiometry. It was discovered that PMN- xPT films could be domain-engineered to exhibit a mixed domain state through chemistry and substrate choice. Such films exhibited a monoclinic distortion similar to that of the bulk compositions near the morphotropic phase boundary. Finally, it was revealed that the piezoelectric response could be greatly enhanced by declamping the film from the substrate via a membrane fabrication technique. The membrane structures exhibited enhanced domain wall mobility, suggesting that domain wall motion is crucial for strong piezoelectric performance in PMN-xPT films. The findings can help guide strain- and domain-engineered relaxor ferroelectric thin films tailored for particular applications.

Executive Power and Scaled-Up Gender Subtexts in Australian Entrepreneurial Universities

ERIC Educational Resources Information Center

Blackmore, Jill; Sawers, Naarah

2015-01-01

Deputy Vice Chancellor and Pro Vice Chancellor positions have proliferated in response to the global, corporatised university landscape [Scott, G., S. Bell, H. Coates, and L. Grebennikov. 2010. "Australian Higher Education Leaders in Times of Change: The Role of Pro Vice Chancellor and Deputy Vice Chancellor." "Journal of Higher…

[Family dynamics and chronic illness: children with diabetes in the context of their families].

PubMed

Wirlach-Bartosik, S; Schubert, M T; Freilinger, M; Schober, E

2005-01-01

The present study is based on the assumption of an interaction between family functioning and chronic illness. Using a systemic approach, the intra-familial situation of families with a diabetes-affected child is examined. 44 families were evaluated using a family diagnostic instrument ("Familienbögen") and compared with 31 control families with a healthy child. Furthermore, the study looked at the influence of the level of family functioning on glycemic control, as measured by HbA1c values, and vice versa. Families with a child affected by diabetes showed significantly more dysfunctional domains and higher discrepancies of the ratings in the family diagnostic instrument (p < 0.05). Unexpectedly, no significant interaction between family functioning and glycemic control was found. Poor glycemic control therefore did not have any negative effects on the family dynamics, in fact, the opposite was often the case. Also, the relationship between siblings was judged more positively when one of the siblings was chronically ill (p < 0.05). The results show that despite the fact that diabetes in children may lead to an increase in impairment of intra-familial dynamics, it may, at the same time, offer opportunities for an improvement of family relationships. However, if physiological parameters deteriorate in the child (poor glycemic control), family problems seem to become less important. Success in the treatment of diabetes patients should therefore not only be measured by the quality of glycemic control, but also by considering psychological factors and aspects of family dynamics.

Measurement of optical to electrical and electrical to optical delays with ps-level uncertainty.

PubMed

Peek, H Z; Pinkert, T J; Jansweijer, P P M; Koelemeij, J C J

2018-05-28

We present a new measurement principle to determine the absolute time delay of a waveform from an optical reference plane to an electrical reference plane and vice versa. We demonstrate a method based on this principle with 2 ps uncertainty. This method can be used to perform accurate time delay determinations of optical transceivers used in fiber-optic time-dissemination equipment. As a result the time scales in optical and electrical domain can be related to each other with the same uncertainty. We expect this method will be a new breakthrough in high-accuracy time transfer and absolute calibration of time-transfer equipment.

Detecting Epistemic Vice in Higher Education Policy: Epistemic Insensibility in the Seven Solutions and the REF

ERIC Educational Resources Information Center

Battaly, Heather

2013-01-01

This article argues that the Seven Solutions in the US, and the Research Excellence Framework in the UK, manifest the vice of epistemic insensibility. Section I provides an overview of Aristotle's analysis of moral vice in people. Section II applies Aristotle's analysis to epistemic vice, developing an account of epistemic insensibility. In so…

The expanding universe of ribonucleoproteins: of novel RNA-binding proteins and unconventional interactions.

PubMed

Beckmann, Benedikt M; Castello, Alfredo; Medenbach, Jan

2016-06-01

Post-transcriptional regulation of gene expression plays a critical role in almost all cellular processes. Regulation occurs mostly by RNA-binding proteins (RBPs) that recognise RNA elements and form ribonucleoproteins (RNPs) to control RNA metabolism from synthesis to decay. Recently, the repertoire of RBPs was significantly expanded owing to methodological advances such as RNA interactome capture. The newly identified RNA binders are involved in diverse biological processes and belong to a broad spectrum of protein families, many of them exhibiting enzymatic activities. This suggests the existence of an extensive crosstalk between RNA biology and other, in principle unrelated, cell functions such as intermediary metabolism. Unexpectedly, hundreds of new RBPs do not contain identifiable RNA-binding domains (RBDs), raising the question of how they interact with RNA. Despite the many functions that have been attributed to RNA, our understanding of RNPs is still mostly governed by a rather protein-centric view, leading to the idea that proteins have evolved to bind to and regulate RNA and not vice versa. However, RNPs formed by an RNA-driven interaction mechanism (RNA-determined RNPs) are abundant and offer an alternative explanation for the surprising lack of classical RBDs in many RNA-interacting proteins. Moreover, RNAs can act as scaffolds to orchestrate and organise protein networks and directly control their activity, suggesting that nucleic acids might play an important regulatory role in many cellular processes, including metabolism.

News in Brief

NASA Astrophysics Data System (ADS)

2011-12-01

China Accomplishes International Evaluation on Science Funding and Management Performance Panel Meeting of NSFC-NIH Joint Program in Beijing NSFC and CAS's New Round Collaboration for Large Scientific Facilities Vice President Shen Wenqing Meets with President of the Helmholtz Association NSFC Supervision Delegation Visits to Japan and Korea NSFC Strengthens Ties with PIs of the Research Fund for International Young Scientists The 9th ASIAHORCs Meeting Held in Daejoen, Korea NSFC Vice President Meets with ICTP Director First U.S.-China Women Chemists Workshop in Beijing Vice President Attends 5th ASIAHORCs Meeting NSFC Vice President Attended IIASA Council Meeting NSFC Vice President Meets With JST Guests

Allostery Mediates Ligand Binding to Grb2 Adaptor in a Mutually Exclusive Manner

PubMed Central

McDonald, Caleb B.; El Hokayem, Jimmy; Zafar, Nawal; Balke, Jordan E.; Bhat, Vikas; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Farooq, Amjad

2012-01-01

Allostery plays a key role in dictating the stoichiometry and thermodynamics of multi-protein complexes driving a plethora of cellular processes central to health and disease. Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in concert in lieu of a composite Sos1-Grb2-Gab1 ternary complex. Of particular interest is the observation that the binding of Sos1 to the nSH3 domain within Grb2 sterically blocks the binding of Gab1 to the cSH3 domain and vice versa in a mutually exclusive manner. Importantly, the formation of both the Grb2-Sos1 and Grb2-Gab1 binary complexes is governed by a stoichiometry of 2:1, whereby the respective SH3 domains within Grb2 homodimer bind to Sos1 and Gab1 via multivalent interactions. Collectively, our study sheds new light on the role of allostery in mediating cellular signaling machinery. PMID:23334917

Biclustering Protein Complex Interactions with a Biclique FindingAlgorithm

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

Ding, Chris; Zhang, Anne Ya; Holbrook, Stephen

2006-12-01

Biclustering has many applications in text mining, web clickstream mining, and bioinformatics. When data entries are binary, the tightest biclusters become bicliques. We propose a flexible and highly efficient algorithm to compute bicliques. We first generalize the Motzkin-Straus formalism for computing the maximal clique from L{sub 1} constraint to L{sub p} constraint, which enables us to provide a generalized Motzkin-Straus formalism for computing maximal-edge bicliques. By adjusting parameters, the algorithm can favor biclusters with more rows less columns, or vice verse, thus increasing the flexibility of the targeted biclusters. We then propose an algorithm to solve the generalized Motzkin-Straus optimizationmore » problem. The algorithm is provably convergent and has a computational complexity of O(|E|) where |E| is the number of edges. It relies on a matrix vector multiplication and runs efficiently on most current computer architectures. Using this algorithm, we bicluster the yeast protein complex interaction network. We find that biclustering protein complexes at the protein level does not clearly reflect the functional linkage among protein complexes in many cases, while biclustering at protein domain level can reveal many underlying linkages. We show several new biologically significant results.« less

Digital processing of radiographic images

NASA Technical Reports Server (NTRS)

Bond, A. D.; Ramapriyan, H. K.

1973-01-01

Some techniques are presented and the software documentation for the digital enhancement of radiographs. Both image handling and image processing operations are considered. The image handling operations dealt with are: (1) conversion of format of data from packed to unpacked and vice versa; (2) automatic extraction of image data arrays; (3) transposition and 90 deg rotations of large data arrays; (4) translation of data arrays for registration; and (5) reduction of the dimensions of data arrays by integral factors. Both the frequency and the spatial domain approaches are presented for the design and implementation of the image processing operation. It is shown that spatial domain recursive implementation of filters is much faster than nonrecursive implementations using fast fourier transforms (FFT) for the cases of interest in this work. The recursive implementation of a class of matched filters for enhancing image signal to noise ratio is described. Test patterns are used to illustrate the filtering operations. The application of the techniques to radiographic images of metallic structures is demonstrated through several examples.

5 CFR 315.602 - Appointment based on service in the Office of the President or Vice-President or on the White...

Code of Federal Regulations, 2013 CFR

2013-01-01

... Office of the President or Vice-President or on the White House Staff. 315.602 Section 315.602... service in the Office of the President or Vice-President or on the White House Staff. (a) Agency authority... Office of the President or Vice-President or on the White House Staff, provided that the appointment is...

5 CFR 315.602 - Appointment based on service in the Office of the President or Vice-President or on the White...

Code of Federal Regulations, 2012 CFR

2012-01-01

... Office of the President or Vice-President or on the White House Staff. 315.602 Section 315.602... service in the Office of the President or Vice-President or on the White House Staff. (a) Agency authority... Office of the President or Vice-President or on the White House Staff, provided that the appointment is...

5 CFR 315.602 - Appointment based on service in the Office of the President or Vice-President or on the White...

Code of Federal Regulations, 2014 CFR

2014-01-01

... Office of the President or Vice-President or on the White House Staff. 315.602 Section 315.602... service in the Office of the President or Vice-President or on the White House Staff. (a) Agency authority... Office of the President or Vice-President or on the White House Staff, provided that the appointment is...

5 CFR 315.602 - Appointment based on service in the Office of the President or Vice-President or on the White...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Office of the President or Vice-President or on the White House Staff. 315.602 Section 315.602... service in the Office of the President or Vice-President or on the White House Staff. (a) Agency authority... Office of the President or Vice-President or on the White House Staff, provided that the appointment is...

Before depression: the medieval vice of acedia.

PubMed

Daly, Robert W

2007-01-01

Given renewed interest in the role of human action in the development of depression, I re-examine a tradition in the West which interpreted phenomena akin to the symptoms and signs of modern depression as "a spiritual disease." In medieval Europe, acedia was a vice, an undesirable trait of character acquired in the course of living a life. Persons suffering from the vice of acedia were implicated as agents in its development and to some extent responsible for overcoming it. In Part I of this paper, I note the contemporary interest of psychiatrists and others in this vice, consider the warrants for asserting that it is akin to some forms of depression, and recount, in brief, the history of this vice from the fourth to the fifteenth centuries. In Part II, I discuss how medieval scholars, confessors, and spiritual guides understood the question of responsibility for acedia and how they distinguished between this vice and melancholia. I argue that acedia was a vice that could be distinguished from melancholia and that, while akin to clinical depression, this vice should not be identified with depression. This investigation of and commentary on acedia is intended as a contribution to the contemporary discussion of the role of human agency in the development of depression and in its treatment.

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey

PubMed Central

Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness–cognition relationship in Chinese older adults (OAs). Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness–cognition relationship. Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Discussion: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness–cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. PMID:27013536

On the balanced quantum hashing

NASA Astrophysics Data System (ADS)

Ablayev, F.; Ablayev, M.; Vasiliev, A.

2016-02-01

In the paper we define a notion of a resistant quantum hash function which combines a notion of pre-image (one-way) resistance and the notion of collision resistance. In the quantum setting one-way resistance property and collision resistance property are correlated: the “more” a quantum function is one-way resistant the “less” it is collision resistant and vice versa. We present an explicit quantum hash function which is “balanced” one-way resistant and collision resistant and demonstrate how to build a large family of balanced quantum hash functions.

Extracellular and circulating redox- and metalloregulated eRNA and eRNP: copper ion-structured RNA cytokines (angiotropin ribokines) and bioaptamer targets imparting RNA chaperone and novel biofunctions to S100-EF-hand and disease-associated proteins.

PubMed

Wissler, Josef H

2004-06-01

Bioassays for cellular differentiation and tissue morphogenesis were used to design methods for isolation of bioactive redox- and metalloregulated nucleic acids and copper ion complexes with proteins from extracellular, circulating, wound, and supernatant fluids of cultured cells. In extracellular biospheres, diversities of nucleic acids were found to be secreted by cells upon activation. They may reflect nucleic acid biolibraries with molecular imprints of cellular history. After removal of protein components, eRNA prototypes exuded by activated cells were sequenced. They are small, endogenous, highly modified and edited, redox- and metalloregulated 5'-end phosphorylated extracellular eRNA (approximately 2-200 bases) with cellular, enzymic, and bioaptamer functions. Fenton-type OH* radical redox reactions may form modified nucleotides in RNA as wobbles eRNA per se, or as copper ion-complex with protein (e.g., S100A12-EF-hand protein, angiotropin-related protein, calgranulin-C, hippocampal neurite differentiation factor) are shown to be bioactive in vivo and in vitro as cytokines (ribokines) and as nonmitogenic angiomorphogens for endothelial cell differentiation in the formation of organoid supracellular capillary structures. As bioaptamers, copper ion-structured eRNA imparts novel biofunctions to proteins that they do not have on their own. The origin of extracellular RNA and intermediate precursors (up to 500 bases) was traced to intracellular parent nucleic acids. Intermediate precursors with and without partial homology were found. This suggests that bioaptamers are not directly retranslatable gene products. Metalloregulated eRNA bioaptamer function was investigated by domains (e.g. 5'...CUG...3' hairpin loop) for folding, bioactivity, and binding of protein with copper, calcium, and alkali metal ion affinity. Vice versa, metalloregulated nucleic acid-binding domains (K3H, R3H) in proteins were identified. Interaction of protein and eRNA docking potentials were visualized by 3D-rapid prototyping of accurate molecular image models based on crystallographic or NMR data. For S100A12-homologous proteins, receptor- and metalloregulated RNA chaperone-shaped protein assemblies were investigated. They suggest insight into signaling cascades as to how eRNA transmits its cytokine (ribokine) bioinformation from the extracellular RNA biosphere into cells. Proteomics of the extracellular RNA biosphere demonstrate the presence of nucleic acid-binding domain homologies in defense-, aging-, and disease-associated neuronal and other proteins as targets for RNA orphans. By structural relationships found to transmissible processes, proteinaceous transfer ("infectivity") and feedback of bioinformation beyond the central dogma of molecular biology are considered in terms of metalloregulated RNA bioaptamer function, nucleic acid-binding domains, and protein conformation.

The academic role of the vice president for health sciences: can a walrus become a unicorn?

PubMed

Pellegrino, E D

1975-03-01

The post of vice president for the health sciences was first developed in an attempt to interpret, modulate, and buffer the growing power of the medical school in the university and the different values that have existed there. The job has been greatly transformed over the past 10 years as a consequence of a variety of factors. Now a genuine creative effort applied to the design of the administration of health sciences centers and how they fit into universities is needed. The present modes of organization are not equal to the challenges that must be faced. New designs must be created which will recognize the special place of the health sciences in today's world and yet keep its function within the university frame.

Theory of mind broad and narrow: reasoning about social exchange engages ToM areas, precautionary reasoning does not.

PubMed

Ermer, Elsa; Guerin, Scott A; Cosmides, Leda; Tooby, John; Miller, Michael B

2006-01-01

Baron-Cohen (1995) proposed that the theory of mind (ToM) inference system evolved to promote strategic social interaction. Social exchange--a form of co-operation for mutual benefit--involves strategic social interaction and requires ToM inferences about the contents of other individuals' mental states, especially their desires, goals, and intentions. There are behavioral and neuropsychological dissociations between reasoning about social exchange and reasoning about equivalent problems tapping other, more general content domains. It has therefore been proposed that social exchange behavior is regulated by social contract algorithms: a domain-specific inference system that is functionally specialized for reasoning about social exchange. We report an fMRI study using the Wason selection task that provides further support for this hypothesis. Precautionary rules share so many properties with social exchange rules--they are conditional, deontic, and involve subjective utilities--that most reasoning theories claim they are processed by the same neurocomputational machinery. Nevertheless, neuroimaging shows that reasoning about social exchange activates brain areas not activated by reasoning about precautionary rules, and vice versa. As predicted, neural correlates of ToM (anterior and posterior temporal cortex) were activated when subjects interpreted social exchange rules, but not precautionary rules (where ToM inferences are unnecessary). We argue that the interaction between ToM and social contract algorithms can be reciprocal: social contract algorithms requires ToM inferences, but their functional logic also allows ToM inferences to be made. By considering interactions between ToM in the narrower sense (belief-desire reasoning) and all the social inference systems that create the logic of human social interaction--ones that enable as well as use inferences about the content of mental states--a broader conception of ToM may emerge: a computational model embodying a Theory of Human Nature (ToHN).

An open-label, multicenter, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men naïve to phosphodiesterase 5 inhibitor therapy

PubMed Central

Bai, Wen-Jun; Li, Hong-Jun; Dai, Yu-Tian; He, Xue-You; Huang, Yi-Ran; Liu, Ji-Hong; Sorsaburu, Sebastian; Ji, Chen; Jin, Jian-Jun; Wang, Xiao-Feng

2015-01-01

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe. PMID:25370206

An open-label, multicenter, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men naïve to phosphodiesterase 5 inhibitor therapy.

PubMed

Bai, Wen-Jun; Li, Hong-Jun; Dai, Yu-Tian; He, Xue-You; Huang, Yi-Ran; Liu, Ji-Hong; Sorsaburu, Sebastian; Ji, Chen; Jin, Jian-Jun; Wang, Xiao-Feng

2015-01-01

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naοve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naοve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.

Functional innovation from changes in protein domains and their combinations.

PubMed

Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A

2016-06-01

Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Upon his arrival at NASA's Kennedy Space Center in Florida, Vice President Mike Pence, back to the camera, is greeted by Deputy Center Director Janet Petro. Behind the Vice President, Sen. Marco Rubio of Florida, shakes hands with Center Director Bob Cabana. To the right of Cabana is Acting NASA Administrator Robert Lightfoot. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Tracking functional status across the spinal cord injury lifespan: linking pediatric and adult patient-reported outcome scores.

PubMed

Tian, Feng; Ni, Pengsheng; Mulcahey, M J; Hambleton, Ronald K; Tulsky, David; Haley, Stephen M; Jette, Alan M

2014-11-01

To use item response theory (IRT) methods to link scores from 2 recently developed contemporary functional outcome measures, the adult Spinal Cord Injury-Functional Index (SCI-FI) and the Pedi SCI (both the parent version and the child version). Secondary data analysis of the physical functioning items of the adult SCI-FI and the Pedi SCI instruments. We used a nonequivalent group design with items common to both instruments and the Stocking-Lord method for the linking. Linking was conducted so that the adult SCI-FI and Pedi SCI scaled scores could be compared. Community. This study included a total sample of 1558 participants. Pedi SCI items were administered to a sample of children (n=381) with SCI aged 8 to 21 years, and of parents/caregivers (n=322) of children with SCI aged 4 to 21 years. Adult SCI-FI items were administered to a sample of adults (n=855) with SCI aged 18 to 92 years. Not applicable. Five scales common to both instruments were included in the analysis: Wheelchair, Daily Routine/Self-care, Daily Routine/Fine Motor, Ambulation, and General Mobility functioning. Confirmatory factor analysis and exploratory factor analysis results indicated that the 5 scales are unidimensional. A graded response model was used to calibrate the items. Misfitting items were identified and removed from the item banks. Items that function differently between the adult and child samples (ie, exhibit differential item functioning) were identified and removed from the common items used for linking. Domain scores from the Pedi SCI instruments were transformed onto the adult SCI-FI metric. This IRT linking allowed estimation of adult SCI-FI scale scores based on Pedi SCI scale scores and vice versa; therefore, it provides clinicians with a means of tracking long-term functional data for children with an SCI across their entire lifespan. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, left, and Vice President Mike Pence, meet with NASA leadership, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

Study of Equatorial Ionospheric irregularities and Mapping of Electron Density Profiles and Ionograms

DTIC Science & Technology

2012-03-09

equation is a product of a complex basis vector in Jackson and a linear combination of plane wave functions. We convert both the amplitudes and the...wave function arguments from complex scalars to complex vectors . This conversion allows us to separate the electric field vector and the imaginary...magnetic field vector , because exponentials of imaginary scalars convert vectors to imaginary vectors and vice versa, while ex- ponentials of imaginary

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Kennedy Space Center Bob Cabana, left, and NASA's Acting Administrator Robert Lightfoot, right present Vice President Mike Pence with a framed plaque. On the back of the plaque are patches from each of Cabana's four space shuttle mission, STS-88, STS-53, STS-65, STS-41, and an inscription thanking the Vice President for his support of NASA. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Vice President Pence Arrives at Kennedy Space Center for National Space Council Meeting

NASA Image and Video Library

2018-02-20

Vice President Mike Pence arrived at the Shuttle Landing Facility at NASA’s Kennedy Space Center, Florida on Feb. 20 ahead of the second meeting of the National Space Council. Vice President Pence, and his wife Karen, were greeted by Robert Lightfoot, acting NASA Administrator and Brig. Gen. Wayne Monteith, commander, 45th Space Wing. On Feb. 21, Vice President Pence will lead the National Space Council meeting inside Kennedy’s Space Station Processing Facility. “Moon, Mars, and Worlds Beyond: Winning the Next Frontier” will include testimonials from leaders in the civil, commercial, and national security sectors about the importance of the United States’ space enterprise. The Vice President will conclude his visit with a tour of Kennedy Space Center.

Gallaudet Research Institute: Progress in Deafness Research, 1981-82.

ERIC Educational Resources Information Center

Harkins, Judith, Comp.

The report discusses 12 research projects on hearing impairment undertaken at the Gallaudet Research Institute. The institute focuses on three major categories of research areas: accommodation to hearing loss, prevention of hearing loss, and restoration of hearing. Following a brief description of the functions of the Office of the Vice President…

76 FR 78225 - Notice of Appointment of Members to the National Agricultural Research, Extension, Education, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

..., Institute of Food Technologists and Vice President of Research & Dean of the School of Graduate Studies..., filing of petitions and applications and agency #0;statements of organization and functions are examples... Secretary Notice of Appointment of Members to the National Agricultural Research, Extension, Education, and...

An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial.

PubMed

Rofail, Diana; Viala, Muriel; Gater, Adam; Abetz-Webb, Linda; Baladi, Jean-Francois; Cappellini, Maria Domenica

2010-08-01

The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach's alpha: 0.75-0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

Research on Bounded Rationality of Fuzzy Choice Functions

PubMed Central

Wu, Xinlin; Zhao, Yong

2014-01-01

The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function. PMID:24782677

Research on bounded rationality of fuzzy choice functions.

PubMed

Wu, Xinlin; Zhao, Yong

2014-01-01

The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function.

22 CFR 40.24 - Prostitution and commercialized vice.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Prostitution and commercialized vice. 40.24... Certain Crimes § 40.24 Prostitution and commercialized vice. (a) Activities within 10 years preceding visa... United States solely, principally, or incidentally to engage in prostitution, or has engaged in...

39 CFR 927.2 - Noncontractual air service for international and military mail.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Vice President, Network Operations Management, Postal Headquarters, and that its written appeal..., the Vice President, Network Operations Management, will review the complete record and decide the... decision. The Vice President, Network Operations Management, may sustain, rescind, or compromise a fine or...

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, left, Vice President Mike Pence, and Chief Financial Officer Jeff DeWit, right, meet with NASA leadership, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Air Force Two, carrying Vice President Mike Pence, taxis on the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

A domain-centric solution to functional genomics via dcGO Predictor

PubMed Central

2013-01-01

Background Computational/manual annotations of protein functions are one of the first routes to making sense of a newly sequenced genome. Protein domain predictions form an essential part of this annotation process. This is due to the natural modularity of proteins with domains as structural, evolutionary and functional units. Sometimes two, three, or more adjacent domains (called supra-domains) are the operational unit responsible for a function, e.g. via a binding site at the interface. These supra-domains have contributed to functional diversification in higher organisms. Traditionally functional ontologies have been applied to individual proteins, rather than families of related domains and supra-domains. We expect, however, to some extent functional signals can be carried by protein domains and supra-domains, and consequently used in function prediction and functional genomics. Results Here we present a domain-centric Gene Ontology (dcGO) perspective. We generalize a framework for automatically inferring ontological terms associated with domains and supra-domains from full-length sequence annotations. This general framework has been applied specifically to primary protein-level annotations from UniProtKB-GOA, generating GO term associations with SCOP domains and supra-domains. The resulting 'dcGO Predictor', can be used to provide functional annotation to protein sequences. The functional annotation of sequences in the Critical Assessment of Function Annotation (CAFA) has been used as a valuable opportunity to validate our method and to be assessed by the community. The functional annotation of all completely sequenced genomes has demonstrated the potential for domain-centric GO enrichment analysis to yield functional insights into newly sequenced or yet-to-be-annotated genomes. This generalized framework we have presented has also been applied to other domain classifications such as InterPro and Pfam, and other ontologies such as mammalian phenotype and disease ontology. The dcGO and its predictor are available at http://supfam.org/SUPERFAMILY/dcGO including an enrichment analysis tool. Conclusions As functional units, domains offer a unique perspective on function prediction regardless of whether proteins are multi-domain or single-domain. The 'dcGO Predictor' holds great promise for contributing to a domain-centric functional understanding of genomes in the next generation sequencing era. PMID:23514627

On counting the rational numbers

NASA Astrophysics Data System (ADS)

Almada, Carlos

2010-12-01

In this study, we show how to construct a function from the set ? of natural numbers that explicitly counts the set ? of all positive rational numbers using a very intuitive approach. The function has the appeal of Cantor's function and it has the advantage that any high school student can understand the main idea at a glance without any prior knowledge of the Unique Prime Factorization Theorem or other nonelementary results. Unlike Cantor's function, the one we propose makes it very easy to determine what rational number, in unreduced form, is in a given position on the list and vice versa.

Vehicle Infrastructure Cash-Flow Estimation--VICE 2.0; Clean Cities, Energy Efficiency & Renewable Energy (EERE)

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

Mitchell, G.

This presentation discusses the differences between the original Vehicle and Infrastructure Cash-Flow Evaluation (VICE) Model and the revamped version, VICE 2.0. The enhanced tool can now help assess projects to acquire vehicles and infrastructure, or to acquire vehicles only.

4 CFR 27.2 - The Chair, Vice Chair.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false The Chair, Vice Chair. 27.2 Section 27.2 Accounts GOVERNMENT ACCOUNTABILITY OFFICE GENERAL PROCEDURES GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL APPEALS BOARD; ORGANIZATION § 27.2 The Chair, Vice Chair. The members of the Board shall select from among its membership a...

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, left, is congratulated by Vice President Mike Pence, as NASA Chief Financial Officer, Jeff DeWit looks on, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

Vice President Mike Pence, left, and NASA Chief Financial Officer, Jeff DeWit, right, shake hands while meeting with NASA leadership, Monday, April 23, 2018 at NASA Headquarters in Washington. Jim Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, left, Vice President Mike Pence, and NASA Chief Financial Officer, Jeff DeWit, right, meet with NASA leadership, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

78 FR 54941 - Self-Regulatory Organizations; NASDAQ OMX BX Inc.; Notice of Designation of Longer Period for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

..., Secretary, Commission, from Janet McGuiness, Executive Vice President, Secretary and General Counsel, NYSE.... Murphy, Secretary, Commission, from Janet McGuiness, Executive Vice President, Secretary and General... Elizabeth M. Murphy, Secretary, Commission, from Janet McGuiness, Executive Vice President, Secretary and...

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Kennedy Space Center Bob Cabana, left, and NASA's Acting Administrator Robert Lightfoot, right present Vice President Mike Pence with a framed plaque. At the top is an illustration featuring NASA's efforts to explore Mars. Also included is the flag of the Vice President's home state of Indiana that was flown on the SpaceX Commercial Resupply Services-10 flight in February and March this year. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Secondary School Vice-Principals: Commitment, Challenge, Efficacy and Synchrony

ERIC Educational Resources Information Center

Yu-kwong, Paula Kwan; Walker, Allan

2010-01-01

The study sought to investigate Hong Kong secondary school vice-principals' job facets leading to overall job satisfaction, and to differentiate the satisfaction of vice-principals of different career orientations and gender groups. The findings indicated that there are four main facets of satisfaction, in rank order of influence on overall…

The Vice-Principal Experience as a Preparation for the Principalship

ERIC Educational Resources Information Center

Kwan, Paula

2009-01-01

Purpose: The purpose of this paper is to examine first the job responsibilities undertaken by vice-principals and second to investigate the respective contribution of each job responsibility in preparing them for the principalship. Because new principals are drawn predominantly from the ranks of vice-principals in Hong Kong, it is important to…

Community College Vice Presidents for Institutional Advancement: Role Expectations, Fundraising Responsibilities, Professional Relationships, and Commitment to the Institution

ERIC Educational Resources Information Center

Ciampa, Donna Lynn

2009-01-01

This study examined how the role expectations, responsibilities toward fundraising, and professional relationships by the vice president of institutional advancement influenced commitment to the institution. A qualitative analysis was conducted across the mid-Atlantic region by interviewing community college vice presidents of institutional…

Vice-Principals' Dilemma--Career Advancement or Harmonious Working Relationship

ERIC Educational Resources Information Center

Kwan, Paula

2009-01-01

Purpose: Although the importance of shared leadership to school success has been widely recognised in the literature, only scant attention has been paid to the feelings of vice-principals over undertaking more responsibilities. Maintained by the researchers in this somewhat neglected area is the assertion that vice-principals who find their jobs…

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, left, Vice President Mike Pence, and NASA Chief Financial Officer Jeff DeWit, right, give a standing ovation to former acting administrator Robert Lightfoot, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

76 FR 33613 - Designation of Officers of the Overseas Private Investment Corporation To Act as President of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

...; (f) Vice President, External Affairs; (g) Vice President, Investment Funds; (h) Vice President... of June 6, 2011 Designation of Officers of the Overseas Private Investment Corporation To Act as President of the Overseas Private Investment Corporation Memorandum for the President of the Overseas...

Career Paths of Female Vice-Presidents in Community Colleges

ERIC Educational Resources Information Center

Quinn, Jacqueline Y.

2017-01-01

The purpose of this qualitative study was to investigate the career paths and preparation of female vice-presidents employed in community colleges in the state of Mississippi. There is limited qualitative information available that describes the career paths of vice-presidents in the state's community colleges. Community colleges are making great…

Vice President Pence Leads National Space Council Meeting, Tours Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence arrived at Kennedy Space Center in Florida on Tuesday, Feb. 20 at 5:10 p.m. aboard Air Force Two. The Vice President was greeted by Robert Lightfoot, acting NASA Administrator and Brig. Gen. Wayne Monteith, commander, 45th Space Wing. After arrival, the vice president toured commercial partner United Launch Alliance’s facility at Cape Canaveral Air Force Station adjacent to Kennedy. He also toured Blue Origin’s new rocket facility located at nearby Exploration Park. On Feb. 21, Vice President Mike Pence led a National Space Council meeting inside NASA Kennedy Space Center’s Space Station Processing Facility. This second meeting of the council, called, “Moon, Mars, and Worlds Beyond: Winning the Next Frontier,” included testimonials from leaders in the civil, commercial, and national security sectors about the importance of the United States’ space enterprise. Vice President Pence concluded his visit with a tour of Kennedy Space Center, which included stops at the Boeing Commercial Crew and Cargo Processing Facility, and SpaceX Launch Complex 39A.

The role of parents in the ontogeny of achievement-related motivation and behavioral choices.

PubMed

Simpkins, Sandra D

2015-06-01

Parents believe what they do matters. But, how does it matter? How do parents' beliefs about their children early on translate into the choices those children make as adolescents? The Eccles' expectancy–value model asserts that parents' beliefs about their children during childhood predict adolescents' achievement-related choices through a sequence of processes that operate in a cumulative, cascading fashion over time. Specifically, parents' beliefs predict parents' behaviors that predict their children's motivational beliefs. Those beliefs predict children's subsequent choices. Using data from the Childhood and Beyond Study (92% European American; N = 723), we tested these predictions in the activity domains of sports, instrumental music, mathematics, and reading across a 12-year period. In testing these predictions, we looked closely at the idea of reciprocal influences and at the role of child gender as a moderator. The cross-lagged models generally supported the bidirectional influences described in Eccles' expectancy-value model. Furthermore, the findings demonstrated that: (a) these relations were stronger in the leisure domains than in the academic domains, (b) these relations did not consistently vary based on youth gender, (c) parents were stronger predictors of their children's beliefs than vice versa, and (d) adolescents' beliefs were stronger predictors of their behaviors than the reverse. The findings presented in this monograph extend our understanding of the complexity of families, developmental processes that unfold over time, and the extent to which these processes are universal across domains and child gender.

Information Infrastructures for Integrated Enterprises

DTIC Science & Technology

1993-05-01

PROCESSING demographic CAM realization; ule leveling; studies; prelimi- rapid tooling; con- accounting/admin- nary CAFE and tinuous cost istrative reports...nies might consider franchising some facets of indirect labor, such as selected functions of administration, finance, and human resources. Incorporate as...vices CAFE Corporate Average Fuel Economy CAD Computer-Aided Design 0 CAE Computer-Aided Engineering CAIS Common Ada Programming Support Environment

Scientific production of Vice Chancellors for Research in Peruvian universities with a medical school.

PubMed

Herrera-Añazco, Percy; Valenzuela-Rodríguez, Germán; Pacheco-Mendoza, Josmel; Málaga, Germán

2017-10-19

To determine the scientific production of Research Vice-chancellors at Peruvian universities that have medical schools, as well as their academic degrees as an indirect way to evaluate their suitability for the position they hold. We searched all Peruvian universities that register medical schools. Of these, the scientific production of the universities registered in SCOPUS was identified in September of the 2016. The scientific production of the vice chancellors of investigation of these faculties of medicine was determined through the search of its scientific publications registered in SCOPUS and those reported in the National Registry of Researchers in Science and Technology. Academic degrees were obtained from the database of the National Superintendence of Higher University Education. The sample included 28 research vice chancellors. Only 4/28 had any publications. The average number of articles published by the vice chancellors of research was 1.71, the number of citations 23.1 on average and the H index 0.64. Besides, 22 Vice-chancellors of research had the degree of doctor, four had the degree of bachelor and two the degree of master. The scientific production of research vice chancellors is poor. The required academic grade requirement for the position is not met in all cases. It is likely that, having no research experience, his leadership in directing a university's research policies may be questioned.

On the detection of functionally coherent groups of protein domains with an extension to protein annotation

PubMed Central

McLaughlin, William A; Chen, Ken; Hou, Tingjun; Wang, Wei

2007-01-01

Background Protein domains coordinate to perform multifaceted cellular functions, and domain combinations serve as the functional building blocks of the cell. The available methods to identify functional domain combinations are limited in their scope, e.g. to the identification of combinations falling within individual proteins or within specific regions in a translated genome. Further effort is needed to identify groups of domains that span across two or more proteins and are linked by a cooperative function. Such functional domain combinations can be useful for protein annotation. Results Using a new computational method, we have identified 114 groups of domains, referred to as domain assembly units (DASSEM units), in the proteome of budding yeast Saccharomyces cerevisiae. The units participate in many important cellular processes such as transcription regulation, translation initiation, and mRNA splicing. Within the units the domains were found to function in a cooperative manner; and each domain contributed to a different aspect of the unit's overall function. The member domains of DASSEM units were found to be significantly enriched among proteins contained in transcription modules, defined as genes sharing similar expression profiles and presumably similar functions. The observation further confirmed the functional coherence of DASSEM units. The functional linkages of units were found in both functionally characterized and uncharacterized proteins, which enabled the assessment of protein function based on domain composition. Conclusion A new computational method was developed to identify groups of domains that are linked by a common function in the proteome of Saccharomyces cerevisiae. These groups can either lie within individual proteins or span across different proteins. We propose that the functional linkages among the domains within the DASSEM units can be used as a non-homology based tool to annotate uncharacterized proteins. PMID:17937820

Developing Virtue and Rehabilitating Vice: Worries about Self-Cultivation and Self-Reform

ERIC Educational Resources Information Center

Battaly, Heather

2016-01-01

Aristotelian virtue theorists have emphasized the role of the self in developing virtue and in rehabilitating vice. But this article argues that, as Aristotelians, we have placed too much emphasis on self-cultivation and self-reform. Self-cultivation is not required for developing virtue or vice. Nor will "sophia"-inspired self-reform…

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence, left, waves as he and Sen. Marco Rubio of Florida arrive aboard Air Force Two at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Relation between Justice Perception and Perception of Trust in School of Secondary School Vice-Directors

ERIC Educational Resources Information Center

Polat, Soner; Celep, Cevat

2008-01-01

The aim of this study is to determine the perception levels of secondary school vice directors towards organizational justice and organizational trust and establish their inter-relations. This research of descriptional nature covers vice directors working in educational institutions in the school year of 2006-2007; work area of the study covers…

Executive Transitions in Student Affairs: A Guide to Getting Started as the Vice President

ERIC Educational Resources Information Center

Carry, Ainsley, Ed.

2014-01-01

Transitions are a critical time for executives at all types of higher education institutions. Some vice presidents for student affairs sail through the transition period, while others stumble because they could not navigate the complexity of the new role. Vice presidents who appropriately match their leadership and management style to the new…

DefenseLink Special: Giambastiani Retirement Ceremony

Science.gov Websites

Videos Publications Bloggers DoD Websites Vice Chairman of the Joint Chiefs of Staff U.S. Navy Adm , vice chairman of the Joint Chiefs of Staff, talks with Secretary of Defense Robert M. Gates before the . Edmund P. Giambastiani, vice chairman of the Joint Chiefs of Staff, talks with Marine Gen. Peter Pace

The Education Election: Guess Who's Coming to School.

ERIC Educational Resources Information Center

Weisman, Jonathan

2000-01-01

Describes Vice President Al Gore's 2000 presidential campaign efforts at one Michigan high school, from the arrival of advance Secret Service agents to scope out the school, to determination of what the Vice President would do during his 7-hour visit, to who would host the Vice President, to how students and staff responded to the visit. (SM)

Combining food type(s) and food quantity choice in a new food choice paradigm based on vice-virtue bundles.

PubMed

Haws, Kelly L; Liu, Peggy J

2016-08-01

Given the prevalence and rising rates of obesity in many countries, including the United States, much food decision-making research ultimately aims at understanding how consumers can make healthier choices. The two predominant choice paradigms used in food decision-making research ask consumers to choose (a) between a "vice" (or unhealthy food) and a "virtue" (or healthy food) or (b) among varying portion sizes of "vice." We propose a new food choice paradigm that encourages consumers to jointly consider both food type(s) choice and food portion size at each decision point. The purpose of this paradigm is two-fold. First, it aims to allow examination of more comprehensive eating behavior (e.g., to examine the overall composition of a plate of food rather than choice of a single food). Second, it aims to shift consumers towards including large proportions of virtues and smaller proportions of vice in their overall consumption portfolios. For this paradigm, we draw upon a recently introduced food product innovation called "vice-virtue bundles" (Liu et al., 2015) that illustrates the basis of this new food choice paradigm, in which food type(s) and portion decisions are made simultaneously. Accordingly, we first discuss relevant findings on vice-virtue bundles as well as the differences between simultaneous and sequential choice of multiple products. Second, we examine the benefits for managing and controlling one's consumption that are provided by vice-virtue bundles and this joint food choice paradigm more generally. Third and finally, we point out opportunities for future research by discussing (a) multiple factors that influence food choices, (b) decision processes affected by food choice paradigms, and (c) issues of generalizability related to the presence of vice-virtue bundles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Listening to Voices at the Educational Frontline: New Administrators' Experiences of the Transition from Teacher to Vice-Principal

ERIC Educational Resources Information Center

Armstrong, Denise E.

2015-01-01

This qualitative study explored the transition from teaching to administration through the voices of four novice vice-principals. An integrative approach was used to capture the interaction between new vice-principals, their external contexts, and the resulting leadership outcomes. The data revealed that in spite of these new administrators'…

Eighties' Film Noir: An Analysis of the Use of the "Double" in "Miami Vice's" Second and Third Seasons.

ERIC Educational Resources Information Center

Matviko, John W.

A comparison of the current television series "Miami Vice" with the "film noir" genre of American movies from the forties and fifties reveals many similar elements, such as visual style, mood, theme, and sensibility. "Miami Vice" is set in a large city whose art deco architecture provides an ironic contrast to noir's…

Impact of Radio Frequency Identification (RFID) on the Marine Corps’ Supply Process

DTIC Science & Technology

2006-09-01

Hypothetical Improvement Using a Real-Time Order Processing System Vice a Batch Order Processing System ................56 3. As-Is: The Current... Processing System Vice a Batch Order Processing System ................58 V. RESULTS ................................................69 A. SIMULATION...Time: Hypothetical Improvement Using a Real-Time Order Processing System Vice a Batch Order Processing System ................71 3. As-Is: The

Vice President Mike Pence Speech at Vehicle Assembly Building

NASA Image and Video Library

2017-07-06

Vice President Mike Pence got a first-hand look at the public-private partnerships at America’s multi-user spaceport on Thursday, July 6, during a visit to NASA’s Kennedy Space Center in Florida. Speaking in the center’s iconic Vehicle Assembly Building, the Vice President thanked employees for their commitment to America’s continued leadership in the space frontier.

2011 Defense Industrial Base Critical Infrastructure Protection Conference (DIBCIP)

DTIC Science & Technology

2011-08-25

Office of the Program Manager, Information Sharing Environment u Mr. Vince Jarvie , Vice President, Corporate Security, L-3 Communications...National Defense University IRM College and in 2008 he obtained the Certified Information System Security Professional certificate. MR. VINCE JARVIE ...Vice President, Corporate Security, L-3 Communciations Corporation Mr. Vincent (Vince) Jarvie is the Vice President, Corporate Security for L-3

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

During his visit of NASA's Kennedy Space Center in Florida, Vice President Mike Pence signs a Kennedy Space Center guest book as the agency's Acting Administrator Robert Lightfoot, left, and Center Director Bob Cabana look on. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Disruption of DNA repair in cancer cells by ubiquitination of a destabilising dimerization domain of nucleotide excision repair protein ERCC1

PubMed Central

Yang, Lanlan; Ritchie, Ann-Marie; Melton, David W.

2017-01-01

DNA repair pathways present in all cells serve to preserve genome stability, but in cancer cells they also act reduce the efficacy of chemotherapy. The endonuclease ERCC1-XPF has an important role in the repair of DNA damage caused by a variety of chemotherapeutic agents and there has been intense interest in the use of ERCC1 as a predictive marker of therapeutic response in non-small cell lung carcinoma, squamous cell carcinoma and ovarian cancer. We have previously validated ERCC1 as a therapeutic target in melanoma, but all small molecule ERCC1-XPF inhibitors reported to date have lacked sufficient potency and specificity for clinical use. In an alternative approach to prevent the repair activity of ERCC1-XPF, we investigated the mechanism of ERCC1 ubiquitination and found that the key region was the C-terminal (HhH)2 domain which heterodimerizes with XPF. This ERCC1 region was modified by non-conventional lysine-independent, but proteasome-dependent polyubiquitination, involving Lys33 of ubiquitin and a linear ubiquitin chain. XPF was not polyubiquitinated and its expression was dependent on presence of ERCC1, but not vice versa. To our surprise we found that ERCC1 can also homodimerize through its C-terminal (HhH)2 domain. We exploited the ability of a peptide containing this C-terminal domain to destabilise both endogenous ERCC1 and XPF in human melanoma cells and fibroblasts, resulting in reductions of up to 85% in nucleotide excision repair and near two-fold increased sensitivity to DNA damaging agents. We suggest that the ERCC1 (HhH)2 domain could be used in an alternative strategy to treat cancer. PMID:28903417

The Impact of Supply Chain Business Processes on Competitive Advantage and Organizational Performance

DTIC Science & Technology

2012-03-22

Manager, Vice President (VP) Distribution & Fulfillment, Transportation Manager, VP of Supply Chain Management, Production Manager, Director of...Logistics/ Transportation /Distribution (75%), and Supply/Purchasing/Procurement (25%) were identified as functions that best describe the respondents...manufacturing industry (50%), one respondent represented the wholesale trade (12.5%), the retail trade (12.5%), and the transportation and warehousing

Project Thrive. Individualized Intervention to Foster Social, Emotional and Self-Related Functions in Primary Programs. Volume II.

ERIC Educational Resources Information Center

Biemiller, Andrew; Richards, Merle

The purposes of this longitudinal study were to examine techniques whereby kindergarten, Grade 1, and Grade 2 teachers might become more aware of differences in children which affect their performance and behavior, and to develop with teachers ways of accommodating classrooms to children and vice versa. Participants were 24 teachers from four…

Concomitant prediction of function and fold at the domain level with GO-based profiles.

PubMed

Lopez, Daniel; Pazos, Florencio

2013-01-01

Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey.

PubMed

Zhong, Bao-Liang; Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness-cognition relationship in Chinese older adults (OAs). Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness-cognition relationship. Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness-cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence arrives at the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. During his visit, Pence spoke inside the iconic building, where he thanked employees for advancing American leadership in space. The Vice President also toured several facilities highlighting the public-private partnerships at Kennedy, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

25 CFR 226.25 - Gas well drilled by oil lessees and vice versa.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Gas well drilled by oil lessees and vice versa. 226.25... OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.25 Gas well drilled by oil lessees and vice versa. Prior to drilling, the oil or gas lessee shall notify the other lessees of his/her intent...

25 CFR 226.25 - Gas well drilled by oil lessees and vice versa.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Gas well drilled by oil lessees and vice versa. 226.25... OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.25 Gas well drilled by oil lessees and vice versa. Prior to drilling, the oil or gas lessee shall notify the other lessees of his/her intent...

25 CFR 226.25 - Gas well drilled by oil lessees and vice versa.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Gas well drilled by oil lessees and vice versa. 226.25... OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.25 Gas well drilled by oil lessees and vice versa. Prior to drilling, the oil or gas lessee shall notify the other lessees of his/her intent...

25 CFR 226.25 - Gas well drilled by oil lessees and vice versa.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Gas well drilled by oil lessees and vice versa. 226.25... OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.25 Gas well drilled by oil lessees and vice versa. Prior to drilling, the oil or gas lessee shall notify the other lessees of his/her intent...

25 CFR 226.25 - Gas well drilled by oil lessees and vice versa.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Gas well drilled by oil lessees and vice versa. 226.25... OSAGE RESERVATION LANDS FOR OIL AND GAS MINING Operations § 226.25 Gas well drilled by oil lessees and vice versa. Prior to drilling, the oil or gas lessee shall notify the other lessees of his/her intent...

Interior prospect and refuge.

PubMed

Stamps, Arthur E

2006-12-01

Prospect and refuge theory has usually been applied to landscapes but recent work suggests that it could also be applied to interiors. This article reports two experiments, covering 14 environments and 97 respondents, in which five hypotheses regarding prospect, refuge, and comfort were tested: H1: the transition from small, dark, and low to large, light, and high and vice-versa; H2: the transition from dark to light vs vice-versa; H3: the transition from low to high vs vice-versa; H4: the transition from small to big horizontally vs vice-versa; and H5: width. Results varied. The effect of width on comfort was substantial (r = .35); effects for the other hypotheses were either subtle or contrary to expectations.

Response of discrete linear systems to forcing functions with inequality constraints.

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.; Riley, T. A.

1972-01-01

An analysis is made of the maximum response of discrete, linear mechanical systems to arbitrary forcing functions which lie within specified bounds. Primary attention is focused on the complete determination of the forcing function which will engender maximum displacement to any particular mass element of a multi-degree-of-freedom system. In general, the desired forcing function is found to be a bang-bang type function, i.e., a function which switches from the maximum to the minimum bound and vice-versa at certain instants of time. Examples of two-degree-of-freedom systems, with and without damping, are presented in detail. Conclusions are drawn concerning the effect of damping on the switching times and the general procedure for finding these times is discussed.

Transient response of multidegree-of-freedom linear systems to forcing functions with inequality constraints

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.

1974-01-01

Optimal control theory is applied to analyze the transient response of discrete linear systems to forcing functions with unknown time dependence but having known bounds. Particular attention is given to forcing functions which include: (1) maximum displacement of any given mass element, (2) maximum relative displacement of any two adjacent masses, and (3) maximum acceleration of a given mass. Linear mechanical systems with an arbitrary number of degrees of freedom and only one forcing function acting are considered. In the general case, the desired forcing function is found to be a function that switches from the upper-to-lower bound and vice-versa at certain moments of time. A general procedure for finding such switching times is set forth.

The Privatisation of Military Force: Economic Virtues, Vices and Government Responsibility

DTIC Science & Technology

1999-01-01

0 The Privatisation of Military Force: Economic Virtues, Vices and Government Responsibility ERIC FREDLAND Professor. Department of Economics...ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response , including the time...COVERED 00-00-1999 to 00-00-1999 4. TITLE AND SUBTITLE The Privatisation of Military Force: Economic Virtues, Vices and Government Responsibility

Correlation effects in the quench-induced phase separation dynamics of a two species ultracold quantum gas

NASA Astrophysics Data System (ADS)

Mistakidis, S. I.; Katsimiga, G. C.; Kevrekidis, P. G.; Schmelcher, P.

2018-04-01

We explore the quench dynamics of a binary Bose–Einstein condensate crossing the miscibility–immiscibility threshold and vice versa, both within and in particular beyond the mean-field approximation. Increasing the interspecies repulsion leads to the filamentation of the density of each species, involving shorter wavenumbers and longer spatial scales in the many-body (MB) approach. These filaments appear to be strongly correlated and exhibit domain-wall structures. Following the reverse quench process multiple dark–antidark solitary waves are spontaneously generated and subsequently found to decay in the MB scenario. We simulate single-shot images to connect our findings to possible experimental realizations. Finally, the growth rate of the variance of a sample of single-shots probes the degree of entanglement inherent in the system.

Technology-Based Communication and the Development of Interpersonal Competencies Within Adolescent Romantic Relationships: A Preliminary Investigation

PubMed Central

Nesi, Jacqueline; Widman, Laura; Choukas-Bradley, Sophia; Prinstein, Mitchell J.

2018-01-01

This study investigated longitudinal associations between adolescents’ technology-based communication and the development of interpersonal competencies within romantic relationships. A school-based sample of 487 adolescents (58% girls; Mage = 14.1) participated at two time points, one year apart. Participants reported (1) proportions of daily communication with romantic partners via traditional modes (in person, on the phone) versus technological modes (text messaging, social networking sites) and (2) competence in the romantic relationship skill domains of negative assertion and conflict management. Results of cross-lagged panel models indicated that adolescents who engaged in greater proportions of technology-based communication with romantic partners reported lower levels of interpersonal competencies one year later, but not vice versa; associations were particularly strong for boys. PMID:28876524

Pathways for learning two languages: lexical and grammatical associations within and across languages in sequential bilingual children*

PubMed Central

PHAM, GIANG

2018-01-01

This study examines the strength and direction of lexical-grammatical associations within and between first and second languages (L1 and L2) in a longitudinal sample of sequential bilinguals. Thirty-three children who spoke Vietnamese (L1) and English (L2) completed picture-naming and story-telling tasks in each language at four yearly intervals. Hierarchical linear modeling across Years 1–4 revealed bidirectional within-language associations and a unidirectional cross-language association from the L1 to L2. Results suggest a conditional relationship between languages in which the L1 supports L2 growth, but not vice versa. Findings contribute to defining pathways for L1 and L2 learning across domains and languages. PMID:29670455

Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

PubMed

Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

2005-07-08

The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains

PubMed Central

Vishwanath, Sneha

2018-01-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in function or regulatory properties. PMID:29432415

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

PubMed

Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

2018-02-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in function or regulatory properties.

MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing.

PubMed

Jin, Seung-Gi; Jiang, Chun-Ling; Rauch, Tibor; Li, Hongwei; Pfeifer, Gerd P

2005-04-01

MBD2 and MBD3 are two proteins that contain methyl-CpG binding domains and have a transcriptional repression function. Both proteins are components of a large CpG-methylated DNA binding complex named MeCP1, which consists of the nucleosome remodeling and histone deacetylase complex Mi2-NuRD and MBD2. MBD3L2 (methyl-CpG-binding protein 3-like 2) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG-binding domain. Unlike MBD3L1, which is specifically expressed in haploid male germ cells, MBD3L2 expression is more widespread. MBD3L2 interacts with MBD3 in vitro and in vivo, co-localizes with MBD3 but not MBD2, and does not localize to methyl-CpG-rich regions in the nucleus. In glutathione S-transferase pull-down assays, MBD3L2 is found associated with several known components of the Mi2-NuRD complex, including HDAC1, HDAC2, MTA1, MBD3, p66, RbAp46, and RbAp48. Gel shift experiments with nuclear extracts and a CpG-methylated DNA probe indicate that recombinant MBD3L2 can displace a form of the MeCP1 complex from methylated DNA. MBD3L2 acts as a transcriptional repressor when tethered to a GAL4-DNA binding domain. Repression by GAL4-MBD3L2 is relieved by MBD2 and vice versa, and repression by MBD2 from a methylated promoter is relieved by MBD3L2. The data are consistent with a role of MBD3L2 as a transcriptional modulator that can interchange with MBD2 as an MBD3-interacting component of the NuRD complex. Thus, MBD3L2 has the potential to recruit the MeCP1 complex away from methylated DNA and reactivate transcription.

Towards reconstructing herbaceous biome dynamics and associated precipitation in Africa: insights from the classification of grass morphological traits

NASA Astrophysics Data System (ADS)

Pasturel, Marine; Alexandre, Anne; Novello, Alice; Moctar Dieye, Amadou; Wele, Abdoulaye; Paradis, Laure; Hely, Christelle

2014-05-01

Inter-tropical herbaceous ecosystems occupy a 1/5th of terrestrial surface, a half of the African continent, and are expected to extend in the next decades. Dynamic of these ecosystems is simulated with poor accuracy by Dynamic Global Vegetation Models (DGVMs). One of the bias results from the fact that the diversity of the grass layer dominating these herbaceous ecosystems is poorly taken into account. Mean annual precipitation and the length of the dry season are the main constrains of the dynamics of these ecosystems. Conversely, changes in vegetation affect the water cycle. Inaccuracy in herbaceous ecosystem simulation thus impacts simulations of the water cycle (including precipitation) and vice versa. In order to increase our knowledge of the relationships between grass morphological traits, taxonomy, biomes and climatic niches in Western and South Africa, a 3-step methodology was followed: i) values of culm height, leaf length and width of dominant grass species from Senegal were gathered from flora and clustered using the Partition Around Medoids (PAM) method; ii) trait group ability to sign climatic domains and biomes was assessed using Kruskal-Wallis tests; iii) genericity and robustness of the trait groups were evaluated through their application to Chadian and South African botanical datasets. Results show that 8 grass trait groups are present either in Senegal, Chad or South Africa. These 8 trait groups are distributed along mean annual precipitation and dry season length gradients. The combination of three of them allow to discriminate mean annual precipitation domains (<250, 250-600, 600-1000 and >1000 mm) and herbaceous biomes (steppes, savannas, South African grasslands and Nama-Karoo). With these results in hand, grass Plant Functional Types (PFTs) of the DGMV LPJ-GUESS will be re-parameterized and particular attention will be given to the herbaceous biomass assigned to each grass trait group. Simultaneously, relationships between grass trait groups and phytolith vegetation proxies will be quantified in order to reconstruct the past dynamics of herbaceous ecosystems and associated mean annual precipitation domains.

Transfer of Short-Term Motor Learning across the Lower Limbs as a Function of Task Conception and Practice Order

ERIC Educational Resources Information Center

Stockel, Tino; Wang, Jinsung

2011-01-01

Interlimb transfer of motor learning, indicating an improvement in performance with one limb following training with the other, often occurs asymmetrically (i.e., from non-dominant to dominant limb or vice versa, but not both). In the present study, we examined whether interlimb transfer of the same motor task could occur asymmetrically and in…

Spatial and Temporal Resolution of Global Protein Synthesis during HSV Infection Using Bioorthogonal Precursors and Click Chemistry

PubMed Central

Serwa, Remigiusz A.; O’Hare, Peter

2016-01-01

We used pulse-labeling with the methionine analogue homopropargylglycine (HPG) to investigate spatiotemporal aspects of protein synthesis during herpes simplex virus (HSV) infection. In vivo incorporation of HPG enables subsequent selective coupling of fluorochrome-capture reagents to newly synthesised proteins. We demonstrate that HPG labeling had no effect on cell viability, on accumulation of test early or late viral proteins, or on overall virus yields. HPG pulse-labeling followed by SDS-PAGE analysis confirmed incorporation into newly synthesised proteins, while parallel processing by in situ cycloaddition revealed new insight into spatiotemporal aspects of protein localisation during infection. A striking feature was the rapid accumulation of newly synthesised proteins not only in a general nuclear pattern but additionally in newly forming sub-compartments represented by small discrete foci. These newly synthesised protein domains (NPDs) were similar in size and morphology to PML domains but were more numerous, and whereas PML domains were progressively disrupted, NPDs were progressively induced and persisted. Immediate-early proteins ICP4 and ICP0 were excluded from NPDs, but using an ICP0 mutant defective in PML disruption, we show a clear spatial relationship between NPDs and PML domains with NPDs frequently forming immediately adjacent and co-joining persisting PML domains. Further analysis of location of the chaperone Hsc70 demonstrated that while NPDs formed early in infection without overt Hsc70 recruitment, later in infection Hsc70 showed pronounced recruitment frequently in a coat-like fashion around NPDs. Moreover, while ICP4 and ICP0 were excluded from NPDs, ICP22 showed selective recruitment. Our data indicate that NPDs represent early recruitment of host and viral de novo translated protein to distinct structural entities which are precursors to the previously described VICE domains involved in protein quality control in the nucleus, and reveal new features from which we propose spatially linked platforms of newly synthesised protein processing after nuclear import. PMID:27706239

Vertical bloch line memory

NASA Technical Reports Server (NTRS)

Katti, R.; Wu, J.; Stadler, H.

1990-01-01

Vertical Bloch Line (VBL) memory is a recently conceived, integrated, solid-state, block-access, VLSI memory which offers the potential of 1Gbit/sq cm real storage density, gigabit per second data rates, and sub-millisecond average access times simultaneously at relatively low mass, volume, and power values when compared to alternative technologies. VBL's are micromagnetic structures within magnetic domain walls which can be manipulated using magnetic fields from integrated conductors. The presence or absence of VBL pairs are used to store binary information. At present, efforts are being directed at developing a single-chip memory using 25Mbit/sq cm technology in magnetic garnet material which integrates, at a single operating point, the writing, storage, reading, and amplification functions needed in a memory. This paper describes the current design architecture, functional elements, and supercomputer simulation results which are used to assist the design process. The current design architecture uses three metal layers, two ion implantation steps for modulating the thickness of the magnetic layer, one ion implantation step for assisting propagation in the major line track, one NiFe soft magnetic layer, one CoPt hard magnetic layer, and one reflective Cr layer for facilitating magneto-optic observation of magnetic structure. Data are stored in a series of elongated magnetic domains, called stripes, which serve as storage sites for arrays of VBL pairs. The ends of these stripes are placed near conductors which serve as VBL read/write gates. A major line track is present to provide a source and propagation path for magnetic bubbles. Writing and reading, respectively, are achieved by converting magnetic bubbles to VBL's and vice versa. The output function is effected by stretching a magnetic bubble and detecting it magnetoresistively. Experimental results from the past design cycle created four design goals for the current design cycle. First, the bias field ranges for the stripes and the major line needed to be matched. Second, the magnetic field barrier between the stripe and the read/write gates needed to be reduced. Third, current conductor routing needed to be improved to reduce occurrences of open-circuiting, short-circuiting, and eddy-current shielding. Fourth, a modified Co-alloy was needed with an increased coercivity and controlled magnetization to allow VBL stabilization to occur without affecting stripe stability.

An Examination of the Role and Career Paths of Chief Research Administrators in Selected Major Research Universities in the United States

ERIC Educational Resources Information Center

Nash, Julie

2013-01-01

The Chief Research Administrator (CRA), also known as the Vice President, Vice Provost, or Vice Chancellor for Research, plays a key role in the research university. It is a position of power and not only affects the mission of the institution, but also controls a very large and vital percentage of external funding. The lack of information on how…

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

NASA Kennedy Space Center Director Robert Cabana addresses agency leaders, U.S. and Florida government officials, and employees inside the Vehicle Assembly Building during a visit by Vice President Mike Pence. Pence thanked employees for advancing American leadership in space. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence speaks before an audience of NASA leaders, U.S. and Florida government officials, and employees inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. Pence thanked employees for advancing American leadership in space. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

An information theory framework for dynamic functional domain connectivity.

PubMed

Vergara, Victor M; Miller, Robyn; Calhoun, Vince

2017-06-01

Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, 2nd from right, is shown the Mars 2020 spacecraft descent stage from inside the Spacecraft Assembly Facility (SAF) by JPL Director Michael Watkins, to the Vice President's left, and NASA Mars Exploration Manager Li Fuk at NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Mars 2020 is a Mars rover mission by NASA's Mars Exploration Program with a planned launch in 2020. Photo Credit: (NASA/Bill Ingalls)

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence, back to the camera, is greeted by NASA officials at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. From the left are, Deputy Center Director Janet Petro, Center Director Bob Cabana and Acting Administrator Robert Lightfoot. To the right of Lightfoot is Sen. Marco Rubio of Florida. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Apparatus, method and system to control accessibility of platform resources based on an integrity level

DOEpatents

Jenkins, Chris; Pierson, Lyndon G.

2016-10-25

Techniques and mechanism to selectively provide resource access to a functional domain of a platform. In an embodiment, the platform includes both a report domain to monitor the functional domain and a policy domain to identify, based on such monitoring, a transition of the functional domain from a first integrity level to a second integrity level. In response to a change in integrity level, the policy domain may configure the enforcement domain to enforce against the functional domain one or more resource accessibility rules corresponding to the second integrity level. In another embodiment, the policy domain automatically initiates operations in aid of transitioning the platform from the second integrity level to a higher integrity level.

Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

PubMed

Merabet, Samir; Litim-Mecheri, Isma; Karlsson, Daniel; Dixit, Richa; Saadaoui, Mehdi; Monier, Bruno; Brun, Christine; Thor, Stefan; Vijayraghavan, K; Perrin, Laurent; Pradel, Jacques; Graba, Yacine

2011-10-01

Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences.

Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains

PubMed Central

Karlsson, Daniel; Dixit, Richa; Saadaoui, Mehdi; Monier, Bruno; Brun, Christine; Thor, Stefan; Vijayraghavan, K.; Perrin, Laurent; Pradel, Jacques; Graba, Yacine

2011-01-01

Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences. PMID:22046139

75 FR 15726 - Polyvinyl Alcohol From Taiwan; Determination

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-30

...\\ Vice Chairman Pearson and Commissioners Okun and Lane dissented, having determined that there is no... remand, Vice Chairman Pearson and Commissioners Okun and Lane reaffirmed their negative preliminary...

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. At left is the vice president's wife, Karen Pence. To his right are Blue Origin CEO Robert Smith, and acting NASA Administrator Robert Lightfoot. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, hidden at right, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. At far right is the vice president's wife, Karen Pence. Behind her at right are Blue Origin CEO Robert Smith, and acting NASA Administrator Robert Lightfoot. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

The relative temporal sequence of decline in mobility and cognition among initially unimpaired older adults: Results from the Baltimore Longitudinal Study of Aging.

PubMed

Tian, Qu; An, Yang; Resnick, Susan M; Studenski, Stephanie

2017-05-01

most older individuals who experience mobility decline, also show cognitive decline, but whether cognitive decline precedes or follows mobility limitation is not well understood. examine the temporal sequence of mobility and cognition among initially unimpaired older adults. mobility and cognition were assessed every 2 years for 6 years in 412 participants aged ≥60 with initially unimpaired cognition and gait speed. Using autoregressive models, accounting for the dependent variable from the prior assessment, baseline age, sex, body mass index and education, we examine the temporal sequence of change in mobility (6 m usual gait speed, 400 m fast walk time) and executive function (visuoperceptual speed: Digit Symbol Substitution Test (DSST); cognitive flexibility: Trail Making Test part B (TMT-B)) or memory (California Verbal Learning Test (CVLT) immediate, short-delay, long-delay). there was a bidirectional relationship over time between slower usual gait speed and both poorer DSST and TMT-B scores (Bonferroni-corrected P < 0.005). In contrast, slower 400 m fast walk time predicted subsequent poorer DSST, TMT-B, CVLT immediate recall and CVLT short-delay scores (P < 0.005), while these measures did not predict subsequent 400 m fast walk time (P > 0.005). among initially unimpaired older adults, the temporal relationship between usual gait speed and executive function is bidirectional, with each predicting change in the other, while poor fast walking performance predicts future executive function and memory changes but not vice versa. Challenging tasks like the 400 m walk appear superior to usual gait speed for predicting executive function and memory change in unimpaired older adults. Published by Oxford University Press on behalf of the British Geriatrics Society 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Simulation of Devices with Molecular Potentials

DTIC Science & Technology

2013-12-22

10] W. R. Frensley, Wigner - function model of a resonant-tunneling semiconductor de- vice, Phys. Rev. B, 36 (1987), pp. 1570–1580. 6 [11] M. J...develop the principal investigator’s Wigner -Poisson code and extend that code to deal with longer devices and more complex barrier profiles. Over...Research Triangle Park, NC 27709-2211 Molecular Confirmation, Sparse Interpolation, Wigner -Poisson Equation, Parallel Algorithms REPORT DOCUMENTATION PAGE 11

Task Analysis of Tactical Leadership Skills for Bradley Infantry Fighting Vehicle Leaders

DTIC Science & Technology

1986-10-01

The Bradley Leader Trainer is conceptualized as a device or set of de - vices that can be used to teach Bradley leaders to perform their full set of...experts. The task list was examined to de - termine critical training requirements, requirements for training device sup- port of this training, and...Functions/ j ITask | |Task | |Task | [Training j , To Further De - | ;Critical Train- | iTninir

Controllably Designed "Vice-Electrode" Interlayers Harvesting High Performance Lithium Sulfur Batteries.

PubMed

Hao, Youchen; Xiong, Dongbin; Liu, Wen; Fan, Linlin; Li, Dejun; Li, Xifei

2017-11-22

An interlayer has been regarded as a promising mediator to prolong the life span of lithium sulfur batteries because its excellent absorbability to soluble polysulfide efficiently hinders the shuttle effect. Herein, we designed various interlayers and understand the working mechanism of an interlayer for lithium sulfur batteries in detail. It was found that the electrochemical performance of a S electrode for an interlayer located in cathode side is superior to the pristine one without interlayers. Surprisingly, the performance of the S electrode for an interlayer located in anode side is poorer than that of pristine one. For comparison, glass fibers were also studied as a nonconductive interlayer for lithium sulfur batteries. Unlike the two interlayers above, these nonconductive interlayer did displays significant capacity fading because polysulfides were adsorbed onto insulated interlayer. Thus, the nonconductive interlayer function as a "dead zone" upon cycling. Based on our findings, it was for the first time proposed that a controllably optimized interlayer, with electrical conductivity as well as the absorbability of polysulfides, may function as a "vice-electrode" of the anode or cathode upon cycling. Therefore, the cathodic conductive interlayer can enhance lithium sulfur battery performance, and the anodic conductive interlayer may be helpful for the rational design of 3D networks for the protection of lithium metal.

Supra-domains: evolutionary units larger than single protein domains.

PubMed

Vogel, Christine; Berzuini, Carlo; Bashton, Matthew; Gough, Julian; Teichmann, Sarah A

2004-02-20

Domains are the evolutionary units that comprise proteins, and most proteins are built from more than one domain. Domains can be shuffled by recombination to create proteins with new arrangements of domains. Using structural domain assignments, we examined the combinations of domains in the proteins of 131 completely sequenced organisms. We found two-domain and three-domain combinations that recur in different protein contexts with different partner domains. The domains within these combinations have a particular functional and spatial relationship. These units are larger than individual domains and we term them "supra-domains". Amongst the supra-domains, we identified some 1400 (1203 two-domain and 166 three-domain) combinations that are statistically significantly over-represented relative to the occurrence and versatility of the individual component domains. Over one-third of all structurally assigned multi-domain proteins contain these over-represented supra-domains. This means that investigation of the structural and functional relationships of the domains forming these popular combinations would be particularly useful for an understanding of multi-domain protein function and evolution as well as for genome annotation. These and other supra-domains were analysed for their versatility, duplication, their distribution across the three kingdoms of life and their functional classes. By examining the three-dimensional structures of several examples of supra-domains in different biological processes, we identify two basic types of spatial relationships between the component domains: the combined function of the two domains is such that either the geometry of the two domains is crucial and there is a tight constraint on the interface, or the precise orientation of the domains is less important and they are spatially separate. Frequently, the role of the supra-domain becomes clear only once the three-dimensional structure is known. Since this is the case for only a quarter of the supra-domains, we provide a list of the most important unknown supra-domains as potential targets for structural genomics projects.

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

Vice President Mike Pence, meets with NASA leadership, after swearing in Jim Bridenstine as NASA's 13th Administrator, Monday, April 23, 2018 at NASA Headquarters in Washington. Photo Credit: (NASA/Aubrey Gemignani)

Exploring the evolution of protein function in Archaea.

PubMed

Goncearenco, Alexander; Berezovsky, Igor N

2012-05-30

Despite recent progress in studies of the evolution of protein function, the questions what were the first functional protein domains and what were their basic building blocks remain unresolved. Previously, we introduced the concept of elementary functional loops (EFLs), which are the functional units of enzymes that provide elementary reactions in biochemical transformations. They are presumably descendants of primordial catalytic peptides. We analyzed distant evolutionary connections between protein functions in Archaea based on the EFLs comprising them. We show examples of the involvement of EFLs in new functional domains, as well as reutilization of EFLs and functional domains in building multidomain structures and protein complexes. Our analysis of the archaeal superkingdom yields the dominating mechanisms in different periods of protein evolution, which resulted in several levels of the organization of biochemical function. First, functional domains emerged as combinations of prebiotic peptides with the very basic functions, such as nucleotide/phosphate and metal cofactor binding. Second, domain recombination brought to the evolutionary scene the multidomain proteins and complexes. Later, reutilization and de novo design of functional domains and elementary functional loops complemented evolution of protein function.

Mutational analysis of the SRC homology 2 domain protein-tyrosine phosphatase Corkscrew.

PubMed

Allard, J D; Herbst, R; Carroll, P M; Simon, M A

1998-05-22

The SRC homology 2 (SH2) domain protein-tyrosine phosphatase, Corkscrew (CSW) is required for signaling by receptor tyrosine kinases, including the Sevenless receptor tyrosine kinase (SEV), which directs Drosophila R7 photoreceptor cell development. To investigate the role of the different domains of CSW, we constructed domain-specific csw mutations and assayed their effects on CSW function. Our results indicate that CSW SH2 domain function is essential, but either CSW SH2 domain can fulfill this requirement. We also found that CSW and activated SEV are associated in vivo in a manner that does not require either CSW SH2 domain function or tyrosine phosphorylation of SEV. In contrast, the interaction between CSW and Daughter of Sevenless, a CSW substrate, is dependent on SH2 domain function. These results suggest that the role of the CSW SH2 domains during SEV signaling is to bind Daughter of Sevenless rather than activated SEV. We also found that although CSW protein-tyrosine phosphatase activity is required for full CSW function, a catalytically inactive CSW is capable of providing partial function. In addition, we found that deletion of either the CSW protein- tyrosine phosphatase insert or the entire CSW carboxyl terminus, which includes a conserved DRK/GRB2 SH2 domain binding sequence, does not abolish CSW function.

Protein domains of unknown function are essential in bacteria.

PubMed

Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter

2013-12-31

More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.

69. Vice President Ford entering SAC command post, February, 1974 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

69. Vice President Ford entering SAC command post, February, 1974 - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Headquarters Building, 901 SAC Boulevard, Bellevue, Sarpy County, NE

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks

PubMed Central

2011-01-01

Background Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. Results A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Conclusions Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced. PMID:21849086

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.

PubMed

Xie, Xueying; Jin, Jing; Mao, Yongyi

2011-08-18

Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced.

COPRED: prediction of fold, GO molecular function and functional residues at the domain level.

PubMed

López, Daniel; Pazos, Florencio

2013-07-15

Only recently the first resources devoted to the functional annotation of proteins at the domain level started to appear. The next step is to develop specific methodologies for predicting function at the domain level based on these resources, and to implement them in web servers to be used by the community. In this work, we present COPRED, a web server for the concomitant prediction of fold, molecular function and functional sites at the domain level, based on a methodology for domain molecular function prediction and a resource of domain functional annotations previously developed and benchmarked. COPRED can be freely accessed at http://csbg.cnb.csic.es/copred. The interface works in all standard web browsers. WebGL (natively supported by most browsers) is required for the in-line preview and manipulation of protein 3D structures. The website includes a detailed help section and usage examples. pazos@cnb.csic.es.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, left, meets with JPL Director Michael Watkins during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

Defense.gov - Special Report - Cybersecurity

Science.gov Websites

Questions Abound in Cyber Theater of Operations, Vice Chairman Says WASHINGTON, June 9, 2009 - The Defense theater of operations, the vice chairman of the Joint Chiefs of Staff said. Story Obama Announces

Bayesian-based estimation of acoustic surface impedance: Finite difference frequency domain approach.

PubMed

Bockman, Alexander; Fackler, Cameron; Xiang, Ning

2015-04-01

Acoustic performance for an interior requires an accurate description of the boundary materials' surface acoustic impedance. Analytical methods may be applied to a small class of test geometries, but inverse numerical methods provide greater flexibility. The parameter estimation problem requires minimizing prediction vice observed acoustic field pressure. The Bayesian-network sampling approach presented here mitigates other methods' susceptibility to noise inherent to the experiment, model, and numerics. A geometry agnostic method is developed here and its parameter estimation performance is demonstrated for an air-backed micro-perforated panel in an impedance tube. Good agreement is found with predictions from the ISO standard two-microphone, impedance-tube method, and a theoretical model for the material. Data by-products exclusive to a Bayesian approach are analyzed to assess sensitivity of the method to nuisance parameters.

Black-on-white polymer-stabilized cholesteric formulations

NASA Astrophysics Data System (ADS)

West, John L.; Magyar, Gregory R.; Francl, James J.; Nixon, Christine M.

1995-08-01

Recent research by Doane, Yang, and Chien demonstrated the use of cholesteric liquid crystals in multiplexed, high resolution, reflective diplays. These materials utilize the bistability of the cholesteric planar and focal conic states for displays with a colored image on a black background. Many commercial applications of these materials, such as electronic books and newspapers, portable faxes and personal data assistants, require, or at least prefer, black-on- white images. We report on relatively high polymer content (equalsV 20% by weight) dispersions of cholesteric liquid crystals that produce a white, reflecting, planar state. The polymer network appears to form cholesteric domains with varying pitch lengths resulting in planar states that reflect in the red, green, and blue portions of the spectrum. Utilizing a black absorbing layer behind a display using these materials offers white images on a black background, or vice-versa.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. To his left is acting NASA Administrator Robert Lightfoot. At right is the vice president's wife, Karen Pence. At far right is Scott Henderson, Blue Origin director of Test and Flight Operations. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. At far left is the vice president's wife, Karen Pence. To the right of Vice President Pence are acting NASA Administrator Robert Lightfoot and Blue Origin CEO Robert Smith. Pence viewed the flown New Shepard Booster and Crew Capsule. The Crew Capsule, in view, flew seven times, including a pad abort test and an escape test at maximum dynamic pressure. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, center, signs a guest book during his tour of the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. At left is the vice president's wife, Karen Pence. To his right is Blue Origin CEO Robert Smith. Behind them is acting NASA Administrator Robert Lightfoot. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Developing a Job Description for a Vice Chair of Education in Radiology: The ADVICER Template.

PubMed

Lewis, Petra J; Probyn, Linda; McGuinness, Georgeann; Nguyen, Jeremy; Mullins, Mark E; Resnik, Charles; Oldham, Sandra

2015-07-01

The newly formed Alliance of Directors and Vice Chairs of Education in Radiology (ADVICER), a group within the Alliance for Clinician Educators in Radiology, identified an acute need for a generic job description template for Vice Chairs of Education in Radiology, a role that is being developed in many academic Departments of Radiology. Eighty-three percent of current members who responded to a survey had no detailed job description, and over half had no job description at all. Having a comprehensive and detailed job description is vital to developing this key position. Using the results of a survey sent to ADVICER members and seven Education Vice Chair job descriptions provided by members, the authors developed a detailed job description encompassing all potential elements of this position. Only 17% of survey respondents had a detailed job description. The role of an Education Vice Chair varies significantly between institutions in its scope and level of responsibilities. The resultant generic job description that was devised is intended to provide a template that would be modified by the candidate or the Department Chair. It is unlikely that any one individual would perform all the described activities. ADVICER has developed a comprehensive, flexible job description for Vice Chair of Education in Radiology that can be adapted by institutions as appropriate. It can be downloaded from http://aur.org/ADVICER/. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.

PubMed

Datta-Chaudhuri, Timir; Smela, Elisabeth; Abshire, Pamela A

2016-12-01

CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.

Vice President Pence lands at Redstone Army Airfield

NASA Image and Video Library

2017-09-25

Air Force Two lands with Vice President Mike Pence along with Congressman Robert Aderholt at the Redstone Army Airfield in Huntsville, Alabama, on Monday, Sept. 25. They were greeted by NASA’s Marshall Space Flight Center Director Todd May and Redstone Arsenal’s Lt. Gen. Edward Daly. The Vice President is visiting NASA’s Marshall Center to meet with employees, view test hardware for NASA’s Space Launch System — America’s new deep-space rocket, and tour the Payload Operations Integration Center, “science central” for the International Space Station.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

JPL Director Michael Watkins, standing, explains the history of NASA's Jet Propulsion Laboratory and the use of the Mission Support Area to Vice President Mike Pence, seated next to his wife Karen and daughter Charlotte Pence, during a tour of JPL, Saturday, April 28, 2018 in Pasadena, California. Joining the Vice President was, JPL Distinguished Visiting Scientist and Spouse of UAG Chairman James Ellis, Elisabeth Pate-Cornell, left, UAG Chairman, Admiral (Ret) James Ellis, JPL Deputy Director Lt. Gen. (Ret) Larry James, and California Institute of Technology President Thomas Rosenbaum. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, 3rd from right, tours NASA's Jet Propulsion Laboratory along with his wife Karen, and daughter Charlotte, Saturday, April 28, 2018 in Pasadena, California. Joining the Vice President t and his family on the tour are: UAG Chairman, Admiral (Ret) James Ellis , left, JPL Distinguished Visiting Scientist and Spouse of UAG Chairman James Ellis, Elisabeth Pate-Cornell, behind Mrs. Pence, California Institute of Technology President Thomas Rosenbaum, JPL Director Michael Watkins, and JPL Deputy Director Lt. Gen. (Ret) Larry James, right. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence can be seen with his wife Karen Pence as they toured NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. The vice President was also joined by his daughter Charlotte Pence, JPL Distinguished Visiting Scientist and Spouse of UAG Chairman James Ellis, Elisabeth Pate-Cornell , UAG Chairman, Admiral (Ret) James Ellis , Executive Director of the National Space Council Scott Pace, JPL Deputy Director Lt. Gen. (Ret) Larry James, and California Institute of Technology President Thomas Rosenbaum. Photo Credit: (NASA/Bill Ingalls)

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence speaks before an audience of NASA leaders, U.S. and Florida government officials, and employees inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. Pence thanked employees for advancing American leadership in space. Behind the podium is the Orion spacecraft flown on Exploration Flight test-1 in 2014. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

Vice President Pence Visits NASA's Marshall Space Flight Center

NASA Image and Video Library

2017-09-25

Vice President Mike Pence offered his thanks Monday to employees working on NASA’s human spaceflight programs during a tour of the agency’s Marshall Space Flight Center in Huntsville, Alabama. The Vice President saw the progress being made on NASA’s Space Launch System (SLS), the world’s most powerful deep space rocket, that will send astronauts on missions around the Moon and ultimately to Mars. He also visited Marshall’s Payload Operations Integration Center, where the agency manages all research aboard the International Space Station.

How hormones influence composition and physiological function of the brain-blood barrier.

PubMed

Hampl, R; Bičíková, M; Sosvorová, L

2015-01-01

Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

Sequential measurement of conjugate variables as an alternative quantum state tomography.

PubMed

Di Lorenzo, Antonio

2013-01-04

It is shown how it is possible to reconstruct the initial state of a one-dimensional system by sequentially measuring two conjugate variables. The procedure relies on the quasicharacteristic function, the Fourier transform of the Wigner quasiprobability. The proper characteristic function obtained by Fourier transforming the experimentally accessible joint probability of observing "position" then "momentum" (or vice versa) can be expressed as a product of the quasicharacteristic function of the two detectors and that unknown of the quantum system. This allows state reconstruction through the sequence (1) data collection, (2) Fourier transform, (3) algebraic operation, and (4) inverse Fourier transform. The strength of the measurement should be intermediate for the procedure to work.

Prompt Charge Collection in Gallium Arsenide Diodes Struck by Energetic Heavy Ions.

DTIC Science & Technology

1986-09-01

Continue on reverse if necessaty and identify by block number) Charge collection was measured as a function of reversebias voltage on GaAs Schottkyarrier...research described above was all directed at SEU in silicon, the semiconductor material from which state-of-the- art electronic switching de- vices are...of the industry dedicated to satellite electronics. There, data processing re- quirements have traditionally pushed the state of the art , both in

Domain architecture conservation in orthologs

PubMed Central

2011-01-01

Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the notion that orthologs are functionally more similar than other types of homologs at the same evolutionary distance. PMID:21819573

Protein domain analysis of genomic sequence data reveals regulation of LRR related domains in plant transpiration in Ficus.

PubMed

Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K

2014-01-01

Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.

Teaching and Research: The Vice of the Sages.

ERIC Educational Resources Information Center

Ney, James W.

1980-01-01

Teachers may be hemmed in by the latest pedagogical fashions or they may be held by strict adherence to the latest research dogmas. Both of these can constitute an iron entrapment, the vice of the sages. (Author)

Different functional modes of BAR domain proteins in formation and plasticity of mammalian postsynapses.

PubMed

Kessels, Michael M; Qualmann, Britta

2015-09-01

A plethora of cell biological processes involve modulations of cellular membranes. By using extended lipid-binding interfaces, some proteins have the power to shape membranes by attaching to them. Among such membrane shapers, the superfamily of Bin-Amphiphysin-Rvs (BAR) domain proteins has recently taken center stage. Extensive structural work on BAR domains has revealed a common curved fold that can serve as an extended membrane-binding interface to modulate membrane topologies and has allowed the grouping of the BAR domain superfamily into subfamilies with structurally slightly distinct BAR domain subtypes (N-BAR, BAR, F-BAR and I-BAR). Most BAR superfamily members are expressed in the mammalian nervous system. Neurons are elaborately shaped and highly compartmentalized cells. Therefore, analyses of synapse formation and of postsynaptic reorganization processes (synaptic plasticity) - a basis for learning and memory formation - has unveiled important physiological functions of BAR domain superfamily members. These recent advances, furthermore, have revealed that the functions of BAR domain proteins include different aspects. These functions are influenced by the often complex domain organization of BAR domain proteins. In this Commentary, we review these recent insights and propose to classify BAR domain protein functions into (1) membrane shaping, (2) physical integration, (3) action through signaling components, and (4) suppression of other BAR domain functions. © 2015. Published by The Company of Biologists Ltd.

Dissection of Swa2p/Auxilin Domain Requirements for Cochaperoning Hsp70 Clathrin-uncoating Activity In Vivo

PubMed Central

Xiao, Jing; Kim, Leslie S.

2006-01-01

The auxilin family of J-domain proteins load Hsp70 onto clathrin-coated vesicles (CCVs) to drive uncoating. In vitro, auxilin function requires its ability to bind clathrin and stimulate Hsp70 ATPase activity via its J-domain. To test these requirements in vivo, we performed a mutational analysis of Swa2p, the yeast auxilin ortholog. Swa2p is a modular protein with three N-terminal clathrin-binding (CB) motifs, a ubiquitin association (UBA) domain, a tetratricopeptide repeat (TPR) domain, and a C-terminal J-domain. In vitro, clathrin binding is mediated by multiple weak interactions, but a Swa2p truncation lacking two CB motifs and the UBA domain retains nearly full function in vivo. Deletion of all CB motifs strongly abrogates clathrin disassembly but does not eliminate Swa2p function in vivo. Surprisingly, mutation of the invariant HPD motif within the J-domain to AAA only partially affects Swa2p function. Similarly, a TPR point mutation (G388R) causes a modest phenotype. However, Swa2p function is abolished when these TPR and J mutations are combined. The TPR and J-domains are not functionally redundant because deletion of either domain renders Swa2p nonfunctional. These data suggest that the TPR and J-domains collaborate in a bipartite interaction with Hsp70 to regulate its activity in clathrin disassembly. PMID:16687570

Blue light-excited LOV1 and LOV2 domains cooperatively regulate the kinase activity of full-length phototropin2 from Arabidopsis.

PubMed

Oide, Mao; Okajima, Koji; Nakagami, Hirofumi; Kato, Takayuki; Sekiguchi, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi

2018-01-19

Phototropin2 (phot2) is a blue-light (BL) receptor that regulates BL-dependent activities for efficient photosynthesis in plants. phot2 comprises two BL-receiving light-oxygen-voltage-sensing domains (LOV1 and LOV2) and a kinase domain. BL-excited LOV2 is thought to be primarily responsible for the BL-dependent activation of the kinase. However, the molecular mechanisms by which small BL-induced conformational changes in the LOV2 domain are transmitted to the kinase remain unclear. Here, we used full-length wild-type and mutant phot2 proteins from Arabidopsis to study their molecular properties in the dark and under BL irradiation. Phosphorylation assays and absorption measurements indicated that the LOV1 domain assists the thermal relaxation of BL-excited LOV2 and vice versa. Using small-angle X-ray scattering and electron microscopy, we observed that phot2 forms a dimer and has a rod shape with a maximum length of 188 Å and a radius of gyration of 44 Å. Under BL, phot2 displayed large conformational changes that bent the rod shape. By superimposing the crystal structures of the LOV1 dimer, LOV2, and a homology model of the kinase to the observed changes, we inferred that the BL-dependent change consisted of positional shifts of both LOV2 and the kinase relative to LOV1. Furthermore, phot2 mutants lacking the photocycle in LOV1 or LOV2 still exhibited conformational changes under BL, suggesting that LOV1 and LOV2 cooperatively contribute to the conformational changes that activate the kinase. These results suggest that BL-activated LOV1 contributes to the kinase activity of phot2. We discuss the possible intramolecular interactions and signaling mechanisms in phot2. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural and functional aspects of the nonribosomal peptide synthetase condensation domain superfamily: discovery, dissection and diversity.

PubMed

Bloudoff, Kristjan; Schmeing, T Martin

2017-11-01

Nonribosomal peptide synthetases (NRPSs) are incredible macromolecular machines that produce a wide range of biologically- and therapeutically-relevant molecules. During synthesis, peptide elongation is performed by the condensation (C) domain, as it catalyzes amide bond formation between the nascent peptide and the amino acid it adds to the chain. Since their discovery more than two decades ago, C domains have been subject to extensive biochemical, bioinformatic, mutagenic, and structural analyses. They are composed of two lobes, each with homology to chloramphenicol acetyltransferase, have two binding sites for their two peptidyl carrier protein-bound ligands, and have an active site with conserved motif HHxxxDG located between the two lobes. This review discusses some of the important insights into the structure, catalytic mechanism, specificity, and gatekeeping functions of C domains revealed since their discovery. In addition, C domains are the archetypal members of the C domain superfamily, which includes several other members that also function as NRPS domains. The other family members can replace the C domain in NRP synthesis, can work in concert with a C domain, or can fulfill diverse and novel functions. These domains include the epimerization (E) domain, the heterocyclization (Cy) domain, the ester-bond forming C domain, the fungal NRPS terminal C domain (C T ), the β-lactam ring forming C domain, and the X domain. We also discuss structural and function insight into C, E, Cy, C T and X domains, to present a holistic overview of historical and current knowledge of the C domain superfamily. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

The Popeye Domain Containing Genes and Their Function as cAMP Effector Proteins in Striated Muscle.

PubMed

Brand, Thomas

2018-03-13

The Popeye domain containing (POPDC) genes encode transmembrane proteins, which are abundantly expressed in striated muscle cells. Hallmarks of the POPDC proteins are the presence of three transmembrane domains and the Popeye domain, which makes up a large part of the cytoplasmic portion of the protein and functions as a cAMP-binding domain. Interestingly, despite the prediction of structural similarity between the Popeye domain and other cAMP binding domains, at the protein sequence level they strongly differ from each other suggesting an independent evolutionary origin of POPDC proteins. Loss-of-function experiments in zebrafish and mouse established an important role of POPDC proteins for cardiac conduction and heart rate adaptation after stress. Loss-of function mutations in patients have been associated with limb-girdle muscular dystrophy and AV-block. These data suggest an important role of these proteins in the maintenance of structure and function of striated muscle cells.

Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations

PubMed Central

Yang, Fan; Petsalaki, Evangelia; Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.

2015-01-01

Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. PMID:25794154

PHTS, a novel putative tumor suppressor, is involved in the transformation reversion of HeLaHF cells independently of the p53 pathway

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

Yu Dehua; Fan, Wufang; Liu, Guohong

2006-04-01

HeLaHF is a non-transformed revertant of HeLa cells, likely resulting from the activation of a putative tumor suppressor(s). p53 protein was stabilized in this revertant and reactivated for certain transactivation functions. Although p53 stabilization has not conclusively been linked to the reversion, it is clear that the genes in p53 pathway are involved. The present study confirms the direct role of p53 in HeLaHF reversion by demonstrating that RNAi-mediated p53 silencing partially restores anchorage-independent growth potential of the revertant through the suppression of anoikis. In addition, we identified a novel gene, named PHTS, with putative tumor suppressor properties, and showedmore » that this gene is also involved in HeLaHF reversion independently of the p53 pathway. Expression profiling revealed that PHTS is one of the genes that is up-regulated in HeLaHF but not in HeLa. It encodes a putative protein with CD59-like domains. RNAi-mediated PHTS silencing resulted in the partial restoration of transformation (anchorage-independent growth) in HeLaHF cells, similar to that of p53 gene silencing, implying its tumor suppressor effect. However, the observed increased transformation potential by PHTS silencing appears to be due to an increased anchorage-independent proliferation rate rather than suppression of anoikis, unlike the effect of p53 silencing. p53 silencing did not affect PHTS gene expression, and vice versa, suggesting PHTS may function in a new and p53-independent tumor suppressor pathway. Furthermore, over-expression of PHTS in different cancer cell lines, in addition to HeLa, reduces cell growth likely via induced apoptosis, confirming the broad PHTS tumor suppressor properties.« less

Advanced Modular "All in One" Battery System with Intelligent Autonomous Cell Balancing Management

NASA Astrophysics Data System (ADS)

Petitdidier, X.; Pasquier, E.; Defer, M.; Koch, M.; Knorr, W.

2008-09-01

A new generation of energy storage systems based on Li-ion technology emerged at the end of the last century.To perform the first tests in safe conditions, Saft designed a simple electronic.Today, all Li-ion batteries for autonomous applications such as drones, launchers, missiles, torpedoes and "human" applications such as cellular, laptop, hybrid vehicle and nearly sub-marines need a Battery Management System.The minimum in terms of functions is the overcharge and over-discharge protections.For a battery made of 2 cells connected in series or more, a balancing system is added to maintain the available energy during all the life of the battery. For stringent/demanding applications, the state of charge and state of health are calculated by one or more computers.It is now time to take benefit of the past 10 years of Saft's experience in the domain to re-evaluate the constraints of Li-ion batteries and provide customers with improved products by optimizing the battery management.Benefits of electronic for satellite applications:• Full control over battery.• Confidence whatever the possible change of conditions in environment.• The battery system can resist long exposure to gradient conditions with mitigated and stabilized impact on performances.• The balancing function allow to use all the energy of all the cells: optimize of installed energy (compact design, mass saving). It started out with the basic fact that electrochemists are not intended to be space rated electronic experts and vice versa, even if Saft has a good heritage in the electronic battery management system. Consequently, considering heritage and expertise in their respective core businesses, Saft and ASP teamed up.It became necessary to provide an "all in one" modular energy storage system with intelligent autonomous cell balancing management.

18 CFR 1304.6 - Appeals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Drive, Knoxville, Tennessee 37902. Otherwise, the initial decision of the Vice President's designee... W. Summit Hill Drive, Knoxville, Tennessee 37902. Otherwise, the Vice President's decision becomes..., Tennessee Valley Authority, 400 West Summit Hill Drive, Knoxville, Tennessee 37902. If within 60 days of...

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence turns and talks with Executive Director of the National Space Council Scott Pace during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

77 FR 38630 - Open Internet Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... Computer Science and Co-Founder of the Berkman Center for Internet and Society, Harvard University, is... of Technology Computer Science and Artificial Intelligence Laboratory, is appointed vice-chairperson... Jennifer Rexford, Professor of Computer Science, Princeton University Dennis Roberson, Vice Provost...

75 FR 70289 - Notice of Appointment of Individuals to Serve as Members of Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... INFORMATION CONTACT: Cynthia Roscoe, Director of Human Resources, U.S. International Trade Commission (202... the PRB: Vice Chairman Irving A. Williamson Vice-Chair of the PRB: Commissioner Daniel R. Pearson...

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Administrator Jim Bridenstine, speaks with NASA leadership by video conference, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by Vice President Mike Pence as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

Identification and analysis of mutational hotspots in oncogenes and tumour suppressors.

PubMed

Baeissa, Hanadi; Benstead-Hume, Graeme; Richardson, Christopher J; Pearl, Frances M G

2017-03-28

The key to interpreting the contribution of a disease-associated mutation in the development and progression of cancer is an understanding of the consequences of that mutation both on the function of the affected protein and on the pathways in which that protein is involved. Protein domains encapsulate function and position-specific domain based analysis of mutations have been shown to help elucidate their phenotypes. In this paper we examine the domain biases in oncogenes and tumour suppressors, and find that their domain compositions substantially differ. Using data from over 30 different cancers from whole-exome sequencing cancer genomic projects we mapped over one million mutations to their respective Pfam domains to identify which domains are enriched in any of three different classes of mutation; missense, indels or truncations. Next, we identified the mutational hotspots within domain families by mapping small mutations to equivalent positions in multiple sequence alignments of protein domainsWe find that gain of function mutations from oncogenes and loss of function mutations from tumour suppressors are normally found in different domain families and when observed in the same domain families, hotspot mutations are located at different positions within the multiple sequence alignment of the domain. By considering hotspots in tumour suppressors and oncogenes independently, we find that there are different specific positions within domain families that are particularly suited to accommodate either a loss or a gain of function mutation. The position is also dependent on the class of mutation.We find rare mutations co-located with well-known functional mutation hotspots, in members of homologous domain superfamilies, and we detect novel mutation hotspots in domain families previously unconnected with cancer. The results of this analysis can be accessed through the MOKCa database (http://strubiol.icr.ac.uk/extra/MOKCa).

Disease Severity and Domain Specific Arthritis Self-Efficacy: Relationships to Pain and Functioning in Rheumatoid Arthritis Patients

PubMed Central

Somers, Tamara J.; Shelby, Rebecca A.; Keefe, Francis J.; Godiwala, Neha; Lumley, Mark A.; Mosley-Williams, Angelia; Rice, John R.; Caldwell, David

2010-01-01

Objective Examining the degree to which disease severity and domains of self-efficacy (pain, function, other symptoms) explain pain and functioning in rheumatoid arthritis patients. Methods Patients (N=263) completed the Arthritis Impact Measurements Scales-2 to assess pain and functioning (physical, affective, and social), the Arthritis Self-Efficacy Scale to assess three self-efficacy domains (pain, physical function, other); disease severity was assessed with C-reactive protein, physician's rating, abnormal joint count. Structural equation modeling was used to examine hypotheses: 1) does disease severity have a direct relationship with pain and each area of functioning, 2) does disease severity have a direct relationship with each arthritis self-efficacy domain, and 3) do the self-efficacy domains mediate the relationship between disease severity and RA pain and each area of functioning. Results Disease severity was related to pain, physical functioning, and each self-efficacy domain (β's=.28-.56; p's<.001). Each self-efficacy domain was related to its respective domain of functioning (e.g., self-efficacy for pain was related to pain) (β's=.36-.54; p's<.001). Self-efficacy mediated the relationship between disease severity and pain and functioning (β's=.12-.19; p's<.001). Self-efficacy for pain control and to perform functional tasks accounted for 32-42% of disease severity's total effect on their respective outcomes (e.g., self-efficacy for pain control accounted for 32% of disease severity's total effect on pain). Variance accounted for by the total model was 52% for pain, 53% for physical functioning, and 44% for affective and social functioning. Conclusions Disease severity and self-efficacy both impact RA functioning and intervening in these areas may lead to better outcomes. PMID:20535796

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

PubMed Central

Rapoport, Basil

2013-01-01

Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves' disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition. The occurrence of “switching” emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare “switch” patients and appropriate Graves' and Hashimoto's controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity. PMID:23025526

Protein domain organisation: adding order.

PubMed

Kummerfeld, Sarah K; Teichmann, Sarah A

2009-01-29

Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and reverse orientation in different proteins relative to random graphs with identical degree distributions. While these features were statistically over-represented, they are still fairly rare. Looking in detail at the proteins involved, we found strong functional relationships within each cluster. In addition, the domains tended to be involved in protein-protein interaction and are able to function as independent structural units. A particularly striking example was the human Jak-STAT signalling pathway which makes use of a set of domains in a range of orders and orientations to provide nuanced signaling functionality. This illustrated the importance of functional and structural constraints (or lack thereof) on domain organisation.

Generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains

PubMed Central

Vasconcelos, Giovani L.

2014-01-01

A generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain. PMID:24910523

Generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains.

PubMed

Vasconcelos, Giovani L

2014-06-08

A generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, 2nd from left, his wife Karen, and daughter Charlotte are given a tour of NASA's Jet Propulsion Laboratory by JPL Director Michael Watkins, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

JPL Director Michael Watkins, left, explains the history of NASA's Jet Propulsion Laboratory and the use of the Mission Support Area to Vice President Mike Pence, seated 4th from left, during a tour of JPL, Saturday, April 28, 2018 in Pasadena, California. Joining the Vice President was, JPL Distinguished Visiting Scientist and Spouse of UAG Chairman James Ellis, Elisabeth Pate-Cornell, left, UAG Chairman, Admiral (Ret) James Ellis, Executive Director of the National Space Council Scott Pace, wife of Mike Pence, Karen Pence, daughter of Mike Pence, Charlotte Pence, and JPL Deputy Director Lt. Gen. (Ret) Larry James. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, 5th from left, joined by his wife Karen Pence, left, and daughter Charlotte Pence. 2nd from left, view the Vehicle System Test Bed (VSTB) rover in the Mars Yard during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. NASA Mars Exploration Manager Li Fuk, 2nd from left, JPL Director Michael Watkins, Mars Curiosity Engineering Operations Team Chief Megan Lin, and MSL Engineer Sean McGill, right, helped explain to the Vice President and his family how they use these test rovers. Photo Credit: (NASA/Bill Ingalls)

Vice President Mike Pence Visits Kennedy Space Center - Tour of

NASA Image and Video Library

2018-02-21

Vice President Mike Pence, left, and John Mulholland, Boeing vice president and program manager for Commercial Crew Programs, walk with members of the National Space Council during a tour of the Boeing Commercial Crew and Cargo Processing Facility at NASA's Kennedy Space Center in Florida, on Feb. 21, 2018. During his visit, Pence chaired a meeting of the council in the high bay of the center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Aperiodic topological order in the domain configurations of functional materials

NASA Astrophysics Data System (ADS)

Huang, Fei-Ting; Cheong, Sang-Wook

2017-03-01

In numerous functional materials, such as steels, ferroelectrics and magnets, new functionalities can be achieved through the engineering of the domain structures, which are associated with the ordering of certain parameters within the material. The recent progress in technologies that enable imaging at atomic-scale spatial resolution has transformed our understanding of domain topology, revealing that, along with simple stripe-like or irregularly shaped domains, intriguing vortex-type topological domain configurations also exist. In this Review, we present a new classification scheme of 'Zm Zn domains with Zl vortices' for 2D macroscopic domain structures with m directional variants and n translational antiphases. This classification, together with the concepts of topological protection and topological charge conservation, can be applied to a wide range of materials, such as multiferroics, improper ferroelectrics, layered transition metal dichalcogenides and magnetic superconductors, as we discuss using selected examples. The resulting topological considerations provide a new basis for the understanding of the formation, kinetics, manipulation and property optimization of domains and domain boundaries in functional materials.

Further insight into BRUTUS domain composition and functionality

PubMed Central

Matthiadis, Anna; Long, Terri A.

2016-01-01

ABSTRACT BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis. PMID:27359166

Further insight into BRUTUS domain composition and functionality.

PubMed

Matthiadis, Anna; Long, Terri A

2016-08-02

BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis.

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

PubMed Central

Kemmer, Danielle; Podowski, Raf M; Arenillas, David; Lim, Jonathan; Hodges, Emily; Roth, Peggy; Sonnhammer, Erik LL; Höög, Christer; Wasserman, Wyeth W

2006-01-01

Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families. PMID:16533400

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

PubMed Central

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

An Examination of the Interrelationship between the Structure of Financial Management and the Internal Audit Function within the Department of Defense.

DTIC Science & Technology

1986-03-01

sites at activities such as system commands and other large commands; 2. Multilocation audits (T audits ): performed vertically throughout Navy to provide...34 of time devoted to multilocation audits and the flexibility gained from generating audit issues vice audit topics. This ’..~ ’. . flexibility...Education College degree College degree in in accounting accounting or equiva- or equivalent lent experience experience Multilocation audits 18 90 Scope

A Note on a Sampling Theorem for Functions over GF(q)n Domain

NASA Astrophysics Data System (ADS)

Ukita, Yoshifumi; Saito, Tomohiko; Matsushima, Toshiyasu; Hirasawa, Shigeichi

In digital signal processing, the sampling theorem states that any real valued function ƒ can be reconstructed from a sequence of values of ƒ that are discretely sampled with a frequency at least twice as high as the maximum frequency of the spectrum of ƒ. This theorem can also be applied to functions over finite domain. Then, the range of frequencies of ƒ can be expressed in more detail by using a bounded set instead of the maximum frequency. A function whose range of frequencies is confined to a bounded set is referred to as bandlimited function. And a sampling theorem for bandlimited functions over Boolean domain has been obtained. Here, it is important to obtain a sampling theorem for bandlimited functions not only over Boolean domain (GF(q)n domain) but also over GF(q)n domain, where q is a prime power and GF(q) is Galois field of order q. For example, in experimental designs, although the model can be expressed as a linear combination of the Fourier basis functions and the levels of each factor can be represented by GF(q)n, the number of levels often take a value greater than two. However, the sampling theorem for bandlimited functions over GF(q)n domain has not been obtained. On the other hand, the sampling points are closely related to the codewords of a linear code. However, the relation between the parity check matrix of a linear code and any distinct error vectors has not been obtained, although it is necessary for understanding the meaning of the sampling theorem for bandlimited functions. In this paper, we generalize the sampling theorem for bandlimited functions over Boolean domain to a sampling theorem for bandlimited functions over GF(q)n domain. We also present a theorem for the relation between the parity check matrix of a linear code and any distinct error vectors. Lastly, we clarify the relation between the sampling theorem for functions over GF(q)n domain and linear codes.

39 CFR 447.31 - Advisory service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... by an agency designee. The Ethical Conduct Officer shall provide advice and guidance for the... Postmaster General. The Chief Operating Officer, Senior Vice Presidents, Vice Presidents, and such other... employee may obtain advice and guidance on questions of conflicts of interest from the Ethical Conduct...

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

JPL Director Michael Watkins, standing, explains the history of NASA's Jet Propulsion Laboratory and the use of the Mission Support Area to Vice President Mike Pence during a tour of JPL, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, his wife Karen, and their daughter Charlotte shake hands with Mars Curiosity Mission ACE Walt Hoffman, right, during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

APOLLO 16 VICE PRESIDENT AGNEW & FIRING ROOM PERSONNEL AT LIFTOFF

NASA Technical Reports Server (NTRS)

1972-01-01

Vice President Spiro T. Agnew, NASA Administrator Dr. James C. Fletcher, center, and Deputy NASA Administrator Dr. George M. Low watch the Apollo 16 liftoff and monitor air-to-ground communications from their viewing area within the Launch Control Center.

Compatibility of information and mode of control: The case for natural control systems

NASA Technical Reports Server (NTRS)

Owen, Dean H.

1993-01-01

The operation of control systems has been determined largely by mechanical constraints. Compatibility with the characteristics of the operator is a secondary consideration, with the result that control may never be optimal, control workload may interfere with performance of secondary tasks, and learning may be more difficult and protracted than necessary. With the introduction of a computer in the control loop, the mode of operation can be adapted to the operator, rather than vice versa. The concept of natural control is introduced to describe a system that supports control of the information used by the operator in achieving an intended goal. As an example, control of speed during simulated approach to a pad by helicopter pilots is used to contrast path-speed control with direct control of global optical flow-pattern information. Differences are evidenced in the performance domains of control activity, speed, and global optical flow velocity.

Reciprocal Associations between Family and Peer Conflict in Adolescents’ Daily Lives1

PubMed Central

Chung, Grace H.; Fuligni, Andrew J.

2012-01-01

Using a daily diary method, this study assessed daily episodes of family and peer conflict among 578 adolescents in the ninth grade in order to examine potential bidirectional associations between the family and peer domains. Adolescents completed a daily diary checklist at the end of each day over a fourteen day period to report events of conflict and their emotional states for a given day. Overall, our within-person models provided evidence for the bidirectional nature of family-peer linkages across gender and ethnicity. Adolescents experienced more peer conflict on days in which they argued with parents or other family members, and vice versa. Effect of family conflict further spilled over into peer relationships the next day and two days later, whereas peer conflict predicted only the following day family conflict. Adolescents’ emotional distress partially explained these short term spillovers between family and peer conflict. PMID:21793820

Symmetry and charge order in Fe2OBO3 studied through polarized resonant x-ray diffraction

NASA Astrophysics Data System (ADS)

Bland, S. R.; Angst, M.; Adiga, S.; Scagnoli, V.; Johnson, R. D.; Herrero-Martín, J.; Hatton, P. D.

2010-09-01

Bond valence sum calculations have previously suggested that iron oxyborate exhibits charge order of the Fe ions with integer 2+/3+ valence states. Meanwhile transition metal oxides typically show much smaller, fractional charge disproportionations. Using resonant x-ray diffraction at the iron K edge, we find resonant features which are much larger than those ordinarily observed in charge ordered oxides. Simulations were subsequently performed using a cluster-based, monoelectronic code. The nanoscale domain structure prevents precise fitting; nevertheless the simulations confirm the diagonal charge order symmetry, as well as the unusually large charge disproportionation. We have demonstrated the conversion of linearly to nonlinearly polarized light and vice versa through full polarization analysis. Simulations show that this effect principally results from interference between the isotropic and anisotropic scattering terms. This mechanism is likely to account for similar observations in alternative systems.

Technology-Based Communication and the Development of Interpersonal Competencies Within Adolescent Romantic Relationships: A Preliminary Investigation.

PubMed

Nesi, Jacqueline; Widman, Laura; Choukas-Bradley, Sophia; Prinstein, Mitchell J

2017-06-01

This study investigated longitudinal associations between adolescents' technology-based communication and the development of interpersonal competencies within romantic relationships. A school-based sample of 487 adolescents (58% girls; M age  = 14.1) participated at two time points, one year apart. Participants reported (1) proportions of daily communication with romantic partners via traditional modes (in person, on the phone) versus technological modes (text messaging, social networking sites) and (2) competence in the romantic relationship skill domains of negative assertion and conflict management. Results of cross-lagged panel models indicated that adolescents who engaged in greater proportions of technology-based communication with romantic partners reported lower levels of interpersonal competencies one year later, but not vice versa; associations were particularly strong for boys. © 2016 The Authors. Journal of Research on Adolescence © 2016 Society for Research on Adolescence.

J domain independent functions of J proteins.

PubMed

Ajit Tamadaddi, Chetana; Sahi, Chandan

2016-07-01

Heat shock proteins of 40 kDa (Hsp40s), also called J proteins, are obligate partners of Hsp70s. Via their highly conserved and functionally critical J domain, J proteins interact and modulate the activity of their Hsp70 partners. Mutations in the critical residues in the J domain often result in the null phenotype for the J protein in question. However, as more J proteins have been characterized, it is becoming increasingly clear that a significant number of J proteins do not "completely" rely on their J domains to carry out their cellular functions, as previously thought. In some cases, regions outside the highly conserved J domain have become more important making the J domain dispensable for some, if not for all functions of a J protein. This has profound effects on the evolution of such J proteins. Here we present selected examples of J proteins that perform J domain independent functions and discuss this in the context of evolution of J proteins with dispensable J domains and J-like proteins in eukaryotes.

The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of brain morphogenesis.

PubMed

Acampora, D; Simeone, A

1999-03-01

The murine homologs of the orthodenticle (otd) gene of Drosophila, Otx1 and Otx2, have an important role in brain morphogenesis. Analysis of Otx1 and Otx2 null mice reveals that Otx1 is required primarily for corticogenesis and sense-organ development,while Otx2 is necessary for specification and maintenance of anterior neural plate as well as for proper gastrulation. Cross-phylum recoveries of Otx1 abnormalities by Drosophila otd, and vice versa, indicate that genetic functions required in mammalian-brain development evolved in a primitive ancestor of flies and mice. Knock-in mouse models in which Otx2 was replaced with Otx1, and vice versa, provide evidence that the existence of Otx1-/- and Otx2-/- divergent phenotypes largely reflects differences in expression patterns rather than in the biochemical activity of OTX1 and OTX2. In evolutionary terms, some of these findings lead us to hypothesize a fascinating and crucial role for Otx genes that contributes to the genetic program required for the specification of the development of the vertebrate head.

Interview. The story of Advanced BioHealing: commercializing bioengineered tissue products. Mr Tozer speaks to Emily Culme-Seymour, Assistant Commissioning Editor.

PubMed

Tozer, Dean

2011-03-01

Dean Tozer is Senior Vice President at Advanced BioHealing, Inc. (ABH), overseeing marketing, corporate development, government affairs, product development, various regulatory functions and international expansion. After completing his Bachelor of Commerce from Saint Mary's University in Halifax, Canada, Mr Tozer spent 10 years in the global pharmaceutical industry, primarily with G.D. Searle (a division of Monsanto) where he had a wide variety of roles in Global Marketing, Sales, Business Redesign, and Accounting and Finance. Mr Tozer then worked as a consultant to the biopharmaceutical industry, assisting start-up organizations in developing commercial strategies for both pharmaceutical products and biomedical devices, prior to joining ABH in March 2006 as Vice President of Marketing & Corporate Development. In addition to his leadership role at ABH, Mr Tozer currently serves as an officer and board member for the Alliance for Regenerative Medicine, a Washington DC-based organization formed to advance regenerative medicine by representing and supporting the community of companies, academic research institutions, patient advocacy groups, foundations, and other organizations before the Congress, federal agencies and the general public.

Pan-Cancer Analysis of Mutation Hotspots in Protein Domains.

PubMed

Miller, Martin L; Reznik, Ed; Gauthier, Nicholas P; Aksoy, Bülent Arman; Korkut, Anil; Gao, Jianjiong; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

2015-09-23

In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain mutation analysis also sharpens the functional interpretation of the impact of mutations, as domains more succinctly embody function than entire genes. By mapping mutations in 22 different tumor types to equivalent positions in multiple sequence alignments of domains, we confirm well-known functional mutation hotspots, identify uncharacterized rare variants in one gene that are equivalent to well-characterized mutations in another gene, detect previously unknown mutation hotspots, and provide hypotheses about molecular mechanisms and downstream effects of domain mutations. With the rapid expansion of cancer genomics projects, protein domain hotspot analysis will likely provide many more leads linking mutations in proteins to the cancer phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroendocrine circuits governing energy balance and stress regulation: functional overlap and therapeutic implications

PubMed Central

Ulrich-Lai, Yvonne M.; Ryan, Karen K.

2014-01-01

Significant co-morbidities between obesity-related metabolic disease and stress-related psychological disorders suggest important functional interactions between energy balance and brain stress integration. Largely overlapping neural circuits control these systems, and this anatomical arrangement optimizes opportunities for mutual influence. Here we first review the current literature identifying effects of metabolic neuroendocrine signals on stress regulation, and vice versa. Next, the contributions of reward driven food intake to these metabolic and stress interactions are discussed. Lastly, we consider the inter-relationships among metabolism, stress and reward in light of their important implications in the development of therapies for metabolism- or stress-related disease. PMID:24630812

Ankyrin Repeat Domain Protein 2 and Inhibitor of DNA Binding 3 Cooperatively Inhibit Myoblast Differentiation by Physical Interaction*

PubMed Central

Mohamed, Junaith S.; Lopez, Michael A.; Cox, Gregory A.; Boriek, Aladin M.

2013-01-01

Ankyrin repeat domain protein 2 (ANKRD2) translocates from the nucleus to the cytoplasm upon myogenic induction. Overexpression of ANKRD2 inhibits C2C12 myoblast differentiation. However, the mechanism by which ANKRD2 inhibits myoblast differentiation is unknown. We demonstrate that the primary myoblasts of mdm (muscular dystrophy with myositis) mice (pMBmdm) overexpress ANKRD2 and ID3 (inhibitor of DNA binding 3) proteins and are unable to differentiate into myotubes upon myogenic induction. Although suppression of either ANKRD2 or ID3 induces myoblast differentiation in mdm mice, overexpression of ANKRD2 and inhibition of ID3 or vice versa is insufficient to inhibit myoblast differentiation in WT mice. We identified that ANKRD2 and ID3 cooperatively inhibit myoblast differentiation by physical interaction. Interestingly, although MyoD activates the Ankrd2 promoter in the skeletal muscles of wild-type mice, SREBP-1 (sterol regulatory element binding protein-1) activates the same promoter in the skeletal muscles of mdm mice, suggesting the differential regulation of Ankrd2. Overall, we uncovered a novel pathway in which SREBP-1/ANKRD2/ID3 activation inhibits myoblast differentiation, and we propose that this pathway acts as a critical determinant of the skeletal muscle developmental program. PMID:23824195

Stick the Landing

ERIC Educational Resources Information Center

Collins, Mary Ellen

2013-01-01

Quick turnover among chief advancement officers or development leaders is no longer a rare occurrence. Recruitment executives report that half or more of the searches they are conducting result from vacancies caused by vice presidents being asked to resign. And those terminations are not because of fundraising failures. Vice presidential…

China Report, Economic Affairs

DTIC Science & Technology

1986-04-11

struggle against serious economic crime. Vice Chairmen of the provincial People’s Congress Standing Committee Chen Anyu, Shang Jingcai, Li Yuhua , Wu...Jingji, Wu Ruoan, Tan Jiazhen, Shu Wen, Cao Tianqin, and Zuo Zhaoji, vice mayors of Shanghai; and leading members of the Shanghai Higher People’s

Virtues, Vices, and Political Influence in the U.S. Senate.

PubMed

ten Brinke, Leanne; Liu, Christopher C; Keltner, Dacher; Srivastava, Sameer B

2016-01-01

What qualities make a political leader more influential or less influential? Philosophers, political scientists, and psychologists have puzzled over this question, positing two opposing routes to political power--one driven by human virtues, such as courage and wisdom, and the other driven by vices, such as Machiavellianism and psychopathy. By coding nonverbal behaviors displayed in political speeches, we assessed the virtues and vices of 151 U.S. senators. We found that virtuous senators became more influential after they assumed leadership roles, whereas senators who displayed behaviors consistent with vices--particularly psychopathy--became no more influential or even less influential after they assumed leadership roles. Our results inform a long-standing debate about the role of morality and ethics in leadership and have important implications for electing effective government officials. Citizens would be wise to consider a candidate's virtue in casting their votes, which might increase the likelihood that elected officials will have genuine concern for their constituents and simultaneously promote cooperation and progress in government. © The Author(s) 2015.

A composite smeared finite element for mass transport in capillary systems and biological tissue.

PubMed

Kojic, M; Milosevic, M; Simic, V; Koay, E J; Fleming, J B; Nizzero, S; Kojic, N; Ziemys, A; Ferrari, M

2017-09-01

One of the key processes in living organisms is mass transport occurring from blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs, immune cells, and - in the reverse direction - transport of waste products of cell metabolism to blood vessels. The mass exchange from blood vessels to tissue and vice versa occurs through blood vessel walls. This vital process has been investigated experimentally over centuries, and also in the last decades by the use of computational methods. Due to geometrical and functional complexity and heterogeneity of capillary systems, it is however not feasible to model in silico individual capillaries (including transport through the walls and coupling to tissue) within whole organ models. Hence, there is a need for simplified and robust computational models that address mass transport in capillary-tissue systems. We here introduce a smeared modeling concept for gradient-driven mass transport and formulate a new composite smeared finite element (CSFE). The transport from capillary system is first smeared to continuous mass sources within tissue, under the assumption of uniform concentration within capillaries. Here, the fundamental relation between capillary surface area and volumetric fraction is derived as the basis for modeling transport through capillary walls. Further, we formulate the CSFE which relies on the transformation of the one-dimensional (1D) constitutive relations (for transport within capillaries) into the continuum form expressed by Darcy's and diffusion tensors. The introduced CSFE is composed of two volumetric parts - capillary and tissue domains, and has four nodal degrees of freedom (DOF): pressure and concentration for each of the two domains. The domains are coupled by connectivity elements at each node. The fictitious connectivity elements take into account the surface area of capillary walls which belongs to each node, as well as the wall material properties (permeability and partitioning). The overall FE model contains geometrical and material characteristics of the entire capillary-tissue system, with physiologically measurable parameters assigned to each FE node within the model. The smeared concept is implemented into our implicit-iterative FE scheme and into FE package PAK. The first three examples illustrate accuracy of the CSFE element, while the liver and pancreas models demonstrate robustness of the introduced methodology and its applicability to real physiological conditions.

CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.

PubMed

Marchler-Bauer, Aron; Bo, Yu; Han, Lianyi; He, Jane; Lanczycki, Christopher J; Lu, Shennan; Chitsaz, Farideh; Derbyshire, Myra K; Geer, Renata C; Gonzales, Noreen R; Gwadz, Marc; Hurwitz, David I; Lu, Fu; Marchler, Gabriele H; Song, James S; Thanki, Narmada; Wang, Zhouxi; Yamashita, Roxanne A; Zhang, Dachuan; Zheng, Chanjuan; Geer, Lewis Y; Bryant, Stephen H

2017-01-04

NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Modelling protein functional domains in signal transduction using Maude

NASA Technical Reports Server (NTRS)

Sriram, M. G.

2003-01-01

Modelling of protein-protein interactions in signal transduction is receiving increased attention in computational biology. This paper describes recent research in the application of Maude, a symbolic language founded on rewriting logic, to the modelling of functional domains within signalling proteins. Protein functional domains (PFDs) are a critical focus of modern signal transduction research. In general, Maude models can simulate biological signalling networks and produce specific testable hypotheses at various levels of abstraction. Developing symbolic models of signalling proteins containing functional domains is important because of the potential to generate analyses of complex signalling networks based on structure-function relationships.

Vice President Mike Pence Visits Kennedy Space Center - Tour of

NASA Image and Video Library

2018-02-21

Vice President Mike Pence, left, is flanked by NASA astronaut Bob Behnken, left, John Mulholland, Boeing vice president and program manager for Commercial Crew Programs, and Chris Ferguson, Boeing’s director of Crew and Mission Systems, during a tour of the company’s Commercial Crew and Cargo Processing Facility at NASA's Kennedy Space Center in Florida, on Feb. 21, 2018. During his visit, Pence chaired a meeting of the National Space Council in the high bay of the center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Visits Marshall Space Flight Center on This Week @NASA – September 29, 2017

NASA Image and Video Library

2017-09-29

Vice President Mike Pence visited our Marshall Space Flight Center on Sept. 25 to thank employees working on NASA’s human spaceflight programs. He also spoke to the three NASA astronauts currently serving onboard the International Space Station. During a tour, the Vice President also saw progress being made on our Space Launch System rocket, that will send astronauts in our Orion spacecraft on missions around the Moon and ultimately to Mars. Also, NASA Data and Tech Aid in Disaster Relief, Congressional Hearing on August 21 Solar Eclipse, OSIRIS-REx Views Earth During Flyby, and “Bladed Terrain” on Pluto Made of Frozen Methane!

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

NASA Kennedy Space Center Deputy Director Janet Petro addresses agency leaders, U.S. and Florida government officials and employees inside the Vehicle Assembly Building during a visit by Vice President Mike Pence. Pence thanked employees for advancing American leadership in space. Behind the podium are, from the left, a flown SpaceX Dragon capsule, the Orion spacecraft flown on Exploration Flight test-1 in 2014, and a mockup of Boeing's CST-100 Starliner. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence speaks before an audience of NASA leaders, U.S. and Florida government officials, and employees inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. Pence thanked employees for advancing American leadership in space. Behind the podium are, from the left, a flown SpaceX Dragon capsule, the Orion spacecraft flown on Exploration Flight test-1 in 2014, and a mockup of Boeing's CST-100 Starliner. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Acting NASA Administrator Robert Lightfoot addresses agency leaders, U.S. and Florida government officials, and employees inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida during a visit by Vice President Mike Pence. Pence thanked employees for advancing American leadership in space. Behind the podium are, from the left, a flown SpaceX Dragon capsule, the Orion spacecraft flown on Exploration Flight test-1 in 2014, and a mockup of Boeing's CST-100 Starliner. During his visit to Kennedy, the Vice President also toured several facilities highlighting the public-private partnerships, as both NASA and commercial companies prepare to launch American astronauts from the multi-user spaceport.

5 CFR 2634.602 - Filing of reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... part. (b) The President, the Vice President, any independent counsel, and persons appointed by independent counsel under 28 U.S.C. chapter 40, shall file the public financial disclosure reports required... part. (e) Candidates for President and Vice President identified in § 2634.201(d), other than an...

Changing Postal ZIP Code Boundaries

DTIC Science & Technology

2006-06-23

the nine postal areas from John E. Potter (now CRS-5 Postmaster General, then senior vice president for operations) and Deborah Wilhite, senior vice...accommodations were reached in 64% of the first 28 reviews to be completed.10 Steve Burkholder , mayor of Lakewood, CO, and point person for the

12 CFR 403.8 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Appeals. 403.8 Section 403.8 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL... Vice President & Vice Chairman, Export-Import Bank of the United States, 811 Vermont Avenue NW...

Evaluating Investments in Natural Gas Vehicles and Infrastructure for Your Fleet: Vehicle Infrastructure Cash-Flow Estimation -- VICE 2.0; Clean Cities, Energy Efficiency & Renewable Energy (EERE)

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

Gonzales, John

2015-04-02

Presentation by Senior Engineer John Gonzales on Evaluating Investments in Natural Gas Vehicles and Infrastructure for Your Fleet using the Vehicle Infrastructure Cash-flow Estimation (VICE) 2.0 model.

Vice President Meets with NASA Leadership

NASA Image and Video Library

2018-04-23

NASA Chief Financial Officer, Jeff DeWit, watches the live uplink with the crew of the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Jim Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Aubrey Gemignani)

T. J. Lee Presents Plaque to Vice President Dan Quayle

NASA Technical Reports Server (NTRS)

1992-01-01

Vice President Dan Quayle holds up an inscribed plaque presented by Marshall Space Flight Center Director T. J. Lee (right) during Quayle's August 31, 1992 visit. While at Marshall, Quayle participated in a roundtable discussion with aerospace managers and addressed Center employees in Building 4755.

The domain organization of the bacterial intermediate filament-like protein crescentin is important for assembly and function

PubMed Central

Cabeen, Matthew T; Herrmann, Harald; Jacobs-Wagner, Christine

2011-01-01

Crescentin is a bacterial filament-forming protein that exhibits domain organization features found in metazoan intermediate filament (IF) proteins. Structure-function studies of eukaryotic IFs have been hindered by a lack of simple genetic systems and easily quantifiable phenotypes. Here we exploit the characteristic localization of the crescentin structure along the inner curvature of Caulobacter crescentus cells and the loss of cell curvature associated with impaired crescentin function to analyze the importance of the domain organization of crescentin. By combining biochemistry and ultrastructural analysis in vitro with cellular localization and functional studies, we show that crescentin requires its distinctive domain organization, and furthermore that different structural elements have distinct structural and functional contributions. The head domain can be functionally subdivided into two subdomains; the first (amino-terminal) is required for function but not assembly, while the second is necessary for structure assembly. The rod domain is similarly required for structure assembly, and the linker L1 appears important to prevent runaway assembly into nonfunctional aggregates. The data also suggest that the stutter and the tail domain have critical functional roles in stabilizing crescentin structures against disassembly by monovalent cations in the cytoplasm. This study suggests that the IF-like behavior of crescentin is a consequence of its domain organization, implying that the IF protein layout is an adaptable cytoskeletal motif, much like the actin and tubulin folds, that is broadly exploited for various functions throughout life from bacteria to humans. © 2011 Wiley-Liss, Inc. PMID:21360832

The phosphatidic acid-binding, polybasic domain is responsible for the differences in the phosphoregulation of lipins 1 and 3.

PubMed

Boroda, Salome; Takkellapati, Sankeerth; Lawrence, Robert T; Entwisle, Samuel W; Pearson, Jennifer M; Granade, Mitchell E; Mullins, Garrett R; Eaton, James M; Villén, Judit; Harris, Thurl E

2017-12-15

Lipins 1, 2, and 3 are Mg 2+ -dependent phosphatidic acid phosphatases and catalyze the penultimate step of triacylglycerol synthesis. We have previously investigated the biochemistry of lipins 1 and 2 and shown that di-anionic phosphatidic acid (PA) augments their activity and lipid binding and that lipin 1 activity is negatively regulated by phosphorylation. In the present study, we show that phosphorylation does not affect the catalytic activity of lipin 3 or its ability to associate with PA in vitro The lipin proteins each contain a conserved polybasic domain (PBD) composed of nine lysine and arginine residues located between the conserved N- and C-terminal domains. In lipin 1, the PBD is the site of PA binding and sensing of the PA electrostatic charge. The specific arrangement and number of the lysines and arginines of the PBD vary among the lipins. We show that the different PBDs of lipins 1 and 3 are responsible for the presence of phosphoregulation on the former but not the latter enzyme. To do so, we generated lipin 1 that contained the PBD of lipin 3 and vice versa. The lipin 1 enzyme with the lipin 3 PBD lost its ability to be regulated by phosphorylation but remained downstream of phosphorylation by mammalian target of rapamycin. Conversely, the presence of the lipin 1 PBD in lipin 3 subjected the enzyme to negative intramolecular control by phosphorylation. These results indicate a mechanism for the observed differences in lipin phosphoregulation in vitro . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

"A battle not man's but God's": origins of the American temperance crusade in the struggle for religious authority.

PubMed

Schmidt, L A

1995-01-01

Major theories of the origins of American temperance have emphasized materialist explanations without taking seriously enough the independent role of ideas--and, in particular, religious ideas--in stimulating the reform. This article develops a new interpretation, focusing on the religious origins of temperance in a "crisis of contested authority" that befell the Protestant denominations descended from Puritanism during the early years of the 19th century. One outgrowth of the crisis over the authority of traditional religious ideas was a new theology focused on religious salvation through the suppression of vice. This new religious ideology provided a core of beliefs and powerful justification for organizing a public crusade to "exterminate" vice, and one that for ideological reasons ultimately narrowed its focus to the specific vice of intemperance. The crusade against vice in the early republic offered clergymen a "solution" to their problems of contested authority by providing new strategies and an organizational base of voluntary societies for carrying out what they perceived to be their sacred duties: winning souls to God, guarding collective salvation and leveraging government to promote obedience to religious prohibitions on vice. At least initially, temperance was part of a new kind of effort to assert the authority of religious ideas in the public sphere, and to regroup religious forces under auspices outside the church.

Extensions of PDZ domains as important structural and functional elements.

PubMed

Wang, Conan K; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

2010-08-01

'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results ( http://bcz102.ust.hk/pdzex/ ). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.

Novel functions of CCM1 delimit the relationship of PTB/PH domains.

PubMed

Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

2017-10-01

Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.

Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer

PubMed Central

Peterson, Thomas A; Nehrt, Nathan L; Park, DoHwan

2012-01-01

Background and objective With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of disease mutation clusters on protein domains by incorporating domain functional annotations to assist in the functional characterization of novel variants. Methods Disease mutations aggregated from multiple databases were mapped to domains, and were classified as either cancer- or non-cancer-related. The statistical method for identifying significantly disease-associated domain positions was applied to both sets of mutations and to randomly generated mutation sets for comparison. To leverage the known function of protein domain regions, the method optionally distributes significant scores to associated functional feature positions. Results Most disease mutations are localized within protein domains and display a tendency to cluster at individual domain positions. The method identified significant disease mutation hotspots in both the cancer and non-cancer datasets. The domain significance scores (DS-scores) for cancer form a bimodal distribution with hotspots in oncogenes forming a second peak at higher DS-scores than non-cancer, and hotspots in tumor suppressors have scores more similar to non-cancers. In addition, on an independent mutation benchmarking set, the DS-score method identified mutations known to alter protein function with very high precision. Conclusion By aggregating mutations with known disease association at the domain level, the method was able to discover domain positions enriched with multiple occurrences of deleterious mutations while incorporating relevant functional annotations. The method can be incorporated into translational bioinformatics tools to characterize rare and novel variants within large-scale sequencing studies. PMID:22319177

Exploring digenic inheritance in arrhythmogenic cardiomyopathy.

PubMed

König, Eva; Volpato, Claudia Béu; Motta, Benedetta Maria; Blankenburg, Hagen; Picard, Anne; Pramstaller, Peter; Casella, Michela; Rauhe, Werner; Pompilio, Giulio; Meraviglia, Viviana; Domingues, Francisco S; Sommariva, Elena; Rossini, Alessandra

2017-12-08

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core

PubMed Central

Lubyova, Barbora; Hodek, Jan; Zabransky, Ales; Prouzova, Hana; Hubalek, Martin; Hirsch, Ivan

2017-01-01

In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV) replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc) protein and dimethylates arginine residues within the arginine-rich domain (ARD) of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI) and R156 (outside ARDs) were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs), arginine methylation and ubiquitination. PMID:29065155

Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer

PubMed Central

2013-01-01

Background With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Findings Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants’ self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Conclusions Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction. PMID:23497200

Characteristics and Impact of Animal Models Used for Sports Medicine Research

DTIC Science & Technology

2012-09-01

arthroscopic ro- tator cuff repairs : double-row compared with single-row fixation. J Bone Joint Surg Am. 2006; 88:403-410. 24. Ma CB, MacGillivary JD...Clabeaux J, et al. Biomechanical evaluation of arthroscopic rotator cuff stitches. J Bone Joint Surg Am. 2004; 86:1211-1216. 25. Elder CL, Dahners LE...absorbable meniscal repair de- vices as a function of hydrolysis time. An in vitro experimental study. Am J Sports Med. 2001; 29:118-123. 15. Proctor CS

Modeling Protein Domain Function

ERIC Educational Resources Information Center

Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

2007-01-01

This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

Broadband Structural Dynamics: Understanding the Impulse-Response of Structures Across Multiple Length and Time Scales

DTIC Science & Technology

2010-08-18

Spectral domain response calculated • Time domain response obtained through inverse transform Approach 4: WASABI Wavelet Analysis of Structural Anomalies...differences at unity scale! Time Function Transform Apply Spectral Domain Transfer Function Time Function Inverse Transform Transform Transform  mtP

The Academic Role of the Vice President for Health Sciences: Can a Walrus Become a Unicorn?

ERIC Educational Resources Information Center

Pellegrino, Edmund D.

1975-01-01

The Vice President for Health Sciences is a term used for the chief administrative officer of a multi-unit health science component of a university. This essay reviews this job, and the transformation it has undergone in the past. (Editor/PG)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence is given instructions on how to drive a rover nicknamed "Scarecrow" by JPL Director Michael Watkins at NASA's Jet Propulsion Laboratory Mars Yard, Saturday, April 28, 2018 in Pasadena, California. Scarecrow is used to test mobility of rovers on Mars. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, 3rd from left, his wife Karen, and their daughter Charlotte meet with JPL Director Michael Watkins, and Mars Curiosity Mission ACE Walt Hoffman, right, during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

78 FR 72850 - Production of Nonpublic Records and Testimony of OPIC Employees in Legal Proceedings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... sufficient time to obtain it by deposition. The Vice-President/General Counsel may well deny a request for testimony at a legal proceeding unless you explain why you could not have used deposition testimony instead. The Vice-President/General Counsel will [[Page 72851

Sensual Surfaces and Stylistic Excess: The Pleasure and Politics of "Miami Vice."

ERIC Educational Resources Information Center

Schwichtenberg, Cathy

Using Jean Baudrillard's postmodernist theories, this paper analyzes how the television program, "Miami Vice," operationalizes his theory through its attention to surfaces and style. The paper notes that Baudrillard proposes life as a surface comprised of animated models indistinguishable from the reality these models represent and…

Vice President Bush visits ESA Astronauts at KSC for Spacelab dedication

NASA Technical Reports Server (NTRS)

1982-01-01

View of Vice President George Bush (center) visiting Astronauts Owen Garriot (left) and Wubbo Ockels of the Netherlands inside the Spacelab after the dedication ceremony in the Kennedy Space Center's Operations and Checkout (O and C) building. The NASA Headquarters alternative photo number is NASA 82-HC-64.

Spacelab Dedication

NASA Image and Video Library

1982-08-12

View of Vice-President George Bush visiting with Astronaut Owen Garriott and Payload Specialist (PS) Wubbo Ockels of the Netherlands, inside the SL after the dedication ceremony, KSC Operations & Checkout (O&C) Building. 1. Astronaut Owen K. Garriott 2. Vice President George Bush 3. Wubbo Ockels - PS 4x5 Color and B&W

39 CFR 927.1 - Noncontractual carriage of international mail by vessel.

Code of Federal Regulations, 2010 CFR

2010-07-01

... may, within 30 days, appeal the action in writing to the Vice President, Network Operations Management... Operations Management, may sustain, rescind, or compromise a fine or penalty. The decision of the Vice President, Network Operations Management on appeal shall be the final decision of the Postal Service. The...

78 FR 37867 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Withdrawal of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... Robert D. Shallish, Jr., Executive Vice President--Finance and Chief Financial Officer, CONMED..., President and Chief Executive Officer, Society of Corporate Secretaries & Governance Professionals, dated Mar. 29, 2013; Letter from Paul R. Oldham, Chief Financial Officer and Vice President Finance...

78 FR 24281 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Pharmaceuticals, Inc., dated March 28, 2013; Robert D. Shallish, Jr., Executive Vice President--Finance and Chief... Executive Officer, Society of Corporate Secretaries & Governance Professionals, dated March 29, 2013; Paul R. Oldham, Chief Financial Officer and Vice President Finance Administration, Electro Scientific Industries...

Democratizing Laughter

ERIC Educational Resources Information Center

York, J. G.

2012-01-01

According to John Banas and colleagues, the research on laughter in the classroom indicates that a classroom full of laughter increases learning. In contrast, Plato argued that laughter is a vice and chastised those who would give in to it. Nonetheless, between the ancient concept of laughter as vice and the modern concept of laughter as learning…

Gender Profiles and Career Aspiration of Administrators in Higher Education.

ERIC Educational Resources Information Center

Hubbard, Susan S.; Robinson, Jacquelyn P.

A study surveyed 370 administrators in four-year institutions in the mid-southern United States to identify factors that enhance administrative placement with regard to gender. By administrative position, the sample included the following: 20 presidents/chancellors/provosts; 50 vice-presidents/vice-chancellors; 100 deans; and 200 department or…

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

NASA's Acting Administrator Robert Lightfoot, left, greets Vide President Mike Pence at the Shuttle Landing Facility at the agency's Kennedy Space Center in Florida. During his visit to Kennedy, the Vice President spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

Vice President Mike Pence Arrival at Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence greets NASA Kennedy Space Center Director Robert Cabana after arriving aboard Air Force Two at NASA's Kennedy Space Center in Florida. During his visit to Kennedy, Pence spoke inside the iconic Vehicle Assembly Building, where he thanked employees for advancing American leadership in space.

36 CFR 1151.3 - Officers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Officers. 1151.3 Section 1151.3 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD... or Vice-Chair has been elected. When the Chair is a public member, the Vice-Chair shall be a Federal...

Educating Lives for Christian Wisdom

ERIC Educational Resources Information Center

Davis, Darin H.; Wadell, Paul J.

2016-01-01

This article explores how educating lives for Christian wisdom might serve as an antidote to the vice of "acedia," a prominent feature of the culture of contemporary higher education. After suggesting that the capital vice of "acedia" seems to capture well various facets of our present age and how the pursuit of wisdom serves…

Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers

PubMed Central

Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

2009-01-01

Background Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Results Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Conclusion Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies. PMID:19154605

Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers.

PubMed

Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

2009-01-20

Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies.

Variable-Domain Functional Regression for Modeling ICU Data.

PubMed

Gellar, Jonathan E; Colantuoni, Elizabeth; Needham, Dale M; Crainiceanu, Ciprian M

2014-12-01

We introduce a class of scalar-on-function regression models with subject-specific functional predictor domains. The fundamental idea is to consider a bivariate functional parameter that depends both on the functional argument and on the width of the functional predictor domain. Both parametric and nonparametric models are introduced to fit the functional coefficient. The nonparametric model is theoretically and practically invariant to functional support transformation, or support registration. Methods were motivated by and applied to a study of association between daily measures of the Intensive Care Unit (ICU) Sequential Organ Failure Assessment (SOFA) score and two outcomes: in-hospital mortality, and physical impairment at hospital discharge among survivors. Methods are generally applicable to a large number of new studies that record a continuous variables over unequal domains.

The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release

PubMed Central

Sette, Paola; Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Snyder, Greg; Smith, Patrick; Xiao, Tsan. Sam; Bouamr, Fadila

2011-01-01

Summary Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1 domain of Alix alleviates HIV-1 release defects due to interrupted access to ESCRT. In an attempt to elucidate this functional discrepancy, we solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They revealed typical “boomerang” folds they share with the Bro1 Alix domain. However, they each contain unique structural features that may be relevant to their specific function(s). In particular, phenylalanine residue in position 105 (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain. Concurrently mutation of Phe105 and surrounding residues at the tip of the loop compromises the function of Alix in HIV-1 budding without affecting its interactions with Gag or CHMP4. These studies identify a new functional determinant in the Bro1 domain of Alix. PMID:21889351

Fungal-type carbohydrate binding modules from the coccolithophore Emiliania huxleyi show binding affinity to cellulose and chitin.

PubMed

Rooijakkers, Bart J M; Ikonen, Martina S; Linder, Markus B

2018-01-01

Six fungal-type cellulose binding domains were found in the genome of the coccolithophore Emiliania huxleyi and cloned and expressed in Escherichia coli. Sequence comparison indicate high similarity to fungal cellulose binding domains, raising the question of why these domains exist in coccolithophores. The proteins were tested for binding with cellulose and chitin as ligands, which resulted in the identification of two functional carbohydrate binding modules: EHUX2 and EHUX4. Compared to benchmark fungal cellulose binding domain Cel7A-CBM1 from Trichoderma reesei, these proteins showed slightly lower binding to birch and bacterial cellulose, but were more efficient chitin binders. Finally, a set of cellulose binding domains was created based on the shuffling of one well-functioning and one non-functional domain. These were characterized in order to get more information of the binding domain's sequence-function relationship, indicating characteristic differences between the molecular basis of cellulose versus chitin recognition. As previous reports have showed the presence of cellulose in coccoliths and here we find functional cellulose binding modules, a possible connection is discussed.

An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.

PubMed

Devkota, Sujan; Joseph, Raji E; Boyken, Scott E; Fulton, D Bruce; Andreotti, Amy H

2017-06-13

Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) binding. Using a combination of nuclear magnetic resonance spectroscopy and mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK PH domain that makes direct contact with the catalytic kinase domain of ITK, inhibiting the phospho-transfer reaction. Moreover, we have elucidated an important interplay between lipid binding by the ITK PH domain and the stability of the autoinhibitory complex formed by full length ITK. The ITK activation loop in the kinase domain becomes accessible to phosphorylation to the exogenous kinase LCK upon binding of the ITK PH domain to PIP 3 . By clarifying the allosteric role of the ITK PH domain in controlling ITK function, we have expanded the functional repertoire of the PH domain generally and opened the door to alternative strategies to target this specific kinase in the context of immune cell signaling.

Functional Independence and Interdependence of the Src Homology Domains of Phospholipase C-γ1 in B-Cell Receptor Signal Transduction

PubMed Central

DeBell, Karen E.; Stoica, Bogdan A.; Verí, Maria-Concetta; Di Baldassarre, Angela; Miscia, Sebastiano; Graham, Laurie J.; Rellahan, Barbara L.; Ishiai, Masamichi; Kurosaki, Tomohiro; Bonvini, Ezio

1999-01-01

B-cell receptor (BCR)-induced activation of phospholipase C-γ1 (PLCγ1) and PLCγ2 is crucial for B-cell function. While several signaling molecules have been implicated in PLCγ activation, the mechanism coupling PLCγ to the BCR remains undefined. The role of PLCγ1 SH2 and SH3 domains at different steps of BCR-induced PLCγ1 activation was examined by reconstitution in a PLCγ-negative B-cell line. PLCγ1 membrane translocation required a functional SH2 N-terminal [SH2(N)] domain, was decreased by mutation of the SH3 domain, but was unaffected by mutation of the SH2(C) domain. Tyrosine phosphorylation did not require the SH2(C) or SH3 domains but depended exclusively on a functional SH2(N) domain, which mediated the association of PLCγ1 with the adapter protein, BLNK. Forcing PLCγ1 to the membrane via a myristoylation signal did not bypass the SH2(N) domain requirement for phosphorylation, indicating that the phosphorylation mediated by this domain is not due to membrane anchoring alone. Mutation of the SH2(N) or the SH2(C) domain abrogated BCR-stimulated phosphoinositide hydrolysis and signaling events, while mutation of the SH3 domain partially decreased signaling. PLCγ1 SH domains, therefore, have interrelated but distinct roles in BCR-induced PLCγ1 activation. PMID:10523627

The cysteine-rich domain regulates ADAM protease function in vivo.

PubMed

Smith, Katherine M; Gaultier, Alban; Cousin, Helene; Alfandari, Dominique; White, Judith M; DeSimone, Douglas W

2002-12-09

ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate "adhesive" domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases.

Function-selective domain architecture plasticity potentials in eukaryotic genome evolution

PubMed Central

Linkeviciute, Viktorija; Rackham, Owen J.L.; Gough, Julian; Oates, Matt E.; Fang, Hai

2015-01-01

To help evaluate how protein function impacts on genome evolution, we introduce a new concept of ‘architecture plasticity potential’ – the capacity to form distinct domain architectures – both for an individual domain, or more generally for a set of domains grouped by shared function. We devise a scoring metric to measure the plasticity potential for these domain sets, and evaluate how function has changed over time for different species. Applying this metric to a phylogenetic tree of eukaryotic genomes, we find that the involvement of each function is not random but highly selective. For certain lineages there is strong bias for evolution to involve domains related to certain functions. In general eukaryotic genomes, particularly animals, expand complex functional activities such as signalling and regulation, but at the cost of reducing metabolic processes. We also observe differential evolution of transcriptional regulation and a unique evolutionary role of channel regulators; crucially this is only observable in terms of the architecture plasticity potential. Our findings provide a new layer of information to understand the significance of function in eukaryotic genome evolution. A web search tool, available at http://supfam.org/Pevo, offers a wide spectrum of options for exploring functional importance in eukaryotic genome evolution. PMID:25980317

More flexibility in representing geometric distortion in astronomical images

NASA Astrophysics Data System (ADS)

Shupe, David L.; Laher, Russ R.; Storrie-Lombardi, Lisa; Surace, Jason; Grillmair, Carl; Levitan, David; Sesar, Branimir

2012-09-01

A number of popular software tools in the public domain are used by astronomers, professional and amateur alike, but some of the tools that have similar purposes cannot be easily interchanged, owing to the lack of a common standard. For the case of image distortion, SCAMP and SExtractor, available from Astromatic.net, perform astrometric calibration and source-object extraction on image data, and image-data geometric distortion is computed in celestial coordinates with polynomial coefficients stored in the FITS header with the PV i_j keywords. Another widely-used astrometric-calibration service, Astrometry.net, solves for distortion in pixel coordinates using the SIP convention that was introduced by the Spitzer Science Center. Up until now, due to the complexity of these distortion representations, it was very difficult to use the output of one of these packages as input to the other. New Python software, along with faster-computing C-language translations, have been developed at the Infrared Processing and Analysis Center (IPAC) to convert FITS-image headers from PV to SIP and vice versa. It is now possible to straightforwardly use Astrometry.net for astrometric calibration and then SExtractor for source-object extraction. The new software also enables astrometric calibration by SCAMP followed by image visualization with tools that support SIP distortion, but not PV . The software has been incorporated into the image-processing pipelines of the Palomar Transient Factory (PTF), which generate FITS images with headers containing both distortion representations. The software permits the conversion of archived images, such as from the Spitzer Heritage Archive and NASA/IPAC Infrared Science Archive, from SIP to PV or vice versa. This new capability renders unnecessary any new representation, such as the proposed TPV distortion convention.

A gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C increases binding to actin.

PubMed

Bezold, Kristina L; Shaffer, Justin F; Khosa, Jaskiran K; Hoye, Elaine R; Harris, Samantha P

2013-07-26

The M-domain is the major regulatory subunit of cardiac myosin-binding protein-C (cMyBP-C) that modulates actin and myosin interactions to influence muscle contraction. However, the precise mechanism(s) and the specific residues involved in mediating the functional effects of the M-domain are not fully understood. Positively charged residues adjacent to phosphorylation sites in the M-domain are thought to be critical for effects of cMyBP-C on cross-bridge interactions by mediating electrostatic binding with myosin S2 and/or actin. However, recent structural studies revealed that highly conserved sequences downstream of the phosphorylation sites form a compact tri-helix bundle. Here we used site-directed mutagenesis to probe the functional significance of charged residues adjacent to the phosphorylation sites and conserved residues within the tri-helix bundle. Results confirm that charged residues adjacent to phosphorylation sites and residues within the tri-helix bundle are important for mediating effects of the M-domain on contraction. In addition, four missense variants within the tri-helix bundle that are associated with human hypertrophic cardiomyopathy caused either loss-of-function or gain-of-function effects on force. Importantly, the effects of the gain-of-function variant, L348P, increased the affinity of the M-domain for actin. Together, results demonstrate that functional effects of the M-domain are not due solely to interactions with charged residues near phosphorylatable serines and provide the first demonstration that the tri-helix bundle contributes to the functional effects of the M-domain, most likely by binding to actin.

Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

PubMed

Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

2014-07-01

With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. © 2013 Wiley Periodicals, Inc.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from right, and his wife, Karen Pence, tour the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The Crew Capsule, in view, flew seven times, including a pad abort test and an escape test at maximum dynamic pressure. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, at left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, Feb. 20, 2018, with the company's CEO Robert Smith. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Insulator function and topological domain border strength scale with architectural protein occupancy

PubMed Central

2014-01-01

Background Chromosome conformation capture studies suggest that eukaryotic genomes are organized into structures called topologically associating domains. The borders of these domains are highly enriched for architectural proteins with characterized roles in insulator function. However, a majority of architectural protein binding sites localize within topological domains, suggesting sites associated with domain borders represent a functionally different subclass of these regulatory elements. How topologically associating domains are established and what differentiates border-associated from non-border architectural protein binding sites remain unanswered questions. Results By mapping the genome-wide target sites for several Drosophila architectural proteins, including previously uncharacterized profiles for TFIIIC and SMC-containing condensin complexes, we uncover an extensive pattern of colocalization in which architectural proteins establish dense clusters at the borders of topological domains. Reporter-based enhancer-blocking insulator activity as well as endogenous domain border strength scale with the occupancy level of architectural protein binding sites, suggesting co-binding by architectural proteins underlies the functional potential of these loci. Analyses in mouse and human stem cells suggest that clustering of architectural proteins is a general feature of genome organization, and conserved architectural protein binding sites may underlie the tissue-invariant nature of topologically associating domains observed in mammals. Conclusions We identify a spectrum of architectural protein occupancy that scales with the topological structure of chromosomes and the regulatory potential of these elements. Whereas high occupancy architectural protein binding sites associate with robust partitioning of topologically associating domains and robust insulator function, low occupancy sites appear reserved for gene-specific regulation within topological domains. PMID:24981874

The evolution of filamin – A protein domain repeat perspective

PubMed Central

Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

2013-01-01

Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

The evolution of filamin-a protein domain repeat perspective.

PubMed

Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

2012-09-01

Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

From Structure to Function: A Comprehensive Compendium of Tools to Unveil Protein Domains and Understand Their Role in Cytokinesis.

PubMed

Rincon, Sergio A; Paoletti, Anne

2016-01-01

Unveiling the function of a novel protein is a challenging task that requires careful experimental design. Yeast cytokinesis is a conserved process that involves modular structural and regulatory proteins. For such proteins, an important step is to identify their domains and structural organization. Here we briefly discuss a collection of methods commonly used for sequence alignment and prediction of protein structure that represent powerful tools for the identification homologous domains and design of structure-function approaches to test experimentally the function of multi-domain proteins such as those implicated in yeast cytokinesis.

Context-specific requirements of functional domains of the Spectraplakin Short stop in vivo.

PubMed

Bottenberg, Wolfgang; Sanchez-Soriano, Natalia; Alves-Silva, Juliana; Hahn, Ines; Mende, Michael; Prokop, Andreas

2009-07-01

Spectraplakins are large multifunctional cytoskeletal interacting molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. It has been speculated that the various functional domains and regions found in Spectraplakins are used in context-specific manners, a model which would provide a crucial explanation for the multifunctional nature of Spectraplakins. Here we tested this possibility by studying domain requirements of the Drosophila Spectraplakin Short stop (Shot) in three different cellular contexts in vivo: (1) neuronal growth, which requires dynamic actin-microtubule interaction; (2) formation and maintenance of tendon cells, which depends on highly stabilised arrays of actin filaments and microtubules, and (3) compartmentalisation in neurons, which is likely to involve cortical F-actin networks. Using these cellular contexts for rescue experiments with Shot deletion constructs in shot mutant background, a number of differential domain requirements were uncovered. First, binding of Shot to F-actin through the first Calponin domain is essential in neuronal contexts but dispensable in tendon cells. This finding is supported by our analyses of shot(kakP2) mutant embryos, which produce only endogenous isoforms lacking the first Calponin domain. Thus, our data demonstrate a functional relevance for these isoforms in vivo. Second, we provide the first functional role for the Plakin domain of Shot, which has a strong requirement for compartmentalisation in neurons and axonal growth, demonstrating that Plakin domains of long Spectraplakin isoforms are of functional relevance. Like the Calponin domain, also the Plakin domain is dispensable in tendon cells, and the currently assumed role of Shot as a linker of microtubules to the tendon cell surface may have to be reconsidered. Third, we demonstrate a function of Shot as an actin-microtubule linker in dendritic growth, thus shedding new light into principal growth mechanisms of this neurite type. Taken together, our data clearly support the view that Spectraplakins function in tissue-specific modes in vivo, and even domains believed to be crucial for Spectraplakin function can be dispensable in specific contexts.

White House Office of the Vice President Announces New Memorandum of Understanding in Clinical Proteogenomics Between the United States and Australia | Office of Cancer Clinical Proteomics Research

Cancer.gov

The White House Office of the Vice President has announced the signing of three Memoranda of Understanding (MOUs) that will make available an unprecedented international dataset to advance cancer research and care.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

JPL Director Michael Watkins, standing, explains the history of NASA's Jet Propulsion Laboratory and the use of the Mission Support Area to Vice President Mike Pence, right, and Executive Director of the National Space Council Scott Pace during a tour of JPL, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, right, is presented a plaque by JPL Director Michael Watkins during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. The plaque presents a view of the Mars Science Laboratory rover Curiosity on the surface of Mars. Photo Credit: (NASA/Bill Ingalls)

An Examination of the Instructional Leadership Role of High School Vice Principals

ERIC Educational Resources Information Center

Larkin, Cynthia

2017-01-01

High school vice principals do not typically play a key role in the instructional leadership duties at their sites, as they are typically responsible for being their school's chief disciplinarians, managers of attendance, and supervisors of student activities and athletics. This study examined the role and responsibilities of high school vice…

Australian Vice-Chancellors' Committee Conference on Management Information Services.

ERIC Educational Resources Information Center

Macquarie Univ., North Ryde (Australia).

Proceedings include: opening remarks (F.J. Willett); a vice-chancellor's needs for management information services (R.W. Russell); the needs of a science dean for information (K.C. Westfold); the perceived needs for management information services from the point of view of a university administrator (R. Marginson); the role of the systems manager…

A "Historical Problem"

ERIC Educational Resources Information Center

Ly, Phuong

2008-01-01

Women are absent from the top ranks at Southern Illinois University Carbondale, a stark contrast to the increase in gender parity at other schools. SIUC's chancellor, vice chancellors, provost and all 10 academic deans are men. Nationally, women made up at least a third of the vice presidents and provosts surveyed and 36 percent of deans,…

Alternative Fuels Data Center: Workplace Charging Success: MetLife

Science.gov Websites

people to use PEVs. " MetLife's Senior Vice President, Global Corporate Services, Joseph Sprouls vehicle (PEV) charging stations at 14 of its U.S. corporate offices as a partner in the Department of benefits of using alternative energy sources. MetLife's Senior Vice President, Global Corporate Services

Entrepreneurial Orientation of Community College Workforce Divisions and the Impact of Organizational Structure: A Grounded Theory Study

ERIC Educational Resources Information Center

Schiefen, Kathleen M.

2010-01-01

This research focused on how organizational structure of community colleges influenced the entrepreneurial orientation of deans, directors, vice presidents, and vice chancellors of workforce units. Using grounded theory methodology, the researcher identified three emergent theories applicable to both integrated and separate workforce units. These…

Bridenstine Sworn In As NASA Administrator

NASA Image and Video Library

2018-04-23

Vice President Mike Pence and NASA Administrator Jim Bridenstine talk with NASA astronauts Andrew Feustel, Scott Tingle, and Ricky Arnold who are onboard the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Joel Kowsky)

Bridenstine Sworn In As NASA Administrator

NASA Image and Video Library

2018-04-23

Vice President Mike Pence, and NASA Administrator Jim Bridenstine talk with NASA astronauts Scott Tingle, Andrew Feustel, and Ricky Arnold who are onboard the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Bill Ingalls)

Bridenstine Sworn In As NASA Administrator

NASA Image and Video Library

2018-04-23

Vice President Mike Pence, and NASA Administrator Jim Bridenstine, right, talk with NASA astronauts Scott Tingle, Andrew Feustel, and Ricky Arnold who are onboard the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Bill Ingalls)

Effects of Vice-Principals' Psychological Empowerment on Job Satisfaction and Burnout

ERIC Educational Resources Information Center

Schermuly, Carsten C.; Schermuly, Rene A.; Meyer, Bertolt

2011-01-01

Purpose: This paper aims to investigate the relationship between psychological empowerment, job satisfaction, and burnout among vice-principals (VPs) in primary schools. Design/methodology/approach: A total of 103 VPs at 103 different primary schools in Germany were surveyed with a questionnaire that assessed the four dimensions of psychological…

United States Pacific Command (USPACOM)

Science.gov Websites

sailors from the Royal Malaysian Navy during an office call with Vice Adm. Dato' Syed Zahiruddin Putra Bin Osman, commander of the Eastern Fleet of the Royal Malaysian Navy. Sawyers is visiting Kota Kinabalu to Malaysian Navy during an office call KOTA KINABALU, Malaysia (May 23, 2018) - Vice Adm. Phil Sawyer

Vice-Principalship: Their Responsibility Roles and Career Aspirations

ERIC Educational Resources Information Center

Lee, John Chi-Kin; Kwan, Paula; Walker, Allan

2009-01-01

A discrepancy exists between the ideal and the actual roles played by vice-principals (VPs). This gap between roles influences the level of job satisfaction, which, in turn, affects their desire for a principalship. This study used a questionnaire survey of about 300 Hong Kong VPs to examine the core responsibility dimensions pertaining to their…

A Vice-President from the Business World Brings a New Bottom Line to Penn.

ERIC Educational Resources Information Center

van der Werf, Martin

1999-01-01

The executive vice-president of the University of Pennsylvania is credited with making significant changes in both the administration and the campus, using cost-cutting and change strategies from his business experience. Outsourcing, training for employees who might be terminated, substantial savings and new revenue, and gentrification of…

Student Town Meeting with Vice President Al Gore. Teacher's Guide.

ERIC Educational Resources Information Center

Edwards, Amy N.

This teacher's guide accompanies a videotape of the same name. Vice President Albert Gore, Jr., discusses current issues with students who question Mr. Gore on such topics as the environment, reinventing government, voter participation, crime, and the United States' role in foreign affairs. Gore tailors his answers to the teenage audience as the…

Domain atrophy creates rare cases of functional partial protein domains.

PubMed

Prakash, Ananth; Bateman, Alex

2015-04-30

Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.

Recombinant spider silk genetically functionalized with affinity domains.

PubMed

Jansson, Ronnie; Thatikonda, Naresh; Lindberg, Diana; Rising, Anna; Johansson, Jan; Nygren, Per-Åke; Hedhammar, My

2014-05-12

Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.

Reconstruction of the domain orientation distribution function of polycrystalline PZT ceramics using vector piezoresponse force microscopy.

PubMed

Kratzer, Markus; Lasnik, Michael; Röhrig, Sören; Teichert, Christian; Deluca, Marco

2018-01-11

Lead zirconate titanate (PZT) is one of the prominent materials used in polycrystalline piezoelectric devices. Since the ferroelectric domain orientation is the most important parameter affecting the electromechanical performance, analyzing the domain orientation distribution is of great importance for the development and understanding of improved piezoceramic devices. Here, vector piezoresponse force microscopy (vector-PFM) has been applied in order to reconstruct the ferroelectric domain orientation distribution function of polished sections of device-ready polycrystalline lead zirconate titanate (PZT) material. A measurement procedure and a computer program based on the software Mathematica have been developed to automatically evaluate the vector-PFM data for reconstructing the domain orientation function. The method is tested on differently in-plane and out-of-plane poled PZT samples, and the results reveal the expected domain patterns and allow determination of the polarization orientation distribution function at high accuracy.

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].

Dreams and acting out.

PubMed

Grinberg, L

1987-01-01

Dreams can be used as containers that free patients from increased tension. This may be the principal function of certain types of dreams, called "evacuative dreams." They are dreams used for getting rid of unbearable affects and unconscious fantasies, or as a safety valve for partial discharge of instinctual drives. These dreams are observed primarily in borderline and psychotic patients, but can also be seen in the regressive states of neurotic patients during weekends and other periods of separation. Such dreams have to be differentiated from "elaborative dreams," which have a working-through function and stand in an inverse relationship to acting out: the greater the production of elaborative dreams, the less the tendency to act out, and vice versa.

The Legendre transform in geometric calculus

NASA Astrophysics Data System (ADS)

McClellan, Gene E.

2013-10-01

This paper explores the extension of the Legendre transform from scalar calculus to geometric calculus. In physics, the Legendre transform provides a change of variables to express equations of motion or other physical relationships in terms of the most convenient dynamical quantities for a given experimental or theoretical analysis. In classical mechanics and in field theory, the Legendre transform generates the Hamiltonian function of a system from the Lagrangian function or vice versa. In thermodynamics, the Legendre transform allows thermodynamic relationships to be written in terms of alternative sets of independent variables. In this paper, we review the properties of the Legendre transform in scalar calculus and show how an analogous transformation with similar properties may be constructed in geometric calculus.

Modular protein domains: an engineering approach toward functional biomaterials.

PubMed

Lin, Charng-Yu; Liu, Julie C

2016-08-01

Protein domains and peptide sequences are a powerful tool for conferring specific functions to engineered biomaterials. Protein sequences with a wide variety of functionalities, including structure, bioactivity, protein-protein interactions, and stimuli responsiveness, have been identified, and advances in molecular biology continue to pinpoint new sequences. Protein domains can be combined to make recombinant proteins with multiple functionalities. The high fidelity of the protein translation machinery results in exquisite control over the sequence of recombinant proteins and the resulting properties of protein-based materials. In this review, we discuss protein domains and peptide sequences in the context of functional protein-based materials, composite materials, and their biological applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.

PubMed

Barkan, Alice; Klipcan, Larik; Ostersetzer, Oren; Kawamura, Tetsuya; Asakura, Yukari; Watkins, Kenneth P

2007-01-01

The CRS1-YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved "GxxG" loop, contributes to its RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes.

Intellectual Growth in Children as a Function of Domain Specific and Domain General Working Memory Subgroups

ERIC Educational Resources Information Center

Swanson, H. Lee

2011-01-01

This study examined whether children's growth on measures of fluid (Raven Colored Progressive Matrices) and crystallized (reading and math achievement) intelligence was attributable to domain-specific or domain-general functions of working memory (WM). A sample of 290 elementary school children was tested on measures of intelligence across three…

Delta Niobium or Delta VICE?

NASA Astrophysics Data System (ADS)

Hofmann, A. W.

2006-12-01

Delta Niobium or Delta VICE? Niobium is one of a few chemical elements that can be used to discriminate between melts derived from upwelling mantle, represented by MORBs and OIBs, and those derived from subduction and continental crust environments. The Nb/U ratio was introduced because these two elements appear to partition nearly identically in upwelling environments, but very differently (from one another) in subduction and continental environments (Hofmann et al., 1986). Fitton et al. (1997, 2003) have taken a radically different approach, using log(Nb/Y)-log(Zr/Y) correlations that appear to discriminate between MORB and OIB (or plume) environments. MORB correlations are parallel to, and at lower Nb/Y ratios than, Iceland basalt correlations. This is expressed by a discrimination parameter defined as Delta Nb = 1.74 + log(Nb/Y) - 1.92 log(Zr/Y). N-MORB have negative Delta-Nb values, whereas Iceland and other OIBs have positive values. Fitton et al. interpret this in terms of a niobium deficiency in MORB that is balanced by a Nb excess in OIBs. This interpretation conflicts with evidence based on Nb/U ratios (Hofmann et al., 1986), that MORB and OIB are parts of a common reservoir, which is different from, and complementary to, the continental crust. Both parts of this MORB-OIB reservoir are characterized by higher-than-primitive Nb/U and Nb/Th ratios, whereas continental crust has dramatically lower Nb/U and Nb/Th ratios. The use of VICE/MICE (very-incompatible- element to moderately-incompatible-element) ratios, such as Nb/Y, obscures this. The significance of the VICE/MICE plot becomes clear if one replaces Nb by other VICEs in the log(Nb/Y)-log(Zr/Y) plot. This shows that any of these VICEs yield similar topologies as Nb/Y. Thus for a given Zr/Y ratio, depleted MORB have consistently lower Ba/Y, Th/Y, and La/Y ratios than do Iceland basalts, even the most incompatible-element- depleted Iceland picrites. This is caused by a less extreme depletion of Icelandic picrites (and tholeiites) in VICEs relative to Y, causing their spidergram patterns to be flatter than those of depleted MORB, which "drop off" more steeply. The important point is that there is no special Nb effect. The difference between Iceland-style and MORB-style depletion might therefore be called "Delta VICE" rather than "Delta Niobium." This assessment of Nb geochemistry is confirmed by new compilations for several MORB and OIB suites, which shows that in some of these suites, Nb and Th yield the most uniform ratios, whereas Nb/U is more uniform in others (including Iceland). Similarly, Ta is similar to Nb in some suites, whereas it is slightly more compatible than Nb in others. These slight regional differences are of minor consequence in the present context. The cause of the greater depletion in VICEs relative to MICEs in N-MORB compared with the most depleted Icelandic is most likely related to the roles of garnet and clinopyroxene during source depletion processes.

A case control study of association between cognition and functional capacity in schizophrenia.

PubMed

Narayanan, Sreelatha S; Bhatia, Triptish; Velligan, Dawn I; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2015-12-01

Cognitive functions are important prognostic factors for schizophrenia (SZ), while ability to perform activities of daily living are important measures of functional capacity. The relationship between cognition and functional capacity has not been tested extensively in India. To compare persons with SZ with controls on measures of cognition and functional capacity, and evaluate correlations between cognitive performance and functional capacity. Schizophrenia outpatients and controls without psychiatric illness (DSM IV) who completed the MATRICS Consensus Cognitive Battery and Functional Assessment Battery comprised of two tests from University of California San Diego (UCSD) Performance Based Skill Assessment (UPSA), one Test of Adaptive Behavior in Schizophrenia (TABS) and one test from University of California San Diego Performance Based Skill Assessment Brief edition (UPSA-B). Cognitive and functional domains were examined using regression analyses, with relevant covariates. Cases (N=51) though younger, were more educated than controls (N=41). Adjusting for education, controls performed better than cases in 3/7 cognitive and 4/5 domains of functional capacity but similarly in 'household management'. Among both cases and controls, cognitive measures of verbal learning and speed of processing overlapped with functional capacity (3 domains). Working memory was associated with one functional domain. Consistent with other studies, Indian patients with schizophrenia performed worse than controls on several domains of cognition and functional capacity; these domains were correlated. Speed of processing and verbal learning are most frequently associated with functional capacity indices and should be targeted to improve skills of daily living among persons with SZ. Copyright © 2015. Published by Elsevier B.V.

An Msh3 ATPase domain mutation has no effect on MMR function.

PubMed

Edwards, Yasmin

2017-11-25

To demonstrate that the Msh3 ATPase domain is required for DNA mismatch repair and tumor suppression in a murine model. The DNA mismatch repair proteins are members of the ABC family of ATPases. ATP binding and hydrolysis regulates their mismatch repair function. In the current study, a mouse model was generated harboring a glycine to aspartic acid residue change in the Walker A motif of the ATPase domain of Msh3. Impaired ATP mediated release of the Msh2-Msh3 GD/GD complex from it's DNA substrate in vitro confirmed the presence of an ATPase defect. However, the mismatch repair function of the protein was not significantly affected. Therefore, mutation of a critical residue within the ATPase domain of Msh3 did not preclude mismatch repair at the genomic sequences tested. Indicating that Msh3 mediated mismatch function is retained the absence of a functional ATPase domain.

Cytochemistry of the functional domains of the nucleus in normal and in pathologic conditions.

PubMed

Maraldi, N M; Zini, N; Santi, S; Ognibene, A; Rizzoli, R; Mazzotti, G; Manzoli, F A

1998-01-01

By means of ultrastructural cytochemistry significant advances have been made in understanding the functional roles of many nuclear domains. This review gives schematic information about the main nuclear domains involved in replication, transcription, processing and transport of the transcripts in normal and in pathologic conditions. Particular attention is paid to a functional domain that appears to be involved in signal transduction. Data are reported on the intranuclear specific localization of key elements of the polyphosphoinositide signal transduction system in different cell types including human osteosarcoma cell lines. Compared with the compartmentalization of the cytoplasm, the nucleus has long been considered as relatively unstructured. On the other hand, fundamental nuclear functions, such as DNA replication and RNA transcription, can be molecularly characterized also in cell-free systems, suggesting that supramolecular organization is not so strictly required as for other cell functions occurring within intact cytoplasmic organelles. Nevertheless, a stringent organization is required for packing about 200 cm of DNA in the about 30 micron 3 of the nucleus. In the absence of membrane-delimited organelles, the nuclear organization is based on functional compartments, or domains, whose spatial localization involves the nuclear matrix, which shares many properties with the cytoskeleton. The nuclear domains are defined as structural compartments, not necessarily stable but dynamically variable, which perform specific metabolic functions through the partitioning of molecular complexes. Their identification has been made possible in the last few years by the development of specific nuclear probes for confocal and electron microscope immunocytochemistry. Therefore, the complex network of structures and enzymatic functions that make up the nucleus is in several cases yielding to molecular analysis, but a large part remains unknown (Strouboulis and Wolffe, 1996; Laemmli and Tjian, 1996). Rapid advances in understanding the functional role of the nuclear domains have been made recently: in particular, of the nuclear envelope, of the nucleolus, and of RNA splicing. In other cases, e.g. the precise localization of the nuclear domains involved in signal transduction, much remains to be clarified (Forbes and Johnson, 1997). It is conceivable that in the near future unexpected new nuclear domains will come to light and new nuclear functions may emerge, especially in field of post-transcriptional processing and transport of RNAs, and in the relationships between the nucleo-skeleton and enzymic fixed sites involved in replication, transcription and signal transduction. The aim of this review is to provide information about the morphological characteristics, the associated functions and the molecular composition of the main nuclear domains found to date. To simplify the exposition, the main data on each nuclear domain are reported in Tables, together with the principal references on the subject. Figures refer to original findings on some aspects of nuclear domain organization.

Fusion and Fission of Cognitive Functions in the Human Parietal Cortex

PubMed Central

Humphreys, Gina F.; Lambon Ralph, Matthew A.

2015-01-01

How is higher cognitive function organized in the human parietal cortex? A century of neuropsychology and 30 years of functional neuroimaging has implicated the parietal lobe in many different verbal and nonverbal cognitive domains. There is little clarity, however, on how these functions are organized, that is, where do these functions coalesce (implying a shared, underpinning neurocomputation) and where do they divide (indicating different underlying neural functions). Until now, there has been no multi-domain synthesis in order to reveal where there is fusion or fission of functions in the parietal cortex. This aim was achieved through a large-scale activation likelihood estimation (ALE) analysis of 386 studies (3952 activation peaks) covering 8 cognitive domains. A tripartite, domain-general neuroanatomical division and 5 principles of cognitive organization were established, and these are discussed with respect to a unified theory of parietal functional organization. PMID:25205661

Detection of an organic-non volatile compound in variable-contaminated volcanic soil samples via Time Domain Reflectometry (TDR) technique: Preliminary results

NASA Astrophysics Data System (ADS)

comegna, alessandro; coppola, antonio; dragonetti, giovanna; chaali, nesrine; sommella, angelo

2014-05-01

Hydrocarbons may be present in soils as non-aqueous phase liquids (NAPLs), which means that these organic compounds, exist as a separate and immiscible phase with respect to water and air commonly present in the soil. NAPLs, which can be accidentally introduced in the environment (for example by waste disposal sites, industrial spills, gasoline stations, etc), constitutes a serious geo-environmental problem, given the toxicity level and the high mobility. Time domain reflectometry (TDR) has became, over several decades, an important technique for water estimation in soils. In order to expand the potentiality of the TDR technique, the main objective of this study is to explore the capacity of dielectric response to detect the presence of NAPLs in volcanic soils. In laboratory, soil samples were oven dried at 105° C and passed through a 2 mm sieve. Known quantities of soil, water and NAPL (corn oil, a non-volatile and non-toxic organic compound) were mixed and repacked into plastic cylinders (16 cm high and 9.5 cm in diameter); in order to obtain forty different volumetric combinations of water and oil (i.e. θfg = θwater + θNAPL), with θNAPL varying from 0.05 to 0.40 by 0.05 cm3/cm3 increments. Data collected were employed to implement a multiphase mixing model which permitted conversion from a dielectric permittivity domain into a θf domain and vice versa. The results of this study show that, the TDR device is NAPL-sensitive, especially for θf values greater than 0.20. Further works will be built on this initial study, concentrating on improving the dielectric response-database, in order to: i) enhancing the model efficiency in terms of NAPL capability detention, and ii) validating the developed TDR interpretation tool with field results.

Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

PubMed

Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

2014-08-12

The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C 2 A domain in asynchronous neurotransmitter release

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

Voleti, Rashmi; Tomchick, Diana R.; Südhof, Thomas C.

Synaptotagmins (Syts) act as Ca2+ sensors in neurotransmitter release by virtue of Ca2+-binding to their two C2 domains, but their mechanisms of action remain unclear. Puzzlingly, Ca2+-binding to the C2B domain appears to dominate Syt1 function in synchronous release, whereas Ca2+-binding to the C2A domain mediates Syt7 function in asynchronous release. Here we show that crystal structures of the Syt7 C2A domain and C2AB region, and analyses of intrinsic Ca2+-binding to the Syt7 C2 domains using isothermal titration calorimetry, did not reveal major differences that could explain functional differentiation between Syt7 and Syt1. However, using liposome titrations under Ca2+ saturatingmore » conditions, we show that the Syt7 C2A domain has a very high membrane affinity and dominates phospholipid binding to Syt7 in the presence or absence of L-α-phosphatidylinositol 4,5-diphosphate (PIP2). For Syt1, the two Ca2+-saturated C2 domains have similar affinities for membranes lacking PIP2, but the C2B domain dominates binding to PIP2-containing membranes. Mutagenesis revealed that the dramatic differences in membrane affinity between the Syt1 and Syt7 C2A domains arise in part from apparently conservative residue substitutions, showing how striking biochemical and functional differences can result from the cumulative effects of subtle residue substitutions. Viewed together, our results suggest that membrane affinity may be a key determinant of the functions of Syt C2 domains in neurotransmitter release.« less

31 CFR 2.2 - Access to classified information by historical researchers, former Treasury Presidential and Vice...

Code of Federal Regulations, 2013 CFR

2013-07-01

... and Vice Presidents. 2.2 Section 2.2 Money and Finance: Treasury Office of the Secretary of the Treasury NATIONAL SECURITY INFORMATION § 2.2 Access to classified information by historical researchers... research projects; (2) Previously occupied a position in the Treasury to which they were appointed by the...

31 CFR 2.2 - Access to classified information by historical researchers, former Treasury Presidential and Vice...

Code of Federal Regulations, 2014 CFR

2014-07-01

... and Vice Presidents. 2.2 Section 2.2 Money and Finance: Treasury Office of the Secretary of the Treasury NATIONAL SECURITY INFORMATION § 2.2 Access to classified information by historical researchers... research projects; (2) Previously occupied a position in the Treasury to which they were appointed by the...

31 CFR 2.2 - Access to classified information by historical researchers, former Treasury Presidential and Vice...

Code of Federal Regulations, 2012 CFR

2012-07-01

... and Vice Presidents. 2.2 Section 2.2 Money and Finance: Treasury Office of the Secretary of the Treasury NATIONAL SECURITY INFORMATION § 2.2 Access to classified information by historical researchers... research projects; (2) Previously occupied a position in the Treasury to which they were appointed by the...

31 CFR 2.2 - Access to classified information by historical researchers, former Treasury Presidential and Vice...

Code of Federal Regulations, 2011 CFR

2011-07-01

... and Vice Presidents. 2.2 Section 2.2 Money and Finance: Treasury Office of the Secretary of the Treasury NATIONAL SECURITY INFORMATION § 2.2 Access to classified information by historical researchers... research projects; (2) Previously occupied a position in the Treasury to which they were appointed by the...

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

JPL Director Michael Watkins, left, explains to U.S. Vice President Mike Pence, daughter of Mike Pence, Charlotte Pence, and wife of Mike Pence, Karen Pence the progress for the Mars 2020 mission while inside the Spacecraft Assembly Facility (SAF) during a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)

Perspectives of UK Vice-Chancellors on Leading Universities in a Knowledge-Based Economy

ERIC Educational Resources Information Center

Bosetti, Lynn; Walker, Keith

2010-01-01

This paper draws upon the experiences and perceptions of ten university vice-chancellors in the United Kingdom on the challenges they face in providing leadership and strategic direction for their institutions into the twenty-first century. The paper reveals the perceptions and spoken words of these leaders as they identify the key challenges…

Black Skin, White Pioneer: Non-Traditional Casting in an Israeli School Pageant

ERIC Educational Resources Information Center

Shem-Tov, Naphtaly

2013-01-01

The casting of a black Ethiopian Jewish girl to play a white Zionist pioneer character in an Israeli school pageant causes feelings of discomfort among the teachers, especially the vice-principal. The vice-principal uses theatrical and historical reasons to justify her opposition to the casting which can actually be perceived as new/colour-blind…

Vice President Mike Pence Visits Kennedy Space Center - National

NASA Image and Video Library

2018-02-21

Members of the National Space Council meet in the high bay of the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, on Feb. 21, 2018. Chaired by Vice President Mike Pence, the council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center - National

NASA Image and Video Library

2018-02-21

Vice President Mike Pence chairs a meeting of the National Space Council in the high bay of the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, on Feb. 21, 2018. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Prices and Values: A Perspective on Adult and Community Education

ERIC Educational Resources Information Center

Wells, Graeme

2007-01-01

Government-provided services are caught in the jaws of a "cost-tax vice". On the cost side, the long-term trend of rising relative prices of services, including education, seems set to continue. The other jaw of the vice is the high efficiency cost of raising additional taxes. Recent research making the case for public provision of…

Psychosemantics of Management Strategy Notions by Comprehensive School Principals and Vice Principals

ERIC Educational Resources Information Center

Saparnis, Gintaras; Saparniene, Diana

2006-01-01

Purpose: The purpose of the research is to reveal the psychosemantics of the opinion of school principals and vice principals on the issues of the development of school management. Methodology: From the methodological point of view the research is based on the teaching of the empirical social research about qualitative and quantitative research…

Am I Their Cup of Tea? Vice-Principals' Perception of Suitability for Principalship

ERIC Educational Resources Information Center

Kwan, Paula

2013-01-01

This paper attempts to address the principal shortage issue from the concept of fit perceived by job applicants. It links vice-principals' perception of suitability for principalship to their conception of how well they can match with the selection criteria set out by school hiring bodies. Based on evidence collected from aspiring principals in…

Letter from House Minority Leader Gerald R. Ford to President Richard M. Nixon. Teaching with Documents.

ERIC Educational Resources Information Center

Potter, Lee Ann; Schamel, Wynell

2001-01-01

Provides historical background on how President Richard Nixon selected someone as vice president after Spiro T. Agnew resigned due to criminal charges. Provides background information on his choice, Gerald Ford, and discusses the process of how Ford officially became vice president. Includes a document from the Nixon Presidential Materials…

Bridenstine Sworn In As NASA Administrator

NASA Image and Video Library

2018-04-23

Vice President Mike Pence, left, and NASA Administrator Jim Bridenstine are seen as they talk with NASA astronauts Scott Tingle, Andrew Feustel, and Ricky Arnold who are onboard the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Bill Ingalls)

Building an Interagency Cadre of National Security Professionals: Proposals, Recent Experience, and Issues for Congress

DTIC Science & Technology

2008-07-08

development program, and individual agencies would implement it. CRS-6 12 General Peter Pace, USMC, Vice Chairman Joint Chiefs of Staff, “ Extemporaneous ...U.S. Code, §619a(a), and see above. 80 General Peter Pace, USMC, Vice Chairman Joint Chiefs of Staff, “ Extemporaneous Remarks as delivered to the Marine

The Lived Experiences of Vice Presidents for Student Affairs: A Study Exploring How Social Identity Impacts Leadership Approach

ERIC Educational Resources Information Center

Jones, David E.

2016-01-01

This study aimed to both draw awareness and increase understanding of how lived experiences across race, gender and sexual orientation social identities impact the leadership approach of Vice Presidents for Student Affairs. As the student demographic becomes increasingly more diverse on college and university campuses, higher education leaders…

75 FR 51292 - Before Commissioners: Ruth Y. Goldway, Chairman; Tony L. Hammond, Vice Chairman; Mark Acton; Dan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-91; CP2010-92; CP2010-93; CP2010-94; Order No. 513] Before Commissioners: Ruth Y. Goldway, Chairman; Tony L. Hammond, Vice Chairman; Mark Acton; Dan G. Blair; and Nanci E. Langley; Competitive Product Prices; Global Expedited Package Services 3...

STS-47/Vice President Dan Quayle's Visit to KSC for Launch

NASA Technical Reports Server (NTRS)

1992-01-01

Footage shows the arrival of Vice President Dan Quayle to the Kennedy Space Center (KSC) for the launch of Endeavour. He is shown greeting the crowd on the runway and later, in the control room, thanking the KSC employees for all their hard work. He also wishes the Endeavour crew good luck shortly before the launch.

Achieving Youth Employment and National Security in Nigeria: TVET Imperatives

ERIC Educational Resources Information Center

Ogbuanya, T. C.; Ofonmbuk, Michael

2015-01-01

The rate of unemployment in Nigeria is alarming and could promote social vices some of which are kidnapping, armed robbery, child trafficking, Cultism, Drug peddling and ritual killing. These social vices could in no small measure constitute a threat to national security as a matter of fact. Therefore, the development of a workable Technical and…

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, center, and his wife, Karen Pence, sign a guest book during a tour of the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. At right is Blue Origin CEO Robert Smith. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. From left, are Karen Pence, Blue Origin CEO Robert Smith, and acting NASA Administrator Robert Lightfoot. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins.

PubMed

Kirubakaran, Palani; Pfeiferová, Lucie; Boušová, Kristýna; Bednarova, Lucie; Obšilová, Veronika; Vondrášek, Jiří

2016-10-01

Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design of chimeric fusion proteins utilizing protein domains or one-domain miniproteins as building blocks is an important advancement for the creation of new biomolecules for biotechnology and medical applications. However, computational studies to describe in detail the dynamics and geometry properties of two-domain constructs made from structurally and functionally different proteins are lacking. Here, we tested an in silico design strategy using all-atom explicit solvent molecular dynamics simulations. The well-characterized PDZ3 and SH3 domains of human zonula occludens (ZO-1) (3TSZ), along with 5 artificial domains and 2 types of molecular linkers, were selected to construct chimeric two-domain molecules. The influence of the artificial domains on the structure and dynamics of the PDZ3 and SH3 domains was determined using a range of analyses. We conclude that the artificial domains can function as allosteric modulators of the PDZ3 and SH3 domains. Proteins 2016; 84:1358-1374. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Magnon-phonon interconversion in a dynamically reconfigurable magnetic material

NASA Astrophysics Data System (ADS)

Guerreiro, Sergio C.; Rezende, Sergio M.

2015-12-01

The ferrimagnetic insulator yttrium iron garnet (YIG) is an important material in the field of magnon spintronics, mainly because of its low magnetic losses. YIG also has very low acoustic losses, and for this reason the conversion of a state of magnetic excitation (magnons) into a state of lattice vibration (phonons), or vice versa, broadens its possible applications in spintronics. Since the magnetic parameters can be varied by some external action, the magnon-phonon interconversion can be tuned to perform a desired function. We present a quantum theory of the interaction between magnons and phonons in a ferromagnetic material subject to a dynamic variation of the applied magnetic field. It is shown that when the field gradient at the magnetoelastic crossover region is much smaller than a critical value, an initial elastic excitation can be completely converted into a magnetic excitation, or vice versa. This occurs with conservation of linear momentum and spin angular momentum, implying that phonons created by the conversion of magnons have spin angular momentum and carry spin current. It is shown further that if the system is initially in a quantum coherent state, its coherence properties are maintained regardless of the time dependence of the field.

Fabrication of Large Domain YBa2Cu3O(x) for Magnetic Suspension Applications

NASA Technical Reports Server (NTRS)

Sengupta, S.; Corpus, J.; Gaines, J. R., Jr.; Todt, V. R.; Zhang, X.; Miller, D. J.

1996-01-01

Large domain YBa2Cu3O(x) levitators have been fabricated using a seeded melt processing technique. Depending upon the seed, either a single or five domained sample can be obtained. The grain boundaries separating each domains in the five domain levitator are found to be 90 degrees. Similar levitation forces can be observed for single and five domained samples. After thermal cycling, however, a small decrease in the levitation force of the five domain levitator was observed as a function of thermal cycles while nearly no change in force was observed in the single domain levitator. Finally, it is shown that both, single and five domain YBCO, behave similarly as a function of sample thickness.

Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

PubMed

Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

1999-04-02

Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the same domains when part of a larger SH(3+2) construct. Increased deuterium incorporation was observed for the SH3 domain in the joint construct, particularly near the SH2 interface and the short sequence that connects SH3 to SH2, implying greater flexibility of SH3 when it is part of SH(3+2). Slow cooperative unfolding of the SH3 domain occurred at the same rate in isolated SH3 as in the SH(3+2) construct, suggesting a functional significance for this unfolding. The SH2 domain displayed relatively smaller changes in flexibility when part of the SH(3+2) construct. These results suggest that the domains influence each other. Further, our results imply a link between functional regulation and structural dynamics of SH3 and SH2 domains. Copyright 1999 Academic Press.

The SLP-76 Src homology 2 domain is required for T cell development and activation.

PubMed

Burns, Jeremy C; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A; Kliche, Stefanie; Jordan, Martha S

2011-11-01

The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adapter proteins that function together to activate second messengers required for TCR signal propagation. The N terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with ADAP and HPK1. Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production, and phosphorylation of protein kinase D and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells.

Cancerouspdomains: comprehensive analysis of cancer type-specific recurrent somatic mutations in proteins and domains.

PubMed

Hashemi, Seirana; Nowzari Dalini, Abbas; Jalali, Adrin; Banaei-Moghaddam, Ali Mohammad; Razaghi-Moghadam, Zahra

2017-08-16

Discriminating driver mutations from the ones that play no role in cancer is a severe bottleneck in elucidating molecular mechanisms underlying cancer development. Since protein domains are representatives of functional regions within proteins, mutations on them may disturb the protein functionality. Therefore, studying mutations at domain level may point researchers to more accurate assessment of the functional impact of the mutations. This article presents a comprehensive study to map mutations from 29 cancer types to both sequence- and structure-based domains. Statistical analysis was performed to identify candidate domains in which mutations occur with high statistical significance. For each cancer type, the corresponding type-specific domains were distinguished among all candidate domains. Subsequently, cancer type-specific domains facilitated the identification of specific proteins for each cancer type. Besides, performing interactome analysis on specific proteins of each cancer type showed high levels of interconnectivity among them, which implies their functional relationship. To evaluate the role of mitochondrial genes, stem cell-specific genes and DNA repair genes in cancer development, their mutation frequency was determined via further analysis. This study has provided researchers with a publicly available data repository for studying both CATH and Pfam domain regions on protein-coding genes. Moreover, the associations between different groups of genes/domains and various cancer types have been clarified. The work is available at http://www.cancerouspdomains.ir .

CD80 and CD86 IgC domains are important for quaternary structure, receptor binding and co-signaling function.

PubMed

Girard, Tanya; Gaucher, Denis; El-Far, Mohamed; Breton, Gaëlle; Sékaly, Rafick-Pierre

2014-09-01

CD86 and CD80, the ligands for the co-stimulatory molecules CD28 and CTLA-4, are members of the Ig superfamily. Their structure includes Ig variable-like (IgV) domains, Ig constant-like (IgC) domains and intracellular domains. Although crystallographic studies have clearly identified the IgV domain to be responsible for receptor interactions, earlier studies suggested that both Ig domains are required for full co-signaling function. Herein, we have used deletion and chimeric human CD80 and CD86 molecules in co-stimulation assays to study the impact of the multimeric state of IgV and IgC domains on receptor binding properties and on co-stimulatory function in a peptide-specific T cell activation model. We report for the first time the presence of CD80 dimers and CD86 monomers in living cells. Moreover, we show that the IgC domain of both molecules inhibits multimer formation and greatly affects binding to the co-receptors CD28 and CTLA-4. Finally, both IgC and intracellular domains are required for full co-signaling function. These findings reveal the distinct but complementary roles of CD80 and CD86 IgV and IgC domains in T cell activation. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

PubMed Central

Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

2014-01-01

ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral membrane. While it is known that the PtdSer binding is essential for the PVEER function of TIM-1, TIM-3 shares this binding activity but does not enhance virus entry. No comprehensive studies have been done to characterize the other domains of TIM-1. In this study, using a variety of chimeric proteins and deletion mutants, we define the features necessary for a functional PVEER. With these features in mind, we generated a TIM-1 mimic using functionally similar domains from other proteins. This mimic, like TIM-1, effectively enhanced transduction. These studies provide insight into the key features necessary for PVEERs and will allow for more effective identification of unknown PVEERs. PMID:24696470

Variable-Domain Displacement Transfer Functions for Converting Surface Strains into Deflections for Structural Deformed Shape Predictions

NASA Technical Reports Server (NTRS)

Ko, William L.; Fleischer, Van Tran

2015-01-01

Variable-Domain Displacement Transfer Functions were formulated for shape predictions of complex wing structures, for which surface strain-sensing stations must be properly distributed to avoid jointed junctures, and must be increased in the high strain gradient region. Each embedded beam (depth-wise cross section of structure along a surface strain-sensing line) was discretized into small variable domains. Thus, the surface strain distribution can be described with a piecewise linear or a piecewise nonlinear function. Through discretization, the embedded beam curvature equation can be piece-wisely integrated to obtain the Variable-Domain Displacement Transfer Functions (for each embedded beam), which are expressed in terms of geometrical parameters of the embedded beam and the surface strains along the strain-sensing line. By inputting the surface strain data into the Displacement Transfer Functions, slopes and deflections along each embedded beam can be calculated for mapping out overall structural deformed shapes. A long tapered cantilever tubular beam was chosen for shape prediction analysis. The input surface strains were analytically generated from finite-element analysis. The shape prediction accuracies of the Variable- Domain Displacement Transfer Functions were then determined in light of the finite-element generated slopes and deflections, and were fofound to be comparable to the accuracies of the constant-domain Displacement Transfer Functions

Cognitive functioning following traumatic brain injury: A five-year follow-up.

PubMed

Marsh, Nigel V; Ludbrook, Maria R; Gaffaney, Lauren C

2016-01-01

To describe the long-term prevalence and severity of cognitive deficits following significant (i.e., ventilation required for >24 hours) traumatic brain injury. To assess a comprehensive range of cognitive functions using psychometric measures with established normative, reliability, and validity data. A group of 71 adults was assessed at approximately five years (mean = 66 months) following injury. Assessment of cognitive functioning covered the domains of intelligence, attention, verbal and visual memory, visual-spatial construction, and executive functions. Impairment was evident across all domains but prevalence varied both within and between domains. Across aspects of intelligence clinical impairment ranged from 8-25% , attention 39-62% , verbal memory 16-46% , visual memory 23-51% , visual-spatial construction 38% , and executive functions (verbal fluency) 13% . In addition, 3-23% of performances across the measures were in the borderline range, suggesting a high prevalence of subclinical deficit. Although the prevalence of impairment may vary across cognitive domains, long-term follow-up documented deficits in all six domains. These findings provide further evidence that while improvement of cognitive functioning following significant traumatic brain injury may be possible, recovery of function is unlikely.

Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation.

PubMed

Yamazaki, Tomohiro; Souquere, Sylvie; Chujo, Takeshi; Kobelke, Simon; Chong, Yee Seng; Fox, Archa H; Bond, Charles S; Nakagawa, Shinichi; Pierron, Gerard; Hirose, Tetsuro

2018-06-21

A class of long noncoding RNAs (lncRNAs) has architectural functions in nuclear body construction; however, specific RNA domains dictating their architectural functions remain uninvestigated. Here, we identified the domains of the architectural NEAT1 lncRNA that construct paraspeckles. Systematic deletion of NEAT1 portions using CRISPR/Cas9 in haploid cells revealed modular domains of NEAT1 important for RNA stability, isoform switching, and paraspeckle assembly. The middle domain, containing functionally redundant subdomains, was responsible for paraspeckle assembly. Artificial tethering of the NONO protein to a NEAT1_2 mutant lacking the functional subdomains rescued paraspeckle assembly, and this required the NOPS dimerization domain of NONO. Paraspeckles exhibit phase-separated properties including susceptibility to 1,6-hexanediol treatment. RNA fragments of the NEAT1_2 subdomains preferentially bound NONO/SFPQ, leading to phase-separated aggregates in vitro. Thus, we demonstrate that the enrichment of NONO dimers on the redundant NEAT1_2 subdomains initiates construction of phase-separated paraspeckles, providing mechanistic insights into lncRNA-based nuclear body formation. Copyright © 2018 Elsevier Inc. All rights reserved.

The regulation of integrin function by divalent cations

PubMed Central

Zhang, Kun; Chen, JianFeng

2012-01-01

Integrins are a family of α/β heterodimeric adhesion metalloprotein receptors and their functions are highly dependent on and regulated by different divalent cations. Recently advanced studies have revolutionized our perception of integrin metal ion-binding sites and their specific functions. Ligand binding to integrins is bridged by a divalent cation bound at the MIDAS motif on top of either α I domain in I domain-containing integrins or β I domain in α I domain-less integrins. The MIDAS motif in β I domain is flanked by ADMIDAS and SyMBS, the other two crucial metal ion binding sites playing pivotal roles in the regulation of integrin affinity and bidirectional signaling across the plasma membrane. The β-propeller domain of α subunit contains three or four β-hairpin loop-like Ca2+-binding motifs that have essential roles in integrin biogenesis. The function of another Ca2+-binding motif located at the genu of α subunit remains elusive. Here, we provide an overview of the integrin metal ion-binding sites and discuss their roles in the regulation of integrin functions. PMID:22647937

Fungal-type carbohydrate binding modules from the coccolithophore Emiliania huxleyi show binding affinity to cellulose and chitin

PubMed Central

Rooijakkers, Bart J. M.

2018-01-01

Six fungal-type cellulose binding domains were found in the genome of the coccolithophore Emiliania huxleyi and cloned and expressed in Escherichia coli. Sequence comparison indicate high similarity to fungal cellulose binding domains, raising the question of why these domains exist in coccolithophores. The proteins were tested for binding with cellulose and chitin as ligands, which resulted in the identification of two functional carbohydrate binding modules: EHUX2 and EHUX4. Compared to benchmark fungal cellulose binding domain Cel7A-CBM1 from Trichoderma reesei, these proteins showed slightly lower binding to birch and bacterial cellulose, but were more efficient chitin binders. Finally, a set of cellulose binding domains was created based on the shuffling of one well-functioning and one non-functional domain. These were characterized in order to get more information of the binding domain’s sequence–function relationship, indicating characteristic differences between the molecular basis of cellulose versus chitin recognition. As previous reports have showed the presence of cellulose in coccoliths and here we find functional cellulose binding modules, a possible connection is discussed. PMID:29782536

A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor.

PubMed

Nie, Zhongzhen; Hirsch, Dianne S; Luo, Ruibai; Jian, Xiaoying; Stauffer, Stacey; Cremesti, Aida; Andrade, Josefa; Lebowitz, Jacob; Marino, Michael; Ahvazi, Bijan; Hinshaw, Jenny E; Randazzo, Paul A

2006-01-24

Arf GAPs are multidomain proteins that function in membrane traffic by inactivating the GTP binding protein Arf1. Numerous Arf GAPs contain a BAR domain, a protein structural element that contributes to membrane traffic by either inducing or sensing membrane curvature. We have examined the role of a putative BAR domain in the function of the Arf GAP ASAP1. ASAP1's N terminus, containing the putative BAR domain together with a PH domain, dimerized to form an extended structure that bound to large unilamellar vesicles containing acidic phospholipids, properties that define a BAR domain. A recombinant protein containing the BAR domain of ASAP1, together with the PH and Arf GAP domains, efficiently bent the surface of large unilamellar vesicles, resulting in the formation of tubular structures. This activity was regulated by Arf1*GTP binding to the Arf GAP domain. In vivo, the tubular structures induced by ASAP1 mutants contained epidermal growth factor receptor (EGFR) and Rab11, and ASAP1 colocalized in tubular structures with EGFR during recycling of receptor. Expression of ASAP1 accelerated EGFR trafficking and slowed cell spreading. An ASAP1 mutant lacking the BAR domain had no effect. The N-terminal BAR domain of ASAP1 mediates membrane bending and is necessary for ASAP1 function. The Arf dependence of the bending activity is consistent with ASAP1 functioning as an Arf effector.

Structural And Functional Studies of ALIX Interactions With YPXnL Late Domains of HIV-1 And EIAV

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

Zhai, Q.; Fisher, R.D.; Chung, H.-Y.

2009-05-28

Retrovirus budding requires short peptide motifs (late domains) located within the viral Gag protein that function by recruiting cellular factors. The YPX{sub n}L late domains of HIV and other lentiviruses recruit the protein ALIX (also known as AIP1), which also functions in vesicle formation at the multivesicular body and in the abscission stage of cytokinesis. Here, we report the crystal structures of ALIX in complex with the YPX{sub n}L late domains from HIV-1 and EIAV. The two distinct late domains bind at the same site on the ALIX V domain but adopt different conformations that allow them to make equivalentmore » contacts. Binding studies and functional assays verified the importance of key interface residues and revealed that binding affinities are tuned by context-dependent effects. These results reveal how YPX{sub n}L late domains recruit ALIX to facilitate virus budding and how ALIX can bind YPX{sub n}L sequences with both n = 1 and n = 3.« less

The structure of the cyanobactin domain of unknown function from PatG in the patellamide gene cluster

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

Mann, Greg; Koehnke, Jesko; Bent, Andrew F.

The highly conserved domain of unknown function in the cyanobactin superfamily has a novel fold. The protein does not appear to bind the most plausible substrates, leaving questions as to its role. Patellamides are members of the cyanobactin family of ribosomally synthesized and post-translationally modified cyclic peptide natural products, many of which, including some patellamides, are biologically active. A detailed mechanistic understanding of the biosynthetic pathway would enable the construction of a biotechnological ‘toolkit’ to make novel analogues of patellamides that are not found in nature. All but two of the protein domains involved in patellamide biosynthesis have been characterized.more » The two domains of unknown function (DUFs) are homologous to each other and are found at the C-termini of the multi-domain proteins PatA and PatG. The domain sequence is found in all cyanobactin-biosynthetic pathways characterized to date, implying a functional role in cyanobactin biosynthesis. Here, the crystal structure of the PatG DUF domain is reported and its binding interactions with plausible substrates are investigated.« less

The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB

PubMed Central

Theos, Alexander C.; Watt, Brenda; Harper, Dawn C.; Janczura, Karolina J.; Theos, Sarah C.; Herman, Kathryn E.; Marks, Michael S.

2013-01-01

SUMMARY Proteolytic fragments of the pigment cell-specific glycoprotein, PMEL, form the amyloid fibrillar matrix underlying melanins in melanosomes. The fibrils form within multivesicular endosomes to which PMEL is selectively sorted and that serve as melanosome precursors. GPNMB is a tissue-restricted glycoprotein with substantial sequence homology to PMEL but no known function, and was proposed to localize to non-fibrillar domains of distinct melanosome subcompartments in melanocytes. Here we confirm that GPNMB localizes to compartments distinct from the PMEL-containing multivesicular premelanosomes or late endosomes in melanocytes and HeLa cells, respectively, and is largely absent from fibrils. Using domain swapping, the unique PMEL localization is ascribed to its PKD domain, whereas the homologous PKD domain of GPNMB lacks apparent sorting function. The difference likely reflects extensive modification of the GPNMB PKD domain by N-glycosylation, nullifying its sorting function. These results reveal the molecular basis for the distinct trafficking and morphogenetic properties of PMEL and GPNMB, and support a deterministic function of the PMEL PKD domain in both protein sorting and amyloidogenesis. PMID:23452376

Annotation of Protein Domains Reveals Remarkable Conservation in the Functional Make up of Proteomes Across Superkingdoms

PubMed Central

Nasir, Arshan; Naeem, Aisha; Khan, Muhammad Jawad; Lopez-Nicora, Horacio D.; Caetano-Anollés, Gustavo

2011-01-01

The functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. The molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden Markov models of structural recognition. Here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. We find there is a remarkable conservation in the distribution of domains with respect to the molecular functions they perform in the three superkingdoms of life. In general, most of the protein repertoire is spent in functions related to metabolic processes but there are significant differences in the usage of domains for regulatory and extra-cellular processes both within and between superkingdoms. Our results support the hypotheses that the proteomes of superkingdom Eukarya evolved via genome expansion mechanisms that were directed towards innovating new domain architectures for regulatory and extra/intracellular process functions needed for example to maintain the integrity of multicellular structure or to interact with environmental biotic and abiotic factors (e.g., cell signaling and adhesion, immune responses, and toxin production). Proteomes of microbial superkingdoms Archaea and Bacteria retained fewer numbers of domains and maintained simple and smaller protein repertoires. Viruses appear to play an important role in the evolution of superkingdoms. We finally identify few genomic outliers that deviate significantly from the conserved functional design. These include Nanoarchaeum equitans, proteobacterial symbionts of insects with extremely reduced genomes, Tenericutes and Guillardia theta. These organisms spend most of their domains on information functions, including translation and transcription, rather than on metabolism and harbor a domain repertoire characteristic of parasitic organisms. In contrast, the functional repertoire of the proteomes of the Planctomycetes-Verrucomicrobia-Chlamydiae superphylum was no different than the rest of bacteria, failing to support claims of them representing a separate superkingdom. In turn, Protista and Bacteria shared similar functional distribution patterns suggesting an ancestral evolutionary link between these groups. PMID:24710297

Functional analysis of conserved aromatic amino acids in the discoidin domain of Paenibacillus β-1,3-glucanase

PubMed Central

2009-01-01

The 190-kDa Paenibacillus β-1,3-glucanase (LamA) contains a catalytic module of the glycoside hydrolase family 16 (GH16) and several auxiliary domains. Of these, a discoidin domain (DS domain), present in both eukaryotic and prokaryotic proteins with a wide variety of functions, exists at the carboxyl-terminus. To better understand the bacterial DS domain in terms of its structure and function, this domain alone was expressed in Escherichia coli and characterized. The results indicate that the DS domain binds various polysaccharides and enhances the biological activity of the GH16 module on composite substrates. We also investigated the importance of several conserved aromatic residues in the domain's stability and substrate-binding affinity. Both were affected by mutations of these residues; however, the effect on protein stability was more notable. In particular, the forces contributed by a sandwiched triad (W1688, R1756, and W1729) were critical for the presumable β-sandwich fold. PMID:19930717

Progress towards the development of SH2 domain inhibitors.

PubMed

Kraskouskaya, Dziyana; Duodu, Eugenia; Arpin, Carolynn C; Gunning, Patrick T

2013-04-21

Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2007-01-30

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2007-02-13

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein. including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2003-11-18

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

In situ dissection of RNA functional subunits by domain-specific chromatin isolation by RNA purification (dChIRP).

PubMed

Quinn, Jeffrey J; Chang, Howard Y

2015-01-01

Here we describe domain-specific chromatin isolation by RNA purification (dChIRP), a technique for dissecting the functional domains of a target RNA in situ. For an RNA of interest, dChIRP can identify domain-level intramolecular and intermolecular RNA-RNA, RNA-protein, and RNA-DNA interactions and maps the RNA's genomic binding sites with higher precision than domain-agnostic methods. We illustrate how this technique has been applied to the roX1 lncRNA to resolve its domain-level architecture, discover its protein- and chromatin-interacting domains, and map its occupancy on the X chromosome.

F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from structure to human diseases.

PubMed

Liu, Suxuan; Xiong, Xinyu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong

2015-05-09

Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.

Pluripotency gene network dynamics: System views from parametric analysis.

PubMed

Akberdin, Ilya R; Omelyanchuk, Nadezda A; Fadeev, Stanislav I; Leskova, Natalya E; Oschepkova, Evgeniya A; Kazantsev, Fedor V; Matushkin, Yury G; Afonnikov, Dmitry A; Kolchanov, Nikolay A

2018-01-01

Multiple experimental data demonstrated that the core gene network orchestrating self-renewal and differentiation of mouse embryonic stem cells involves activity of Oct4, Sox2 and Nanog genes by means of a number of positive feedback loops among them. However, recent studies indicated that the architecture of the core gene network should also incorporate negative Nanog autoregulation and might not include positive feedbacks from Nanog to Oct4 and Sox2. Thorough parametric analysis of the mathematical model based on this revisited core regulatory circuit identified that there are substantial changes in model dynamics occurred depending on the strength of Oct4 and Sox2 activation and molecular complexity of Nanog autorepression. The analysis showed the existence of four dynamical domains with different numbers of stable and unstable steady states. We hypothesize that these domains can constitute the checkpoints in a developmental progression from naïve to primed pluripotency and vice versa. During this transition, parametric conditions exist, which generate an oscillatory behavior of the system explaining heterogeneity in expression of pluripotent and differentiation factors in serum ESC cultures. Eventually, simulations showed that addition of positive feedbacks from Nanog to Oct4 and Sox2 leads mainly to increase of the parametric space for the naïve ESC state, in which pluripotency factors are strongly expressed while differentiation ones are repressed.

Temperature control and measurement with tunable femtosecond optical tweezers

NASA Astrophysics Data System (ADS)

Mondal, Dipankar; Goswami, Debabrata

2016-09-01

We present the effects of wavelength dependent temperature rise in a femtosecond optical tweezers. Our experiments involve the femtosecond trapping laser tunable from 740-820 nm at low power 25 mW to cause heating in the trapped volume within a homogeneous solution of sub micro-molar concentration of IR dye. The 780 nm high repetition rate laser acts as a resonant excitation source which helps to create the local heating effortlessly within the trapping volume. We have used both position autocorrelation and equipartion theorem to evaluate temperature at different wavelength having different absorption coefficient. Fixing the pulse width in the temporal domain gives constant bandwidth at spatial domain, which makes our system behave as a tunable temperature rise device with high precision. This observation leads us to calculate temperature as well as viscosity within the vicinity of the trapping zone. A mutual energy transfer occurs between the trapped bead and solvents that leads to transfer the thermal energy of solvents into the kinetic energy of the trap bead and vice-versa. Thus hot solvated molecules resulting from resonant and near resonant excitation of trapping wavelength can continuously dissipate heat to the trapped bead which will be reflected on frequency spectrum of Brownian noise exhibited by the bead. Temperature rise near the trapping zone can significantly change the viscosity of the medium. We observe temperature rise profile according to its Gaussian shaped absorption spectrum with different wavelength.

Two roles of the context in Pavlovian fear conditioning.

PubMed

Urcelay, Gonzalo P; Miller, Ralph R

2010-04-01

At both empirical and theoretical levels, multiple functional roles of contextual information upon memory performance have been proposed without a clear dissociation of these roles. Some theories have assumed that contexts are functionally similar to cues, whereas other views emphasize the retrieval facilitating properties of contextual information. In Experiment 1, we observed that one critical parameter, the spacing of trials, could determine whether the context would function as a conditioned stimulus or as a retrieval cue for memories trained in different phases. Experiments 2 and 3 doubly dissociated these functions by selectively disrupting one role but not the other, and vice versa. Overall, these observations identify one determinant of different functions of contextual information and pose a major challenge to theories of learning that assume exclusively one or the other function of the context. Moreover, these data emphasize the importance of parametric variations on behavioral control, which has critical implications for studies designed to understand the role of the hippocampus in processing of contextual attributes.

Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

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

Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

2013-03-07

Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life.

PubMed

Kamminga, Tjerko; Koehorst, Jasper J; Vermeij, Paul; Slagman, Simen-Jan; Martins Dos Santos, Vitor A P; Bijlsma, Jetta J E; Schaap, Peter J

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the "minimal" synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life.

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life

PubMed Central

Kamminga, Tjerko; Koehorst, Jasper J.; Vermeij, Paul; Slagman, Simen-Jan; Martins dos Santos, Vitor A. P.; Bijlsma, Jetta J. E.; Schaap, Peter J.

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the “minimal” synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life. PMID:28224116

Structural-Functional Analysis Reveals a Specific Domain Organization in Family GH20 Hexosaminidases.

PubMed

Val-Cid, Cristina; Biarnés, Xevi; Faijes, Magda; Planas, Antoni

2015-01-01

Hexosaminidases are involved in important biological processes catalyzing the hydrolysis of N-acetyl-hexosaminyl residues in glycosaminoglycans and glycoconjugates. The GH20 enzymes present diverse domain organizations for which we propose two minimal model architectures: Model A containing at least a non-catalytic GH20b domain and the catalytic one (GH20) always accompanied with an extra α-helix (GH20b-GH20-α), and Model B with only the catalytic GH20 domain. The large Bifidobacterium bifidum lacto-N-biosidase was used as a model protein to evaluate the minimal functional unit due to its interest and structural complexity. By expressing different truncated forms of this enzyme, we show that Model A architectures cannot be reduced to Model B. In particular, there are two structural requirements general to GH20 enzymes with Model A architecture. First, the non-catalytic domain GH20b at the N-terminus of the catalytic GH20 domain is required for expression and seems to stabilize it. Second, the substrate-binding cavity at the GH20 domain always involves a remote element provided by a long loop from the catalytic domain itself or, when this loop is short, by an element from another domain of the multidomain structure or from the dimeric partner. Particularly, the lacto-N-biosidase requires GH20b and the lectin-like domain at the N- and C-termini of the catalytic GH20 domain to be fully soluble and functional. The lectin domain provides this remote element to the active site. We demonstrate restoration of activity of the inactive GH20b-GH20-α construct (model A architecture) by a complementation assay with the lectin-like domain. The engineering of minimal functional units of multidomain GH20 enzymes must consider these structural requirements.

The organization of domains in proteins obeys Menzerath-Altmann's law of language.

PubMed

Shahzad, Khuram; Mittenthal, Jay E; Caetano-Anollés, Gustavo

2015-08-11

The combination of domains in multidomain proteins enhances their function and structure but lengthens the molecules and increases their cost at cellular level. The dependence of domain length on the number of domains a protein holds was surveyed for a set of 60 proteomes representing free-living organisms from all kingdoms of life. Distributions were fitted using non-linear functions and fitted parameters interpreted with a formulation of decreasing returns. We find that domain length decreases with increasing number of domains in proteins, following the Menzerath-Altmann (MA) law of language. Highly significant negative correlations exist for the set of proteomes examined. Mathematically, the MA law expresses as a power law relationship that unfolds when molecular persistence P is a function of domain accretion. P holds two terms, one reflecting the matter-energy cost of adding domains and extending their length, the other reflecting how domain length and number impinges on information and biophysics. The pattern of diminishing returns can therefore be explained as a frustrated interplay between the strategies of economy, flexibility and robustness, matching previously observed trade-offs in the domain makeup of proteomes. Proteomes of Archaea, Fungi and to a lesser degree Plants show the largest push towards molecular economy, each at their own economic stratum. Fungi increase domain size in single domain proteins while reinforcing the pattern of diminishing returns. In contrast, Metazoa, and to lesser degrees Protista and Bacteria, relax economy. Metazoa achieves maximum flexibility and robustness by harboring compact molecules and complex domain organization, offering a new functional vocabulary for molecular biology. The tendency of parts to decrease their size when systems enlarge is universal for language and music, and now for parts of macromolecules, extending the MA law to natural systems.

Emergence of novel domains in proteins

PubMed Central

2013-01-01

Background Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. Results To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. Conclusions We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently. PMID:23425224

From non-trivial geometries to power spectra and vice versa

NASA Astrophysics Data System (ADS)

Brooker, D. J.; Tsamis, N. C.; Woodard, R. P.

2018-04-01

We review a recent formalism which derives the functional forms of the primordial—tensor and scalar—power spectra of scalar potential inflationary models. The formalism incorporates the case of geometries with non-constant first slow-roll parameter. Analytic expressions for the power spectra are given that explicitly display the dependence on the geometric properties of the background. Moreover, we present the full algorithm for using our formalism, to reconstruct the model from the observed power spectra. Our techniques are applied to models possessing "features" in their potential with excellent agreement.

Three-dimensional video imaging of drainage and imbibition processes in model porous medium

NASA Astrophysics Data System (ADS)

Sharma, Prerna; Aswathi, P.; Sane, Anit; Ghosh, Shankar; Bhattacharya, Sabyasachi

2011-03-01

We report experimental results where we have performed three dimensional video imaging of the displacement of an oil phase by an aqueous phase and vice versa in a model porous medium. The stability of the oil water interface was studied as a function of their viscosity ratios, the wettability of the porous medium and the variation in the pore size distribution. Our experiments captures the pore scale information of the displacement process and its role in determining the long time structure of the interface.

Contributions of individual domains to function of the HIV-1 Rev response element.

PubMed

O'Carroll, Ina P; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A; Smith, Sean; Wang, Yun-Xing; Rein, Alan

2017-08-16

The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using SAXS and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev Response Element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is "A"-shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains, and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function. Copyright © 2017 American Society for Microbiology.

Contributions of Individual Domains to Function of the HIV-1 Rev Response Element

PubMed Central

O'Carroll, Ina P.; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A.; Smith, Sean; Wang, Yun-Xing

2017-01-01

ABSTRACT The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an “A” shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using small-angle X-ray scattering (SAXS) and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev response element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is “A” shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function. PMID:28814520

The Effect of Role Ambiguity and Role Conflict on Performance of Vice Principals: The Mediating Role of Burnout

ERIC Educational Resources Information Center

Celik, Kazim

2013-01-01

Problem Statement: Role ambiguity and role conflict are considered issues that affect performance and lead to burnout. While numerous studies have analyzed role ambiguity or role conflict in relation to burnout or performance, few studies have studied all of these issues together. Since vice principals are expected to carry out a variety of…

VICE PRESIDENT PENCE VIEWS SOLAR ECLIPSE WITH STUDENTS AT U.S. NAVAL OBSERVATORY

NASA Image and Video Library

2017-08-21

On Monday, Aug. 21, Vice President Mike Pence welcomed students from a Washington area school to the U.S. Naval Observatory, to view the 2017 solar eclipse and learn about heliophysics – the study of our sun. The event was also attended by former NASA astronaut Pam Melroy, NASA scientist Brad Bailey, and education specialist Evelina Felicite-Maurice.

Is Managing Academics "Women's Work"? Exploring the Glass Cliff in Higher Education Management

ERIC Educational Resources Information Center

Peterson, Helen

2016-01-01

Sweden is among the countries with the highest per cent of women university Vice Chancellors in Europe. In "She Figures 2012" the average proportion of female Vice Chancellors in the 27 European Union countries is estimated to be 10 per cent. In Sweden the number is much higher: 43 per cent. Swedish higher education management has…

UK University Leaders at the Turn of the 21st Century: Changing Patterns in Their Socio-Demographic Characteristics

ERIC Educational Resources Information Center

Breakwell, Glynis M.; Tytherleigh, Michelle Y.

2008-01-01

While not the only title used by UK university leaders, the term Vice Chancellor will be used throughout this paper to include the other titles used (including Rector, Provost, Principal and President). According to data obtained pre-1997, UK Vice Chancellors (VCs) were predominantly scientists, largely former professors, Pro-VCs or deputy…

Strategies Deans and Vice-Presidents Can Use to Enhance Teaching in Their Institutions.

ERIC Educational Resources Information Center

Bowker, Lee H.; Lynch, David M.

Four strategies that deans and vice-presidents can use to enhance teaching are suggested. The first strategy is to seek out and fund teaching support activities that are the state of the art in each discipline. The second is to reward professors for excellence in teaching more than for excellence in research. Third, administrators should develop…

Annual Trauma Anesthesia and Critical Care Symposium (4th) Held in Baltimore, Maryland on May 2 - 5, 1991

DTIC Science & Technology

1991-07-01

Chairman for the Clinic of Anaesthesiology University Hospital Mainz, Germany Vice-President, European Academy of Anaesthesiology Medical Director...Consultant Anesthetist Department of Anaesthesiology Frenchay Hospital President, Association of Anaesthetists of Great Britain and Ireland President...of the Institute for Anaesthesiology University Hospital-Nijmegen Member of the National Health Council (Gezondheidsraad) Vice-President, National

Selection Criteria, Skill Sets and Competencies: What Is Their Role in the Appointment of Vice-Chancellors in Australian Universities?

ERIC Educational Resources Information Center

O'Meara, Bernard; Petzall, Stanley

2009-01-01

Purpose: The research presented here attempts to identify and analyse the reported selection criteria used in the appointment of Australian vice-chancellors (VCs) and to contrast this with the selection criteria actually used. Design/methodology/approach: Contemporary research into the nature, role and purpose of section criteria in appointment…

The Ω-loop lid domain of phosphoenolpyruvate carboxykinase is essential for catalytic function

PubMed Central

Johnson, Troy A.; Holyoak, Todd

2012-01-01

Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Recent studies have demonstrated that the enzyme contains a mobile active site lid domain that transitions between an open/disorded conformation to a closed/ordered conformation as the enzyme progresses through the catalytic cycle. The understanding of how this mobile domain functions in catalysis is incomplete. Previous studies show that the closure of the lid domain stabilizes the reaction intermediate and protects the reactive intermediate from spurious protonation and thus contributes to the fidelity of the enzyme. In order to more fully investigate the roles of the lid domain in PEPCK function we created three mutations that replaced the 11-residue lid domain with one, two or three glycine residues. Kinetic analysis of the mutant enzymes demonstrates that none of the enzyme constructs exhibit any measurable kinetic activity resulting in a decrease in the catalytic parameters by at least 106. Structural characterization of the mutants in complexes representing the catalytic cycle suggest that the inactivity is due to a role for the lid domain in the formation of the fully closed state of the enzyme that is required for catalytic function. In the absence of the lid domain, the enzyme is unable to achieve the fully closed state and is rendered inactive despite possessing all of the residues and substrates required for catalytic function. This work demonstrates how enzyme catalytic function can be abolished through the alteration of conformational equilibria despite all elements required for chemical conversion of substrates to products remaining intact. PMID:23127136

The history of the CATH structural classification of protein domains.

PubMed

Sillitoe, Ian; Dawson, Natalie; Thornton, Janet; Orengo, Christine

2015-12-01

This article presents a historical review of the protein structure classification database CATH. Together with the SCOP database, CATH remains comprehensive and reasonably up-to-date with the now more than 100,000 protein structures in the PDB. We review the expansion of the CATH and SCOP resources to capture predicted domain structures in the genome sequence data and to provide information on the likely functions of proteins mediated by their constituent domains. The establishment of comprehensive function annotation resources has also meant that domain families can be functionally annotated allowing insights into functional divergence and evolution within protein families. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

PubMed

Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

2013-05-01

The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

Investigation of multilayer magnetic domain lattice file

NASA Technical Reports Server (NTRS)

Torok, E. J.; Kamin, M.; Tolman, C. H.

1980-01-01

The feasibility of the self structured multilayered bubble domain memory as a mass memory medium for satellite applications is examined. Theoretical considerations of multilayer bubble supporting materials are presented, in addition to the experimental evaluation of current accessed circuitry for various memory functions. The design, fabrication, and test of four device designs is described, and a recommended memory storage area configuration is presented. Memory functions which were demonstrated include the current accessed propagation of bubble domains and stripe domains, pinning of stripe domain ends, generation of single and double bubbles, generation of arrays of coexisting strip and bubble domains in a single garnet layer, and demonstration of different values of the strip out field for single and double bubbles indicating adequate margins for data detection. All functions necessary to develop a multilayer self structured bubble memory device were demonstrated in individual experiments.

Extrapolation of Functions of Many Variables by Means of Metric Analysis

NASA Astrophysics Data System (ADS)

Kryanev, Alexandr; Ivanov, Victor; Romanova, Anastasiya; Sevastianov, Leonid; Udumyan, David

2018-02-01

The paper considers a problem of extrapolating functions of several variables. It is assumed that the values of the function of m variables at a finite number of points in some domain D of the m-dimensional space are given. It is required to restore the value of the function at points outside the domain D. The paper proposes a fundamentally new method for functions of several variables extrapolation. In the presented paper, the method of extrapolating a function of many variables developed by us uses the interpolation scheme of metric analysis. To solve the extrapolation problem, a scheme based on metric analysis methods is proposed. This scheme consists of two stages. In the first stage, using the metric analysis, the function is interpolated to the points of the domain D belonging to the segment of the straight line connecting the center of the domain D with the point M, in which it is necessary to restore the value of the function. In the second stage, based on the auto regression model and metric analysis, the function values are predicted along the above straight-line segment beyond the domain D up to the point M. The presented numerical example demonstrates the efficiency of the method under consideration.

The SLP-76 SH2 domain is required for T cell development and activation

PubMed Central

Burns, Jeremy C.; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A.; Kliche, Stefanie; Jordan, Martha S.

2011-01-01

The adaptor protein Src homology 2 (SH2) domain containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adaptor proteins that function together to activate second messengers required for TCR signal propagation. The N-terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with the adhesion- and degranulation-promoting adaptor protein (ADAP) and hematopoietic progenitor kinase 1 (HPK1). Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production and phosphorylation of protein kinase D (PKD) and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells. PMID:21949020

Oncology Nurses and the Cancer Moonshot 2020.

PubMed

Kennedy Sheldon, Lisa

2016-08-01

When Vice President Joe Biden's son, Beau, died of a brain tumor in May 2015, the Vice President's grief was profound. Yet, his grief generated an idea, a big idea: Let's collaborate and focus the talent and resources in our country to eliminate cancer as we know it. When Vice President Biden shared his idea with President Barack Obama in the fall of 2015, not only did President Obama endorse the idea, he announced the National Cancer Moonshot Initiative during his January 2016 State of the Union Address. The goal is to double progress against cancer and break down silos that prevent science and industry from working together. The initiative centers around the development and implementation of new vaccine-based immunotherapies to target individual tumors based on their genomic signature.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2018-02-20

Vice President Mike Pence, second from left, tours the Blue Origin Manufacturing Facility near NASA's Kennedy Space Center in Florida, on Feb. 20, 2018. To his left is his wife, Karen Pence. To his right are Blue Origin CEO Robert Smith, and acting NASA Administrator Robert Lightfoot. Vice President Pence viewed the flown New Shepard Booster and Crew Capsule. The booster was the first launch vehicle with a successful vertical takeoff and vertical landing to demonstrate reusability. During his visit, Pence will chair a meeting of the National Space Council on Feb. 21, 2018 in the high bay of NASA Kennedy Space Center's Space Station Processing Facility. The council's role is to advise the president regarding national space policy and strategy, and review the nation's long-range goals for space activities.

Programmable hydrogels.

PubMed

Wang, Yong

2018-03-05

Programmable hydrogels are defined as hydrogels that are able to change their properties and functions periodically, reversibly and/or sequentially on demand. They are different from those responsive hydrogels whose changes are passive or cannot be stopped or reversed once started and vice versa. The purpose of this review is to summarize major progress in developing programmable hydrogels from the viewpoints of principles, functions and biomedical applications. The principles are first introduced in three categories including biological, chemical and physical stimulation. With the stimulation, programmable hydrogels can undergo functional changes in dimension, mechanical support, cell attachment and molecular sequestration, which are introduced in the middle of this review. The last section is focused on the introduction and discussion of four biomedical applications including mechanistic studies in mechanobiology, tissue engineering, cell separation and protein delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interdependence of the rad50 hook and globular domain functions.

PubMed

Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

2015-02-05

Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

PubMed Central

Iglesias-Bexiga, Manuel; Castillo, Francisco; Cobos, Eva S.; Oka, Tsutomu; Sudol, Marius; Luque, Irene

2015-01-01

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling. PMID:25607641

Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members

PubMed Central

Yan, Xiping; Wang, Guosong; Liu, Hehe; Gan, Xiang; Zhang, Tao; Wang, Jiwen; Li, Liang

2015-01-01

Peroxisome proliferators-activated receptor (PPAR) gene family members exhibit distinct patterns of distribution in tissues and differ in functions. The purpose of this study is to investigate the evolutionary impacts on diversity functions of PPAR members and the regulatory differences on gene expression patterns. 63 homology sequences of PPAR genes from 31 species were collected and analyzed. The results showed that three isolated types of PPAR gene family may emerge from twice times of gene duplication events. The conserved domains of HOLI (ligand binding domain of hormone receptors) domain and ZnF_C4 (C4 zinc finger in nuclear in hormone receptors) are essential for keeping basic roles of PPAR gene family, and the variant domains of LCRs may be responsible for their divergence in functions. The positive selection sites in HOLI domain are benefit for PPARs to evolve towards diversity functions. The evolutionary variants in the promoter regions and 3′ UTR regions of PPARs result into differential transcription factors and miRNAs involved in regulating PPAR members, which may eventually affect their expressions and tissues distributions. These results indicate that gene duplication event, selection pressure on HOLI domain, and the variants on promoter and 3′ UTR are essential for PPARs evolution and diversity functions acquired. PMID:25961030

Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions Existed within PPAR Gene Family Members.

PubMed

Zhou, Tianyu; Yan, Xiping; Wang, Guosong; Liu, Hehe; Gan, Xiang; Zhang, Tao; Wang, Jiwen; Li, Liang

2015-01-01

Peroxisome proliferators-activated receptor (PPAR) gene family members exhibit distinct patterns of distribution in tissues and differ in functions. The purpose of this study is to investigate the evolutionary impacts on diversity functions of PPAR members and the regulatory differences on gene expression patterns. 63 homology sequences of PPAR genes from 31 species were collected and analyzed. The results showed that three isolated types of PPAR gene family may emerge from twice times of gene duplication events. The conserved domains of HOLI (ligand binding domain of hormone receptors) domain and ZnF_C4 (C4 zinc finger in nuclear in hormone receptors) are essential for keeping basic roles of PPAR gene family, and the variant domains of LCRs may be responsible for their divergence in functions. The positive selection sites in HOLI domain are benefit for PPARs to evolve towards diversity functions. The evolutionary variants in the promoter regions and 3' UTR regions of PPARs result into differential transcription factors and miRNAs involved in regulating PPAR members, which may eventually affect their expressions and tissues distributions. These results indicate that gene duplication event, selection pressure on HOLI domain, and the variants on promoter and 3' UTR are essential for PPARs evolution and diversity functions acquired.

C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

PubMed

Huang, J; Wu, C; Liu, D; Yang, X; Wu, R; Zhang, J; Ma, C; He, H

2017-01-01

C-terminal domains widely exist in the C-terminal region of multidomain proteases. As a β-sandwich domain in multidomain protease, the C-terminal domain plays an important role in proteolysis including regulation of the secretory process, anchoring and swelling the substrate molecule, presenting as an inhibitor for the preprotease and adapting the protein structural flexibility and stability. In this review, the diversity, structural characteristics and biological function of C-terminal protease domains are described. Furthermore, the application prospects of C-terminal domains, including polycystic kidney disease, prepeptidase C-terminal and collagen-binding domain, in the area of medicine and biological artificial materials are also discussed. © 2016 The Society for Applied Microbiology.

Reciprocal associations between family and peer conflict in adolescents' daily lives.

PubMed

Chung, Grace H; Flook, Lisa; Fuligni, Andrew J

2011-01-01

Using a daily diary method, this study assessed daily episodes of family and peer conflict among 578 adolescents in the 9th grade to examine potential bidirectional associations between the family and peer domains. Adolescents completed a daily diary checklist at the end of each day over a 14-day period to report events of conflict and their emotional states for a given day. Overall, the within-person models provided evidence for the bidirectional nature of family peer linkages across gender and ethnicity. Adolescents experienced more peer conflict on days in which they argued with parents or other family members, and vice versa. Effect of family conflict further spilled over into peer relationships the next day and 2 days later, whereas peer conflict predicted only the following day family conflict. Adolescents' emotional distress partially explained these short-term spillovers between family and peer conflict. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

International collaboration to enhance the fight against HIV/AIDS: report of a consultative meeting between the University of Buea in Cameroon and the Goldfarb School of Nursing in the USA.

PubMed

Nsagha, Dickson S; Rosenburg, Neal; Diesel, Holly; Sab, Clement M; Taliaferro, Donna

2011-09-05

HIV/AIDS is a major public health pandemic affecting the development, survival and life of young people both in Cameroon and the USA. Youths are more adaptive to change and less hindered by prejudice than adults. Student-to-student peer mentoring is a non-formal way for students to learn new life skills and different cross-cultural values. We report on a two-day consultative meeting in 2010 on developing international collaboration for the fight against HIV/AIDS between Cameroonian and USA nursing students. We used adult learning approaches consisting of presentations, discussions, questions and answer sessions, role plays and demonstrations. Deliberations and resolutions from the consultative meeting enabled the Vice-Chancellor of the University of Buea to sign a memorandum of understanding with the Goldfarb School of Nursing in the USA on HIV/AIDS international collaboration paving the way forward for more developmental health projects in this domain.

The experience of agency in human-computer interactions: a review

PubMed Central

Limerick, Hannah; Coyle, David; Moore, James W.

2014-01-01

The sense of agency is the experience of controlling both one’s body and the external environment. Although the sense of agency has been studied extensively, there is a paucity of studies in applied “real-life” situations. One applied domain that seems highly relevant is human-computer-interaction (HCI), as an increasing number of our everyday agentive interactions involve technology. Indeed, HCI has long recognized the feeling of control as a key factor in how people experience interactions with technology. The aim of this review is to summarize and examine the possible links between sense of agency and understanding control in HCI. We explore the overlap between HCI and sense of agency for computer input modalities and system feedback, computer assistance, and joint actions between humans and computers. An overarching consideration is how agency research can inform HCI and vice versa. Finally, we discuss the potential ethical implications of personal responsibility in an ever-increasing society of technology users and intelligent machine interfaces. PMID:25191256

Thinking about touch facilitates tactile but not auditory processing.

PubMed

Anema, Helen A; de Haan, Alyanne M; Gebuis, Titia; Dijkerman, H Chris

2012-05-01

Mental imagery is considered to be important for normal conscious experience. It is most frequently investigated in the visual, auditory and motor domain (imagination of movement), while the studies on tactile imagery (imagination of touch) are scarce. The current study investigated the effect of tactile and auditory imagery on the left/right discriminations of tactile and auditory stimuli. In line with our hypothesis, we observed that after tactile imagery, tactile stimuli were responded to faster as compared to auditory stimuli and vice versa. On average, tactile stimuli were responded to faster as compared to auditory stimuli, and stimuli in the imagery condition were on average responded to slower as compared to baseline performance (left/right discrimination without imagery assignment). The former is probably due to the spatial and somatotopic proximity of the fingers receiving the taps and the thumbs performing the response (button press), the latter to a dual task cost. Together, these results provide the first evidence of a behavioural effect of a tactile imagery assignment on the perception of real tactile stimuli.

International collaboration to enhance the fight against HIV/AIDS: report of a consultative meeting between the University of Buea in Cameroon and the Goldfarb School of Nursing in the USA

PubMed Central

Nsagha, Dickson S.; Rosenburg, Neal; Diesel, Holly; Sab, Clement M.; Taliaferro, Donna

2011-01-01

HIV/AIDS is a major public health pandemic affecting the development, survival and life of young people both in Cameroon and the USA. Youths are more adaptive to change and less hindered by prejudice than adults. Student-to-student peer mentoring is a non-formal way for students to learn new life skills and different cross-cultural values. We report on a two-day consultative meeting in 2010 on developing international collaboration for the fight against HIV/AIDS between Cameroonian and USA nursing students. We used adult learning approaches consisting of presentations, discussions, questions and answer sessions, role plays and demonstrations. Deliberations and resolutions from the consultative meeting enabled the Vice-Chancellor of the University of Buea to sign a memorandum of understanding with the Goldfarb School of Nursing in the USA on HIV/AIDS international collaboration paving the way forward for more developmental health projects in this domain. PMID:28299063

Parkin, A Top Level Manager in the Cell’s Sanitation Department

PubMed Central

Rankin, Carolyn A; Roy, Ambrish; Zhang, Yang; Richter, Mark

2011-01-01

Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship of the Parkin protein. Parkin contains three RING domains plus a ubiquitin-like domain and an in-between-RING (IBR) domain. RING domains are rich in cysteine amino acids that act as ligands to bind zinc ions. RING domains may interact with DNA or with other proteins and perform a wide range of functions. Some function as E3 ubiquitin ligases, participating in attachment of ubiquitin chains to signal proteasome degradation; however, ubiquitin may be attached for purposes other than proteasome degradation. It was determined that the C-terminal most RING, RING2, is essential for Parkin to function as an E3 ubiquitin ligase and a number of substrates have been identified. However, Parkin also participates in a number of other fiunctions, such as DNA repair, microtubule stabilization, and formation of aggresomes. Some functions, such as participation in a multi-protein complex implicated in NMDA activity at the post synaptic density, do not require ubiquitination of substrate molecules. Recent observations of RING proteins suggest their function may be regulated by zinc ion binding. We have modeled the three RING domains of Parkin and have identified a new set of RING2 ligands. This set allows for binding of two rather than just one zinc ion, opening the possibility that the number of zinc ions bound acts as a molecular switch to modulate Parkin function. PMID:21633666

Characterization of the Functional Domains of a Mammalian Voltage-Sensitive Phosphatase.

PubMed

Rosasco, Mario G; Gordon, Sharona E; Bajjalieh, Sandra M

2015-12-15

Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to inositol lipid phosphatase activity. VSPs thus couple two signaling pathways that are critical for cellular functioning. Although a number of nonmammalian VSPs have been characterized biophysically, mammalian VSPs are less well understood at both the physiological and biophysical levels. In this study, we aimed to address this gap in knowledge by determining whether the VSP from mouse, Mm-VSP, is expressed in the brain and contains a functional voltage-sensing domain (VSD) and a phosphatase domain. We report that Mm-VSP is expressed in neurons and is developmentally regulated. To address whether the functions of the VSD and phosphatase domain are retained in Mm-VSP, we took advantage of the modular nature of these domains and expressed each independently as a chimeric protein in a heterologous expression system. We found that the Mm-VSP VSD, fused to a viral potassium channel, was able to drive voltage-dependent gating of the channel pore. The Mm-VSP phosphatase domain, fused to the VSD of a nonmammalian VSP, was also functional: activation resulted in PI(4,5)P2 depletion that was sufficient to inhibit the PI(4,5)P2-regulated KCNQ2/3 channels. While testing the functionality of the VSD and phosphatase domain, we observed slight differences between the activities of Mm-VSP-based chimeras and those of nonmammalian VSPs. Although the properties of VSP chimeras may not completely reflect the properties of native VSPs, the differences we observed in voltage-sensing and phosphatase activity provide a starting point for future experiments to investigate the function of Mm-VSP and other mammalian VSPs. In conclusion, our data reveal that both the VSD and the lipid phosphatase domain of Mm-VSP are functional, indicating that Mm-VSP likely plays an important role in mouse neurophysiology. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Control of Anther Cell Differentiation by the Small Protein Ligand TPD1 and Its Receptor EMS1 in Arabidopsis

PubMed Central

Huang, Jian; Zhang, Tianyu; Linstroth, Lisa; Tillman, Zachary; Otegui, Marisa S.; Owen, Heather A.

2016-01-01

A fundamental feature of sexual reproduction in plants and animals is the specification of reproductive cells that conduct meiosis to form gametes, and the associated somatic cells that provide nutrition and developmental cues to ensure successful gamete production. The anther, which is the male reproductive organ in seed plants, produces reproductive microsporocytes (pollen mother cells) and surrounding somatic cells. The microsporocytes yield pollen via meiosis, and the somatic cells, particularly the tapetum, are required for the normal development of pollen. It is not known how the reproductive cells affect the differentiation of these somatic cells, and vice versa. Here, we use molecular genetics, cell biological, and biochemical approaches to demonstrate that TPD1 (TAPETUM DETERMINANT1) is a small secreted cysteine-rich protein ligand that interacts with the LRR (Leucine-Rich Repeat) domain of the EMS1 (EXCESS MICROSPOROCYTES1) receptor kinase at two sites. Analyses of the expressions and localizations of TPD1 and EMS1, ectopic expression of TPD1, experimental missorting of TPD1, and ablation of microsporocytes yielded results suggesting that the precursors of microsporocyte/microsporocyte-derived TPD1 and pre-tapetal-cell-localized EMS1 initially promote the periclinal division of secondary parietal cells and then determine one of the two daughter cells as a functional tapetal cell. Our results also indicate that tapetal cells suppress microsporocyte proliferation. Collectively, our findings show that tapetal cell differentiation requires reproductive-cell-secreted TPD1, illuminating a novel mechanism whereby signals from reproductive cells determine somatic cell fate in plant sexual reproduction. PMID:27537183

Challenges in application of bioanalytical method on different populations and effect of population on PK.

PubMed

Kale, Prashant; Shukla, Manoj; Soni, Gunjan; Patel, Ronak; Gupta, Shailendra

2014-01-01

Prashant Kale has 22 years of immense experience in the analytical and bioanalytical domain. He is Senior Vice President, Bioequivalence Operations of Lambda Therapeutic Research, India which includes Bioanalytical, Clinics, Clinical data management, Pharmacokinetics and Biostatistics, Protocol writing, Clinical lab and Quality Assurance departments. He has been with Lambda for over 14 years. By qualification he is a M.Sc. and an MBA. Mr. Kale is responsible for the management, technical and administrative functions of the BE unit located at Ahmedabad and Mumbai, India. He is also responsible for leading the process of integration between bioanalytical laboratories and services offered by Lambda at global locations (India and Canada). Mr. Kale has faced several regulatory audits and inspections from leading regulatory bodies including but not limited to DCGI, USFDA, ANVISA, Health Canada, UK MHRA, Turkey MoH, WHO. There are many challenges involved in the application of bioanalytical method on different populations. This includes difference in equipment, material and environment across laboratories, variations in the matrix characteristics in different populations, differences in techniques between analysts such as sample processing and handling and others. Additionally, there is variability in the PK of a drug in different populations. This article shows the effect of different populations on validated bioanalytical method and on the PK of a drug. Hence, the bioanalytical method developed and validated for a specific population may need required modification when applied to another population. Critical consideration of all such aspects is the key to successful implementation of a validated method on different populations.

Comprehensive Diagnostic Assessment of Health Status of Patients with Asthma or COPD: A Delphi Panel Study among Dutch Experts.

PubMed

van den Akker, Edmée F M M; Van't Hul, Alex J; Birnie, Erwin; Chavannes, Niels H; Rutten-van Mölken, Maureen P M H; In't Veen, Johannes C C M

2017-04-01

A comprehensive diagnostic assessment is needed to improve understanding of the health status of patients with chronic obstructive pulmonary disease (COPD) or asthma. Therefore, this study investigated which components and subsequent instruments should be part of a holistic assessment in secondary care. We also explored which data need to be exchanged for an adequate transfer of patients between primary and secondary care, and vice versa. A cross-sectional Web-based survey was conducted among Dutch healthcare professionals using a Delphi-like procedure; these included professionals working in primary or secondary care, medical advisors of health insurance companies and patients' representatives. The national guidelines were used as a starting point, resulting in a questionnaire addressing 55 components related to a comprehensive diagnostic assessment, covering the domains physiological impairments, symptoms, functional limitations and quality of life. Of the 151 experts and stakeholders invited, 92 (60.9%) completed the first round and 79 (52.3%) the second round; most respondents were pulmonologists. There was a high level of agreement between respondents from primary versus secondary care regarding which components should be measured during a comprehensive assessment of patients with asthma or COPD in secondary care and the instruments to measure these components. Regarding the exchange of information, upon referral, pulmonologists required little information from the general practitioners, whereas general practitioners required more extensive information after referral. An overview is provided of what should be part of a holistic assessment of health status in asthma and COPD. This information can be used as input for integrated care pathways.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

Second Lady Karen Pence gives commands to a rover nicknamed "Scarecrow" as NASA Mars Exploration Manager Li Fuk, left, Mars Curiosity Engineering Operations Team Chief Megan Lin, Vice President Mike Pence, daughter of Mike Pence, Charlotte Pence, and JPL Director Michael Watkins, right, look on, Saturday, April 28, 2018 in Pasadena, California. Scarecrow is used to test mobility of rovers on Mars. Photo Credit: (NASA/Bill Ingalls)

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence gives commands to a rover nicknamed "Scarecrow" as NASA Mars Exploration Manager Li Fuk, left, Mars Curiosity Engineering Operations Team Chief Megan Lin, JPL Director Michael Watkins, and daughter of Mike Pence, Charlotte Pence, right, look on, Saturday, April 28, 2018 in Pasadena, California. Scarecrow is used to test mobility of rovers on Mars. Photo Credit: (NASA/Bill Ingalls)

Discuss: If Essays Are Dead, Then Where Does That Leave Everything Else? A Response to: Shirley Alexander's "Buying Essays: How to Make Sure Assessment Is Authentic"

ERIC Educational Resources Information Center

McQueen, Kelvin

2015-01-01

Professor Shirley Alexander is the Deputy Vice-Chancellor and Vice-President (Teaching, Learning & Equity) at the University of Technology, Sydney. On 12 November 2014, an article of hers appeared in "The Conversation": "Buying essays: how to make sure assessment is authentic." That article traverses, in an abbreviated way,…

Strengthening the University Executive: The Expanding Roles and Remit of Deputy and Pro-Vice-Chancellors

ERIC Educational Resources Information Center

Shepherd, Sue

2018-01-01

Deputy and pro-vice-chancellors (DVCs and PVCs) are core members of the executive team and play a pivotal role in university management. Nevertheless, they have rarely been the subject of empirical investigation. This study addresses this research gap, utilising a census to examine the size and remit of the DVC and PVC cohort in English pre-1992…

Filling Position of Governor and Vice Governor of Yogyakarta Special Region in Indonesia

ERIC Educational Resources Information Center

Sugiaryo; Pujiyono; Hartiwiningsih

2016-01-01

Act No. 13 Year 2012 on Previleges of Yogyakarta as a Special Region provides a constitutional basis in establishing that the Governor was enthroned as Sultan and to the Vice Governor as Adipati Paku Alam. However, in the case of succession of the Governor of Yogyakarta, there is an exception because it is basically a privileges of DIY that has…

"We Alone Are Passive": The Committee of Vice-Chancellors and Principals and the Organisation of British Universities, C.1918-1939

ERIC Educational Resources Information Center

Vernon, Keith

2014-01-01

The Committee of Vice-chancellors and Principals (CVCP) was a leading collective body for British universities for most of the twentieth century, yet there has been very little historical study of its organisation and work. Brief references tend to be dismissive of its effectiveness, although some authors have been more favourable. This article…

Bridenstine Sworn In As NASA Administrator

NASA Image and Video Library

2018-04-23

Jen Rae Wang, NASA Associate Administrator for NASA’s Office of Communications, left, NASA Administrator Jim Bridenstine, and Vice President Mike Pence, talk with NASA astronauts Scott Tingle, Andrew Feustel, and Ricky Arnold who are onboard the International Space Station, Monday, April 23, 2018 at NASA Headquarters in Washington. Bridenstine was just sworn in by the Vice President as NASA's 13th Administrator. Photo Credit: (NASA/Joel Kowsky)

Creating an effective marketing team. Six leading healthcare marketers offer their perspectives. Interview by Richard D. Stier.

PubMed

Bernstein, N D; Dorothy, J; Flexner, W A; Ireland, R C; Newbold, P A; Rice, A

1989-01-01

Richard D. Stier, senior vice president and chief marketing officer, Adventist Health System, Shawnee Mission, Kansas, asked six top healthcare marketers to assume they had just been appointed vice president and chief marketing officer for a medium-sized, 300-bed, not-for-profit community hospital. Their mission: Create the most effective, powerhouse marketing team in the country.

5 CFR 315.602 - Appointment based on service in the Office of the President or Vice-President or on the White...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Appointment based on service in the Office of the President or Vice-President or on the White House Staff. 315.602 Section 315.602 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CAREER AND CAREER-CONDITIONAL EMPLOYMENT Career or Career-Conditional...

National Space Council

NASA Image and Video Library

2018-06-18

President Donald Trump delivers opening remarks as Vice President Mike Pence looks on during a meeting of the National Space Council in the East Room of the White House, Monday, June 18, 2018, in Washington. Chaired by the Vice President, the council's role is to advise the President regarding national space policy and strategy, and review the nation's long-range goals for space activities. Photo Credit: (NASA/Bill Ingalls)

1401315

NASA Image and Video Library

2014-09-12

RIBBON CUTTING AT VERTICAL ASSEMBLY CENTER, MICHOUD ASSEMBLY FACILITY, SEPTEMBER 12, 2014, (L TO R): CLAY KIEFABER, CEO OF ESAB (COMPANY THAT BUILT WELDING TOOL)…PATRICK SCHEUERMANN…ROBERT LIGHTFOOT…TODD MAY…MISSISSIPPI CONGRESSMAN STEVEN PALAZZO…CHARLIE BOLDEN…LOUISIANA SENATOR DAVID VITTER…VIRGINIA BARNES, VICE-PRESIDENT AND PROGRAM MANAGER FOR SLS - BOEING… MITCH LANDRIEU, MAYOR OF NEW ORLEANS… JOHN ELBON, VICE PRESIDENT/GENERAL MANAGER, SPACE EXPLORATIONS – BOEING…PATRICK FORRESTER, ASTRONAUT…ROY MALONE.

Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

PubMed

Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

2016-02-25

Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Unfolding of a temperature-sensitive domain controls voltage-gated channel activation

PubMed Central

Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A.; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S.; Minor, Daniel L.

2016-01-01

Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNaV) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNaV CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNaV CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNaV voltage dependencies, and demonstrate that a discrete domain can encode the temperature dependent response of a channel. PMID:26919429

Close encounters of the third kind: disordered domains and the interactions of proteins.

PubMed

Tompa, Peter; Fuxreiter, Monika; Oldfield, Christopher J; Simon, Istvan; Dunker, A Keith; Uversky, Vladimir N

2009-03-01

Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing.

PubMed

Ghadie, Mohamed Ali; Lambourne, Luke; Vidal, Marc; Xia, Yu

2017-08-01

Alternative splicing is known to remodel protein-protein interaction networks ("interactomes"), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing.

Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing

PubMed Central

Lambourne, Luke; Vidal, Marc

2017-01-01

Alternative splicing is known to remodel protein-protein interaction networks (“interactomes”), yet large-scale determination of isoform-specific interactions remains challenging. We present a domain-based method to predict the isoform interactome from the reference interactome. First, we construct the domain-resolved reference interactome by mapping known domain-domain interactions onto experimentally-determined interactions between reference proteins. Then, we construct the isoform interactome by predicting that an isoform loses an interaction if it loses the domain mediating the interaction. Our prediction framework is of high-quality when assessed by experimental data. The predicted human isoform interactome reveals extensive network remodeling by alternative splicing. Protein pairs interacting with different isoforms of the same gene tend to be more divergent in biological function, tissue expression, and disease phenotype than protein pairs interacting with the same isoforms. Our prediction method complements experimental efforts, and demonstrates that integrating structural domain information with interactomes provides insights into the functional impact of alternative splicing. PMID:28846689

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

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

Syeda, Farisa; Fagan, Rebecca L.; Wean, Matthew

Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenicmore » DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.« less

Synaptic vesicle pool‐specific modification of neurotransmitter release by intravesicular free radical generation

PubMed Central

Afuwape, Olusoji A. T.; Wasser, Catherine R.; Schikorski, Thomas

2016-01-01

Key points Synaptic transmission is mediated by the release of neurotransmitters from synaptic vesicles in response to stimulation or through the spontaneous fusion of a synaptic vesicle with the presynaptic plasma membrane.There is growing evidence that synaptic vesicles undergoing spontaneous fusion versus those fusing in response to stimuli are functionally distinct.In this study, we acutely probe the effects of intravesicular free radical generation on synaptic vesicles that fuse spontaneously or in response to stimuli.By targeting vesicles that preferentially release spontaneously, we can dissociate the effects of intravesicular free radical generation on spontaneous neurotransmission from evoked neurotransmission and vice versa.Taken together, these results further advance our knowledge of the synapse and the nature of the different synaptic vesicle pools mediating neurotransmission. Abstract Earlier studies suggest that spontaneous and evoked neurotransmitter release processes are maintained by synaptic vesicles which are segregated into functionally distinct pools. However, direct interrogation of the link between this putative synaptic vesicle pool heterogeneity and neurotransmission has been difficult. To examine this link, we tagged vesicles with horseradish peroxidase (HRP) – a haem‐containing plant enzyme – or antibodies against synaptotagmin‐1 (syt1). Filling recycling vesicles in hippocampal neurons with HRP and subsequent treatment with hydrogen peroxide (H2O2) modified the properties of neurotransmitter release depending on the route of HRP uptake. While strong depolarization‐induced uptake of HRP suppressed evoked release and augmented spontaneous release, HRP uptake during mild activity selectively impaired evoked release, whereas HRP uptake at rest solely potentiated spontaneous release. Expression of a luminal HRP‐tagged syt1 construct and subsequent H2O2 application resulted in a similar increase in spontaneous release and suppression as well as desynchronization of evoked release, recapitulating the canonical syt1 loss‐of‐function phenotype. An antibody targeting the luminal domain of syt1, on the other hand, showed that augmentation of spontaneous release and suppression of evoked release phenotypes are dissociable depending on whether the antibody uptake occurred at rest or during depolarization. Taken together, these findings indicate that vesicles that maintain spontaneous and evoked neurotransmitter release preserve their identity during recycling and syt1 function in suppression of spontaneous neurotransmission can be acutely dissociated from syt1 function to synchronize synaptic vesicle exocytosis upon stimulation. PMID:27723113

The (lack of) relation between straylight and visual acuity. Two domains of the point-spread-function.

PubMed

van den Berg, Thomas J T P

2017-05-01

The effect of cataract and other media opacities on functional vision is typically assessed clinically using visual acuity. In both clinical and basic research, straylight (the functional result of light scattering in the eye) is commonly measured. The purpose of the present study was to determine the link between these two measures: is visual acuity in cataract and other media opacities related to straylight? Interdependence between acuity and straylight is addressed from three different points of view: (1) Methodological: can acuity differences affect the measurement value of straylight, and vice versa? (2) Basic optics: does the optical process of light scattering in the human eye affect both straylight and visual acuity? (3) Statistical: how strongly are acuity and straylight correlated in the practice of important clinical conditions? Experimental and theoretical aspects will be considered, with a focus on normal ageing and cataract formation. (1) Methodological: testing potential effects of acuity, artificially manipulated with positive trial lenses, showed no effect on measured straylight values. Since light scattering in the eye involves a low percentage of the light and has large angular spreading, contrast reduction due to straylight is limited, resulting in virtually absent acuity effects. (2) Basic optics: light scattering from the human donor eye lens is found to have virtually no effect in the centre of the point-spread-function, also for cataractous lenses, resulting in virtually absent acuity effects. (3) Statistical: literature data on straylight and visual acuity show a weak correlation for the important groups of normal ageing and cataract populations. The point-spread-function of the normal ageing and cataractous human eye is built upon two rather independent basic parts. Aberrations control the central peak. Light scattering controls the periphery from about 1° onwards. The way acuity and straylight are measured ensures no confounding between them. Statistically within the normal ageing and cataract populations, visual acuity and straylight vary quite independently from each other. Visual acuity losses with cataract and other media opacities are not due to straylight, but caused by aberrations and micro-aberrations. Straylight defines disability glare, and causes symptoms of glare, haloes, hazy vision etc. Overall, visual acuity and straylight are rather independent aspects of quality of vision. © 2017 The Author Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

Purification of SOCS (Suppressor of Cytokine Signaling) SH2 Domains for Structural and Functional Studies.

PubMed

Liau, Nicholas P D; Laktyushin, Artem; Babon, Jeffrey J

2017-01-01

Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs. Here, we describe the protocol for the recombinant production and purification of SOCS SH2 domains, with an emphasis on SOCS3.

Domain fusion analysis by applying relational algebra to protein sequence and domain databases

PubMed Central

Truong, Kevin; Ikura, Mitsuhiko

2003-01-01

Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

PubMed

Panigrahi, Rashmi; Lemieux, M Joanne

2015-01-01

Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

Evolutionary history and functional implications of protein domains and their combinations in eukaryotes.

PubMed

Itoh, Masumi; Nacher, Jose C; Kuma, Kei-ichi; Goto, Susumu; Kanehisa, Minoru

2007-01-01

In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes. We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors. Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.

The Identification and Structure of an N-Terminal PR Domain Show that FOG1 Is a Member of the PRDM Family of Proteins

PubMed Central

Clifton, Molly K.; Westman, Belinda J.; Thong, Sock Yue; O’Connell, Mitchell R.; Webster, Michael W.; Shepherd, Nicholas E.; Quinlan, Kate G.; Crossley, Merlin; Blobel, Gerd A.; Mackay, Joel P.

2014-01-01

FOG1 is a transcriptional regulator that acts in concert with the hematopoietic master regulator GATA1 to coordinate the differentiation of platelets and erythrocytes. Despite considerable effort, however, the mechanisms through which FOG1 regulates gene expression are only partially understood. Here we report the discovery of a previously unrecognized domain in FOG1: a PR (PRD-BF1 and RIZ) domain that is distantly related in sequence to the SET domains that are found in many histone methyltransferases. We have used NMR spectroscopy to determine the solution structure of this domain, revealing that the domain shares close structural similarity with SET domains. Titration with S-adenosyl-L-homocysteine, the cofactor product synonymous with SET domain methyltransferase activity, indicated that the FOG PR domain is not, however, likely to function as a methyltransferase in the same fashion. We also sought to define the function of this domain using both pulldown experiments and gel shift assays. However, neither pulldowns from mammalian nuclear extracts nor yeast two-hybrid assays reproducibly revealed binding partners, and we were unable to detect nucleic-acid-binding activity in this domain using our high-diversity Pentaprobe oligonucleotides. Overall, our data demonstrate that FOG1 is a member of the PRDM (PR domain containing proteins, with zinc fingers) family of transcriptional regulators. The function of many PR domains, however, remains somewhat enigmatic for the time being. PMID:25162672

Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.

PubMed

Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

2009-04-01

The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3'-5' exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg(2+)/Mn(2+)-dependent DNA/RNA polymerase, Mn(2+)-dependent 3'-5' exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn(2+)-dependent 3'-5' exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3'-5' exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3'-5' exonuclease activity.

Functional analysis of the relative growth rate, chemical composition, construction and maintenance costs, and the payback time of Coffea arabica L. leaves in response to light and water availability.

PubMed

Cavatte, Paulo C; Rodríguez-López, Nélson F; Martins, Samuel C V; Mattos, Mariela S; Sanglard, Lílian M V P; Damatta, Fábio M

2012-05-01

In this study, the combined effects of light and water availability on the functional relationships of the relative growth rate (RGR), leaf chemical composition, construction and maintenance costs, and benefits in terms of payback time for Coffea arabica are presented. Coffee plants were grown for 8 months in 100% or 15% full sunlight and then a four-month water shortage was implemented. Plants grown under full sunlight were also transferred to shade and vice versa. Overall, most of the traits assessed were much more responsive to the availability of light than to the water supply. Larger construction costs (12%), primarily associated with elevated phenol and alkaloid pools, were found under full sunlight. There was a positive correlation between these compounds and the RGR, the mass-based net carbon assimilation rate and the carbon isotope composition ratio, which, in turn, correlated negatively with the specific leaf area. The payback time was remarkably lower in the sun than in shade leaves and increased greatly in water-deprived plants. The differences in maintenance costs among the treatments were narrow, with no significant impact on the RGR, and there was no apparent trade-off in resource allocation between growth and defence. The current irradiance during leaf bud formation affected both the specific leaf area and leaf physiology upon transferring the plants from low to high light and vice versa. In summary, sun-grown plants fixed more carbon for growth and secondary metabolism, with the net effect of an increased RGR.

Structure-informed insights for NLR functioning in plant immunity.

PubMed

Sukarta, Octavina C A; Slootweg, Erik J; Goverse, Aska

2016-08-01

To respond to foreign invaders, plants have evolved a cell autonomous multilayered immune system consisting of extra- and intracellular immune receptors. Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) mediate recognition of pathogen effectors inside the cell and trigger a host specific defense response, often involving controlled cell death. NLRs consist of a central nucleotide-binding domain, which is flanked by an N-terminal CC or TIR domain and a C-terminal leucine-rich repeat domain (LRR). These multidomain proteins function as a molecular switch and their activity is tightly controlled by intra and inter-molecular interactions. In contrast to metazoan NLRs, the structural basis underlying NLR functioning as a pathogen sensor and activator of immune responses in plants is largely unknown. However, the first crystal structures of a number of plant NLR domains were recently obtained. In addition, biochemical and structure-informed analyses revealed novel insights in the cooperation between NLR domains and the formation of pre- and post activation complexes, including the coordinated activity of NLR pairs as pathogen sensor and executor of immune responses. Moreover, the discovery of novel integrated domains underscores the structural diversity of NLRs and provides alternative models for how these immune receptors function in plants. In this review, we will highlight these recent advances to provide novel insights in the structural, biochemical and molecular aspects involved in plant NLR functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Single TRAM domain RNA-binding proteins in Archaea: functional insight from Ctr3 from the Antarctic methanogen Methanococcoides burtonii.

PubMed

Taha; Siddiqui, K S; Campanaro, S; Najnin, T; Deshpande, N; Williams, T J; Aldrich-Wright, J; Wilkins, M; Curmi, P M G; Cavicchioli, R

2016-09-01

TRAM domain proteins present in Archaea and Bacteria have a β-barrel shape with anti-parallel β-sheets that form a nucleic acid binding surface; a structure also present in cold shock proteins (Csps). Aside from protein structures, experimental data defining the function of TRAM domains is lacking. Here, we explore the possible functional properties of a single TRAM domain protein, Ctr3 (cold-responsive TRAM domain protein 3) from the Antarctic archaeon Methanococcoides burtonii that has increased abundance during low temperature growth. Ribonucleic acid (RNA) bound by Ctr3 in vitro was determined using RNA-seq. Ctr3-bound M. burtonii RNA with a preference for transfer (t)RNA and 5S ribosomal RNA, and a potential binding motif was identified. In tRNA, the motif represented the C loop; a region that is conserved in tRNA from all domains of life and appears to be solvent exposed, potentially providing access for Ctr3 to bind. Ctr3 and Csps are structurally similar and are both inferred to function in low temperature translation. The broad representation of single TRAM domain proteins within Archaea compared with their apparent absence in Bacteria, and scarcity of Csps in Archaea but prevalence in Bacteria, suggests they represent distinct evolutionary lineages of functionally equivalent RNA-binding proteins. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor

PubMed Central

2015-01-01

Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1–WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1–WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology. PMID:25662954

Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor.

PubMed

Farooq, Amjad

2015-03-01

Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1-WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1-WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology. © 2015 by the Society for Experimental Biology and Medicine.

The Influence of Domain Knowledge on the Functional Capacity of Working Memory

ERIC Educational Resources Information Center

Ricks, Travis Rex; Wiley, Jennifer

2009-01-01

Theories of expertise have proposed that superior cognitive performance is in part due to increases in the functional capacity of working memory during domain-related tasks. Consistent with this approach Fincher-Kiefer et al. (1988), found that domain knowledge increased scores on baseball-related reading span tasks. The present studies extended…

Cation reordering in natural titanomagnetites and implications for paleointensity studies

NASA Astrophysics Data System (ADS)

Bowles, J. A.; Jackson, M. J.; Gee, J. S.

2013-05-01

Successful paleointensity experiments hinge on the underlying assumption of reciprocity; the remanence acquired over a particular temperature range should be fully removed over the same temperature range, and vice versa. This means that the blocking (TB) and unblocking (TUB) temperature spectra are identical and do not change during the course of the experiment. We will present the results of recent work demonstrating that some natural titanomagnetites undergo cation reordering on laboratory timescales and at temperatures at or below the Curie temperature (TC). The bulk composition of the titanomagnetites (Fe3-xTixO4) varies between approximately 0.2 < x < 0.4, with moderate degrees of Mg and Al substitution. Although there is no attendant structural or chemical alteration, the re-distribution of ferric and ferrous iron cations results in reversible changes in Curie temperature of up to 150°C. This necessarily changes the blocking temperature spectrum as a function of prior thermal history. These changes in TC, TUB and TB clearly pose problems for all paleointensity experiments, but the effects may be most apparent during Thellier-type experiments where the sample is step-wise heated to increasingly higher temperatures. The blocking temperature distribution will be expected to change over the course of the experiment even in the absence of chemical alteration, and one can expect the experiment to fail. We will explore the effects of cation redistribution on paleointensity experiments through numerical models and by comparison with paleointensity data from pumice samples taken from the 1980 pyroclastic flows at Mt. St. Helens (MSH). In the MSH samples, two phases are typically present: a predominantly multi-domain, homogeneous titanomagnetite (associated with the cation reordering) and an oxyexsolved, single-domain to pseudo-single-domain phase with ilmenite lamellae in a magnetite-rich host. Samples that result in technically successful paleointensity experiments that give the correct field value are most likely to be dominated by the oxyexsolved phase. By contrast, samples with a considerable proportion of the homogeneous phase typically fail the paleointensity experiments and have unstable magnetization behavior at temperatures associated with cation reordering on laboratory time scales. In many samples with both phases, pTRM checks pass at both low (<300°C) and high (>500°C) temperatures, but fail in the intermediate temperature window. The composition of the titanomagnetites that exhibit this cation reordering effect are extremely common in rocks of andesitic, dacitic, and rhyolitic composition, as well as in some basalts. Cation reordering may therefore be a previously unrecognized cause for failure in paleointensity experiments.

Bile acids modulate signaling by functional perturbation of plasma membrane domains.

PubMed

Zhou, Yong; Maxwell, Kelsey N; Sezgin, Erdinc; Lu, Maryia; Liang, Hong; Hancock, John F; Dial, Elizabeth J; Lichtenberger, Lenard M; Levental, Ilya

2013-12-13

Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

Molecular Structures and Functional Relationships in Clostridial Neurotoxins

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

Swaminathan S.

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structuresmore » have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here.« less

Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

PubMed Central

Siaud, Nicolas; Lam, Isabel; Christ, Nicole; Schlacher, Katharina; Xia, Bing; Jasin, Maria

2011-01-01

The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations. PMID:22194698

HIV-associated cognitive disorders in perinatally infected children and adolescents: a novel composite cognitive domains score.

PubMed

Phillips, Nicole J; Hoare, Jacqueline; Stein, Dan J; Myer, Landon; Zar, Heather J; Thomas, Kevin G F

2018-04-22

Accurate assessment of HIV-associated cognitive disorders in perinatally infected children and adolescents is challenging. Assessments of general intellectual functioning, or global cognition, may not provide information regarding domain-specific strengths and weaknesses, and may therefore fail to detect, impaired trajectories of development within particular cognitive domains. We compare the efficacy of global cognitive scores to that of composite cognitive domain scores in detecting cognitive disorders in a sample of perinatally HIV-infected children, and a demographically matched HIV negative control group, drawn from the Cape Town Adolescent Antiretroviral Cohort (CTAAC) study. All children were administered a comprehensive neuropsychological test battery. Using data from that test battery, we created ten separate composite cognitive domains: general intellectual functioning, attention, working memory, visual memory, verbal memory, language, visual spatial ability, motor coordination, processing speed and executive function. Within each domain, each test bore a high level of association with each of the other tests in that domain (Cronbach's α ≥ .70 for all domains). We found that composite domain scores calculated on whole-sample data were significantly higher than those calculated using control-sample data. Our comparison of a global cognitive score to composite domain scores suggested that the latter provided more detailed information (regarding strengths, weaknesses, areas of impairment), and when compared to global scores, were more sensitive in detecting HIV-associated cognitive disorders, and were able to distinguish HIV-infected patients from uninfected controls. Hence, we recommend using this method of composite cognitive domains scores, rather than global aggregate scores, when assessing cognitive function in paediatric HIV. This method provides a convenient and relatively accurate assessment that might help with cross-cultural and cross-region comparisons as researchers try to detect cognitive impairment patterns in HIV-infected children and adolescents globally.

Vice President Sees Mars InSight Spacecraft in Colorado

NASA Image and Video Library

2017-10-27

Vice President Mike Pence joined NASA Associate Administrator for the Science Mission Directorate, Thomas Zurbuchen for a close-up view of NASA’s Mars InSight spacecraft during a visit to Lockheed Martin’s facility in Littleton, Colorado, on Thursday, October 26. InSight is being prepped for a May 2018 launch to the Red Planet, with a landing in November. It will study the deep interior of Mars, with a primary goal of helping scientists understand how rocky planets – including Earth – formed and evolved.   The vice president also visited a Lockheed Martin Virtual Reality lab, featuring demos of the company’s human exploration efforts. Lockheed Martin is the prime contractor building NASA’s Orion spacecraft, which will launch on the agency’s Space Launch System rocket, and take humans farther into the solar system than ever before.

Vice President Mike Pence Visits Kennedy Space Center

NASA Image and Video Library

2017-07-06

Vice President Mike Pence got a first-hand look at the public-private partnerships at America's multi-user spaceport on Thursday, July 6, during a visit to NASA's Kennedy Space Center in Florida. The Vice President started his visit at Shuttle Landing Facility, the former space shuttle landing strip now leased and operated by Space Florida. Speaking in the center's iconic Vehicle Assembly Building, Pence thanked employees for their commitment to America's continued leadership in the space frontier. He then embarked on a spaceport tour showcasing both NASA and commercial work that will soon lead to U.S.-based astronaut launches and eventual missions into deep space. The tour included a visit to the Neil Armstrong Operations and Checkout Building, where the Orion spacecraft is being prepped for its first integrated flight with the Space Launch System (SLS) in 2019.

Modulating the processing of emotional stimuli by cognitive demand

PubMed Central

Sternkopf, Melanie A.; Schneider, Frank; Habel, Ute; Turetsky, Bruce I.; Zilles, Karl; Eickhoff, Simon B.

2012-01-01

Emotional processing is influenced by cognitive processes and vice versa, indicating a profound interaction of these domains. The investigation of the neural mechanisms underlying this interaction is not only highly relevant for understanding the organization of human brain function. Rather, it may also help in understanding dysregulated emotions in affective disorders and in elucidating the neurobiology of cognitive behavioural therapy (e.g. in borderline personality disorder), which aims at modulating dysfunctional emotion processes by cognitive techniques, such as restructuring. In the majority of earlier studies investigating the interaction of emotions and cognition, the main focus has been on the investigation of the effects of emotional stimuli or, more general, emotional processing, e.g. instituted by emotional material that needed to be processed, on cognitive performance and neural activation patterns. Here we pursued the opposite approach and investigated the modulation of implicit processing of emotional stimuli by cognitive demands using an event-related functional magnetic resonance imaging––study on a motor short-term memory paradigm with emotional interferences. Subjects were visually presented a finger-sequence consisting either of four (easy condition) or six (difficult condition) items, which they had to memorize. After a short pause positive, negative or neutral International affective picture system pictures or a green dot (as control condition) were presented. Subjects were instructed to reproduce the memorized sequence manually as soon as the picture disappeared. Analysis showed that with increasing cognitive demand (long relative to short sequences), neural responses to emotional pictures were significantly reduced in amygdala and orbitofrontal cortex. In contrast, the more difficult task evoked stronger activation in a widespread frontoparietal network. As stimuli were task-relevant go-cues and hence had to be processed perceptually, we would interpret this as a specific attenuation of affective responses by concurrent cognitive processing––potentially reflecting a relocation of resources mediated by the frontoparietal network. PMID:21258093

Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder.

PubMed

Samalin, Ludovic; de Chazeron, Ingrid; Vieta, Eduard; Bellivier, Frank; Llorca, Pierre-Michel

2016-03-01

The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real-life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment. This was a multicenter, cross-sectional, non-interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms. Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time). Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing the predictive value of a neuropsychological model on concurrent function in acute stroke recovery and rehabilitation.

PubMed

Leitner, Damian; Miller, Harry; Libben, Maya

2018-06-25

Few studies have examined the relationship between cognition and function for acute stroke inpatients utilizing comprehensive methods. This study aimed to assess the relationship of a neuropsychological model, above and beyond a baseline model, with concurrent functional status across multiple domains in the early weeks of stroke recovery and rehabilitation. Seventy-four acute stroke patients were administered a comprehensive neuropsychological assessment. Functional domains of ability, adjustment, and participation were assessed using the Mayo-Portland Adaptability Inventory - 4 (MPAI-4). Hierarchical linear regression was used to assess a neuropsychological model comprised of cognitive tests scores on domains of executive function, memory, and visuospatial-constructional skills (VSC), after accounting for a baseline model comprised of common demographic and stroke variants used to predict outcome. The neuropsychological model was significantly associated, above and beyond the baseline model, with MPAI-4 Ability, Participation, and Total scores (all p-values < .05). The strength of association varied across functional domains. Analyzing tests of executive function, the Color Trails Test-Part 2 predicted MPAI-4 Participation (β = -.46, p = .001), and Total score (β = -.32, p = .02). Neuropsychological assessment contributes independently to the determination of multiple domains of functional function, above and beyond common medical variants of stroke, in the early weeks of recovery and rehabilitation. Multiple tests of executive function are recommended to develop a greater appreciation of a patient's concurrent functional abilities.

Functional CAR models for large spatially correlated functional datasets.

PubMed

Zhang, Lin; Baladandayuthapani, Veerabhadran; Zhu, Hongxiao; Baggerly, Keith A; Majewski, Tadeusz; Czerniak, Bogdan A; Morris, Jeffrey S

2016-01-01

We develop a functional conditional autoregressive (CAR) model for spatially correlated data for which functions are collected on areal units of a lattice. Our model performs functional response regression while accounting for spatial correlations with potentially nonseparable and nonstationary covariance structure, in both the space and functional domains. We show theoretically that our construction leads to a CAR model at each functional location, with spatial covariance parameters varying and borrowing strength across the functional domain. Using basis transformation strategies, the nonseparable spatial-functional model is computationally scalable to enormous functional datasets, generalizable to different basis functions, and can be used on functions defined on higher dimensional domains such as images. Through simulation studies, we demonstrate that accounting for the spatial correlation in our modeling leads to improved functional regression performance. Applied to a high-throughput spatially correlated copy number dataset, the model identifies genetic markers not identified by comparable methods that ignore spatial correlations.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

PubMed

Keeney, Tamra; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Heinemann, Allen W; Charlifue, Susan; Fyffe, Denise C; Marino, Ralph J; Morse, Leslie R; Worobey, Lynn A; Tate, Denise; Rosenblum, David; Zafonte, Ross; Tulsky, David; Jette, Alan M

2018-03-31

To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). Multisite longitudinal (12-mo follow-up) study. Nine SCI Model Systems programs. Adults (N=165) with SCI enrolled in the SCI Model Systems database. Not applicable. SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

PubMed Central

2011-01-01

Background The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families. Results We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. Conclusions The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA. PMID:21569384

Cellulase Linkers Are Optimized Based on Domain Type and Function: Insights from Sequence Analysis, Biophysical Measurements, and Molecular Simulation

PubMed Central

Sammond, Deanne W.; Payne, Christina M.; Brunecky, Roman; Himmel, Michael E.; Crowley, Michael F.; Beckham, Gregg T.

2012-01-01

Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs) to carbohydrate-binding modules (CBMs). Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests that cellulase linkers may exhibit function in enzyme action, and highlights the need for additional studies to elucidate cellulase linker functions. PMID:23139804

CoMoDo: identifying dynamic protein domains based on covariances of motion.

PubMed

Wieninger, Silke A; Ullmann, G Matthias

2015-06-09

Most large proteins are built of several domains, compact units which enable functional protein motions. Different domain assignment approaches exist, which mostly rely on concepts of stability, folding, and evolution. We describe the automatic assignment method CoMoDo, which identifies domains based on protein dynamics. Covariances of atomic fluctuations, here calculated by an Elastic Network Model, are used to group residues into domains of different hierarchical levels. The so-called dynamic domains facilitate the study of functional protein motions involved in biological processes like ligand binding and signal transduction. By applying CoMoDo to a large number of proteins, we demonstrate that dynamic domains exhibit features absent in the commonly assigned structural domains, which can deliver insight into the interactions between domains and between subunits of multimeric proteins. CoMoDo is distributed as free open source software at www.bisb.uni-bayreuth.de/CoMoDo.html .

A systematic analysis of the in vitro and in vivo functions of the HD-GYP domain proteins of Vibrio cholerae.

PubMed

McKee, Robert W; Kariisa, Ankunda; Mudrak, Benjamin; Whitaker, Courtney; Tamayo, Rita

2014-10-25

The second messenger cyclic diguanylate (c-di-GMP) plays a central role in bacterial adaptation to extracellular stimuli, controlling processes such as motility, biofilm development, cell development and, in some pathogens, virulence. The intracellular level of c-di-GMP is controlled by the complementary activities of diguanylate cyclases containing a GGDEF domain and two classes of c-di-GMP phosphodiesterases containing an EAL or HD-GYP hydrolytic domain. Compared to the GGDEF and EAL domains, the functions of HD-GYP domain family proteins are poorly characterized. The human diarrheal pathogen Vibrio cholerae encodes nine putative HD-GYP domain proteins. To determine the contributions of HD-GYP domain proteins to c-di-GMP signaling in V. cholerae, we systematically analyzed the enzymatic functionality of each protein and their involvement in processes known to be regulated by c-di-GMP: motility, biofilm development and virulence. Complementary in vitro and in vivo experiments showed that four HD-GYP domain proteins are active c-di-GMP phosphodiesterases: VC1295, VC1348, VCA0210 and VCA0681. Mutation of individual HD-GYP domain genes, as well as combinatorial mutations of multiple HD-GYP domain genes, had no effect on motility or biofilm formation of V. cholerae under the conditions tested. Furthermore, no single HD-GYP domain gene affected intestinal colonization by V. cholerae in an infant mouse model. However, inactivation of multiple HD-GYP domain genes, including the four encoding functional phosphodiesterases, significantly attenuated colonization. These results indicate that the HD-GYP family of c-di-GMP phosphodiesterases impacts signaling by this second messenger during infection. Altogether, this work greatly furthers the understanding of this important family of c-di-GMP metabolic enzymes and demonstrates a role for HD-GYP domain proteins in the virulence of V. cholerae.

[Formula: see text] regularity properties of singular parameterizations in isogeometric analysis.

PubMed

Takacs, T; Jüttler, B

2012-11-01

Isogeometric analysis (IGA) is a numerical simulation method which is directly based on the NURBS-based representation of CAD models. It exploits the tensor-product structure of 2- or 3-dimensional NURBS objects to parameterize the physical domain. Hence the physical domain is parameterized with respect to a rectangle or to a cube. Consequently, singularly parameterized NURBS surfaces and NURBS volumes are needed in order to represent non-quadrangular or non-hexahedral domains without splitting, thereby producing a very compact and convenient representation. The Galerkin projection introduces finite-dimensional spaces of test functions in the weak formulation of partial differential equations. In particular, the test functions used in isogeometric analysis are obtained by composing the inverse of the domain parameterization with the NURBS basis functions. In the case of singular parameterizations, however, some of the resulting test functions do not necessarily fulfill the required regularity properties. Consequently, numerical methods for the solution of partial differential equations cannot be applied properly. We discuss the regularity properties of the test functions. For one- and two-dimensional domains we consider several important classes of singularities of NURBS parameterizations. For specific cases we derive additional conditions which guarantee the regularity of the test functions. In addition we present a modification scheme for the discretized function space in case of insufficient regularity. It is also shown how these results can be applied for computational domains in higher dimensions that can be parameterized via sweeping.

Vice President Pence Tours Jet Propulsion Laboratory

NASA Image and Video Library

2018-04-28

U.S. Vice President Mike Pence, left, thanks JPL Deputy Director Lt. Gen. (Ret) Larry James, JPL Director Michael Watkins, JPL Distinguished Visiting Scientist and Spouse of UAG Chairman James Ellis, Elisabeth Pate-Cornell , UAG Chairman, Admiral (Ret) James Ellis , and California Institute of Technology President Thomas Rosenbaum, right, for giving him a tour of NASA's Jet Propulsion Laboratory, Saturday, April 28, 2018 in Pasadena, California. Photo Credit: (NASA/Bill Ingalls)