Regionally and seasonally differentiated primary production in the North Atlantic

Science.gov (United States)

Sathyendranath, Shubha; Longhurst, Alan; Caverhill, Carla M.; Platt, Trevor

1995-10-01

A bio-geochemical classification of the N. Atlantic Basin is presented according to which the basin is first divided into four primary algal domains: Polar, West-Wind, Trades and Coastal. These are in turn sub-divided into smaller provinces. The classification is based on differences in the physical environment which are likely to influence regional algal dynamics. The seasonally-differentiated parameters of the photosynthesis-light curve ( P-I curve) and parameters that define the vertical structure in chlorophyll profile are then established for each province, based on an analysis of an archive of over 6000 chlorophyll profiles, and over 1800 P-I curves. These are then combined with satellite-derived chlorophyll data for the N. Atlantic, and information on cloud cover, to compute primary production at the annual scale. using a model that computes spectral transmission of light underwater, and spectral, photosynthetic response of phytoplankton to available light. The results are compared with earlier, satellite-derived, estimates of basin-scale primary production.

Changing the cubic ferrimagnetic domain structure in temperature region of spin flip transition

International Nuclear Information System (INIS)

Djuraev, D.R.; Niyazov, L.N.; Saidov, K.S.; Sokolov, B.Yu.

2011-01-01

The transformation of cubic ferrimagnetic Tb 0.2 Y 2.8 Fe 5 O 12 domain structure has been studied by magneto optic method in the temperature region of spontaneous spin flip phase transition (SPT). It has been found that SPT occurs in a finite temperature interval where the coexistence of low- and high- temperature magnetic phase domains has observed. A character of domain structure evolution in temperature region of spin flip essentially depends on the presence of mechanical stresses in crystal. Interpretation of experimental results has been carried out within the framework of SPT theory for a cubic crystal. (authors)

Differential associations between domains of sibling conflict and adolescent emotional adjustment.

Science.gov (United States)

Campione-Barr, Nicole; Greer, Kelly Bassett; Kruse, Anna

2013-01-01

Issues of equality and fairness and invasion of the personal domain, 2 previously identified topic areas of adolescent sibling conflict (N. Campione-Barr & J. G. Smetana, 2010), were examined in 145 dyads (Mfirst-born = 14.97, SD = 1.69 years; Msecond-born = 12.20, SD = 1.90 years) for their differential effects on youths' emotional adjustment over 1 year. The impact of internalizing symptoms on later sibling conflicts also was tested. Invasion of the personal domain conflicts were associated with higher levels of anxiety and lower self-esteem 1 year later, whereas Equality and Fairness issues were associated with greater depressed mood. Conversely, greater internalizing symptomatology and lower self-esteem predicted more of both types of conflict. Moderating influences of gender and ordinal position were also examined. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

D1/D2 domain of large-subunit ribosomal DNA for differentiation of Orpinomyces spp.

Science.gov (United States)

Dagar, Sumit S; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K

2011-09-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation.

Generalized query-based active learning to identify differentially methylated regions in DNA.

Science.gov (United States)

Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

2013-01-01

Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

Vector domain decomposition schemes for parabolic equations

Science.gov (United States)

Vabishchevich, P. N.

2017-09-01

A new class of domain decomposition schemes for finding approximate solutions of timedependent problems for partial differential equations is proposed and studied. A boundary value problem for a second-order parabolic equation is used as a model problem. The general approach to the construction of domain decomposition schemes is based on partition of unity. Specifically, a vector problem is set up for solving problems in individual subdomains. Stability conditions for vector regionally additive schemes of first- and second-order accuracy are obtained.

D1/D2 Domain of Large-Subunit Ribosomal DNA for Differentiation of Orpinomyces spp.▿

Science.gov (United States)

Dagar, Sumit S.; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K.

2011-01-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation. PMID:21784906

Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

Energy Technology Data Exchange (ETDEWEB)

Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang, E-mail: wonsang@catholic.ac.kr

2013-11-01

Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

Mapping the Landscape of Domain-Wall Pinning in Ferromagnetic Films Using Differential Magneto-Optical Microscopy

Science.gov (United States)

Badea, Robert; Berezovsky, Jesse

2016-06-01

The propagation of domain walls in a ferromagnetic film is largely determined by domain-wall pinning at defects in the material. In this article, we map the effective potential landscape for domain-wall pinning in permalloy films by raster scanning a single ferromagnetic vortex and monitoring the hysteretic vortex displacement vs applied magnetic field. The measurement is carried out using a differential magneto-optical microscopy technique which yields spatial sensitivity of approximately 10 nm. We present a simple algorithm for extracting an effective pinning potential from the measurement of vortex displacement vs applied field. The resulting maps of the pinning potential reveal distinct types of pinning sites, which we attribute to quasi-zero-, one-, and two-dimensional defects in the permalloy film.

Chapter 4: Regional magnetic domains of the Circum-Arctic: A framework for geodynamic interpretation

Science.gov (United States)

Saltus, R.W.; Miller, E.L.; Gaina, C.; Brown, P.J.

2011-01-01

We identify and discuss 57 magnetic anomaly pattern domains spanning the Circum-Arctic. The domains are based on analysis of a new Circum-Arctic data compilation. The magnetic anomaly patterns can be broadly related to general geodynamic classification of the crust into stable, deformed (magnetic and nonmagnetic), deep magnetic high, oceanic and large igneous province domains. We compare the magnetic domains with topography/bathymetry, regional geology, regional free air gravity anomalies and estimates of the relative magnetic 'thickness' of the crust. Most of the domains and their geodynamic classification assignments are consistent with their topographic/bathymetric and geological expression. A few of the domains are potentially controversial. For example, the extent of the Iceland Faroe large igneous province as identified by magnetic anomalies may disagree with other definitions for this feature. Also the lack of definitive magnetic expression of oceanic crust in Baffin Bay, the Norwegian-Greenland Sea and the Amerasian Basin is at odds with some previous interpretations. The magnetic domains and their boundaries provide clues for tectonic models and boundaries within this poorly understood portion of the globe. ?? 2011 The Geological Society of London.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing.

Science.gov (United States)

Olivares, Ela I; Lage-Castellanos, Agustín; Bobes, María A; Iglesias, Jaime

2018-01-01

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called "Fusiform Face Area", "FFA" and "Occipital Face Area", "OFA", respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing

Directory of Open Access Journals (Sweden)

Ela I. Olivares

2018-03-01

Full Text Available We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs in both intra-domain (face-feature and cross-domain (face-occupation matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called “Fusiform Face Area”, “FFA” and “Occipital Face Area”, “OFA”, respectively, the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

Mycoplasma hyopneumoniae and Mycoplasma flocculare differential domains from orthologous surface proteins induce distinct cellular immune responses in mice.

Science.gov (United States)

Leal, Fernanda Munhoz Dos Anjos; Virginio, Veridiana Gomes; Martello, Carolina Lumertz; Paes, Jéssica Andrade; Borges, Thiago J; Jaeger, Natália; Bonorino, Cristina; Ferreira, Henrique Bunselmeyer

2016-07-15

Mycoplasma hyopneumoniae and Mycoplasma flocculare are two genetically close species found in the swine respiratory tract. Despite their similarities, while M. hyopneumoniae is the causative agent of porcine enzootic pneumonia, M. flocculare is a commensal bacterium. Genomic and transcriptional comparative analyses so far failed to explain the difference in pathogenicity between these two species. We then hypothesized that such difference might be, at least in part, explained by amino acid sequence and immunological or functional differences between ortholog surface proteins. In line with that, it was verified that approximately 85% of the ortholog surface proteins from M. hyopneumoniae 7448 and M. flocculare present one or more differential domains. To experimentally assess possible immunological implications of this kind of difference, the extracellular differential domains from one pair of orthologous surface proteins (MHP7448_0612, from M. hyopneumoniae, and MF_00357, from M. flocculare) were expressed in E. coli and used to immunize mice. The recombinant polypeptides (rMHP61267-169 and rMF35767-196, respectively) induced distinct cellular immune responses. While, rMHP61267-169 induced both Th1 and Th2 responses, rMF35767-196 induced just an early pro-inflammatory response. These results indicate that immunological properties determined by differential domains in orthologous surface protein might play a role in pathogenicity, contributing to elicit specific and differential immune responses against each species. Copyright © 2016 Elsevier B.V. All rights reserved.

Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.

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Waqasuddin Khan

Full Text Available Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58.Next, we trained a bidirectional recurrent neural network (BRNN using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72 showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.

Regional climate projections for the MENA-CORDEX domain: analysis of projected temperature and precipitation changes

Science.gov (United States)

Hänsler, Andreas; Weber, Torsten; Eggert, Bastian; Saeed, Fahad; Jacob, Daniela

2014-05-01

Within the CORDEX initiative a multi-model suite of regionalized climate change information will be made available for several regions of the world. The German Climate Service Center (CSC) is taking part in this initiative by applying the regional climate model REMO to downscale global climate projections of different coupled general circulation models (GCMs) for several CORDEX domains. Also for the MENA-CORDEX domain, a set of regional climate change projections has been established at the CSC by downscaling CMIP5 projections of the Max-Planck-Institute Earth System Model (MPI-ESM) for the scenarios RCP4.5 and RCP8.5 with the regional model REMO for the time period from 1950 to 2100 to a horizontal resolution of 0.44 degree. In this study we investigate projected changes in future climate conditions over the domain towards the end of the 21st century. Focus in the analysis is given to projected changes in the temperature and rainfall characteristics and their differences for the two scenarios will be highlighted.

Polarization of concave domains by traveling wave pinning.

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Slawomir Bialecki

Full Text Available Pattern formation is one of the most fundamental yet puzzling phenomena in physics and biology. We propose that traveling front pinning into concave portions of the boundary of 3-dimensional domains can serve as a generic gradient-maintaining mechanism. Such a mechanism of domain polarization arises even for scalar bistable reaction-diffusion equations, and, depending on geometry, a number of stationary fronts may be formed leading to complex spatial patterns. The main advantage of the pinning mechanism, with respect to the Turing bifurcation, is that it allows for maintaining gradients in the specific regions of the domain. By linking the instant domain shape with the spatial pattern, the mechanism can be responsible for cellular polarization and differentiation.

MR differentiation of cystic lesions in the maxillomandibular region

International Nuclear Information System (INIS)

Minami, M.; Kaneda, T.; Ozawa, K.; Ozawa, M.; Itaz, Y.; Sasaki, Y.

1991-01-01

This paper examines the capability of MR imaging in differentiating cystic lesions in the maxillomandibular region. MR imaging of 34 patients with cystic lesions in the maxillomandibular region was performed prospectively. After T1-weighted axial imaging, T1-weighted axial and sagittal/coronal imaging with Gd-DTPA and T2-weighted axial imaging was performed. The pathologic examinations of the cases showed 9 ameloblastomas, 13 odontogenic keratocysts, and 11 other types of cysts. MR differentiation between ameloblastoma and cysts was possible in all cases but one. MR images of ameloblastoma showed solid and cystic components, multilocularity, irregularly thickened walls, mural nodules, marked Gd-DTPA enhancement of the wall, and low T1-weighted signal fluids. MR differentiation between various kinds of cysts was difficult without information from conventional radiography, except odontogenic keratocysts. MR images of 17 keratocysts showed cystic patterns, regularly thin walls monolocular cysts, weak Gd-DTPA enhancement of the walls, and inhomogeneous intensity of the contents

Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

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Alvarez-Bolado Gonzalo

2012-01-01

Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

Energy Technology Data Exchange (ETDEWEB)

Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

Sensitivity of simulated regional Arctic climate to the choice of coupled model domain

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Dmitry V. Sein

2014-07-01

Full Text Available The climate over the Arctic has undergone changes in recent decades. In order to evaluate the coupled response of the Arctic system to external and internal forcing, our study focuses on the estimation of regional climate variability and its dependence on large-scale atmospheric and regional ocean circulations. A global ocean–sea ice model with regionally high horizontal resolution is coupled to an atmospheric regional model and global terrestrial hydrology model. This way of coupling divides the global ocean model setup into two different domains: one coupled, where the ocean and the atmosphere are interacting, and one uncoupled, where the ocean model is driven by prescribed atmospheric forcing and runs in a so-called stand-alone mode. Therefore, selecting a specific area for the regional atmosphere implies that the ocean–atmosphere system can develop ‘freely’ in that area, whereas for the rest of the global ocean, the circulation is driven by prescribed atmospheric forcing without any feedbacks. Five different coupled setups are chosen for ensemble simulations. The choice of the coupled domains was done to estimate the influences of the Subtropical Atlantic, Eurasian and North Pacific regions on northern North Atlantic and Arctic climate. Our simulations show that the regional coupled ocean–atmosphere model is sensitive to the choice of the modelled area. The different model configurations reproduce differently both the mean climate and its variability. Only two out of five model setups were able to reproduce the Arctic climate as observed under recent climate conditions (ERA-40 Reanalysis. Evidence is found that the main source of uncertainty for Arctic climate variability and its predictability is the North Pacific. The prescription of North Pacific conditions in the regional model leads to significant correlation with observations, even if the whole North Atlantic is within the coupled model domain. However, the inclusion of the

Domain-to-domain coupling in voltage-sensing phosphatase.

Science.gov (United States)

Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

2017-01-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

Incremental localized boundary-domain integro-differential equations of elastic damage mechanics for inhomogeneous body

OpenAIRE

Mikhailov, SE

2006-01-01

Copyright @ 2006 Tech Science Press A quasi-static mixed boundary value problem of elastic damage mechanics for a continuously inhomogeneous body is considered. Using the two-operator Green-Betti formula and the fundamental solution of an auxiliary homogeneous linear elasticity with frozen initial, secant or tangent elastic coe±cients, a boundary-domain integro-differential formulation of the elasto-plastic problem with respect to the displacement rates and their gradients is derived. Usin...

Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single-Domain Antibody Specific for Ebola Virus Nucleoprotein.

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George P Anderson

Full Text Available Single-domain antibodies derived from the unique New Antigen Receptor found in sharks have numerous potential applications, ranging from diagnostic reagents to therapeutics. Shark-derived single-domain antibodies possess the same characteristic ability to refold after heat denaturation found in single-domain antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark derived single-domain antibodies specific for the nucleoprotein of Ebola virus were described. Our evaluation confirmed their high affinity for the nucleoprotein, but found their melting temperatures to be low relative to most single-domain antibodies. Our first approach towards improving their stability was grafting antigen-binding regions (complementarity determining regions of one of these single-domain antibodies onto a high melting temperature shark single-domain antibody. This resulted in two variants: one that displayed excellent affinity with a low melting temperature, while the other had poor affinity but a higher melting temperature. These new proteins, however, differed in only 3 amino acids within the complementarity determining region 2 sequence. In shark single-domain antibodies, the complementarity determining region 2 is often referred to as hypervariable region 2, as this segment of the antibody domain is truncated compared to the sequence in camelid single-domain antibodies and conventional heavy chain variable domains. To elucidate which of the three amino acids or combinations thereof were responsible for the affinity and stability we made the 6 double and single point mutants that covered the intermediates between these two clones. We found a single amino acid change that achieved a 10°C higher melting temperature while maintaining sub nM affinity. This research gives insights into the impact of the shark sdAb hypervariable 2 region on both stability and affinity.

Regional climate simulations with COSMO-CLM over MENA-CORDEX domain

Science.gov (United States)

Galluccio, Salvatore; Bucchignani, Edoardo; Mercogliano, Paola; Montesarchio, Myriam

2014-05-01

In the frame of WCRP Coordinated Regional Downscaling Experiment (CORDEX), a set of common Regional Climate Downscaling (RCD) domains has been defined, as a prerequisite for the development of model evaluation and climate projection frameworks. CORDEX domains encompass the majority of land areas of the world. In this work, climate simulations have been performed over MENA-CORDEX domain, which includes North-Africa, southern Europe and the whole Arabian peninsula. The non-hydrostatic regional climate model COSMO-CLM has been used. At CMCC, regional climate modelling is a part of an integrated simulation system and it has been used in different European and African projects to provide qualitative and quantitative evaluation of the hydrogeological and public health risks. A series of simulations has been conducted over the MENA-CORDEX area at spatial resolution of 0.44°. A sensitivity analysis was conducted to adjust the model configuration to better reproduce the observed climate data. The numerical simulations were driven by ERA-Interim reanalysis (horizontal resolution of 0.703°) for the period 1979-1984; the first year, was considered as a spin up period. The validation was performed by using several data sets: CRU data set was used to validate temperature, precipitation and cloud cover; MERRA data set was used to validate temperature and precipitation and GPCP for precipitation. The model sensitivity to the external parameters was tested considering two different configurations for the surface albedo. In the first one, albedo is only function of soil-type whereas in the second configuration it is prescribed by two external fields for dry and saturated soil based on MODIS data. Moreover, we tested two aerosol distributions as well, namely the default Tanre aerosol distribution and aerosol maps according to Tegen (NASA/GISS). We found, as expected, a significant sensitivity, in particular on the African region. We also varied tuning and physical parameters, such

Differential dynamic and structural behavior of lipid-cholesterol domains in model membranes.

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Luis F Aguilar

Full Text Available Changes in the cholesterol (Chol content of biological membranes are known to alter the physicochemical properties of the lipid lamella and consequently the function of membrane-associated enzymes. To characterize these changes, we used steady-state and time resolved fluorescence spectroscopy and two photon-excitation microscopy techniques. The membrane systems were chosen according to the techniques that were used: large unilamellar vesicles (LUVs for cuvette and giant unilamellar vesicles (GUVs for microscopy measurements; they were prepared from dipalmitoyl phosphatidylcholine (DPPC and dioctadecyl phosphatidylcholine (DOPC in mixtures that are well known to form lipid domains. Two fluorescent probes, which insert into different regions of the bilayer, were selected: 1,6-diphenyl-1,3,5-hexatriene (DPH was located at the deep hydrophobic core of the acyl chain regions and 2-dimethylamino-6-lauroylnaphthalene (Laurdan at the hydrophilic-hydrophobic membrane interface. Our spectroscopy results show that (i the changes induced by cholesterol in the deep hydrophobic phospholipid acyl chain domain are different from the ones observed in the superficial region of the hydrophilic-hydrophobic interface, and these changes depend on the state of the lamella and (ii the incorporation of cholesterol into the lamella induces an increase in the orientation dynamics in the deep region of the phospholipid acyl chains with a corresponding decrease in the orientation at the region close to the polar lipid headgroups. The microscopy data from DOPC/DPPC/Chol GUVs using Laurdan generalized polarization (Laurdan GP suggest that a high cholesterol content in the bilayer weakens the stability of the water hydrogen bond network and hence the stability of the liquid-ordered phase (Lo.

Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis

DEFF Research Database (Denmark)

Svendsen, Anders J; Gervin, Kristina; Lyle, Robert

2016-01-01

: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6......OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated......: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA....

Domain-General Brain Regions Do Not Track Linguistic Input as Closely as Language-Selective Regions.

Science.gov (United States)

Blank, Idan A; Fedorenko, Evelina

2017-10-11

Language comprehension engages a cortical network of left frontal and temporal regions. Activity in this network is language-selective, showing virtually no modulation by nonlinguistic tasks. In addition, language comprehension engages a second network consisting of bilateral frontal, parietal, cingulate, and insular regions. Activity in this "multiple demand" (MD) network scales with comprehension difficulty, but also with cognitive effort across a wide range of nonlinguistic tasks in a domain-general fashion. Given the functional dissociation between the language and MD networks, their respective contributions to comprehension are likely distinct, yet such differences remain elusive. Prior neuroimaging studies have suggested that activity in each network covaries with some linguistic features that, behaviorally, influence on-line processing and comprehension. This sensitivity of the language and MD networks to local input characteristics has often been interpreted, implicitly or explicitly, as evidence that both networks track linguistic input closely, and in a manner consistent across individuals. Here, we used fMRI to directly test this assumption by comparing the BOLD signal time courses in each network across different people ( n = 45, men and women) listening to the same story. Language network activity showed fewer individual differences, indicative of closer input tracking, whereas MD network activity was more idiosyncratic and, moreover, showed lower reliability within an individual across repetitions of a story. These findings constrain cognitive models of language comprehension by suggesting a novel distinction between the processes implemented in the language and MD networks. SIGNIFICANCE STATEMENT Language comprehension recruits both language-specific mechanisms and domain-general mechanisms that are engaged in many cognitive processes. In the human cortex, language-selective mechanisms are implemented in the left-lateralized "core language network

Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

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Luciano Polonelli

Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

LOCAL DEVELOPMENT IN NORTHEST REGION THROUGH ACTIVITIES IN ITC DOMAIN

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Daniela\tENACHESCU

2015-06-01

Full Text Available Economic areas with high technology are key drivers in sustainable regional development, including unemployment and consequently decreasing population migration in the region. Northeast Region is the largest development region of Romania in terms of number of inhabitants and the owned area. On 01/01/2014, according to balance employment, labor resources of the region were numbered 2,428,700, which represent 49.6% of employed population. The registered unemployment rate at 31 August 2014 was 6.5%, with 82 thousand unemployed registered. In terms of participation in the main economic activities, civilian employment in agriculture, forestry and fishing is predominant (40.1% while in service, civilian employment is 37.1%, while industry and construction is 22.8%. The paper aims to analyze the situation that the potential employment and development opportunities for the Northeast region through activities in the field of ITC domain. Unfortunately, this area was the worst in most indicators, the use of computers and the internet to the turnover of companies and investments in the IT & C and unfortunately in terms of employment population that is under 50%

DIFFERENTIAL EFFECT OF NATIONAL VS. REGIONAL CELEBRITIES ON CONSUMER ATTITUDES

OpenAIRE

Varsha JAIN; Subhadip ROY; Abhishek KUMAR; Anusha KABRA

2010-01-01

The present study explores the differential effects of having a National/Regional celebrity in an advertisement/ endorsement. More specifically the study intends to find out whether a National celebrity would have a more favorable impact on consumer attitudes than a Regional celebrity when endorsing the same product. Experimental design was used as the research methodology. A 3 (National Celebrity/Regional Celebrity/No Celebrity) X 2 (High/Low Involvement Product) design was conducted on stud...

Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases.

NARCIS (Netherlands)

Asheim, B.T.; Boschma, R.A.; Cooke, P.

2011-01-01

Constructing regional advantage: platform policies based on related variety and differentiated knowledge bases, Regional Studies. This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related

SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

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Sai Krishnan

Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

Peculiar long-range supercurrent in superconductor-ferromagnet-superconductor junction containing a noncollinear magnetic domain in the ferromagnetic region

Energy Technology Data Exchange (ETDEWEB)

Meng, Hao, E-mail: menghao1982@shu.edu.cn [School of Physics and Telecommunication Engineering, Shaanxi University of Technology, Hanzhong 723001 (China); National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Wu, Xiuqiang [National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Ren, Yajie [School of Physics and Telecommunication Engineering, Shaanxi University of Technology, Hanzhong 723001 (China)

2015-01-14

We study the supercurrent in clean superconductor-ferromagnet-superconductor heterostructure containing a noncollinear magnetic domain in the ferromagnetic region. It is demonstrated that the magnetic domain can lead to a spin-flip scattering process, which reverses the spin orientations of the singlet Cooper pair and simultaneously changes the sign of the corresponding electronic momentum. If the ferromagnetic layers on both sides of magnetic domain have the same features, the long-range proximity effect will take place. That is because the singlet Cooper pair will create an exact phase-cancellation effect and gets an additional π phase shift as it passes through the entire ferromagnetic region. Then, the equal spin triplet pair only exists in the magnetic domain region and can not diffuse into the other two ferromagnetic layers. So, the supercurrent mostly arises from the singlet Cooper pairs, and the equal spin triplet pairs are not involved. This result can provide a approach for generating the long-range supercurrent.

Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction

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Mate Suzanne E

2012-09-01

Full Text Available Abstract Background Recycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ. We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD1 proteinin the Torpedo californica electric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/− NMJs. Methods Localization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/− mouse skeletal muscle. Results Endogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal muscle in vivo. EHD1−/− mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in the T. californica electric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/− mouse skeletal muscle than in wild-type skeletal muscle. Conclusion EHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/− muscle may be due to functional compensation by other EHD paralogs.

On parametric domain for asymptotic stability with probability one of zero solution of linear Ito stochastic differential equations

International Nuclear Information System (INIS)

Phan Thanh An; Phan Le Na; Ngo Quoc Chung

2004-05-01

We describe a practical implementation for finding parametric domain for asymptotic stability with probability one of zero solution of linear Ito stochastic differential equations based on Korenevskij and Mitropolskij's sufficient condition and our sufficient conditions. Numerical results show that all of these sufficient conditions are crucial in the implementation. (author)

A role for chromatin topology in imprinted domain regulation.

Science.gov (United States)

MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

2016-02-01

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

Enhanced performance for differential detection in coherent Brillouin optical time-domain analysis sensors

Science.gov (United States)

Shao, Liyang; Zhang, Yunpeng; Li, Zonglei; Zhang, Zhiyong; Zou, Xihua; Luo, Bin; Pan, Wei; Yan, Lianshan

2016-11-01

Logarithmic detectors (LogDs) have been used in coherent Brillouin optical time-domain analysis (BOTDA) sensors to reduce the effect of phase fluctuation, demodulation complexities, and measurement time. However, because of the inherent properties of LogDs, a DC component at the level of hundreds of millivolts that prohibits high-gain signal amplification (SA) could be generated, resulting in unacceptable data acquisition (DAQ) inaccuracies and decoding errors in the process of prototype integration. By generating a reference light at a level similar to the probe light, differential detection can be applied to remove the DC component automatically using a differential amplifier before the DAQ process. Therefore, high-gain SA can be employed to reduce quantization errors. The signal-to-noise ratio of the weak Brillouin gain signal is improved from ˜11.5 to ˜21.8 dB. A BOTDA prototype is implemented based on the proposed scheme. The experimental results show that the measurement accuracy of the Brillouin frequency shift (BFS) is improved from ±1.9 to ±0.8 MHz at the end of a 40-km sensing fiber.

Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

Science.gov (United States)

Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

2007-11-03

PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

Spectral nudging to eliminate the effects of domain position and geometry in regional climate model simulations

Science.gov (United States)

Miguez-Macho, Gonzalo; Stenchikov, Georgiy L.; Robock, Alan

2004-07-01

It is well known that regional climate simulations are sensitive to the size and position of the domain chosen for calculations. Here we study the physical mechanisms of this sensitivity. We conducted simulations with the Regional Atmospheric Modeling System (RAMS) for June 2000 over North America at 50 km horizontal resolution using a 7500 km × 5400 km grid and NCEP/NCAR reanalysis as boundary conditions. The position of the domain was displaced in several directions, always maintaining the U.S. in the interior, out of the buffer zone along the lateral boundaries. Circulation biases developed a large scale structure, organized by the Rocky Mountains, resulting from a systematic shifting of the synoptic wave trains that crossed the domain. The distortion of the large-scale circulation was produced by interaction of the modeled flow with the lateral boundaries of the nested domain and varied when the position of the grid was altered. This changed the large-scale environment among the different simulations and translated into diverse conditions for the development of the mesoscale processes that produce most of precipitation for the Great Plains in the summer season. As a consequence, precipitation results varied, sometimes greatly, among the experiments with the different grid positions. To eliminate the dependence of results on the position of the domain, we used spectral nudging of waves longer than 2500 km above the boundary layer. Moisture was not nudged at any level. This constrained the synoptic scales to follow reanalysis while allowing the model to develop the small-scale dynamics responsible for the rainfall. Nudging of the large scales successfully eliminated the variation of precipitation results when the grid was moved. We suggest that this technique is necessary for all downscaling studies with regional models with domain sizes of a few thousand kilometers and larger embedded in global models.

On the solution of elliptic partial differential equations on regions with corners

International Nuclear Information System (INIS)

Serkh, Kirill; Rokhlin, Vladimir

2016-01-01

In this paper we investigate the solution of boundary value problems on polygonal domains for elliptic partial differential equations. We observe that when the problems are formulated as the boundary integral equations of classical potential theory, the solutions are representable by series of elementary functions. In addition to being analytically perspicuous, the resulting expressions lend themselves to the construction of accurate and efficient numerical algorithms. The results are illustrated by a number of numerical examples.

Efficient detection of differentially methylated regions using DiMmeR

DEFF Research Database (Denmark)

Almeida, Diogo Marinho; Uhrenfeldt Skov, Ida; Silva, Artur

2017-01-01

in the programming language R, have no user interface, and do not offer all necessary steps to guide users from raw data all the way down to statistically significant differentially methylated regions (DMRs) and the associated genes. RESULTS: Here, we present DiMmeR (Discovery of Multiple Differentially Methylated...... Regions), the first free standalone software that interactively guides with a user-friendly graphical user interface (GUI) scientists the whole way through EWAS data analysis. It offers parallelized statistical methods for efficiently identifying DMRs in both Illumina 450K and 850K EPIC chip data. Di......MmeR computes empirical p-values through randomization tests, even for big data sets of hundreds of patients and thousands of permutations within a few minutes on a standard desktop PC. It is independent of any third-party libraries, computes regression coefficients, p-values and empirical p...

A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

Science.gov (United States)

Williams, K P; Shoelson, S E

1993-03-15

Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

Preliminary Experience Using Eye-Tracking Technology to Differentiate Novice and Expert Image Interpretation for Ultrasound-Guided Regional Anesthesia.

Science.gov (United States)

Borg, Lindsay K; Harrison, T Kyle; Kou, Alex; Mariano, Edward R; Udani, Ankeet D; Kim, T Edward; Shum, Cynthia; Howard, Steven K

2018-02-01

Objective measures are needed to guide the novice's pathway to expertise. Within and outside medicine, eye tracking has been used for both training and assessment. We designed this study to test the hypothesis that eye tracking may differentiate novices from experts in static image interpretation for ultrasound (US)-guided regional anesthesia. We recruited novice anesthesiology residents and regional anesthesiology experts. Participants wore eye-tracking glasses, were shown 5 sonograms of US-guided regional anesthesia, and were asked a series of anatomy-based questions related to each image while their eye movements were recorded. The answer to each question was a location on the sonogram, defined as the area of interest (AOI). The primary outcome was the total gaze time in the AOI (seconds). Secondary outcomes were the total gaze time outside the AOI (seconds), total time to answer (seconds), and time to first fixation on the AOI (seconds). Five novices and 5 experts completed the study. Although the gaze time (mean ± SD) in the AOI was not different between groups (7 ± 4 seconds for novices and 7 ± 3 seconds for experts; P = .150), the gaze time outside the AOI was greater for novices (75 ± 18 versus 44 ± 4 seconds for experts; P = .005). The total time to answer and total time to first fixation in the AOI were both shorter for experts. Experts in US-guided regional anesthesia take less time to identify sonoanatomy and spend less unfocused time away from a target compared to novices. Eye tracking is a potentially useful tool to differentiate novices from experts in the domain of US image interpretation. © 2017 by the American Institute of Ultrasound in Medicine.

Towards a Differentiated and Domain-Specific View of Educational Technology: An Exploratory Study of History Teachers' Technology Use

Science.gov (United States)

Voet, Michiel; De Wever, Bram

2017-01-01

Adopting a differentiated and domain-specific view of educational technology, the present study focuses on the case of school history. It argues that, in this particular context, one of technology's main assets is its ability to support inquiry-based learning activities, during which students interpret the past through historical reasoning. As…

The consequences of price differentiation for regional development in Poland

Directory of Open Access Journals (Sweden)

Grzegorz Przekota

2017-07-01

Full Text Available Each region in Poland has a different economic potential due to its own specific features. Taking account of the specific nature of individual regions is important for the management of the country as a whole and of its particular regions. Existing disparities in the economic development may lead to many negative phenomena, such as internal migration or regional marginalization. Excessive price and income inequalities may weaken economic growth throughout the country. It is important for the coherence of the whole country that the disparities between regions are not too big. The study determines the consequences of price differentiation for regional development in Poland. The analysis was conducted using the coefficient of variation, correlation coefficient, regression coefficient and medium pace. The regions differ in terms of development, dynamic growth and wages. However, prices are much less diverse.

An optimized algorithm for detecting and annotating regional differential methylation.

Science.gov (United States)

Li, Sheng; Garrett-Bakelman, Francine E; Akalin, Altuna; Zumbo, Paul; Levine, Ross; To, Bik L; Lewis, Ian D; Brown, Anna L; D'Andrea, Richard J; Melnick, Ari; Mason, Christopher E

2013-01-01

DNA methylation profiling reveals important differentially methylated regions (DMRs) of the genome that are altered during development or that are perturbed by disease. To date, few programs exist for regional analysis of enriched or whole-genome bisulfate conversion sequencing data, even though such data are increasingly common. Here, we describe an open-source, optimized method for determining empirically based DMRs (eDMR) from high-throughput sequence data that is applicable to enriched whole-genome methylation profiling datasets, as well as other globally enriched epigenetic modification data. Here we show that our bimodal distribution model and weighted cost function for optimized regional methylation analysis provides accurate boundaries of regions harboring significant epigenetic modifications. Our algorithm takes the spatial distribution of CpGs into account for the enrichment assay, allowing for optimization of the definition of empirical regions for differential methylation. Combined with the dependent adjustment for regional p-value combination and DMR annotation, we provide a method that may be applied to a variety of datasets for rapid DMR analysis. Our method classifies both the directionality of DMRs and their genome-wide distribution, and we have observed that shows clinical relevance through correct stratification of two Acute Myeloid Leukemia (AML) tumor sub-types. Our weighted optimization algorithm eDMR for calling DMRs extends an established DMR R pipeline (methylKit) and provides a needed resource in epigenomics. Our method enables an accurate and scalable way of finding DMRs in high-throughput methylation sequencing experiments. eDMR is available for download at http://code.google.com/p/edmr/.

Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

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Alok K. Sharma

2014-02-01

Full Text Available Background: Molecular dynamics (MD simulations provide valuable information on the conformational changes that accompany time-dependent motions in proteins. The reported crystal structure of rat prestin (PDB 3LLO is remarkable for an α1-α2 inter-helical angle that differs substantially from those observed in bacterial STAS domains of SulP anion transporters and anti-sigma factor antagonists. However, NMR data on the rat prestin STAS domain in solution suggests dynamic features at or near the α1-α2 helical region (Pasqualetto et al JMB, 2010. We therefore performed a 100 ns 300K MD simulation study comparing the STAS domains of rat prestin and (modeled human pendrin, to explore possible conformational flexibility in the region of the α1 and α2 helices. Methods: The conformation of the loop missing in the crystal structure of rat prestin STAS (11 amino acids between helix α1 and strand β3 was built using Modeller. MD simulations were performed with GROMACSv4.6 using GROMOS96 53a6 all-atom force field. Results: A subset of secondary structured elements of the STAS domains exhibits significant conformational changes during the simulation time course. The conformationally perturbed segments include the majority of loop regions, as well as the α1 and α2 helices. A significant decrease in the α1-α2 inter-helical angle observed across the simulation trajectory leads to closer helical packing at their C-termini. The end-simulation conformations of the prestin and pendrin STAS domains, including their decreased α1-α2 inter-helical angles, resemble more closely the packing of corresponding helices in the STAS structures of bacterial SulP transporters Rv1739c and ychM, as well as those of the anti-sigma factor antagonists. Several structural segments of the modeled human pendrin STAS domain exhibit larger atomic motions and greater conformational deviations than the corresponding regions of rat prestin, predicting that the human pendrin STAS

Genome-wide Anaplasma phagocytophilum AnkA-DNA interactions are enriched in intergenic regions and gene promoters and correlate with infection-induced differential gene expression.

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J Stephen Dumler

2016-09-01

Full Text Available Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects neutrophils and alters cardinal functions via reprogrammed transcription. Large contiguous regions of neutrophil chromosomes are differentially expressed during infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil or granulocyte nucleus to complex with DNA in heterochromatin across all chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also has features of matrix attachment region (MAR-binding proteins that regulate three-dimensional chromatin architecture and coordinate transcriptional programs encoded in topologically-associated chromatin domains. We hypothesize that identification of additional AnkA binding sites will better delineate how A. phagocytophilum infection results in reprogramming of the neutrophil genome. Using AnkA-binding ChIP-seq, we showed that AnkA binds broadly throughout all chromosomes in a reproducible pattern, especially at: i intergenic regions predicted to be matrix attachment regions (MARs; ii within predicted lamina-associated domains; and iii at promoters ≤3,000 bp upstream of transcriptional start sites. These findings provide genome-wide support for AnkA as a regulator of cis-gene transcription. Moreover, the dominant mark of AnkA in distal intergenic regions known to be AT-enriched, coupled with frequent enrichment in the nuclear lamina, provides strong support for its role as a MAR-binding protein and genome re-organizer. AnkA must be considered a prime candidate to promote neutrophil reprogramming and subsequent functional changes that belie improved microbial fitness and pathogenicity.

A Domain Specific Embedded Language in C++ for Automatic Differentiation, Projection, Integration and Variational Formulations

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Christophe Prud'homme

2006-01-01

Full Text Available In this article, we present a domain specific embedded language in C++ that can be used in various contexts such as numerical projection onto a functional space, numerical integration, variational formulations and automatic differentiation. Albeit these tools operate in different ways, the language overcomes this difficulty by decoupling expression constructions from evaluation. The language is implemented using expression templates and meta-programming techniques and uses various Boost libraries. The language is exercised on a number of non-trivial examples and a benchmark presents the performance behavior on a few test problems.

Differential and Domain-Specific Associations Among Right-Wing Authoritarianism, Social Dominance Orientation, and Adolescent Delinquency.

Science.gov (United States)

Oosterhoff, Benjamin; Shook, Natalie J; Clay, Russ; Metzger, Aaron

2017-09-01

Using a dual-process model (DPM) framework, this research examined whether right-wing authoritarianism (RWA) and social dominance orientation (SDO) are differentially associated with adolescent delinquency. In Study 1 ( N = 847; M age = 15.96) and Study 2 ( N = 340; M age = 16.64), adolescents completed measures of RWA, SDO, and engagement in different forms of delinquency. In Study 2, adolescents also reported their beliefs about obeying different laws. Across both studies, adolescents who endorsed greater RWA engaged in lower levels of delinquency and those who endorsed greater SDO engaged in higher levels of delinquency. Findings from Study 2 suggest that these associations are contingent on the domain-specific purpose of the law being violated and are also present with adolescents' beliefs about their obligation to obey laws. These results extend the DPM, demonstrating that RWA and SDO are differentially linked with youth delinquency.

Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.

Science.gov (United States)

Chang, Kai-Wei; Huang, Nancy A; Liu, I-Hsuan; Wang, Yi-Hui; Wu, Ping; Tseng, Yen-Tzu; Hughes, Michael W; Jiang, Ting Xin; Tsai, Mong-Hsun; Chen, Chien-Yu; Oyang, Yen-Jen; Lin, En-Chung; Chuong, Cheng-Ming; Lin, Shau-Ping

2015-01-23

Regional specificity allows different skin regions to exhibit different characteristics, enabling complementary functions to make effective use of the integumentary surface. Chickens exhibit a high degree of regional specificity in the skin and can serve as a good model for when and how these regional differences begin to emerge. We used developing feather and scale regions in embryonic chickens as a model to gauge the differences in their molecular pathways. We employed cosine similarity analysis to identify the differentially regulated and co-regulated genes. We applied low cell techniques for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer identification to overcome limited cell availabilities from embryonic chicken skin. We identified a specific set of genes demonstrating a high correlation as being differentially expressed during feather and scale development and maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be involved in feathering skin differentiation were found to be differentially regulated. Interestingly, we also found genes along calcium channel pathways that are differentially regulated. From the analysis of differentially regulated pathways, we used calcium signaling pathways as an example for further verification. Some voltage-gated calcium channel subunits, particularly CACNA1D, are expressed spatio-temporally in the skin epithelium. These calcium signaling pathway members may be involved in developmental decisions, morphogenesis, or epithelial maturation. We further characterized enhancers associated with histone modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel-related genes and identified signature intensive hotspots that may be correlated with certain voltage-gated calcium channel genes. We demonstrated the applicability of cosine similarity analysis for identifying novel regulatory pathways that are differentially regulated during development. Our study

Alternative splicing targeting the hTAF4-TAFH domain of TAF4 represses proliferation and accelerates chondrogenic differentiation of human mesenchymal stem cells.

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Jekaterina Kazantseva

Full Text Available Transcription factor IID (TFIID activity can be regulated by cellular signals to specifically alter transcription of particular subsets of genes. Alternative splicing of TFIID subunits is often the result of external stimulation of upstream signaling pathways. We studied tissue distribution and cellular expression of different splice variants of TFIID subunit TAF4 mRNA and biochemical properties of its isoforms in human mesenchymal stem cells (hMSCs to reveal the role of different isoforms of TAF4 in the regulation of proliferation and differentiation. Expression of TAF4 transcripts with exons VI or VII deleted, which results in a structurally modified hTAF4-TAFH domain, increases during early differentiation of hMSCs into osteoblasts, adipocytes and chondrocytes. Functional analysis data reveals that TAF4 isoforms with the deleted hTAF4-TAFH domain repress proliferation of hMSCs and preferentially promote chondrogenic differentiation at the expense of other developmental pathways. This study also provides initial data showing possible cross-talks between TAF4 and TP53 activity and switching between canonical and non-canonical WNT signaling in the processes of proliferation and differentiation of hMSCs. We propose that TAF4 isoforms generated by the alternative splicing participate in the conversion of the cellular transcriptional programs from the maintenance of stem cell state to differentiation, particularly differentiation along the chondrogenic pathway.

Drug detection by terahertz time-domain spectroscopy

International Nuclear Information System (INIS)

Duan Ruixin; Zhu Yiming; Zhao Hongwei

2013-01-01

Due to unique spectral region, functional imaging ability, excellent penetration and safety characteristics of terahertz radiation, the terahertz technology rapidly becomes a vital method to detect and analyze drugs. In this paper, firstly, we identify the functional groups of anti-diabetic drugs by density functional theory (DFT), HIPHOP models and experimental results from terahertz time-domain spectroscopy measurements. Secondly, we identify four kinds of herbs of radix curcumae by using the support vector machine (SVM) analysis. Besides, we analyze the absorption of anhydrous and hydrous glucose, and determine the state of water in the crystalized D-glucose·H 2 O through the results of differential scanning calorimetry measurement. Finally, we summarize the advantages and disadvantages of terahertz time-domain spectroscopy method in drug detection and analyzing. (authors)

Income differentials on regional labour markets in Southwest Germany

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Guyot Alice

2009-01-01

Full Text Available The aim of our paper is to identify explanatory variables for income disparities between women and men across different regional types. Using data from the BA Employment Panel (BEP descriptive statistics show that the gender pay gap grows wider from core regions to periphery. The main explanatory variables for the income differentials are vocational education in the men's case and size of enterprise in the women's case. Whereas in the case of women the importance of vocational status increases and the importance of size of enterprise decreases from rural areas to urban areas.

Sequential assignment of proline-rich regions in proteins: Application to modular binding domain complexes

International Nuclear Information System (INIS)

Kanelis, Voula; Donaldson, Logan; Muhandiram, D.R.; Rotin, Daniela; Forman-Kay, Julie D.; Kay, Lewis E.

2000-01-01

Many protein-protein interactions involve amino acid sequences containing proline-rich motifs and even poly-proline stretches. The lack of amide protons in such regions complicates assignment, since 1 HN-based triple-resonance assignment strategies cannot be employed. Two such systems that we are currently studying include an SH2 domain from the protein Crk with a region containing 9 prolines in a 14 amino acid sequence, as well as a WW domain that interacts with a proline-rich target. A modified version of the HACAN pulse scheme, originally described by Bax and co-workers [Wang et al. (1995) J. Biomol. NMR, 5, 376-382], and an experiment which correlates the intra-residue 1 H α , 13 C α / 13 C β chemical shifts with the 15 N shift of the subsequent residue are presented and applied to the two systems listed above, allowing sequential assignment of the molecules

Differential gene expression in porcine SK6 cells infected with wild-type and SAP domain-mutant foot-and-mouth disease virus.

Science.gov (United States)

Ni, Zixin; Yang, Fan; Cao, Weijun; Zhang, Xiangle; Jin, Ye; Mao, Ruoqing; Du, Xiaoli; Li, Weiwei; Guo, Jianhong; Liu, Xiangtao; Zhu, Zixiang; Zheng, Haixue

2016-06-01

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease in livestock. The viral proteinase L(pro) of FMDV is involved in pathogenicity, and mutation of the L(pro) SAP domain reduces FMDV pathogenicity in pigs. To determine the gene expression profiles associated with decreased pathogenicity in porcine cells, we performed transcriptome analysis using next-generation sequencing technology and compared differentially expressed genes in SK6 cells infected with FMDV containing L(pro) with either a wild-type or mutated version of the SAP domain. This analysis yielded 1,853 genes that exhibited a ≥ 2-fold change in expression and was validated by real-time quantitative PCR detection of several differentially expressed genes. Many of the differentially expressed genes correlated with antiviral responses corresponded to genes associated with transcription factors, immune regulation, cytokine production, inflammatory response, and apoptosis. Alterations in gene expression profiles may be responsible for the variations in pathogenicity observed between the two FMDV variants. Our results provided genes of interest for the further study of antiviral pathways and pathogenic mechanisms related to FMDV L(pro).

Causality between regional stock markets: A frequency domain approach

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Gradojević Nikola

2013-01-01

Full Text Available Using a data set from five regional stock exchanges (Serbia, Croatia, Slovenia, Hungary and Germany, this paper presents a frequency domain analysis of a causal relationship between the returns on the CROBEX, SBITOP, CETOP and DAX indices, and the return on the major Serbian stock exchange index, BELEX 15. We find evidence of a somewhat dominant effect of the CROBEX and CETOP stock indices on the BELEX 15 stock index across a range of frequencies. The results also indicate that the BELEX 15 index and the SBITOP index interact in a bi-directional causal fashion. Finally, the DAX index movements consistently drive the BELEX 15 index returns for cycle lengths between 3 and 11 days without any feedback effect.

The cysteine-rich core domain of REIC/Dkk-3 is critical for its effect on monocyte differentiation and tumor regression.

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Kinoshita, Rie; Watanabe, Masami; Huang, Peng; Li, Shun-Ai; Sakaguchi, Masakiyo; Kumon, Hiromi; Futami, Junichiro

2015-06-01

Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor-suppressor gene and has been studied as a promising therapeutic gene for cancer gene therapy. Intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) elicits cancer cell-specific apoptosis and anticancer immune responses. The cytokine-like effect of secretory REIC/Dkk-3 on the induction of dendritic cell (DC)-like cell differentiation from monocytes plays a role in systemic anticancer immunity. In the present study, we generated recombinant full-length and N-terminally truncated REIC/Dkk-3 to characterize the biological activity of the protein. During the purification procedure, we identified a 17 kDa cysteine-rich stable product (C17-REIC) showing limited degradation. Further analysis showed that the C17-REIC domain was sufficient for the induction of DC-like cell differentiation from monocytes. Concomitant with the differentiation of DCs, the REIC/Dkk-3 protein induced the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and signal transducers and activators of transcription (STAT) at a level comparable to that of granulocyte/macrophage colony-stimulating factor. In a mouse model of subcutaneous renal adenocarcinoma, intraperitoneal injection of full-length and C17-REIC proteins exerted anticancer effects in parallel with the activation of immunocompetent cells such as DCs and cytotoxic T lymphocytes in peripheral blood. Taken together, our results indicate that the stable cysteine-rich core region of REIC/Dkk-3 is responsible for the induction of anticancer immune responses. Because REIC/Dkk-3 is a naturally circulating serum protein, the upregulation REIC/Dkk-3 protein expression could be a promising option for cancer therapy.

Short forms of the Utrecht-Management of Identity Commitments Scale (U-MICS) with the domains of job, romantic relationship, and region.

Science.gov (United States)

Schubach, Elisabeth; Zimmermann, Julia; Noack, Peter; Neyer, Franz J

2017-01-01

The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (n Sample1  = 95, 84% female, mean age 22.45 years; n Sample2  = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site*

Science.gov (United States)

Lu, Shaoyong; Banerjee, Avik; Jang, Hyunbum; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

2015-01-01

K-Ras4B, a frequently mutated oncogene in cancer, plays an essential role in cell growth, differentiation, and survival. Its C-terminal membrane-associated hypervariable region (HVR) is required for full biological activity. In the active GTP-bound state, the HVR interacts with acidic plasma membrane (PM) headgroups, whereas the farnesyl anchors in the membrane; in the inactive GDP-bound state, the HVR may interact with both the PM and the catalytic domain at the effector binding region, obstructing signaling and nucleotide exchange. Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. The mutations are away from or directly at the HVR switch I/effector binding site. Our results suggest that full-length wild-type GDP-bound K-Ras4B (K-Ras4BWT-GDP) is in an intrinsically autoinhibited state via tight HVR-catalytic domain interactions. The looser association in K-Ras4BWT-GTP may release the HVR. Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Thus, our results suggest that mutations can exert their effects in more than one way, abolishing GTP hydrolysis and facilitating effector binding. PMID:26453300

Sarcocystis neurona: molecular characterization of enolase domain I region and a comparison to other protozoa.

Science.gov (United States)

Bolten, K E; Marsh, A E; Reed, S M; Dubey, J P; Toribio, R E; Saville, W J A

2008-09-01

Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to infect a wide host range in contrast to other Sarcocystis species. In the current study, five S. neurona isolates from a variety of sources, three Sarcocystis falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia darlingi isolate were used to compare the enolase 2 gene segment containing the domain I region to previously sequenced enolase genes from Neospora caninum, Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma cruzi; enolase 2 segment containing domain I region is highly conserved amongst these parasites of veterinary and medical importance. Immunohistochemistry results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S. neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S. neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting expression differences between organisms.

Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

Science.gov (United States)

Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

2013-11-01

The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

[Differential mortality according to region of residence in Benin].

Science.gov (United States)

Laourou, H M

1995-01-01

"The first mortality tables of Benin elaborated by direct estimation for the whole country deal with relatively different regional realities. It is in this regard that the data, whether it is death from multiround surveys or information about survival of parents, allows one to distinguish between the North (with a higher mortality) and the South (which has a lower mortality). Moreover, this differential study reveals that the level of male adult mortality after 35 years in the South, is well above the national average, probably because of the increase in deaths through violence (road accident or victim of a fire) in this part of Benin....The originality of this study is to have highlighted the mortality differentials at almost all age groups of life...." (SUMMARY IN ENG AND ITA) excerpt

The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

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Yue Ma

Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale

Science.gov (United States)

Portela-Buelvas, Katherin; Oviedo, Heidi C.; Herazo, Edwin; Campo-Arias, Adalberto

2016-01-01

Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (X ± SD). A p value <0.001 was considered statistically significant. Results. In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women (p < 0.001). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct. PMID:27847825

Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale.

Science.gov (United States)

Monterrosa-Castro, Alvaro; Portela-Buelvas, Katherin; Oviedo, Heidi C; Herazo, Edwin; Campo-Arias, Adalberto

2016-01-01

Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective . To establish the DIF of the psychological domain of the MRS in Colombian women. Methods . 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation ( X ± SD). A p value <0.001 was considered statistically significant. Results . In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women ( p < 0.001). Conclusions . The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct.

Requirement of the coiled-coil domain of PML-RARα oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation

International Nuclear Information System (INIS)

Kim, Young-Eui; Kim, Dong-Yeon; Lee, Jang-Mi; Kim, Seong-Tae; Han, Tae-Hee; Ahn, Jin-Hyun

2005-01-01

Homo-oligomerization via a coiled-coil (C-C) domain has been shown to be necessary for the promyelocytic leukemia (PML)-retinoic acid receptor-α (RARα) fusion protein to acquire oncogenic potential in acute promyelocytic leukemia. We show here that PML(ΔC-C)-RARα, which contains a deletion in its C-C domain, is neither localized as characteristic microspeckles nor modified by small ubiquitin-like modifiers (SUMO). The absence of sumoylation of the ΔC-C mutant was due to the lack of binding to Ubc9, a SUMO conjugation enzyme. The integrity of RING finger domain was also needed for both sumoylation and microspeckle formation. In GAL4-DNA tethering assays, the ΔC-C mutant completely lost the inhibitory effect on retinoic acid (RA)-mediated transactivation. Furthermore, the expression of CD14 in U937 cells expressing the ΔC-C mutant in response to vitamin D3 was markedly higher than in cells expressing PML-RARα. However, the RA-mediated induction of C/EBPβ in cells expressing the ΔC-C mutant was comparable to that of control cells. Thus, our results suggest that the C-C domain-associated functions of sumoylation, localization as microspeckles, and the inhibition of monocyte differentiation all contribute to the oncogenic activity of PML-RARα

Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

Energy Technology Data Exchange (ETDEWEB)

Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun, E-mail: tztong@bjmu.edu.cn

2016-01-15

The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

International Nuclear Information System (INIS)

Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun

2016-01-01

The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

DEFF Research Database (Denmark)

Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

2004-01-01

CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine.

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Hannah E Gavin

2017-01-01

Full Text Available Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs-a key step in V. vulnificus foodborne pathogenesis-even before onset of overt intestinal pathology.

The PLAC1-homology region of the ZP domain is sufficient for protein polymerisation

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Litscher Eveline S

2006-04-01

Full Text Available Abstract Background Hundreds of extracellular proteins polymerise into filaments and matrices by using zona pellucida (ZP domains. ZP domain proteins perform highly diverse functions, ranging from structural to receptorial, and mutations in their genes are responsible for a number of severe human diseases. Recently, PLAC1, Oosp1-3, Papillote and CG16798 proteins were identified that share sequence homology with the N-terminal half of the ZP domain (ZP-N, but not with its C-terminal half (ZP-C. The functional significance of this partial conservation is unknown. Results By exploiting a highly engineered bacterial strain, we expressed in soluble form the PLAC1-homology region of mammalian sperm receptor ZP3 as a fusion to maltose binding protein. Mass spectrometry showed that the 4 conserved Cys residues within the ZP-N moiety of the fusion protein adopt the same disulfide bond connectivity as in full-length native ZP3, indicating that it is correctly folded, and electron microscopy and biochemical analyses revealed that it assembles into filaments. Conclusion These findings provide a function for PLAC1-like proteins and, by showing that ZP-N is a biologically active folding unit, prompt a re-evaluation of the architecture of the ZP domain and its polymers. Furthermore, they suggest that ZP-C might play a regulatory role in the assembly of ZP domain protein complexes.

The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

Science.gov (United States)

Moore, S. E.; Stabeno, P. J.

2016-02-01

The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site.

Science.gov (United States)

Lu, Shaoyong; Banerjee, Avik; Jang, Hyunbum; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

2015-11-27

K-Ras4B, a frequently mutated oncogene in cancer, plays an essential role in cell growth, differentiation, and survival. Its C-terminal membrane-associated hypervariable region (HVR) is required for full biological activity. In the active GTP-bound state, the HVR interacts with acidic plasma membrane (PM) headgroups, whereas the farnesyl anchors in the membrane; in the inactive GDP-bound state, the HVR may interact with both the PM and the catalytic domain at the effector binding region, obstructing signaling and nucleotide exchange. Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. The mutations are away from or directly at the HVR switch I/effector binding site. Our results suggest that full-length wild-type GDP-bound K-Ras4B (K-Ras4B(WT)-GDP) is in an intrinsically autoinhibited state via tight HVR-catalytic domain interactions. The looser association in K-Ras4B(WT)-GTP may release the HVR. Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Thus, our results suggest that mutations can exert their effects in more than one way, abolishing GTP hydrolysis and facilitating effector binding. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Generalized vector calculus on convex domain

Science.gov (United States)

Agrawal, Om P.; Xu, Yufeng

2015-06-01

In this paper, we apply recently proposed generalized integral and differential operators to develop generalized vector calculus and generalized variational calculus for problems defined over a convex domain. In particular, we present some generalization of Green's and Gauss divergence theorems involving some new operators, and apply these theorems to generalized variational calculus. For fractional power kernels, the formulation leads to fractional vector calculus and fractional variational calculus for problems defined over a convex domain. In special cases, when certain parameters take integer values, we obtain formulations for integer order problems. Two examples are presented to demonstrate applications of the generalized variational calculus which utilize the generalized vector calculus developed in the paper. The first example leads to a generalized partial differential equation and the second example leads to a generalized eigenvalue problem, both in two dimensional convex domains. We solve the generalized partial differential equation by using polynomial approximation. A special case of the second example is a generalized isoperimetric problem. We find an approximate solution to this problem. Many physical problems containing integer order integrals and derivatives are defined over arbitrary domains. We speculate that future problems containing fractional and generalized integrals and derivatives in fractional mechanics will be defined over arbitrary domains, and therefore, a general variational calculus incorporating a general vector calculus will be needed for these problems. This research is our first attempt in that direction.

Earning differentials by occupational categories: Gender, race and regions

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Ronaldo de Albuquerque e Arraes

2014-09-01

Full Text Available Analyzing the income differentials amongst the Brazilian workers’ occupations is the focus of this paper. Due to the wide diversity of occupations cataloged by the IBGE (around 800, a theoretical procedure is applied to reduce them to only seven in order to allow statistical treatment of the data. The methodological approach is based on Mincerian quantile equations to be estimated in various strata of the workers’ income distribution, on which a breakdown is made to check the gap among the individuals’ income with distinct inherent attributes and between those living in both more and less developed regions. The estimation results ensure the importance of breakdown analysis for occupational strata as well as for quantiles, since the effects of explanatory variables are distinct along the income distribution and vary among occupations. Regarding the gaps in this distribution, there is a glass ceiling effect in some occupations, that is, the gap is greater at the top of distribution, although in most cases the wider gap occurs at the bottom of the distribution – sticky floor effect, which makes this a distinguished result from other studies. Moreover, contrary to the gap in gender, which is due to the compensation characteristics of individuals only (discrimination, income differentials between regions and races also occur from the heterogeneous characteristics of workers.

Empirical study on regional differentiation of rural household energy use in Northwest China

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Wu, Wenheng; Zhang, Xin; Guo, Xiaodong

2018-02-01

To better understand regional differentiation of rural household energy use, data of energy use of 232 rural households in the Linwei District located in the lower reaches of the Weihe River of Northwest China were collected by questionnaires combined with face-to-face interview. Location quotient of energy use (LQEU) method is adopted in the paper. The results show that multiple energy sources are utilized due to market orientation in the plain area, and biogas is prominent as a result of policy orientation in the loess tableland, whereas firewood is dominant due to the influence of natural environment in the Qinling mountainous area. Regional differentiation of energy use is comprehensively affected by income level, air temperature, development conditions, energy policy, etc.

Basis adaptation and domain decomposition for steady-state partial differential equations with random coefficients

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Tipireddy, R.; Stinis, P.; Tartakovsky, A. M.

2017-12-01

We present a novel approach for solving steady-state stochastic partial differential equations (PDEs) with high-dimensional random parameter space. The proposed approach combines spatial domain decomposition with basis adaptation for each subdomain. The basis adaptation is used to address the curse of dimensionality by constructing an accurate low-dimensional representation of the stochastic PDE solution (probability density function and/or its leading statistical moments) in each subdomain. Restricting the basis adaptation to a specific subdomain affords finding a locally accurate solution. Then, the solutions from all of the subdomains are stitched together to provide a global solution. We support our construction with numerical experiments for a steady-state diffusion equation with a random spatially dependent coefficient. Our results show that highly accurate global solutions can be obtained with significantly reduced computational costs.

Brain region-dependent differential expression of alpha-synuclein.

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Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tsujimura, Atsushi; Tanaka, Masaki

2016-04-15

α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions. © 2015 Wiley Periodicals, Inc.

Differential subcellular localization of insulin receptor substrates depends on C-terminal regions and importin β

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Kabuta, Tomohiro; Take, Kazumi; Kabuta, Chihana; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2008-01-01

Insulin receptor substrates (IRSs) play essential roles in signal transduction of insulin and insulin-like growth factors. Previously, we showed that IRS-3 is localized to the nucleus as well as the cytosol, while IRS-1 and 2 are mainly localized to the cytoplasm. In the present study, we found that importin β directly interacts with IRS-3 and is able to mediate nuclear transport of IRS-3. Importin β interacted with the pleckstrin homology domain, the phosphotyrosine binding domain and the C-terminal region of IRS-3; indeed all of these fragments exhibited predominant nuclear localization. By contrast, almost no interaction of importin β with IRS-1 and -2 was observed, and their C-terminal regions displayed discrete spotty images in the cytosol. In addition, using chimeric proteins between IRS-1 and IRS-3, we revealed that the C-terminal regions are the main determinants of the differing subcellular localizations of IRS-1 and IRS-3.

Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

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Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

2012-02-14

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

SH2 Domain Histochemistry.

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Buhs, Sophia; Nollau, Peter

2017-01-01

Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.

The generation and selection of single-domain, v region libraries from nurse sharks.

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Flajnik, Martin F; Dooley, Helen

2009-01-01

The cartilaginous fish (sharks, skates, and rays) are the oldest phylogenetic group in which a human-type adaptive immune system and immunoglobulins (Igs) have been found. In addition to their conventional (heavy-light chain heterodimeric) isotypes, IgM and IgW, sharks produce the novel isotype, IgNAR, a heavy chain homodimer that does not associate with light chains. Instead, its variable (V) regions act as independent, soluble units in order to bind antigen. In this chapter, we detail our immunization protocol in order to raise a humoral IgNAR response in the nurse shark (Ginglymostoma cirratum) and the subsequent cloning of the single-domain V regions from this isotype in order to select antigen-specific binders by phage display.

Case Library Construction Technology of Energy Loss in Distribution Networks Considering Regional Differentiation Theory

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Ze Yuan

2017-11-01

Full Text Available The grid structures, load levels, and running states of distribution networks in different supply regions are known as the influencing factors of energy loss. In this paper, the case library of energy loss is constructed to differentiate the crucial factors of energy loss in the different supply regions. First of all, the characteristic state values are selected as the representation of the cases based on the analysis of energy loss under various voltage classes and in different types of regions. Then, the methods of Grey Relational Analysis and the K-Nearest Neighbor are utilized to implement the critical technologies of case library construction, including case representation, processing, analysis, and retrieval. Moreover, the analysis software of the case library is designed based on the case library construction technology. Some case studies show that there are many differences and similarities concerning the factors that influence the energy loss in different types of regions. In addition, the most relevant sample case can be retrieved from the case library. Compared with the traditional techniques, constructing a case library provides a new way to find out the characteristics of energy loss in different supply regions and constitutes differentiated loss-reducing programs.

Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.

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Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

2007-05-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes approximately 90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

Functional Anthology of Intrinsic Disorder. II. Cellular Components, Domains, Technical Terms, Developmental Processes and Coding Sequence Diversities Correlated with Long Disordered Regions

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Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

2008-01-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions. PMID:17391015

Origins of the Xylella fastidiosa prophage-like regions and their impact in genome differentiation.

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Alessandro de Mello Varani

Full Text Available Xylella fastidiosa is a Gram negative plant pathogen causing many economically important diseases, and analyses of completely sequenced X. fastidiosa genome strains allowed the identification of many prophage-like elements and possibly phage remnants, accounting for up to 15% of the genome composition. To better evaluate the recent evolution of the X. fastidiosa chromosome backbone among distinct pathovars, the number and location of prophage-like regions on two finished genomes (9a5c and Temecula1, and in two candidate molecules (Ann1 and Dixon were assessed. Based on comparative best bidirectional hit analyses, the majority (51% of the predicted genes in the X. fastidiosa prophage-like regions are related to structural phage genes belonging to the Siphoviridae family. Electron micrograph reveals the existence of putative viral particles with similar morphology to lambda phages in the bacterial cell in planta. Moreover, analysis of microarray data indicates that 9a5c strain cultivated under stress conditions presents enhanced expression of phage anti-repressor genes, suggesting switches from lysogenic to lytic cycle of phages under stress-induced situations. Furthermore, virulence-associated proteins and toxins are found within these prophage-like elements, thus suggesting an important role in host adaptation. Finally, clustering analyses of phage integrase genes based on multiple alignment patterns reveal they group in five lineages, all possessing a tyrosine recombinase catalytic domain, and phylogenetically close to other integrases found in phages that are genetic mosaics and able to perform generalized and specialized transduction. Integration sites and tRNA association is also evidenced. In summary, we present comparative and experimental evidence supporting the association and contribution of phage activity on the differentiation of Xylella genomes.

Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

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Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

2012-09-01

For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

Structure and function of the Juxta membrane domain of the human epidermal growth factor receptor by NMR spectroscopy

International Nuclear Information System (INIS)

Choowongkomon, Kiattawee; Carlin, Cathleen; Sonnichsen, Frank D.

2005-10-01

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family involved in the regulation of cellular proliferation and differentiation. Its juxta membrane domain (JX), the region located between the transmembrane and kinase domains, plays important roles in receptor trafficking since both basolateral sorting in polarized epithelial cells and lysosomal sorting signals are identified in this region. In order to understand the regulation of these signals, we characterized the structural properties of recombinant JX domain in dodecyl phosphocholine detergent (DPC) by nuclear magnetic resonance (NMR) spectroscopy. In DPC micelles, structures derived from NMR data showed three amphipathic, helical segments. Two equivalent average structural models on the surface of micelles were obtained that differ only in the relative orientation between the first and second helices. Our data suggests that the activity of sorting signals may be regulated by their membrane association and restricted accessibility in the intact receptor

U-Pb age in zircon of intrusive granite at Acopiara complex, Crystal region, domain Central Ceara, Brazil

International Nuclear Information System (INIS)

Neri, T.F.O.; Hamelak, G.M.S.; Azevedo, L.R.; Mattos, I.C.; Verissimo, C.U.V.; Nogueira Neto, J.A.; Lima, M.N.

2015-01-01

Granitic body mineralogically composed by two micas, located at Crystal region, Ceara Central domain and intruded into lithotypes from Acopiara complex, provided an age of ∼526 Ma, indicating important period of magma generation of granitic composition associated with crustal anatexia, during Paleozoic

Elemental Profiles of Whisk(ey Allow Differentiation by Type and Region

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Helene Hopfer

2017-01-01

Full Text Available Elemental fingerprints could provide an analytical approach to product differentiation and authentication, and have been used in the past for various distilled spirits, including brandy, gin, bourbon and tequila. However, a comparison of elemental differences between different whisk(ey types, such as Bourbon and Scotch, is still missing. In this study we compare the elemental fingerprints of 68 commercial whiskies for differentiation by type (Bourbon, Tennessee, Scotch, Irish, Japanese and region. Concentrations from sub-μg/L to mid-mg/L of 53 different elements were determined with inductively-coupled plasma—mass spectrometry (ICP-MS and microwave plasma—atomic emission spectroscopy (MP-AES, and used in subsequent statistical analyses. Significant differences in several elements were found for type, and allowed a classification according to whisk(ey type. Elemental differences were also found for different production areas within Scotland, thus, providing further evidence that Scotch whiskies could be differentiated by elemental analysis. Major sources of elemental differences seem to be processing equipment (Cu, Fe, Ni, Cd, Sn, Mo, V and raw materials, such as water (Ca, Mg, Fe, Mn, Sr.

Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

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Caplan, Steve; Sorgen, Paul L.

2013-01-01

The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

Age-related functional changes in domain-specific medial temporal lobe pathways.

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Berron, David; Neumann, Katja; Maass, Anne; Schütze, Hartmut; Fliessbach, Klaus; Kiven, Verena; Jessen, Frank; Sauvage, Magdalena; Kumaran, Dharshan; Düzel, Emrah

2018-05-01

There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this

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

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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

Individual globular domains and domain unfolding visualized in overstretched titin molecules with atomic force microscopy.

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Zsolt Mártonfalvi

Full Text Available Titin is a giant elastomeric protein responsible for the generation of passive muscle force. Mechanical force unfolds titin's globular domains, but the exact structure of the overstretched titin molecule is not known. Here we analyzed, by using high-resolution atomic force microscopy, the structure of titin molecules overstretched with receding meniscus. The axial contour of the molecules was interrupted by topographical gaps with a mean width of 27.7 nm that corresponds well to the length of an unfolded globular (immunoglobulin and fibronectin domain. The wide gap-width distribution suggests, however, that additional mechanisms such as partial domain unfolding and the unfolding of neighboring domain multimers may also be present. In the folded regions we resolved globules with an average spacing of 5.9 nm, which is consistent with a titin chain composed globular domains with extended interdomain linker regions. Topographical analysis allowed us to allocate the most distal unfolded titin region to the kinase domain, suggesting that this domain systematically unfolds when the molecule is exposed to overstretching forces. The observations support the prediction that upon the action of stretching forces the N-terminal ß-sheet of the titin kinase unfolds, thus exposing the enzyme's ATP-binding site and hence contributing to the molecule's mechanosensory function.

Differential influences of local subpopulations on regional diversity and differentiation for greater sage-grouse (Centrocercus urophasianus)

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Row, Jeffery R.; Oyler-McCance, Sara J.; Fedy, Brad C.

2016-01-01

The distribution of spatial genetic variation across a region can shape evolutionary dynamics and impact population persistence. Local population dynamics and among-population dispersal rates are strong drivers of this spatial genetic variation, yet for many species we lack a clear understanding of how these population processes interact in space to shape within-species genetic variation. Here, we used extensive genetic and demographic data from 10 subpopulations of greater sage-grouse to parameterize a simulated approximate Bayesian computation (ABC) model and (i) test for regional differences in population density and dispersal rates for greater sage-grouse subpopulations in Wyoming, and (ii) quantify how these differences impact subpopulation regional influence on genetic variation. We found a close match between observed and simulated data under our parameterized model and strong variation in density and dispersal rates across Wyoming. Sensitivity analyses suggested that changes in dispersal (via landscape resistance) had a greater influence on regional differentiation, whereas changes in density had a greater influence on mean diversity across all subpopulations. Local subpopulations, however, varied in their regional influence on genetic variation. Decreases in the size and dispersal rates of central populations with low overall and net immigration (i.e. population sources) had the greatest negative impact on genetic variation. Overall, our results provide insight into the interactions among demography, dispersal and genetic variation and highlight the potential of ABC to disentangle the complexity of regional population dynamics and project the genetic impact of changing conditions.

Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

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Ogawara, Hiroshi

2016-09-01

PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

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Yiping Fan

Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

A Highly Accurate Regular Domain Collocation Method for Solving Potential Problems in the Irregular Doubly Connected Domains

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Zhao-Qing Wang

2014-01-01

Full Text Available Embedding the irregular doubly connected domain into an annular regular region, the unknown functions can be approximated by the barycentric Lagrange interpolation in the regular region. A highly accurate regular domain collocation method is proposed for solving potential problems on the irregular doubly connected domain in polar coordinate system. The formulations of regular domain collocation method are constructed by using barycentric Lagrange interpolation collocation method on the regular domain in polar coordinate system. The boundary conditions are discretized by barycentric Lagrange interpolation within the regular domain. An additional method is used to impose the boundary conditions. The least square method can be used to solve the overconstrained equations. The function values of points in the irregular doubly connected domain can be calculated by barycentric Lagrange interpolation within the regular domain. Some numerical examples demonstrate the effectiveness and accuracy of the presented method.

Regional differentiation of retinoic acid-induced human pluripotent embryonic carcinoma stem cell neurons.

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Dennis E Coyle

Full Text Available The NTERA2 cl D1 (NT2 cell line, derived from human teratocarcinoma, exhibits similar properties as embryonic stem (ES cells or very early neuroepithelial progenitors. NT2 cells can be induced to become postmitotic central nervous system neurons (NT2N with retinoic acid. Although neurons derived from pluripotent cells, such as NT2N, have been characterized for their neurotransmitter phenotypes, their potential suitability as a donor source for neural transplantation also depends on their ability to respond to localized environmental cues from a specific region of the CNS. Therefore, our study aimed to characterize the regional transcription factors that define the rostocaudal and dorsoventral identity of NT2N derived from a monolayer differentiation paradigm using quantitative PCR (qPCR. Purified NT2N mainly expressed both GABAergic and glutamatergic phenotypes and were electrically active but did not form functional synapses. The presence of immature astrocytes and possible radial glial cells was noted. The NT2N expressed a regional transcription factor code consistent with forebrain, hindbrain and spinal cord neural progenitors but showed minimal expression of midbrain phenotypes. In the dorsoventral plane NT2N expressed both dorsal and ventral neural progenitors. Of major interest was that even under the influence of retinoic acid, a known caudalization factor, the NT2N population maintained a rostral phenotype subpopulation which expressed cortical regional transcription factors. It is proposed that understanding the regional differentiation bias of neurons derived from pluripotent stem cells will facilitate their successful integration into existing neuronal networks within the CNS.

Tlx controls proliferation and patterning of lateral telencephalic progenitor domains.

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Stenman, Jan M; Wang, Bei; Campbell, Kenneth

2003-11-19

We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.

A mixed finite element domain decomposition method for nearly elastic wave equations in the frequency domain

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Feng, Xiaobing [Univ. of Tennessee, Knoxville, TN (United States)

1996-12-31

A non-overlapping domain decomposition iterative method is proposed and analyzed for mixed finite element methods for a sequence of noncoercive elliptic systems with radiation boundary conditions. These differential systems describe the motion of a nearly elastic solid in the frequency domain. The convergence of the iterative procedure is demonstrated and the rate of convergence is derived for the case when the domain is decomposed into subdomains in which each subdomain consists of an individual element associated with the mixed finite elements. The hybridization of mixed finite element methods plays a important role in the construction of the discrete procedure.

Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

International Nuclear Information System (INIS)

Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

2011-01-01

Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

The finite element model for the propagation of light in scattering media: a direct method for domains with nonscattering regions.

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Arridge, S R; Dehghani, H; Schweiger, M; Okada, E

2000-01-01

We present a method for handling nonscattering regions within diffusing domains. The method develops from an iterative radiosity-diffusion approach using Green's functions that was computationally slow. Here we present an improved implementation using a finite element method (FEM) that is direct. The fundamental idea is to introduce extra equations into the standard diffusion FEM to represent nondiffusive light propagation across a nonscattering region. By appropriate mesh node ordering the computational time is not much greater than for diffusion alone. We compare results from this method with those from a discrete ordinate transport code, and with Monte Carlo calculations. The agreement is very good, and, in addition, our scheme allows us to easily model time-dependent and frequency domain problems.

Differential pleiotropy and HOX functional organization.

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Sivanantharajah, Lovesha; Percival-Smith, Anthony

2015-02-01

Key studies led to the idea that transcription factors are composed of defined modular protein motifs or domains, each with separable, unique function. During evolution, the recombination of these modular domains could give rise to transcription factors with new properties, as has been shown using recombinant molecules. This archetypic, modular view of transcription factor organization is based on the analyses of a few transcription factors such as GAL4, which may represent extreme exemplars rather than an archetype or the norm. Recent work with a set of Homeotic selector (HOX) proteins has revealed differential pleiotropy: the observation that highly-conserved HOX protein motifs and domains make small, additive, tissue specific contributions to HOX activity. Many of these differentially pleiotropic HOX motifs may represent plastic sequence elements called short linear motifs (SLiMs). The coupling of differential pleiotropy with SLiMs, suggests that protein sequence changes in HOX transcription factors may have had a greater impact on morphological diversity during evolution than previously believed. Furthermore, differential pleiotropy may be the genetic consequence of an ensemble nature of HOX transcription factor allostery, where HOX proteins exist as an ensemble of states with the capacity to integrate an extensive array of developmental information. Given a new structural model for HOX functional domain organization, the properties of the archetypic TF may require reassessment. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel heavy domain antibody library with functionally optimized complementarity determining regions.

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Ole Aalund Mandrup

Full Text Available Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.

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

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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.

Ordinary differential equations with applications in molecular biology.

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Ilea, M; Turnea, M; Rotariu, M

2012-01-01

Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

Expansion of protein domain repeats.

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Asa K Björklund

2006-08-01

Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

Generalization of the World Experience in Differentiation of Regions on Account of Innovation

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Blahun Ivan S.

2016-01-01

Full Text Available One of the main strategic objectives of our State is to promote innovation, which should include development and launch of new products at the national market, development and introduction of new technologies, creation and application of new knowledge. In accordance with the said above, the article has examined the experience of European Union Member States to improve the efficiency of innovation and differentiation of regions in terms of innovation, tools for evaluation of the innovation activity status has been determined in relation to the territories of the European Union at the level of regions.

Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice.

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Yang, H; Egan, J M; Rodgers, B D; Bernier, M; Montrose-Rafizadeh, C

1999-06-01

To identify novel seven transmembrane domain proteins from 3T3-L1 adipocytes, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with primers homologous to the N- and C-termini of pancreatic glucagon-like peptide-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differentiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein describes the isolation and characterization of a 1.6-kb cDNA clone that encodes a novel 298-amino acid protein that we termed TPRA40 (transmembrane domain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative transmembrane domains and shows little homology with the known GLP-1 receptor or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 mRNA levels were significantly increased by 2- to 3-fold in epididymal fat of 24-month-old mice vs. young controls as well as in db/db and ob/ob mice vs. nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expression in white adipose tissue is altered with aging and type 2 diabetes.

Primary (Poorly Differentiated Sclerosing Liposarcoma of Temporal Region. An Uncommon Tumor in a Rare Site: A Case Report

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Anuradha CK Rao

2015-02-01

Full Text Available Liposarcoma (LS in the head and neck region is a rare tumor. The sclerosing variant of LS is a subtype of well-differentiated LS characterized by areas of conventional LS admixed with hypocellular areas of stromal sclerosis that show atypical lipomatous cells. The (poorly differentiated sclerosing LS, on the other hand, is more cellular with atypical, pleomorphic and often bizarre giant tumor cells admixed with atypical lipoblasts. We report a case of poorly differentiated sclerosing LS of temporal region in a 49-year-old man. Radiologically, the tumor was dumbbell shaped with intra and extra cranial extension. In this case, we discuss the clinico-radiological and pathological findings of an unusual tumor in a rare location. [J Interdiscipl Histopathol 2015; 3(1.000: 33-35

Modelling biochemical reaction systems by stochastic differential equations with reflection.

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Niu, Yuanling; Burrage, Kevin; Chen, Luonan

2016-05-07

In this paper, we gave a new framework for modelling and simulating biochemical reaction systems by stochastic differential equations with reflection not in a heuristic way but in a mathematical way. The model is computationally efficient compared with the discrete-state Markov chain approach, and it ensures that both analytic and numerical solutions remain in a biologically plausible region. Specifically, our model mathematically ensures that species numbers lie in the domain D, which is a physical constraint for biochemical reactions, in contrast to the previous models. The domain D is actually obtained according to the structure of the corresponding chemical Langevin equations, i.e., the boundary is inherent in the biochemical reaction system. A variant of projection method was employed to solve the reflected stochastic differential equation model, and it includes three simple steps, i.e., Euler-Maruyama method was applied to the equations first, and then check whether or not the point lies within the domain D, and if not perform an orthogonal projection. It is found that the projection onto the closure D¯ is the solution to a convex quadratic programming problem. Thus, existing methods for the convex quadratic programming problem can be employed for the orthogonal projection map. Numerical tests on several important problems in biological systems confirmed the efficiency and accuracy of this approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long range epigenetic silencing is a trans-species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells.

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Forn, Marta; Muñoz, Mar; Tauriello, Daniele V F; Merlos-Suárez, Anna; Rodilla, Verónica; Bigas, Anna; Batlle, Eduard; Jordà, Mireia; Peinado, Miguel A

2013-12-01

DNA methylation and chromatin remodeling are frequently implicated in the silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. However, it is unknown whether there is a coordinated regulation of the genes embedded in these regions in normal cells and in early stages of tumor progression. To better characterize the molecular events associated with the regulation and remodeling of these regions we analyzed two regions undergoing LRES in human colon cancer in the mouse model. We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands. The genes embedded in these regions showed a dynamic and autonomous regulation during mouse intestinal cell differentiation, indicating that, in the framework considered here, the coordinated regulation in LRES is restricted to cancer. Unexpectedly, benign adenomas in Apc(Min/+) mice showed overexpression of most of the genes affected by LRES in cancer, which suggests that the repressive remodeling of the region is a late event. Chromatin immunoprecipitation analysis of the transcriptional insulator CTCF in mouse colon cancer cells revealed disrupted chromatin domain boundaries as compared with normal cells. Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. We conclude that genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All

Genome-wide genetic diversity and differentially selected regions among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep.

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Lifan Zhang

Full Text Available Sheep are among the major economically important livestock species worldwide because the animals produce milk, wool, skin, and meat. In the present study, the Illumina OvineSNP50 BeadChip was used to investigate genetic diversity and genome selection among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds from the United States. After quality-control filtering of SNPs (single nucleotide polymorphisms, we used 48,026 SNPs, including 46,850 SNPs on autosomes that were in Hardy-Weinberg equilibrium and 1,176 SNPs on chromosome × for analysis. Phylogenetic analysis based on all 46,850 SNPs clearly separated Suffolk from Rambouillet, Columbia, Polypay, and Targhee, which was not surprising as Rambouillet contributed to the synthesis of the later three breeds. Based on pair-wise estimates of F(ST, significant genetic differentiation appeared between Suffolk and Rambouillet (F(ST = 0.1621, while Rambouillet and Targhee had the closest relationship (F(ST = 0.0681. A scan of the genome revealed 45 and 41 differentially selected regions (DSRs between Suffolk and Rambouillet and among Rambouillet-related breed populations, respectively. Our data indicated that regions 13 and 24 between Suffolk and Rambouillet might be good candidates for evaluating breed differences. Furthermore, ovine genome v3.1 assembly was used as reference to link functionally known homologous genes to economically important traits covered by these differentially selected regions. In brief, our present study provides a comprehensive genome-wide view on within- and between-breed genetic differentiation, biodiversity, and evolution among Suffolk, Rambouillet, Columbia, Polypay, and Targhee sheep breeds. These results may provide new guidance for the synthesis of new breeds with different breeding objectives.

TAIL1: an isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region.

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Rossi, Valeria; Beffagna, Giorgia; Rampazzo, Alessandra; Bauce, Barbara; Danieli, Gian Antonio

2004-06-23

Isthmins represent a novel family of vertebrate secreted proteins containing one copy of the thrombospondin type 1 repeat (TSR), which in mammals is shared by several proteins with diverse biological functions, including cell adhesion, angiogenesis, and patterning of developing nervous system. We have determined the genomic organization of human TAIL1 (thrombospondin and AMOP containing isthmin-like 1), a novel isthmin-like gene encoding a protein that contains a TSR and a C-terminal AMOP domain (adhesion-associated domain in MUC4 and other proteins), characteristic of extracellular proteins involved in adhesion processes. TAIL1 gene encompasses more than 24.4 kb. Analysis of the DNA sequence surrounding the putative transcriptional start region revealed a TATA-less promoter located in a CpG island. Several consensus binding sites for the transcription factors Sp1 and MZF-1 were identified in this promoter region. In humans, TAIL1 gene is located on chromosome 14q24.3 within ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region; preliminary evidence suggests that it is expressed in several tissues, showing multiple alternative splicing.

Building Measures of Instructional Differentiation from Teacher Checklists

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Williams, Ryan; Swanlund, Andrew; Miller, Shazia; Konstantopoulos, Spyros; van der Ploeg, Arie

2012-01-01

Differentiated instruction is commonly believed to be critical to improving the quality and efficiency of teachers' instructional repertoires (Fischer & Rose, 2001; Tomlinson, 2004). Tomlinson (2000) describes differentiation in four domains: content, process, product, and learning environment. Content differentiation involves varying…

Labour Market Performance Differentials and Dynamics in EU-15 Countries and Regions

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Cristiano Perugini

2007-09-01

Full Text Available The aim of this paper is to contribute to empirical analysis of the differentials, dynamics and determinants of labour market performance in EU-15. One innovation of the paper reflects our decision not to use a single indicator of labour market performance, but to adopt three variables: employment rate, unemployment rate, and long-term unemployment rate. In addition to national data (1997-2006, the use of data at regional NUTS-2 level (1999-2005 is a key characteristic of this study. Empirical analyses are carried out by means of various comparative statistics and econometric approaches. In the latter, a large set of explicative variables is applied to examine the potential determinants of regional (unemployment levels and dynamics.

T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

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Usha Bughani

Full Text Available CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1 specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17 have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab'2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an

KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion during the Early Stage of Adipocyte Differentiation

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Makoto Nishizuka

2014-12-01

Full Text Available KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE, a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling.

Wavelength Selection Method Based on Differential Evolution for Precise Quantitative Analysis Using Terahertz Time-Domain Spectroscopy.

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Li, Zhi; Chen, Weidong; Lian, Feiyu; Ge, Hongyi; Guan, Aihong

2017-12-01

Quantitative analysis of component mixtures is an important application of terahertz time-domain spectroscopy (THz-TDS) and has attracted broad interest in recent research. Although the accuracy of quantitative analysis using THz-TDS is affected by a host of factors, wavelength selection from the sample's THz absorption spectrum is the most crucial component. The raw spectrum consists of signals from the sample and scattering and other random disturbances that can critically influence the quantitative accuracy. For precise quantitative analysis using THz-TDS, the signal from the sample needs to be retained while the scattering and other noise sources are eliminated. In this paper, a novel wavelength selection method based on differential evolution (DE) is investigated. By performing quantitative experiments on a series of binary amino acid mixtures using THz-TDS, we demonstrate the efficacy of the DE-based wavelength selection method, which yields an error rate below 5%.

Galectin-12 in Cellular Differentiation, Apoptosis and Polarization

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Lei Wan

2018-01-01

Full Text Available Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.

Study of domain structure in segmented polyether polyurethaneureas by PAT

International Nuclear Information System (INIS)

Yin Chuanyuan; Xu Weizheng; Gu Qingchao

1990-01-01

The domain structure of segmented polyether polyurethaneureas is investigated by means of positron annihilation technique, small angle X-ray scattering and differential scanning calorimetry. The experimental results show that the decrease of domain volume and free volume results from the increase of hard segment contents, and that the increase of domain volume and free volume results from the increase of molecular weight of soft segments

Contribution of glacier melt to sea-level rise since AD 1865: a regionally differentiated calculation

NARCIS (Netherlands)

Zuo, Z.; Oerlemans, J.

1997-01-01

The contribution of glacier melt, including the Greenland ice-sheet, to sea-level change since AD 1865 is estimated on the basis of modelled sensitivity of glacier mass balance to climate change and historical temperature data. Calculations are done in a regionally differentiated manner to overcome

Characterization of Bovine 5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells

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Hye-Jeong Jang

2015-12-01

Full Text Available Embryonic stem cells (ESCs have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181 bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181 promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells.

Functional analysis of SH3 domain containing ring finger 2 during the myogenic differentiation of quail myoblast cells

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Si Won Kim

2017-08-01

Full Text Available Objective Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2 gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7 cells during muscle differentiation. Results Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process

Directory of Open Access Journals (Sweden)

El Sawaf Gamal

2009-07-01

Full Text Available Abstract Background The E1 protein of Hepatitis C Virus (HCV can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP, and a C-terminal domain (CT comprising two segments, a pre-anchor and a trans-membrane (TM region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1. Results Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis. The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA. This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT

Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

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Nisha Puthiyedth

Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

Ordinary differential equations introduction to the theory of ordinary differential equations in the real domain

CERN Document Server

Kurzweil, J

1986-01-01

The author, Professor Kurzweil, is one of the world's top experts in the area of ordinary differential equations - a fact fully reflected in this book. Unlike many classical texts which concentrate primarily on methods of integration of differential equations, this book pursues a modern approach: the topic is discussed in full generality which, at the same time, permits us to gain a deep insight into the theory and to develop a fruitful intuition. The basic framework of the theory is expanded by considering further important topics like stability, dependence of a solution on a parameter, Car

Differentiation regional climate impact indicators at 1.5°C and 2°C warming above pre-industrial levels

Science.gov (United States)

Schleussner, C. F.

2016-12-01

Robust appraisals of climate impacts at different levels of global-mean temperature increase are vital to guide assessments of dangerous anthropogenic interference with the climate system. By establishing 1.5°C as the long term temperature limit for global average temperature increase and inviting a special report of the IPCC on the impacts of 1.5°C, the Paris Agreement has put such assessments high on the post-Paris science agenda. Here I will present recent findings of climate impacts at 1.5°C, including extreme weather events, water availability, agricultural yields, sea-level rise and risk of coral reef loss. In particular, I will present findings from a recent study that attempts to differentiate between such impacts at warming levels of 1.5°¸C and 2°C above pre-industrial (Schleussner et al., 2016). By analyzing changes in indicators for 26 world regions as applicable, the study found regional dependent differences between a 1.5°C and 2°C warming. Regional hot-spots of change emerge with tropical regions bearing the brunt of the impacts of an additional 0.5°C warming. These findings highlight the importance of regional differentiation to assess both future climate risks and different vulnerabilities to incremental increases in global-mean temperature. Building on that analysis, I will discuss limitations of existing approaches to differentiate between warming levels and outline opportunities for future work on refining our understanding of the difference between impacts at 1.5°C and 2°C warming. ReferencesSchleussner, C.-F. et al. Differential climate impacts for policy relevant limits to global warming: the case of 1.5°C and 2°C. Earth Syst. Dyn. 7, 327-351 (2016).

Noise Analysis of Single-Ended Input Differential Amplifier using Stochastic Differential Equation

OpenAIRE

Tarun Kumar Rawat; Abhirup Lahiri; Ashish Gupta

2008-01-01

In this paper, we analyze the effect of noise in a single- ended input differential amplifier working at high frequencies. Both extrinsic and intrinsic noise are analyzed using time domain method employing techniques from stochastic calculus. Stochastic differential equations are used to obtain autocorrelation functions of the output noise voltage and other solution statistics like mean and variance. The analysis leads to important design implications and suggests changes in the device parame...

Differential Roles of the Glycogen-Binding Domains of β Subunits in Regulation of the Snf1 Kinase Complex▿

Science.gov (United States)

Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R.; Elbing, Karin; Schmidt, Martin C.

2010-01-01

Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic α subunit and regulatory β and γ subunits. In this study, the role of the β subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (α), Snf4 (γ), and one of three alternative β subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three β subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the β subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation. PMID:19897735

Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

Science.gov (United States)

Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C

2010-01-01

Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

U.S. EPA Environmental Quality Index - Air Domain

Science.gov (United States)

This is an invited presentation by Region 5, Air Office, who asked me to provide an overview of the Air Domain and health results associated with the Air Domain of the Environmental Quality Index. Region 5 is hosting an Air Toxics meeting for its member states (Ohio, Michigan, I...

C-terminal region of MAP7 domain containing protein 3 (MAP7D3 promotes microtubule polymerization by binding at the C-terminal tail of tubulin.

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Saroj Yadav

Full Text Available MAP7 domain containing protein 3 (MAP7D3, a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7 family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD with the C-terminal tail (CT of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

Science.gov (United States)

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

genotype. AET differentially affects the ACE C- and N-domain activities, and the N-domain activity is dependent on ACE polymorphism.

Methyl CpG–binding proteins induce large-scale chromatin reorganization during terminal differentiation

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Brero, Alessandro; Easwaran, Hariharan P.; Nowak, Danny; Grunewald, Ingrid; Cremer, Thomas; Leonhardt, Heinrich; Cardoso, M. Cristina

2005-01-01

Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG–binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG–binding domain (MBD) only. Similar to MeCP2, another methyl CpG–binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation. PMID:15939760

Perceptual and categorical decision making: goal-relevant representation of two domains at different levels of abstraction.

Science.gov (United States)

Shankar, Swetha; Kayser, Andrew S

2017-06-01

To date it has been unclear whether perceptual decision making and rule-based categorization reflect activation of similar cognitive processes and brain regions. On one hand, both map potentially ambiguous stimuli to a smaller set of motor responses. On the other hand, decisions about perceptual salience typically concern concrete sensory representations derived from a noisy stimulus, while categorization is typically conceptualized as an abstract decision about membership in a potentially arbitrary set. Previous work has primarily examined these types of decisions in isolation. Here we independently varied salience in both the perceptual and categorical domains in a random dot-motion framework by manipulating dot-motion coherence and motion direction relative to a category boundary, respectively. Behavioral and modeling results suggest that categorical (more abstract) information, which is more relevant to subjects' decisions, is weighted more strongly than perceptual (more concrete) information, although they also have significant interactive effects on choice. Within the brain, BOLD activity within frontal regions strongly differentiated categorical salience and weakly differentiated perceptual salience; however, the interaction between these two factors activated similar frontoparietal brain networks. Notably, explicitly evaluating feature interactions revealed a frontal-parietal dissociation: parietal activity varied strongly with both features, but frontal activity varied with the combined strength of the information that defined the motor response. Together, these data demonstrate that frontal regions are driven by decision-relevant features and argue that perceptual decisions and rule-based categorization reflect similar cognitive processes and activate similar brain networks to the extent that they define decision-relevant stimulus-response mappings. NEW & NOTEWORTHY Here we study the behavioral and neural dynamics of perceptual categorization when

Socio-cognitive influences on the domain-specificity of prosocial behavior in the second year.

Science.gov (United States)

Kärtner, Joscha; Schuhmacher, Nils; Collard, Jenny

2014-11-01

The main aim of this study was to explain the domain-specificity of early prosocial behavior in different domains (i.e., helping, comforting, and cooperation) by simultaneously assessing specific socio-cognitive factors (i.e., self-other-differentiation and joint attentional skills) that were hypothesized to be differentially related to the three domains of prosocial behavior. Based on a longitudinal study design, observational and parental report data were collected when toddlers (N=42) from German urban middle-class families were 15 and 18 months of age. At 15 months, regression analyses indicated differential relationships between socio-cognitive development and prosocial behavior (i.e., joint attentional skills were positively related with helping and, as hypothesized, both joint attentional skills and self-other differentiation were positively related with cooperation). Furthermore, self-other differentiation at 15 months predicted increases in coordination between 15 and 18 months. Finally, between 15 and 18 months, parental reports of socio-cognitive measures increased significantly while behavioral measures of both socio-cognitive concepts and prosocial behavior were stable across time. In sum, these results support the theoretical assumption of domain-specific socio-cognitive influences that constitute differential development of prosocial behavior. Implications of the results for theory and future studies are discussed from different perspectives with a focus on an interference interpretation calling for the integration of socialization approaches to the study of prosocial development. Copyright © 2014 Elsevier Inc. All rights reserved.

Image-domain full waveform inversion

KAUST Repository

Zhang, Sanzong

2013-08-20

The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

Image-domain full waveform inversion

KAUST Repository

Zhang, Sanzong; Schuster, Gerard T.

2013-01-01

The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

Transforming p21 ras protein: flexibility in the major variable region linking the catalytic and membrane-anchoring domains

DEFF Research Database (Denmark)

Willumsen, B M; Papageorge, A G; Hubbert, N

1985-01-01

or increasing it to 50 amino acids has relatively little effect on the capacity of the gene to induce morphological transformation of NIH 3T3 cells. Assays of GTP binding, GTPase and autophosphorylating activities of such mutant v-rasH-encoded proteins synthesized in bacteria indicated that the sequences...... that is required for post-translational processing, membrane localization and transforming activity of the proteins. We have now used the viral oncogene (v-rasH) of Harvey sarcoma virus to study the major variable region by deleting or duplicating parts of the gene. Reducing this region to five amino acids...... that encode these biochemical activities are located upstream from the major variable region. In the context of transformation, we propose that the region of sequence heterogeneity serves principally to connect the N-terminal catalytic domain with amino acids at the C terminus that are required to anchor...

Multimedia applications in differential services

International Nuclear Information System (INIS)

Mahfooz, S.; Merabti, M.; Pereira, R.

2003-01-01

In this paper we present a mechanism to provide Quality of Service (QoS) guarantees to different multimedia applications that share link bandwidth in IP-based differential services domain. In this mechanism weights are associated with each and to individual users according to their priorities. In order to evaluate the performance of our scheme we conducted simulations. The test data used portray different multimedia applications i.e. MPEG-2, IP telephony. The simulation results obtained show the effectiveness of our scheme for multimedia applications by allocating link share to each multimedia application and minimising end-to-end transmission delay 9Y bringing them in line with the recommended standard acceptable transmission delay for multimedia applications. This paper also presents extension to our proposed Relative Bandwidth Sharing (RES) scheme for differential services. We have identified and highlighted the role of border routers and core routers in differential services domain. Exploring features of Internet Protocol IPv6 in our architecture. (author)

Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

Science.gov (United States)

Paliwal, Anupam; Temkin, Alexis M; Kerkel, Kristi; Yale, Alexander; Yotova, Iveta; Drost, Natalia; Lax, Simon; Nhan-Chang, Chia-Ling; Powell, Charles; Borczuk, Alain; Aviv, Abraham; Wapner, Ronald; Chen, Xiaowei; Nagy, Peter L; Schork, Nicholas; Do, Catherine; Torkamani, Ali; Tycko, Benjamin

2013-08-01

Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.

Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

Directory of Open Access Journals (Sweden)

Anupam Paliwal

2013-08-01

Full Text Available Allele-specific DNA methylation (ASM is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons, one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs, each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS peaks near CTCF binding sites with ASM.

Oxidative Unfolding of the Rubredoxin Domain and the Natively Disordered N-terminal Region Regulate the Catalytic Activity of Mycobacterium tuberculosis Protein Kinase G.

Science.gov (United States)

Wittwer, Matthias; Luo, Qi; Kaila, Ville R I; Dames, Sonja A

2016-12-30

Mycobacterium tuberculosis escapes killing in human macrophages by secreting protein kinase G (PknG). PknG intercepts host signaling to prevent fusion of the phagosome engulfing the mycobacteria with the lysosome and, thus, their degradation. The N-terminal NORS (no regulatory secondary structure) region of PknG (approximately residues 1-75) has been shown to play a role in PknG regulation by (auto)phosphorylation, whereas the following rubredoxin-like metal-binding motif (RD, residues ∼74-147) has been shown to interact tightly with the subsequent catalytic domain (approximately residues 148-420) to mediate its redox regulation. Deletions or mutations in NORS or the redox-sensitive RD significantly decrease PknG survival function. Based on combined NMR spectroscopy, in vitro kinase assay, and molecular dynamics simulation data, we provide novel insights into the regulatory roles of the N-terminal regions. The NORS region is indeed natively disordered and rather dynamic. Consistent with most earlier data, autophosphorylation occurs in our assays only when the NORS region is present and, thus, in the NORS region. Phosphorylation of it results only in local conformational changes and does not induce interactions with the subsequent RD. Although the reduced, metal-bound RD makes tight interactions with the following catalytic domain in the published crystal structures, it can also fold in its absence. Our data further suggest that oxidation-induced unfolding of the RD regulates substrate access to the catalytic domain and, thereby, PknG function under different redox conditions, e.g. when exposed to increased levels of reactive oxidative species in host macrophages. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings

Science.gov (United States)

Epel, B. L.; Bandurski, R. S.

1990-01-01

Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.

Differential Regulation of Disheveled in a Novel Vegetal Cortical Domain in Sea Urchin Eggs and Embryos: Implications for the Localized Activation of Canonical Wnt Signaling

Science.gov (United States)

Peng, ChiehFu Jeff; Wikramanayake, Athula H.

2013-01-01

Pattern formation along the animal-vegetal (AV) axis in sea urchin embryos is initiated when canonical Wnt (cWnt) signaling is activated in vegetal blastomeres. The mechanisms that restrict cWnt signaling to vegetal blastomeres are not well understood, but there is increasing evidence that the egg’s vegetal cortex plays a critical role in this process by mediating localized “activation” of Disheveled (Dsh). To investigate how Dsh activity is regulated along the AV axis, sea urchin-specific Dsh antibodies were used to examine expression, subcellular localization, and post-translational modification of Dsh during development. Dsh is broadly expressed during early sea urchin development, but immunolocalization studies revealed that this protein is enriched in a punctate pattern in a novel vegetal cortical domain (VCD) in the egg. Vegetal blastomeres inherit this VCD during embryogenesis, and at the 60-cell stage Dsh puncta are seen in all cells that display nuclear β-catenin. Analysis of Dsh post-translational modification using two-dimensional Western blot analysis revealed that compared to Dsh pools in the bulk cytoplasm, this protein is differentially modified in the VCD and in the 16-cell stage micromeres that partially inherit this domain. Dsh localization to the VCD is not directly affected by disruption of microfilaments and microtubules, but unexpectedly, microfilament disruption led to degradation of all the Dsh pools in unfertilized eggs over a period of incubation suggesting that microfilament integrity is required for maintaining Dsh stability. These results demonstrate that a pool of differentially modified Dsh in the VCD is selectively inherited by the vegetal blastomeres that activate cWnt signaling in early embryos, and suggests that this domain functions as a scaffold for localized Dsh activation. Localized cWnt activation regulates AV axis patterning in many metazoan embryos. Hence, it is possible that the VCD is an evolutionarily conserved

Domain observations of Fe and Co based amorphous wires

International Nuclear Information System (INIS)

Takajo, M.; Yamasaki, J.

1993-01-01

Domain observations were made on Fe and Co based amorphous magnetic wires that exhibit a large Barkhausen discontinuity during flux reversal. Domain patterns observed on the wire surface were compared with those found on a polished section through the center of the wire. It was confirmed that the Fe based wire consists of a shell and core region as previously proposed, however, there is a third region between them. This fairly thick transition region made up of domains at an angle of about 45 degree to the wire axis clearly lacking the closure domains of the previous model. The Co based wire does not have a clear core and shell domain structure. The center of the wire had a classic domain structure expected of uniaxial anisotropy with the easy axis normal to the wire axis. When a model for the residual stress quenched-in during cooling of large Fe bars is applied to the wire, the expected anisotropy is consistent with the domain patterns in the Fe based wire, however, shape anisotropy still plays a dominant role in defining the wire core in the Co based wire

Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig) proteins.

Science.gov (United States)

Raman, Rajeev; Rajanikanth, V; Palaniappan, Raghavan U M; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P; Sharma, Yogendra; Chang, Yung-Fu

2010-12-29

Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th) (Lig A9) and 10(th) repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

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Jitendra Maharana

Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

Non-dense domain operator matrices and Cauchy problems

International Nuclear Information System (INIS)

Lalaoui Rhali, S.

2002-12-01

In this work, we study Cauchy problems with non-dense domain operator matrices. By assuming that the entries of an unbounded operator matrix are Hille-Yosida operators, we give a necessary and sufficient condition ensuring that the part of this operator matrix generates a semigroup in the closure of its domain. This allows us to prove the well-posedness of the corresponding Cauchy problem. Our results are applied to delay and neutral differential equations. (author)

A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

Science.gov (United States)

Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-02-01

Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

Remote-sensing image encryption in hybrid domains

Science.gov (United States)

Zhang, Xiaoqiang; Zhu, Guiliang; Ma, Shilong

2012-04-01

Remote-sensing technology plays an important role in military and industrial fields. Remote-sensing image is the main means of acquiring information from satellites, which always contain some confidential information. To securely transmit and store remote-sensing images, we propose a new image encryption algorithm in hybrid domains. This algorithm makes full use of the advantages of image encryption in both spatial domain and transform domain. First, the low-pass subband coefficients of image DWT (discrete wavelet transform) decomposition are sorted by a PWLCM system in transform domain. Second, the image after IDWT (inverse discrete wavelet transform) reconstruction is diffused with 2D (two-dimensional) Logistic map and XOR operation in spatial domain. The experiment results and algorithm analyses show that the new algorithm possesses a large key space and can resist brute-force, statistical and differential attacks. Meanwhile, the proposed algorithm has the desirable encryption efficiency to satisfy requirements in practice.

Effects of sub-domain structure on initial magnetization curve and domain size distribution of stacked media

International Nuclear Information System (INIS)

Sato, S.; Kumagai, S.; Sugita, R.

2015-01-01

In this paper, in order to confirm the sub-domain structure in stacked media demagnetized with in-plane field, initial magnetization curves and magnetic domain size distribution were investigated. Both experimental and simulation results showed that an initial magnetization curve for the medium demagnetized with in-plane field (MDI) initially rose faster than that for the medium demagnetized with perpendicular field (MDP). It is inferred that this is because the MDI has a larger number of domain walls than the MDP due to the existence of the sub-domains, resulting in an increase in the probability of domain wall motion. Dispersion of domain size for the MDI was larger than that for the MDP. This is because sub-domains are formed not only inside the domain but also at the domain boundary region, and they change the position of the domain boundary to affect the domain size. - Highlights: • An initial magnetization curve for MDI initially rose faster than that for MDP. • Dispersion of domain size for the MDI was larger than that for the MDP. • Experimental and simulation results can be explained by existence of sub-domains

Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.

Science.gov (United States)

Travassos, Mark A; Coulibaly, Drissa; Bailey, Jason A; Niangaly, Amadou; Adams, Matthew; Nyunt, Myaing M; Ouattara, Amed; Lyke, Kirsten E; Laurens, Matthew B; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Berry, Andrea A; Takala-Harrison, Shannon; Kone, Abdoulaye K; Kouriba, Bourema; Rowe, J Alexandra; Doumbo, Ogobara K; Thera, Mahamadou A; Laufer, Miriam K; Felgner, Philip L; Plowe, Christopher V

2015-06-01

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria. © The American Society of Tropical Medicine and Hygiene.

The Differential Effects of Task Complexity on Domain-Specific and Peer Assessment Skills

Science.gov (United States)

van Zundert, Marjo J.; Sluijsmans, Dominique M. A.; Konings, Karen D.; van Merrienboer, Jeroen J. G.

2012-01-01

In this study the relationship between domain-specific skills and peer assessment skills as a function of task complexity is investigated. We hypothesised that peer assessment skills were superposed on domain-specific skills and will therefore suffer more when higher cognitive load is induced by increased task complexity. In a mixed factorial…

The regional differentiation of the demographic movements in the Republic of Macedonia

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Madjevikj Mirjanka

2016-09-01

Full Text Available The Republic of Macedonia covers an area of 25,713 km² and according to data from the census conducted in 2002, it has a population of 2,022,547 inhabitants. In the past, the Republic of Macedonia was characterized by some significant demographic changes, including a decline in the average annual rate of population increase. The enhanced immigration movements and sudden decline in the rates of natural population increase have led to changes in distribution of the population and to a spatial differentiation in the population. The long period of transition in the country has been reflected in the spatial development of the country and its demographic processes and to relocation of the population. The different natural-geographical characteristics, unequal regional development potentials, unequal economic development, and demographic characteristics have led to changes in the demographic situation of certain regions. The regions that continually lose part of its population clearly differ from these regions that are characterized by an increased population which is leading to a greater concentration of people in certain location. Further decades with a declining birth rate, followed by a change in the values of population increase, together with migration movements, particularly from the rural and less developed economic regions, has resulted in a decline in the population. The different zones of depopulation and concentration in a simple way express the complex relationships in the population composition.

Allosteric Regulation in the Ligand Binding Domain of Retinoic Acid Receptorγ.

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Yassmine Chebaro

Full Text Available Retinoic acid (RA plays key roles in cell differentiation and growth arrest through nuclear retinoic acid receptors (RARs, which are ligand-dependent transcription factors. While the main trigger of RAR activation is the binding of RA, phosphorylation of the receptors has also emerged as an important regulatory signal. Phosphorylation of the RARγ N-terminal domain (NTD is known to play a functional role in neuronal differentiation. In this work, we investigated the phosphorylation of RARγ ligand binding domain (LBD, and present evidence that the phosphorylation status of the LBD affects the phosphorylation of the NTD region. We solved the X-ray structure of a phospho-mimetic mutant of the LBD (RARγ S371E, which we used in molecular dynamics simulations to characterize the consequences of the S371E mutation on the RARγ structural dynamics. Combined with simulations of the wild-type LBD, we show that the conformational equilibria of LBD salt bridges (notably R387-D340 are affected by the S371E mutation, which likely affects the recruitment of the kinase complex that phosphorylates the NTD. The molecular dynamics simulations also showed that a conservative mutation in this salt bridge (R387K affects the dynamics of the LBD without inducing large conformational changes. Finally, cellular assays showed that the phosphorylation of the NTD of RARγ is differentially regulated by retinoic acid in RARγWT and in the S371N, S371E and R387K mutants. This multidisciplinary work highlights an allosteric coupling between phosphorylations of the LBD and the NTD of RARγ and supports the importance of structural dynamics involving electrostatic interactions in the regulation of RARs activity.

Late replication domains are evolutionary conserved in the Drosophila genome.

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Andreyenkova, Natalya G; Kolesnikova, Tatyana D; Makunin, Igor V; Pokholkova, Galina V; Boldyreva, Lidiya V; Zykova, Tatyana Yu; Zhimulev, Igor F; Belyaeva, Elena S

2013-01-01

Drosophila chromosomes are organized into distinct domains differing in their predominant chromatin composition, replication timing and evolutionary conservation. We show on a genome-wide level that genes whose order has remained unaltered across 9 Drosophila species display late replication timing and frequently map to the regions of repressive chromatin. This observation is consistent with the existence of extensive domains of repressive chromatin that replicate extremely late and have conserved gene order in the Drosophila genome. We suggest that such repressive chromatin domains correspond to a handful of regions that complete replication at the very end of S phase. We further demonstrate that the order of genes in these regions is rarely altered in evolution. Substantial proportion of such regions significantly coincide with large synteny blocks. This indicates that there are evolutionary mechanisms maintaining the integrity of these late-replicating chromatin domains. The synteny blocks corresponding to the extremely late-replicating regions in the D. melanogaster genome consistently display two-fold lower gene density across different Drosophila species.

Understanding and simulating the link between African easterly waves and Atlantic tropical cyclones using a regional climate model: the role of domain size and lateral boundary conditions

Energy Technology Data Exchange (ETDEWEB)

Caron, Louis-Philippe [MISU, Stockholm University, Stockholm (Sweden); Universite du Quebec a Montreal, CRCMD Network, Montreal, QC (Canada); Jones, Colin G. [Swedish Meterological and Hydrological Institute, Rossby Center, Norrkoeping (Sweden)

2012-07-15

Using a suite of lateral boundary conditions, we investigate the impact of domain size and boundary conditions on the Atlantic tropical cyclone and african easterly Wave activity simulated by a regional climate model. Irrespective of boundary conditions, simulations closest to observed climatology are obtained using a domain covering both the entire tropical Atlantic and northern African region. There is a clear degradation when the high-resolution model domain is diminished to cover only part of the African continent or only the tropical Atlantic. This is found to be the result of biases in the boundary data, which for the smaller domains, have a large impact on TC activity. In this series of simulations, the large-scale Atlantic atmospheric environment appears to be the primary control on simulated TC activity. Weaker wave activity is usually accompanied by a shift in cyclogenesis location, from the MDR to the subtropics. All ERA40-driven integrations manage to capture the observed interannual variability and to reproduce most of the upward trend in tropical cyclone activity observed during that period. When driven by low-resolution global climate model (GCM) integrations, the regional climate model captures interannual variability (albeit with lower correlation coefficients) only if tropical cyclones form in sufficient numbers in the main development region. However, all GCM-driven integrations fail to capture the upward trend in Atlantic tropical cyclone activity. In most integrations, variations in Atlantic tropical cyclone activity appear uncorrelated with variations in African easterly wave activity. (orig.)

Partial differential equations for scientists and engineers

CERN Document Server

Farlow, Stanley J

1993-01-01

Most physical phenomena, whether in the domain of fluid dynamics, electricity, magnetism, mechanics, optics, or heat flow, can be described in general by partial differential equations. Indeed, such equations are crucial to mathematical physics. Although simplifications can be made that reduce these equations to ordinary differential equations, nevertheless the complete description of physical systems resides in the general area of partial differential equations.This highly useful text shows the reader how to formulate a partial differential equation from the physical problem (constructing th

Terahertz time-domain spectroscopy response of amines and amino acids intercalated smectites in far-infrared region

Energy Technology Data Exchange (ETDEWEB)

Janek, M., E-mail: marian.janek@fns.uniba.sk [Comenius University, Faculty of Natural Sciences, Department of Physical and Theoretical Chemistry, Mlynská dolina CH1, SK-84215 Bratislava (Slovakia); Zich, D. [Comenius University, Faculty of Natural Sciences, Department of Physical and Theoretical Chemistry, Mlynská dolina CH1, SK-84215 Bratislava (Slovakia); Naftaly, M., E-mail: mira.naftaly@npl.co.uk [National Physical Laboratory, Hampton Rd, Teddington, Middlesex TW11 0LW (United Kingdom)

2014-06-01

Layered clay minerals from the smectite group with different chemical composition and resulting layer charge (e.g. pyrophyllite, illite, hectorite and montmorillonite) were characterised for their dielectric properties in the far-infrared region using terahertz-time domain spectroscopy (THz-TDS). Samples with distinct cation exchange capacity such as hectorite and montmorillonite were modified using cation exchange reaction with alkylamines or amino acids. The presence of these species in 2D gallery was proved by X-ray diffraction and Fourier transform infrared spectroscopy. The frequency-dependent refractive index of these minerals was determined in the experimentally accessible range of 0.1–3.0 THz (3–100 cm{sup −1}) using THz-TDS. Pristine samples revealed their refractive indices to be 1.82–2.15 at about 1 THz while the modified montmorillonite samples had their refractive indices changed by organic molecules used for their modification to 1.70–2.35 for amines and 1.97–2.36 for amino acids. The presence of organic substances in 2D gallery of clays was detectable despite the relatively high absorption of smectites with magnitude of 100 cm{sup −1}. - Graphical abstract: Display Omitted - Highlights: • “Guest” molecules in “host” layered material were investigated. • Amines and amino-acids were selected as guest molecules. • Natural and synthetic host with smectite phyllosilicate structure were used. • Dielectric properties were investigated by terahertz time domain spectroscopy. • Resonance absorption peaks of guest were detected in far infrared region.

Autonomic Differentiation Map: A Novel Statistical Tool for Interpretation of Heart Rate Variability

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Daniela Lucini

2018-04-01

Full Text Available In spite of the large body of evidence suggesting Heart Rate Variability (HRV alone or combined with blood pressure variability (providing an estimate of baroreflex gain as a useful technique to assess the autonomic regulation of the cardiovascular system, there is still an ongoing debate about methodology, interpretation, and clinical applications. In the present investigation, we hypothesize that non-parametric and multivariate exploratory statistical manipulation of HRV data could provide a novel informational tool useful to differentiate normal controls from clinical groups, such as athletes, or subjects affected by obesity, hypertension, or stress. With a data-driven protocol in 1,352 ambulant subjects, we compute HRV and baroreflex indices from short-term data series as proxies of autonomic (ANS regulation. We apply a three-step statistical procedure, by first removing age and gender effects. Subsequently, by factor analysis, we extract four ANS latent domains that detain the large majority of information (86.94%, subdivided in oscillatory (40.84%, amplitude (18.04%, pressure (16.48%, and pulse domains (11.58%. Finally, we test the overall capacity to differentiate clinical groups vs. control. To give more practical value and improve readability, statistical results concerning individual discriminant ANS proxies and ANS differentiation profiles are displayed through peculiar graphical tools, i.e., significance diagram and ANS differentiation map, respectively. This approach, which simultaneously uses all available information about the system, shows what domains make up the difference in ANS discrimination. e.g., athletes differ from controls in all domains, but with a graded strength: maximal in the (normalized oscillatory and in the pulse domains, slightly less in the pressure domain and minimal in the amplitude domain. The application of multiple (non-parametric and exploratory statistical and graphical tools to ANS proxies defines

Differential erosion and the formation of layered yardangs in the Loulan region (Lop Nur), eastern Tarim Basin

Science.gov (United States)

Lin, Yongchong; Xu, Lishuai; Mu, Guijin

2018-02-01

Yardangs are a type of wind-sculpted landform which generally form in hyper-arid regions. Several factors affect the development of yardangs, and the relative importance of these factors likely varies with differences in regional environmental factors. In the Loulan region of Lop Nur, wind dynamics are the principal factor affecting the development of yardangs. However, layered yardangs, which have undergone a unique form of differential erosion, are common in the region. These erosional landforms differ from typical yardangs which are eroded solely by abrasion and deflation. We conducted field and laboratory investigations of layered yardangs to determine their origin. The results indicate that there are two types of strata comprising the yardangs: uncompacted sand-silt layers, with a lower carbonate content; and compacted clay-silt layers, with a higher carbonate content. Both types of strata are horizontal and occur in alternating layers. This type of structure enables the wind to more easily erode the less resistant sand-silt layers at different heights, leaving the more resistant compacted clay-silt layers relatively intact. Eventually the undercut remnant clay-silt layers collapse once the weight of the suspended strata exceeds their elastic resistance (more than 90% of the fallen blocks have length/thickness ratios between 1.2 and 2.5). Therefore, in addition to wind dynamics, the lithology and structure of the strata are important factors affecting the development of the layered yardangs. This type of differential erosion accelerates the development of the yardangs in the Loulan region.

ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

International Nuclear Information System (INIS)

Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

2007-01-01

The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

Domain decomposition methods and deflated Krylov subspace iterations

NARCIS (Netherlands)

Nabben, R.; Vuik, C.

2006-01-01

The balancing Neumann-Neumann (BNN) and the additive coarse grid correction (BPS) preconditioner are fast and successful preconditioners within domain decomposition methods for solving partial differential equations. For certain elliptic problems these preconditioners lead to condition numbers which

Domain decomposition methods for solving an image problem

Energy Technology Data Exchange (ETDEWEB)

Tsui, W.K.; Tong, C.S. [Hong Kong Baptist College (Hong Kong)

1994-12-31

The domain decomposition method is a technique to break up a problem so that ensuing sub-problems can be solved on a parallel computer. In order to improve the convergence rate of the capacitance systems, pre-conditioned conjugate gradient methods are commonly used. In the last decade, most of the efficient preconditioners are based on elliptic partial differential equations which are particularly useful for solving elliptic partial differential equations. In this paper, the authors apply the so called covering preconditioner, which is based on the information of the operator under investigation. Therefore, it is good for various kinds of applications, specifically, they shall apply the preconditioned domain decomposition method for solving an image restoration problem. The image restoration problem is to extract an original image which has been degraded by a known convolution process and additive Gaussian noise.

Time domain calculation of connector loads of a very large floating structure

Science.gov (United States)

Gu, Jiayang; Wu, Jie; Qi, Enrong; Guan, Yifeng; Yuan, Yubo

2015-06-01

Loads generated after an air crash, ship collision, and other accidents may destroy very large floating structures (VLFSs) and create additional connector loads. In this study, the combined effects of ship collision and wave loads are considered to establish motion differential equations for a multi-body VLFS. A time domain calculation method is proposed to calculate the connector load of the VLFS in waves. The Longuet-Higgins model is employed to simulate the stochastic wave load. Fluid force and hydrodynamic coefficient are obtained with DNV Sesam software. The motion differential equation is calculated by applying the time domain method when the frequency domain hydrodynamic coefficient is converted into the memory function of the motion differential equation of the time domain. As a result of the combined action of wave and impact loads, high-frequency oscillation is observed in the time history curve of the connector load. At wave directions of 0° and 75°, the regularities of the time history curves of the connector loads in different directions are similar and the connector loads of C1 and C2 in the X direction are the largest. The oscillation load is observed in the connector in the Y direction at a wave direction of 75° and not at 0°. This paper presents a time domain calculation method of connector load to provide a certain reference function for the future development of Chinese VLFS

Functions of Heterogeneous Nuclear Ribonucleoproteins in Stem Cell Potency and Differentiation

Directory of Open Access Journals (Sweden)

Qishan Chen

2013-01-01

Full Text Available Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3′UTR or 5′UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.

Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig proteins.

Directory of Open Access Journals (Sweden)

Rajeev Raman

Full Text Available BACKGROUND: Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. PRINCIPAL FINDINGS: We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th (Lig A9 and 10(th repeats (Lig A10; and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon. All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm, probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. CONCLUSIONS: We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix.

Science.gov (United States)

Rothrauff, Benjamin B; Shimomura, Kazunori; Gottardi, Riccardo; Alexander, Peter G; Tuan, Rocky S

2017-02-01

Extracellular matrix (ECM) derived from decellularized tissues has been found to promote tissue neogenesis, most likely mediated by specific biochemical and physical signaling motifs that promote tissue-specific differentiation of progenitor cells. Decellularized ECM has been suggested to be efficacious for the repair of tissue injuries. However, decellularized meniscus contains a dense collagenous structure, which impedes cell seeding and infiltration and is not readily applicable for meniscus repair. In addition, the meniscus consists of two distinct anatomical regions that differ in vascularity and cellular phenotype. The purpose of this study was to explore the region-specific bioactivity of solubilized ECM derived from the inner and outer meniscal regions as determined in 2D and 3D cultures of adult mesenchymal stem cells (MSCs). When added as a medium supplement to 2D cultures of MSCs, urea-extracted fractions of the inner (imECM) and outer meniscal ECM (omECM) enhanced cell proliferation while imECM most strongly upregulated fibrochondrogenic differentiation on the basis of gene expression profiles. When added to 3D cultures of MSCs seeded in photocrosslinked methacrylated gelatin (GelMA) hydrogels, both ECM fractions upregulated chondrogenic differentiation as determined by gene expression and protein analyses, as well as elevated sulfated glycosaminoglycan sGAG content, compared to ECM-free controls. The chondrogenic effect at day 21 was most pronounced with imECM supplementation, but equivalent between ECM groups by day 42. Despite increased cartilage matrix, imECM and omECM constructs possessed compressive moduli similar to controls. In conclusion, soluble meniscal ECM may be considered for use as a tissue-specific reagent to enhance chondrogenesis for MSC-based 3D cartilage tissue engineering. The inner region of the knee meniscus is frequently injured and possesses a poor intrinsic healing capacity. Solubilized extracellular matrix (ECM) derived from

Collage-type approach to inverse problems for elliptic PDEs on perforated domains

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Herb E. Kunze

2015-02-01

Full Text Available We present a collage-based method for solving inverse problems for elliptic partial differential equations on a perforated domain. The main results of this paper establish a link between the solution of an inverse problem on a perforated domain and the solution of the same model on a domain with no holes. The numerical examples at the end of the paper show the goodness of this approach.

Annual Precipitation Fluctuation and Spatial Differentiation Characteristics of the Horqin Region

Directory of Open Access Journals (Sweden)

Liangxu Liu

2017-01-01

Full Text Available Precipitation is the main water source for vegetation survival in arid and semi-arid areas. However, previous studies always focus on the effects of precipitation in different time scales, but ignore the effects of precipitation in different spatial scales. To further study the effects of precipitation fluctuation in different spatial scales, we used the wavelet analysis method to analyze its temporal and spatial change based on data from eighteen meteorological stations during 1961–2015 in Horqin region. Results showed that: (1 from the overall tendency of precipitation changes, the precipitation inter-annual variations in Horqin region had the tendency of gradually decreasing from the southeast (District IV to the northwest; (2 the precipitation anomalies of District I–IV between 1960 and 1980 were small and approximate to the normal value; (3 in the time scale of 23–32 years, the cyclical fluctuations were very significant and the annual precipitation underwent two cyclical fluctuations from a period of low precipitation to a period of high precipitation; and (4 as results of analyzing the spatial wavelet variance of sub-region, the main cycle of precipitation in District I, District II and District III was between 10 and 11 years, while the main cycle of precipitation in District IV was 25 years. The main conclusions include the following. (1 This region tended to be arid, and the precipitation gradually decreased from the southeast (District IV to northwest (District I. (2 The influence of spatial differentiation characteristics on precipitation fluctuation in this region was cyclical fluctuation, which gradually decreased from the southeast to the northwest. The length of the cyclical change period gradually shortened. In the first main cycle, whose annual precipitation changes were most significant, the changing characteristic was District IV and District I decreased from 25 years to 10 years. (3 Predicated from the cyclical

Analysis of the Diffuse Domain Method for Second Order Elliptic Boundary Value Problems

NARCIS (Netherlands)

Burger, Martin; Elvetun, Ole; Schlottbom, Matthias

2017-01-01

The diffuse domain method for partial differential equations on complicated geometries recently received strong attention in particular from practitioners, but many fundamental issues in the analysis are still widely open. In this paper, we study the diffuse domain method for approximating second

Aromatic amino acids in the cellulose binding domain of Penicillium crustosum endoglucanase EGL1 differentially contribute to the cellulose affinity of the enzyme.

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Jiang-Ke Yang

Full Text Available The cellulose binding domain (CBD of cellulase binding to cellulosic materials is the initiation of a synergistic action on the enzymatic hydrolysis of the most abundant renewable biomass resources in nature. The binding of the CBD domain to cellulosic substrates generally relies on the interaction between the aromatic amino acids structurally located on the flat face of the CBD domain and the glucose rings of cellulose. In this study, we found the CBD domain of a newly cloned Penicillium crustosum endoglucanase EGL1, which was phylogenetically related to Aspergillus, Fusarium and Rhizopus, and divergent from the well-characterized Trichoderma reeseis cellulase CBD domain, contain two conserved aromatic amino acid-rich regions, Y451-Y452 and Y477-Y478-Y479, among which three amino acids Y451, Y477, and Y478 structurally sited on a flat face of this domain. Cellulose binding assays with green fluorescence protein as the marker, adsorption isotherm assays and an isothermal titration calorimetry assays revealed that although these three amino acids participated in this process, the Y451-Y452 appears to contribute more to the cellulose binding than Y477-Y478-Y479. Further glycine scanning mutagenesis and structural modelling revealed that the binding between CBD domain and cellulosic materials might be multi-amino-acids that participated in this process. The flexible poly-glucose molecule could contact Y451, Y477, and Y478 which form the contacting flat face of CBD domain as the typical model, some other amino acids in or outside the flat face might also participate in the interaction. Thus, it is possible that the conserved Y451-Y452 of CBD might have a higher chance of contacting the cellulosic substrates, contributing more to the affinity of CBD than the other amino acids.

Identification of regions involved in substrate binding and dimer stabilization within the central domains of yeast Hsp40 Sis1.

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Júlio C Borges

Full Text Available Protein folding, refolding and degradation are essential for cellular life and are regulated by protein homeostatic processes such those that involve the molecular chaperone DnaK/Hsp70 and its co-chaperone DnaJ. Hsp70 action is initiated when proteins from the DnaJ family bind an unfolded protein for delivery purposes. In eukaryotes, the DnaJ family can be divided into two main groups, Type I and Type II, represented by yeast cytosolic Ydj1 and Sis1, respectively. Although sharing some unique features both members of the DnaJ family, Ydj1 and Sis1 are structurally and functionally distinct as deemed by previous studies, including the observation that their central domains carry the structural and functional information even in switched chimeras. In this study, we combined several biophysical tools for evaluating the stability of Sis1 and mutants that had the central domains (named Gly/Met rich domain and C-terminal Domain I deleted or switched to those of Ydj1 to gain insight into the role of these regions in the structure and function of Sis1. The mutants retained some functions similar to full length wild-type Sis1, however they were defective in others. We found that: 1 Sis1 unfolds in at least two steps as follows: folded dimer to partially folded monomer and then to an unfolded monomer. 2 The Gly/Met rich domain had intrinsically disordered characteristics and its deletion had no effect on the conformational stability of the protein. 3 The deletion of the C-terminal Domain I perturbed the stability of the dimer. 4 Exchanging the central domains perturbed the conformational stability of the protein. Altogether, our results suggest the existence of two similar subdomains in the C-terminal domain of DnaJ that could be important for stabilizing each other in order to maintain a folded substrate-binding site as well as the dimeric state of the protein.

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

Science.gov (United States)

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

Topological domain walls in helimagnets

Science.gov (United States)

Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

2018-05-01

Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

Application of frequency domain line edge roughness characterization methodology in lithography

Science.gov (United States)

Sun, Lei; Wang, Wenhui; Beique, Genevieve; Wood, Obert; Kim, Ryoung-Han

2015-03-01

A frequency domain 3 sigma LER characterization methodology combining the standard deviation and power spectral density (PSD) methods is proposed. In the new method, the standard deviation is calculated in the frequency domain instead of the spatial domain as in the conventional method. The power spectrum of the LER is divided into three regions: low frequency (LF), middle frequency (MF) and high frequency (HF) regions. The frequency region definition is based on process visual comparisons. Three standard deviation numbers are used to characterize the LER in the three frequency regions. Pattern wiggling can be detected quantitatively with a wiggling factor which is also proposed in this paper.

Classical solutions of mixed problems for quasilinear first order PFDEs on a cylindrical domain

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Wojciech Czernous

2014-01-01

Full Text Available We abandon the setting of the domain as a Cartesian product of real intervals, customary for first order PFDEs (partial functional differential equations with initial boundary conditions. We give a new set of conditions on the possibly unbounded domain \\(\\Omega\\ with Lipschitz differentiable boundary. Well-posedness is then reliant on a variant of the normal vector condition. There is a neighbourhood of \\(\\partial\\Omega\\ with the property that if a characteristic trajectory has a point therein, then its every earlier point lies there as well. With local assumptions on coefficients and on the free term, we prove existence and Lipschitz dependence on data of classical solutions on \\((0,c\\times\\Omega\\ to the initial boundary value problem, for small \\(c\\. Regularity of solutions matches this domain, and the proof uses the Banach fixed-point theorem. Our general model of functional dependence covers problems with deviating arguments and integro-differential equations.

Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

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Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

2007-05-15

Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication

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Belhumeur Pierre

2008-11-01

Full Text Available Abstract Background HIV-1 integrase (IN is a key viral enzymatic molecule required for the integration of the viral cDNA into the genome. Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. Interestingly, previous studies have demonstrated that the expression of HIV-1 IN induces the lethal phenotype in some strains of Saccharomyces cerevisiae. In this study, we performed mutagenic analyses of the C-terminal region of the catalytic core domain of HIV-1 IN in order to delineate the critical amino acid(s and/or motif(s required for the induction of the lethal phenotype in the yeast strain HP16, and to further elucidate the molecular mechanism which causes this phenotype. Results Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. Conclusion Overall, this study demonstrates that three mutations located in the C-terminal region of the catalytic core domain of HIV-1 IN inhibit the IN-induced lethal phenotype in yeast by inhibiting the binding of IN to the host chromatin. These results demonstrate that the C-terminal region of the catalytic core domain of HIV-1 IN is important for binding to host chromatin and is crucial for both viral replication and the promotion of

The Successor Function and Pareto Optimal Solutions of Cooperative Differential Systems with Concavity. I

DEFF Research Database (Denmark)

Andersen, Kurt Munk; Sandqvist, Allan

1997-01-01

We investigate the domain of definition and the domain of values for the successor function of a cooperative differential system x'=f(t,x), where the coordinate functions are concave in x for any fixed value of t. Moreover, we give a characterization of a weakly Pareto optimal solution.......We investigate the domain of definition and the domain of values for the successor function of a cooperative differential system x'=f(t,x), where the coordinate functions are concave in x for any fixed value of t. Moreover, we give a characterization of a weakly Pareto optimal solution....

Algorithmic differentiation of pragma-defined parallel regions differentiating computer programs containing OpenMP

CERN Document Server

Förster, Michael

2014-01-01

Numerical programs often use parallel programming techniques such as OpenMP to compute the program's output values as efficient as possible. In addition, derivative values of these output values with respect to certain input values play a crucial role. To achieve code that computes not only the output values simultaneously but also the derivative values, this work introduces several source-to-source transformation rules. These rules are based on a technique called algorithmic differentiation. The main focus of this work lies on the important reverse mode of algorithmic differentiation. The inh

Differentiated responses of apple tree floral phenology to global warming in contrasting climatic regions

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Jean-Michel eLegave

2015-12-01

Full Text Available The responses of flowering phenology to temperature increases in temperate fruit trees have rarely been investigated in contrasting climatic regions. This is an appropriate framework for highlighting varying responses to diverse warming contexts, which would potentially combine chill accumulation declines and heat accumulation increases. To examine this issue, a data set was constituted in apple tree from flowering dates collected for two phenological stages of three cultivars in seven climate-contrasting temperate regions of Western Europe and in three mild regions, one in Northern Morocco and two in Southern Brazil. Multiple change-point models were applied to flowering date series, as well as to corresponding series of mean temperature during two successive periods, respectively determining for the fulfillment of chill and heat requirements. A new overview in space and time of flowering date changes was provided in apple tree highlighting not only flowering date advances as in previous studies but also stationary flowering date series. At global scale, differentiated flowering time patterns result from varying interactions between contrasting thermal determinisms of flowering dates and contrasting warming contexts. This may explain flowering date advances in most of European regions and in Morocco vs. stationary flowering date series in the Brazilian regions. A notable exception in Europe was found in the French Mediterranean region where the flowering date series was stationary. While the flowering duration series were stationary whatever the region, the flowering durations were far longer in mild regions compared to temperate regions. Our findings suggest a new warming vulnerability in temperate Mediterranean regions, which could shift towards responding more to chill decline and consequently experience late and extended flowering under future warming scenarios.

Differentiated Responses of Apple Tree Floral Phenology to Global Warming in Contrasting Climatic Regions.

Science.gov (United States)

Legave, Jean-Michel; Guédon, Yann; Malagi, Gustavo; El Yaacoubi, Adnane; Bonhomme, Marc

2015-01-01

The responses of flowering phenology to temperature increases in temperate fruit trees have rarely been investigated in contrasting climatic regions. This is an appropriate framework for highlighting varying responses to diverse warming contexts, which would potentially combine chill accumulation (CA) declines and heat accumulation (HA) increases. To examine this issue, a data set was constituted in apple tree from flowering dates collected for two phenological stages of three cultivars in seven climate-contrasting temperate regions of Western Europe and in three mild regions, one in Northern Morocco and two in Southern Brazil. Multiple change-point models were applied to flowering date series, as well as to corresponding series of mean temperature during two successive periods, respectively determining for the fulfillment of chill and heat requirements. A new overview in space and time of flowering date changes was provided in apple tree highlighting not only flowering date advances as in previous studies but also stationary flowering date series. At global scale, differentiated flowering time patterns result from varying interactions between contrasting thermal determinisms of flowering dates and contrasting warming contexts. This may explain flowering date advances in most of European regions and in Morocco vs. stationary flowering date series in the Brazilian regions. A notable exception in Europe was found in the French Mediterranean region where the flowering date series was stationary. While the flowering duration series were stationary whatever the region, the flowering durations were far longer in mild regions compared to temperate regions. Our findings suggest a new warming vulnerability in temperate Mediterranean regions, which could shift toward responding more to chill decline and consequently experience late and extended flowering under future warming scenarios.

Prostate segmentation by feature enhancement using domain knowledge and adaptive region based operations

International Nuclear Information System (INIS)

Nanayakkara, Nuwan D; Samarabandu, Jagath; Fenster, Aaron

2006-01-01

Estimation of prostate location and volume is essential in determining a dose plan for ultrasound-guided brachytherapy, a common prostate cancer treatment. However, manual segmentation is difficult, time consuming and prone to variability. In this paper, we present a semi-automatic discrete dynamic contour (DDC) model based image segmentation algorithm, which effectively combines a multi-resolution model refinement procedure together with the domain knowledge of the image class. The segmentation begins on a low-resolution image by defining a closed DDC model by the user. This contour model is then deformed progressively towards higher resolution images. We use a combination of a domain knowledge based fuzzy inference system (FIS) and a set of adaptive region based operators to enhance the edges of interest and to govern the model refinement using a DDC model. The automatic vertex relocation process, embedded into the algorithm, relocates deviated contour points back onto the actual prostate boundary, eliminating the need of user interaction after initialization. The accuracy of the prostate boundary produced by the proposed algorithm was evaluated by comparing it with a manually outlined contour by an expert observer. We used this algorithm to segment the prostate boundary in 114 2D transrectal ultrasound (TRUS) images of six patients scheduled for brachytherapy. The mean distance between the contours produced by the proposed algorithm and the manual outlines was 2.70 ± 0.51 pixels (0.54 ± 0.10 mm). We also showed that the algorithm is insensitive to variations of the initial model and parameter values, thus increasing the accuracy and reproducibility of the resulting boundaries in the presence of noise and artefacts

Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

International Nuclear Information System (INIS)

Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B.

1991-01-01

To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites

Domain wall engineering through exchange bias

International Nuclear Information System (INIS)

Albisetti, E.; Petti, D.

2016-01-01

The control of the structure and position of magnetic domain walls is at the basis of the development of different magnetic devices and architectures. Several nanofabrication techniques have been proposed to geometrically confine and shape domain wall structures; however, a fine tuning of the position and micromagnetic configuration is hardly achieved, especially in continuous films. This work shows that, by controlling the unidirectional anisotropy of a continuous ferromagnetic film through exchange bias, domain walls whose spin arrangement is generally not favored by dipolar and exchange interactions can be created. Micromagnetic simulations reveal that the domain wall width, position and profile can be tuned by establishing an abrupt change in the direction and magnitude of the exchange bias field set in the system. - Highlights: • Micromagnetic simulations study domain walls in exchange biased thin films. • Novel domain wall configurations can be stabilized via exchange bias. • Domain walls nucleate at the boundary of regions with different exchange bias. • Domain wall width and spin profile are controlled by tuning the exchange bias.

Quantifying the mechanisms of domain gain in animal proteins.

Science.gov (United States)

Buljan, Marija; Frankish, Adam; Bateman, Alex

2010-01-01

Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms. Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events. The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.

Time-domain Green's Function Method for three-dimensional nonlinear subsonic flows

Science.gov (United States)

Tseng, K.; Morino, L.

1978-01-01

The Green's Function Method for linearized 3D unsteady potential flow (embedded in the computer code SOUSSA P) is extended to include the time-domain analysis as well as the nonlinear term retained in the transonic small disturbance equation. The differential-delay equations in time, as obtained by applying the Green's Function Method (in a generalized sense) and the finite-element technique to the transonic equation, are solved directly in the time domain. Comparisons are made with both linearized frequency-domain calculations and existing nonlinear results.

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

Science.gov (United States)

Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

2017-07-15

Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

Sensitivity analysis with the regional climate model COSMO-CLM over the CORDEX-MENA domain

Science.gov (United States)

Bucchignani, E.; Cattaneo, L.; Panitz, H.-J.; Mercogliano, P.

2016-02-01

The results of a sensitivity work based on ERA-Interim driven COSMO-CLM simulations over the Middle East-North Africa (CORDEX-MENA) domain are presented. All simulations were performed at 0.44° spatial resolution. The purpose of this study was to ascertain model performances with respect to changes in physical and tuning parameters which are mainly related to surface, convection, radiation and cloud parameterizations. Evaluation was performed for the whole CORDEX-MENA region and six sub-regions, comparing a set of 26 COSMO-CLM runs against a combination of available ground observations, satellite products and reanalysis data to assess temperature, precipitation, cloud cover and mean sea level pressure. The model proved to be very sensitive to changes in physical parameters. The optimized configuration allows COSMO-CLM to improve the simulated main climate features of this area. Its main characteristics consist in the new parameterization of albedo, based on Moderate Resolution Imaging Spectroradiometer data, and the new parameterization of aerosol, based on NASA-GISS AOD distributions. When applying this configuration, Mean Absolute Error values for the considered variables are as follows: about 1.2 °C for temperature, about 15 mm/month for precipitation, about 9 % for total cloud cover, and about 0.6 hPa for mean sea level pressure.

Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

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Adam Z. Blatt

2017-11-01

Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

A protein domain interaction interface database: InterPare

Directory of Open Access Journals (Sweden)

Lee Jungsul

2005-08-01

Full Text Available Abstract Background Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently. Description We introduce a large-scale protein domain interaction interface database called InterPare http://interpare.net. It contains both inter-chain (between chains interfaces and intra-chain (within chain interfaces. InterPare uses three methods to detect interfaces: 1 the geometric distance method for checking the distance between atoms that belong to different domains, 2 Accessible Surface Area (ASA, a method for detecting the buried region of a protein that is detached from a solvent when forming multimers or complexes, and 3 the Voronoi diagram, a computational geometry method that uses a mathematical definition of interface regions. InterPare includes visualization tools to display protein interior, surface, and interaction interfaces. It also provides statistics such as the amino acid propensities of queried protein according to its interior, surface, and interface region. The atom coordinates that belong to interface, surface, and interior regions can be downloaded from the website. Conclusion InterPare is an open and public database server for protein interaction interface information. It contains the large-scale interface data for proteins whose 3D-structures are known. As of November 2004, there were 10,583 (Geometric distance, 10,431 (ASA, and 11,010 (Voronoi diagram entries in the Protein Data Bank (PDB containing interfaces, according to the above three methods. In the case of the geometric distance method, there are 31,620 inter-chain domain-domain

Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia.

Science.gov (United States)

Novakovic, Boris; Evain-Brion, Danièle; Murthi, Padma; Fournier, Thiery; Saffery, Richard

2017-06-01

Placental functioning relies on the appropriate differentiation of progenitor villous cytotrophoblasts (CTBs) into extravillous cytotrophoblasts (EVCTs), including invasive EVCTs, and the multinucleated syncytiotrophoblast (ST) layer. This is accompanied by a general move away from a proliferative, immature phenotype. Genome-scale expression studies have provided valuable insight into genes that are associated with the shift to both an invasive EVCT and ST phenotype, whereas genome-scale DNA methylation analysis has shown that differentiation to ST involves widespread methylation shifts, which are counteracted by low oxygen. In the current study, we sought to identify DNA methylation variation that is associated with transition from CTB to ST in vitro and from a noninvasive to invasive EVCT phenotype after culture on Matrigel. Of the several hundred differentially methylated regions that were identified in each comparison, the majority showed a loss of methylation with differentiation. This included a large differentially methylated region (DMR) in the gene body of death domain-associated protein 6 ( DAXX ), which lost methylation during both CTB syncytialization to ST and EVCT differentiation to invasive EVCT. Comparison to publicly available methylation array data identified the same DMR as among the most consistently differentially methylated genes in placental samples from preeclampsia pregnancies. Of interest, in vitro culture of CTB or ST in low oxygen increases methylation in the same region, which correlates with delayed differentiation. Analysis of combined epigenomics signatures confirmed DAXX DMR as a likely regulatory element, and direct gene expression analysis identified a positive association between methylation at this site and DAXX expression levels. The widespread dynamic nature of DAXX methylation in association with trophoblast differentiation and placenta-associated pathologies is consistent with an important role for this gene in proper

LWD lithostratigraphy, physical properties and correlations across tectonic domains at the NanTroSEIZE drilling transect, Nankai Trough subduction zone, Japan

Science.gov (United States)

Tudge, J.; Webb, S. I.; Tobin, H. J.

2013-12-01

Since 2007 the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) has drilled a total of 15 sites across the Nankai Trough subduction zone, including two sites on the incoming sediments of the Philippine Sea plate (PSP). Logging-while-drilling (LWD) data was acquired at 11 of these sites encompassing the forearc Kumano Basin, upper accretionary prism, toe region and input sites. Each of these tectonic domains is investigated for changes in physical properties and LWD characteristics, and this work fully integrates a large data set acquired over multiple years and IODP expeditions, most recently Expedition 338. Using the available logging-while-drilling data, primarily consisting of gamma ray, resistivity and sonic velocity, a log-based lithostratigraphy is developed at each site and integrated with the core, across the entire NanTroSEIZE transect. In addition to simple LWD characterization, the use of Iterative Non-hierarchical Cluster Analysis (INCA) on the sites with the full suite of LWD data clearly differentiates the unaltered forearc and slope basin sediments from the deformed sediments of the accretionary prism, suggesting the LWD is susceptible to the subtle changes in the physical properties between the tectonic domains. This differentiation is used to guide the development of tectonic-domain specific physical properties relationships. One of the most important physical property relationships between is the p-wave velocity and porosity. To fully characterize the character and properties of each tectonic domain we develop new velocity-porosity relationships for each domain found across the NanTroSEIZE transect. This allows the porosity of each domain to be characterized on the seismic scale and the resulting implications for porosity and pore pressure estimates across the plate interface fault zone.

Finite difference method and algebraic polynomial interpolation for numerically solving Poisson's equation over arbitrary domains

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Tsugio Fukuchi

2014-06-01

Full Text Available The finite difference method (FDM based on Cartesian coordinate systems can be applied to numerical analyses over any complex domain. A complex domain is usually taken to mean that the geometry of an immersed body in a fluid is complex; here, it means simply an analytical domain of arbitrary configuration. In such an approach, we do not need to treat the outer and inner boundaries differently in numerical calculations; both are treated in the same way. Using a method that adopts algebraic polynomial interpolations in the calculation around near-wall elements, all the calculations over irregular domains reduce to those over regular domains. Discretization of the space differential in the FDM is usually derived using the Taylor series expansion; however, if we use the polynomial interpolation systematically, exceptional advantages are gained in deriving high-order differences. In using the polynomial interpolations, we can numerically solve the Poisson equation freely over any complex domain. Only a particular type of partial differential equation, Poisson's equations, is treated; however, the arguments put forward have wider generality in numerical calculations using the FDM.

Differentiated parietal connectivity of frontal regions for "what" and "where" memory.

Science.gov (United States)

Rottschy, C; Caspers, S; Roski, C; Reetz, K; Dogan, I; Schulz, J B; Zilles, K; Laird, A R; Fox, P T; Eickhoff, S B

2013-11-01

In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann's area BA 44). As similar locations have been discussed as part of a dorsal frontal-superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related "what" and "where" processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may

Discontinuous Galerkin Time-Domain Modeling of Graphene Nano-Ribbon Incorporating the Spatial Dispersion Effects

KAUST Repository

Li, Ping; Jiang, Li Jun; Bagci, Hakan

2018-01-01

It is well known that graphene demonstrates spatial dispersion properties, i.e., its conductivity is nonlocal and a function of spectral wave number (momentum operator) q. In this paper, to account for effects of spatial dispersion on transmission of high speed signals along graphene nano-ribbon (GNR) interconnects, a discontinuous Galerkin time-domain (DGTD) algorithm is proposed. The atomically-thick GNR is modeled using a nonlocal transparent surface impedance boundary condition (SIBC) incorporated into the DGTD scheme. Since the conductivity is a complicated function of q (and one cannot find an analytical Fourier transform pair between q and spatial differential operators), an exact time domain SIBC model cannot be derived. To overcome this problem, the conductivity is approximated by its Taylor series in spectral domain under low-q assumption. This approach permits expressing the time domain SIBC in the form of a second-order partial differential equation (PDE) in current density and electric field intensity. To permit easy incorporation of this PDE with the DGTD algorithm, three auxiliary variables, which degenerate the second-order (temporal and spatial) differential operators to first-order ones, are introduced. Regarding to the temporal dispersion effects, the auxiliary differential equation (ADE) method is utilized to eliminates the expensive temporal convolutions. To demonstrate the applicability of the proposed scheme, numerical results, which involve characterization of spatial dispersion effects on the transfer impedance matrix of GNR interconnects, are presented.

Discontinuous Galerkin Time-Domain Modeling of Graphene Nano-Ribbon Incorporating the Spatial Dispersion Effects

KAUST Repository

Li, Ping

2018-04-13

It is well known that graphene demonstrates spatial dispersion properties, i.e., its conductivity is nonlocal and a function of spectral wave number (momentum operator) q. In this paper, to account for effects of spatial dispersion on transmission of high speed signals along graphene nano-ribbon (GNR) interconnects, a discontinuous Galerkin time-domain (DGTD) algorithm is proposed. The atomically-thick GNR is modeled using a nonlocal transparent surface impedance boundary condition (SIBC) incorporated into the DGTD scheme. Since the conductivity is a complicated function of q (and one cannot find an analytical Fourier transform pair between q and spatial differential operators), an exact time domain SIBC model cannot be derived. To overcome this problem, the conductivity is approximated by its Taylor series in spectral domain under low-q assumption. This approach permits expressing the time domain SIBC in the form of a second-order partial differential equation (PDE) in current density and electric field intensity. To permit easy incorporation of this PDE with the DGTD algorithm, three auxiliary variables, which degenerate the second-order (temporal and spatial) differential operators to first-order ones, are introduced. Regarding to the temporal dispersion effects, the auxiliary differential equation (ADE) method is utilized to eliminates the expensive temporal convolutions. To demonstrate the applicability of the proposed scheme, numerical results, which involve characterization of spatial dispersion effects on the transfer impedance matrix of GNR interconnects, are presented.

Calcium-Dependent Energetics of Calmodulin Domain Interactions with Regulatory Regions of the Ryanodine Receptor Type 1 (RyR1)

Science.gov (United States)

Newman, Rhonda A.; Sorensen, Brenda R.; Kilpatrick, Adina M.; Shea, Madeline A.

2014-01-01

Calmodulin (CaM) plays a vital role in calcium homeostasis by allosterically modulating intracellular calcium channels including the homo-tetrameric human Ryanodine Receptor Type 1 (hRyR1). Apo (calcium-free) CaM activates hRyR1 while calcium-saturated CaM inhibits it. Two CaM-binding regions (residues 1975–1999 and 3614–3643) identified in each RyR1 monomer were proposed to allow CaM to bridge adjacent RyR1 subunits. We explored the distinct roles of CaM domains by using fluorescence anisotropy to determine the affinity of CaM1–148 (full-length), CaM1–80 (N-domain) and CaM76–148 (C-domain) for peptides encompassing hRyR1 residues 1975–1999 or 3614–3643. Both CaM1–148 and CaM76–148 associated in a calcium-independent manner with similar affinities for hRyR1(3614–3643)p while CaM1–80 required calcium and bound ~250-fold more weakly. Association of CaM1–148, CaM1–80 and CaM76–148 with hRyR1(1975–1999)p was much less favorable than with hRyR1(3614–3643)p; differences between the two CaM domains were smaller. Equilibrium calcium titrations monitored by steady-state fluorescence demonstrated that both hRyR1 peptides increased the calcium-binding affinity of both CaM domains. These thermodynamic properties support a prior model in which the CaM C-domain associates with RyR1(3614–3643) at low levels of calcium, positioning CaM to rapidly respond to calcium efflux. However, the affinity of the N-domain of CaM for hRyR1(1975–1999)p is insufficient to explain a model in which CaM bridges adjacent RyR1 subunits within the tetramer. This indicates that other protein factors or properties of the tertiary or quaternary structure of hRyR1 contribute to the energetics of CaM-mediated regulation. PMID:25145833

Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum and Domain Architectures with Other Mycoplasma species

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Chandra Sekhar Reddy Chilamakuri

2011-01-01

Full Text Available Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence search approach to establish new domain relationships in the unassigned regions of gene products at the whole genome level by taking Mycoplasma gallisepticum as a specific example and established new domain relationships. In this paper, we report a detailed comparison of the conservation status of the domain and domain architectures of the gene products that bear our newly predicted domains amongst 14 other Mycoplasma genomes and reported the probable implications for the organisms. Some of the domain associations, observed in Mycoplasma that afflict humans and other non-human primates, are involved in regulation of solute transport and DNA binding suggesting specific modes of host-pathogen interactions.

The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

Science.gov (United States)

Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

2013-09-01

Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

Pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions: differentiation using MRI

Energy Technology Data Exchange (ETDEWEB)

Choi, S.H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Kwon, B.J. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of)]. E-mail: bjkwon@radiol.snu.ac.kr; Na, D.G. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Kim, J.-H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Han, M.H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Clinical Research Institute, Seoul National University Hospital (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Chang, K.-H. [Department of Radiology, Seoul National University College of Medicine (Korea, Republic of); Clinical Research Institute, Seoul National University Hospital (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

2007-05-15

Aims: To determine the differential magnetic resonance imaging (MRI) features of pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions. Materials and methods: The MRI images of 64 patients with pituitary adenoma (n = 38), craniopharyngioma (n = 13), or Rathke cleft cyst (n = 13) were retrospectively reviewed by three neuroradiologists. The following characteristics were evaluated: shape, volume, extent, component characteristics, signal intensities of solid portions on T2-weighted images, signal intensities of cystic portions on T1-weighted images, and enhancement patterns of solid portions and cyst walls of tumours. Fisher's exact test applied with Bonferroni correction was used for multiple comparison. A flowchart for differential diagnosis was constructed based on statistical analysis of the results. Results: A snowman shape, solid characteristics, and homogeneous enhancement of the solid portion were more common in pituitary adenomas (p < 0.017). A superiorly lobulated shape, third ventricle compression by superior tumour extension, mixed solid and cystic characteristics, and reticular enhancement of the solid portion were more common in craniopharyngiomas (p < 0.017). Finally, an ovoid shape, a small tumour volume, cystic characteristics, and no or thin cyst wall enhancement were more common in Rathke cleft cysts (p < 0.017). The flowchart yielded diagnostic accuracies as follows: 92.1% in pituitary adenoma; 92.3% in craniopharyngioma; 92.3% in Rathke cleft cyst; and 92.2% overall. Conclusion: A combination of MRI findings is helpful in the differential diagnosis of the three tumours involving both intrasellar and suprasellar regions.

Pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions: differentiation using MRI

International Nuclear Information System (INIS)

Choi, S.H.; Kwon, B.J.; Na, D.G.; Kim, J.-H.; Han, M.H.; Chang, K.-H.

2007-01-01

Aims: To determine the differential magnetic resonance imaging (MRI) features of pituitary adenoma, craniopharyngioma, and Rathke cleft cyst involving both intrasellar and suprasellar regions. Materials and methods: The MRI images of 64 patients with pituitary adenoma (n = 38), craniopharyngioma (n = 13), or Rathke cleft cyst (n = 13) were retrospectively reviewed by three neuroradiologists. The following characteristics were evaluated: shape, volume, extent, component characteristics, signal intensities of solid portions on T2-weighted images, signal intensities of cystic portions on T1-weighted images, and enhancement patterns of solid portions and cyst walls of tumours. Fisher's exact test applied with Bonferroni correction was used for multiple comparison. A flowchart for differential diagnosis was constructed based on statistical analysis of the results. Results: A snowman shape, solid characteristics, and homogeneous enhancement of the solid portion were more common in pituitary adenomas (p < 0.017). A superiorly lobulated shape, third ventricle compression by superior tumour extension, mixed solid and cystic characteristics, and reticular enhancement of the solid portion were more common in craniopharyngiomas (p < 0.017). Finally, an ovoid shape, a small tumour volume, cystic characteristics, and no or thin cyst wall enhancement were more common in Rathke cleft cysts (p < 0.017). The flowchart yielded diagnostic accuracies as follows: 92.1% in pituitary adenoma; 92.3% in craniopharyngioma; 92.3% in Rathke cleft cyst; and 92.2% overall. Conclusion: A combination of MRI findings is helpful in the differential diagnosis of the three tumours involving both intrasellar and suprasellar regions

AGAMOUS controls GIANT KILLER, a multifunctional chromatin modifier in reproductive organ patterning and differentiation.

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Kian-Hong Ng

2009-11-01

Full Text Available The Arabidopsis homeotic protein AGAMOUS (AG, a MADS domain transcription factor, specifies reproductive organ identity during flower development. Using a binding assay and expression analysis, we identified a direct target of AG, GIANT KILLER (GIK, which fine-tunes the expression of multiple genes downstream of AG. The GIK protein contains an AT-hook DNA binding motif that is widely found in chromosomal proteins and that binds to nuclear matrix attachment regions of DNA elements. Overexpression and loss of function of GIK cause wide-ranging defects in patterning and differentiation of reproductive organs. GIK directly regulates the expression of several key transcriptional regulators, including ETTIN/AUXIN RESPONSE FACTOR 3 (ETT/ARF3 that patterns the gynoecium, by binding to the matrix attachment regions of target promoters. Overexpression of GIK causes a swift and dynamic change in repressive histone modification in the ETT promoter. We propose that GIK acts as a molecular node downstream of the homeotic protein AG, regulating patterning and differentiation of reproductive organs through chromatin organization.

Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

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Jamie A Moroco

Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

Science.gov (United States)

Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

2016-11-20

The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

Thermal response of domains in cardiolipin content bilayers

Energy Technology Data Exchange (ETDEWEB)

Domenech, Oscar [Departament de Quimica-Fisica, Facultat de Quimica, U.B. 08028 (Spain); Morros, Antoni [Unitat de Biofisica, Departament de Bioquimica i Biologia Molecular, Facultat de Medicina (Spain); Servei de Ressonancia Magnetica Nuclear (SeRMN), U.A.B., 08193 Bellaterra, Barcelona (Spain); Cabanas, Miquel E. [Servei de Ressonancia Magnetica Nuclear (SeRMN), U.A.B., 08193 Bellaterra, Barcelona (Spain); Montero, M. Teresa [Departament de Fisicoquimica, Facultat de Farmacia, U.B. 08028 (Spain); Hernandez-Borrell, Jordi [Departament de Fisicoquimica, Facultat de Farmacia, U.B. 08028 (Spain)], E-mail: jordihernandezborrell@ub.edu

2007-10-15

In the study described here, supported planar bilayers (SPBs) of 1-palmitoy-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE):cardiolipin (CL) (0.8:0.2, mol/mol) were examined using atomic force microscopy (AFM). SPBs were formed from suspensions of POPE:CL (0.8:0.2, mol/mol) in inverted hexagonal (H{sub II}) phases (buffer containing Ca{sup 2+}). Three laterally segregated domains which differ in height were observed at 24 degC. Based on the area accounted for each domain and the nominal composition of the mixture, we interpret that the higher domain is formed by CL, while the intermediate and lower domains (LDs) are formed by POPE. The three domains respond to temperature increase with relative changes in their area. At 37 degC, we observed that the increase in the area of the intermediate domain occurs at the expense of the LD. {sup 31}P-nuclear magnetic resonance ({sup 31}P-NMR) and Differential scanning calorimetry (DSC) were used in combination with AFM to characterize the phase behavior of the suspensions and to elucidate the nature of the structures observed.

Modelling of groundwater flow and flow paths for a large regional domain in northeast Uppland. A three-dimensional, mathematical modelling of groundwater flows and flow paths on a super-regional scale, for different complexity levels of the flow domain

International Nuclear Information System (INIS)

Holmen, Johan G.; Stigsson, Martin; Marsic, Niko; Gylling, Bjoern

2003-12-01

The general purpose of this study is to estimate the groundwater flow for a large regional domain by use of groundwater models; and to do that with such a resolution (degree of detail) that important local properties of the flow system studied is represented in the established models. Based on the results of the groundwater modelling, we have compared different theoretical locations of a repository for nuclear waste, considering length and breakthrough time (advective flow) for flow paths from such a repository. The area studied is located in Sweden, in the Northeast of the Uppland province. The area has a maximum horizontal extension of 90 km by 50 km, and the size of the area is approximately 2,000 km 2 . The study is based on a system analysis approach. The studied system is the groundwater flow in the rock mass of Northeast Uppland. To reach the objectives of the study, different mathematical models were devised of the studied domain; these models will, in an idealised and simplified way, reproduce the groundwater movements at the area studied. The formal models (the mathematical models) used for simulation of the groundwater flow are three dimensional mathematical descriptions of the studied hydraulic system. For establishment of the formal models we used two different numerical codes GEOAN, which is based on the finite difference method and NAMMU, which is based on the finite element method. Considering flow path lengths and breakthrough times from a theoretical repository, we have evaluated the following: Importance of the local and regional topography; Importance of cell size in the numerical model; Importance of depth of domain represented in the numerical model; Importance of regional fracture zones; Importance of local lakes; Importance of areas covered by a clay layer; Importance of a modified topography; Importance of the shore level progress. Importance of density dependent flow. The results of the study includes: Length and breakthrough time of flow

Modelling of groundwater flow and flow paths for a large regional domain in northeast Uppland. A three-dimensional, mathematical modelling of groundwater flows and flow paths on a super-regional scale, for different complexity levels of the flow domain

Energy Technology Data Exchange (ETDEWEB)

Holmen, Johan G.; Stigsson, Martin [Golder Associates, Stockholm (Sweden); Marsic, Niko; Gylling, Bjoern [Kemakta Konsult AB, Stockholm (Sweden)

2003-12-01

The general purpose of this study is to estimate the groundwater flow for a large regional domain by use of groundwater models; and to do that with such a resolution (degree of detail) that important local properties of the flow system studied is represented in the established models. Based on the results of the groundwater modelling, we have compared different theoretical locations of a repository for nuclear waste, considering length and breakthrough time (advective flow) for flow paths from such a repository. The area studied is located in Sweden, in the Northeast of the Uppland province. The area has a maximum horizontal extension of 90 km by 50 km, and the size of the area is approximately 2,000 km{sup 2}. The study is based on a system analysis approach. The studied system is the groundwater flow in the rock mass of Northeast Uppland. To reach the objectives of the study, different mathematical models were devised of the studied domain; these models will, in an idealised and simplified way, reproduce the groundwater movements at the area studied. The formal models (the mathematical models) used for simulation of the groundwater flow are three dimensional mathematical descriptions of the studied hydraulic system. For establishment of the formal models we used two different numerical codes GEOAN, which is based on the finite difference method and NAMMU, which is based on the finite element method. Considering flow path lengths and breakthrough times from a theoretical repository, we have evaluated the following: Importance of the local and regional topography; Importance of cell size in the numerical model; Importance of depth of domain represented in the numerical model; Importance of regional fracture zones; Importance of local lakes; Importance of areas covered by a clay layer; Importance of a modified topography; Importance of the shore level progress. Importance of density dependent flow. The results of the study includes: Length and breakthrough time of

Multi-ensemble regional simulation of Indian monsoon during contrasting rainfall years: role of convective schemes and nested domain

Science.gov (United States)

Devanand, Anjana; Ghosh, Subimal; Paul, Supantha; Karmakar, Subhankar; Niyogi, Dev

2018-06-01

Regional simulations of the seasonal Indian summer monsoon rainfall (ISMR) require an understanding of the model sensitivities to physics and resolution, and its effect on the model uncertainties. It is also important to quantify the added value in the simulated sub-regional precipitation characteristics by a regional climate model (RCM), when compared to coarse resolution rainfall products. This study presents regional model simulations of ISMR at seasonal scale using the Weather Research and Forecasting (WRF) model with the synoptic scale forcing from ERA-interim reanalysis, for three contrasting monsoon seasons, 1994 (excess), 2002 (deficit) and 2010 (normal). Impact of four cumulus schemes, viz., Kain-Fritsch (KF), Betts-Janjić-Miller, Grell 3D and modified Kain-Fritsch (KFm), and two micro physical parameterization schemes, viz., WRF Single Moment Class 5 scheme and Lin et al. scheme (LIN), with eight different possible combinations are analyzed. The impact of spectral nudging on model sensitivity is also studied. In WRF simulations using spectral nudging, improvement in model rainfall appears to be consistent in regions with topographic variability such as Central Northeast and Konkan Western Ghat sub-regions. However the results are also dependent on choice of cumulus scheme used, with KF and KFm providing relatively good performance and the eight member ensemble mean showing better results for these sub-regions. There is no consistent improvement noted in Northeast and Peninsular Indian monsoon regions. Results indicate that the regional simulations using nested domains can provide some improvements on ISMR simulations. Spectral nudging is found to improve upon the model simulations in terms of reducing the intra ensemble spread and hence the uncertainty in the model simulated precipitation. The results provide important insights regarding the need for further improvements in the regional climate simulations of ISMR for various sub-regions and contribute

Multi-ensemble regional simulation of Indian monsoon during contrasting rainfall years: role of convective schemes and nested domain

Science.gov (United States)

Devanand, Anjana; Ghosh, Subimal; Paul, Supantha; Karmakar, Subhankar; Niyogi, Dev

2017-08-01

Regional simulations of the seasonal Indian summer monsoon rainfall (ISMR) require an understanding of the model sensitivities to physics and resolution, and its effect on the model uncertainties. It is also important to quantify the added value in the simulated sub-regional precipitation characteristics by a regional climate model (RCM), when compared to coarse resolution rainfall products. This study presents regional model simulations of ISMR at seasonal scale using the Weather Research and Forecasting (WRF) model with the synoptic scale forcing from ERA-interim reanalysis, for three contrasting monsoon seasons, 1994 (excess), 2002 (deficit) and 2010 (normal). Impact of four cumulus schemes, viz., Kain-Fritsch (KF), Betts-Janjić-Miller, Grell 3D and modified Kain-Fritsch (KFm), and two micro physical parameterization schemes, viz., WRF Single Moment Class 5 scheme and Lin et al. scheme (LIN), with eight different possible combinations are analyzed. The impact of spectral nudging on model sensitivity is also studied. In WRF simulations using spectral nudging, improvement in model rainfall appears to be consistent in regions with topographic variability such as Central Northeast and Konkan Western Ghat sub-regions. However the results are also dependent on choice of cumulus scheme used, with KF and KFm providing relatively good performance and the eight member ensemble mean showing better results for these sub-regions. There is no consistent improvement noted in Northeast and Peninsular Indian monsoon regions. Results indicate that the regional simulations using nested domains can provide some improvements on ISMR simulations. Spectral nudging is found to improve upon the model simulations in terms of reducing the intra ensemble spread and hence the uncertainty in the model simulated precipitation. The results provide important insights regarding the need for further improvements in the regional climate simulations of ISMR for various sub-regions and contribute

Differentiation of illicit drugs with THz time-domain spectroscopy

International Nuclear Information System (INIS)

Liu Guifeng; Ma Shihua; Ji Te; Zhao Hongwei; Wang Wenfeng

2010-01-01

The tera hertz time-domain spectroscopy (THz-TDS) was used for sensing and identifying illicit drugs. The absorption spectra of seven illicit drug samples(morphine and its hydrochloride, cocaine hydrochloride, codeine phosphate, papaverine hydrochloride, pethidine hydrochloride, and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature. The geometric structure and vibration frequencies of morphine were calculated by density functional theory. The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes. Each illicit drug has a distinct signature in its THz spectra. The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints. (authors)

Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED

Directory of Open Access Journals (Sweden)

Gouet Patrice

2008-02-01

Full Text Available Abstract Background The human EED protein, a member of the superfamily of Polycomb group proteins, is involved in multiple cellular protein complexes. Its C-terminal domain, which is common to the four EED isoforms, contains seven repeats of a canonical WD-40 motif. EED is an interactor of three HIV-1 proteins, matrix (MA, integrase (IN and Nef. An antiviral activity has been found to be associated with isoforms EED3 and EED4 at the late stage of HIV-1 replication, due to a negative effect on virus assembly and genomic RNA packaging. The aim of the present study was to determine the regions of the EED C-terminal core domain which were accessible and available to protein interactions, using three-dimensional (3D protein homology modelling with a WD-40 protein of known structure, and epitope mapping of anti-EED antibodies. Results Our data suggested that the C-terminal domain of EED was folded as a seven-bladed β-propeller protein. During the completion of our work, crystallographic data of EED became available from co-crystals of the EED C-terminal core with the N-terminal domain of its cellular partner EZH2. Our 3D-model was in good congruence with the refined structural model determined from crystallographic data, except for a unique α-helix in the fourth β-blade. More importantly, the position of flexible loops and accessible β-strands on the β-propeller was consistent with our mapping of immunogenic epitopes and sites of interaction with HIV-1 MA and IN. Certain immunoreactive regions were found to overlap with the EZH2, MA and IN binding sites, confirming their accessibility and reactivity at the surface of EED. Crystal structure of EED showed that the two discrete regions of interaction with MA and IN did not overlap with each other, nor with the EZH2 binding pocket, but were contiguous, and formed a continuous binding groove running along the lateral face of the β-propeller. Conclusion Identification of antibody-, MA-, IN- and EZH2

A systemic domain model for ambient pervasive persuasive games

OpenAIRE

Eglin, Roger; Eyles, Mark; Dansey, Neil

2008-01-01

By the development of the system domain model it is hoped that a greater conceptual and theoretical clarity may be brought to understanding the complex and multifaceted nature of pervasive and ambient computer games. This paper presents a conceptual model, the system domain model, to illustrate domain areas that exist in a console, pervasive or ambient game. It is implicit that the regions that the systemic domain model describes are contextually dependent. By developing this model it is poss...

SU-E-J-272: Auto-Segmentation of Regions with Differentiating CT Numbers for Treatment Response Assessment

International Nuclear Information System (INIS)

Yang, C; Noid, G; Dalah, E; Paulson, E; Li, X; Gilat-Schmidt, T

2015-01-01

Purpose: It has been reported recently that the change of CT number (CTN) during and after radiation therapy (RT) may be used to assess RT response. The purpose of this work is to develop a tool to automatically segment the regions with differentiating CTN and/or with change of CTN in a series of CTs. Methods: A software tool was developed to identify regions with differentiating CTN using K-mean Cluster of CT numbers and to automatically delineate these regions using convex hull enclosing method. Pre- and Post-RT CT, PET, or MRI images acquired for sample lung and pancreatic cancer cases were used to test the software tool. K-mean cluster of CT numbers within the gross tumor volumes (GTVs) delineated based on PET SUV (standard uptake value of fludeoxyglucose) and/or MRI ADC (apparent diffusion coefficient) map was analyzed. The cluster centers with higher value were considered as active tumor volumes (ATV). The convex hull contours enclosing preset clusters were used to delineate these ATVs with color washed displays. The CTN defined ATVs were compared with the SUV- or ADC-defined ATVs. Results: CTN stability of the CT scanner used to acquire the CTs in this work is less than 1.5 Hounsfield Unit (HU) variation annually. K-mean cluster centers in the GTV have difference of ∼20 HU, much larger than variation due to CTN stability, for the lung cancer cases studied. The dice coefficient between the ATVs delineated based on convex hull enclosure of high CTN centers and the PET defined GTVs based on SUV cutoff value of 2.5 was 90(±5)%. Conclusion: A software tool was developed using K-mean cluster and convex hull contour to automatically segment high CTN regions which may not be identifiable using a simple threshold method. These CTN regions were reasonably overlapped with the PET or MRI defined GTVs

Income differentiation of agricultural households in regions of Czech Republic

Directory of Open Access Journals (Sweden)

Zuzana Procházková

2012-01-01

Full Text Available The Czech Republic has recently experienced phases of economic growth and periods of economic crisis. This fact affects the standard of living and household behaviour and affects the formation of life-style. This paper deals with the income situation of households. The main source of data is EU SILC survey from the years 2005 to 2008. The result of the enquiry and processing of primary data is information about the average income per household member, the poverty level and the number of households at risk of poverty. For the formulation of income differentiation is used Gini coefficient. Attention is paid to factors that affect income inequality (the number of household members, social group, and age. The analysis and subsequent problem solving of income inequality may be contributed with further analysis of empirical data of this type. Household income is one of the decisive factors determining the style of family life, their priorities, meeting their needs, and ensure-time activities. Differences between regions determine preferences and identify opportunities.

A Stochastic Climate Generator for Agriculture in Southeast Asian Domains

Science.gov (United States)

Greene, A. M.; Allis, E. C.

2014-12-01

We extend a previously-described method for generating future climate scenarios, suitable for driving agricultural models, to selected domains in Lao PDR, Bangladesh and Indonesia. There are notable differences in climatology among the study regions, most importantly the inverse seasonal relationship of southeast Asian and Australian monsoons. These differences necessitate a partially-differentiated modeling approach, utilizing common features for better estimation while allowing independent modeling of divergent attributes. The method attempts to constrain uncertainty due to both anthropogenic and natural influences, providing a measure of how these effects may combine during specified future decades. Seasonal climate fields are downscaled to the daily time step by resampling the AgMERRA dataset, providing a full suite of agriculturally relevant variables and enabling the propagation of climate uncertainty to agricultural outputs. The role of this research in a broader project, conducted under the auspices of the International Fund for Agricultural Development (IFAD), is discussed.

Domain-Specific Impulsivity in School-Age Children

Science.gov (United States)

Tsukayama, Eli; Duckworth, Angela Lee; Kim, Betty

2013-01-01

Impulsivity is a salient individual difference in children with well-established predictive validity for life outcomes. The current investigation proposes that impulsive behaviors vary systematically by domain. In a series of studies with ethnically and socioeconomically diverse samples of middle school students, we find that schoolwork-related and interpersonal-related impulsivity, as observed by teachers, parents, and the students themselves, are distinct, moderately correlated behavioral tendencies. Each demonstrates differentiated relationships with dimensions of childhood temperament, Big Five personality factors, and outcomes, such as sociometric popularity, report card grades, and classroom conduct. Implications for theoretical conceptions of impulsivity as well as for practical applications (e.g., domain-specific interventions) are discussed. PMID:24118714

Pod systems: an equivariant ordinary differential equation approach to dynamical systems on a spatial domain

International Nuclear Information System (INIS)

Elmhirst, Toby; Stewart, Ian; Doebeli, Michael

2008-01-01

We present a class of systems of ordinary differential equations (ODEs), which we call 'pod systems', that offers a new perspective on dynamical systems defined on a spatial domain. Such systems are typically studied as partial differential equations, but pod systems bring the analytic techniques of ODE theory to bear on the problems, and are thus able to study behaviours and bifurcations that are not easily accessible to the standard methods. In particular, pod systems are specifically designed to study spatial dynamical systems that exhibit multi-modal solutions. A pod system is essentially a linear combination of parametrized functions in which the coefficients and parameters are variables whose dynamics are specified by a system of ODEs. That is, pod systems are concerned with the dynamics of functions of the form Ψ(s, t) = y 1 (t) φ(s; x 1 (t)) + ··· + y N (t) φ(s; x N (t)), where s in R n is the spatial variable and φ: R n × R d → R. The parameters x i in R d and coefficients y i in R are dynamic variables which evolve according to some system of ODEs, x-dot i = G i (x, y) and y-dot i = H i (x, y), for i = 1, ..., N. The dynamics of Ψ in function space can then be studied through the dynamics of the x and y in finite dimensions. A vital feature of pod systems is that the ODEs that specify the dynamics of the x and y variables are not arbitrary; restrictions on G i and H i are required to guarantee that the dynamics of Ψ in function space are well defined (that is, that trajectories are unique). One important restriction is symmetry in the ODEs which arises because Ψ is invariant under permutations of the indices of the (x i , y i ) pairs. However, this is not the whole story, and the primary goal of this paper is to determine the necessary structure of the ODEs explicitly to guarantee that the dynamics of Ψ are well defined

Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source

Science.gov (United States)

Peters, Bradley J.; Carlson, Richard W.; Day, James M. D.; Horan, Mary F.

2018-03-01

Active volcanic hotspots can tap into domains in Earth’s deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth’s interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth’s interior.

Pseudo-differential operators on manifolds with singularities

CERN Document Server

Schulze, B-W

1991-01-01

The analysis of differential equations in domains and on manifolds with singularities belongs to the main streams of recent developments in applied and pure mathematics. The applications and concrete models from engineering and physics are often classical but the modern structure calculus was only possible since the achievements of pseudo-differential operators. This led to deep connections with index theory, topology and mathematical physics. The present book is devoted to elliptic partial differential equations in the framework of pseudo-differential operators. The first chapter contains the Mellin pseudo-differential calculus on R+ and the functional analysis of weighted Sobolev spaces with discrete and continuous asymptotics. Chapter 2 is devoted to the analogous theory on manifolds with conical singularities, Chapter 3 to manifolds with edges. Employed are pseudo-differential operators along edges with cone-operator-valued symbols.

The analysis of decimation and interpolation in the linear canonical transform domain.

Science.gov (United States)

Xu, Shuiqing; Chai, Yi; Hu, Youqiang; Huang, Lei; Feng, Li

2016-01-01

Decimation and interpolation are the two basic building blocks in the multirate digital signal processing systems. As the linear canonical transform (LCT) has been shown to be a powerful tool for optics and signal processing, it is worthwhile and interesting to analyze the decimation and interpolation in the LCT domain. In this paper, the definition of equivalent filter in the LCT domain have been given at first. Then, by applying the definition, the direct implementation structure and polyphase networks for decimator and interpolator in the LCT domain have been proposed. Finally, the perfect reconstruction expressions for differential filters in the LCT domain have been presented as an application. The proposed theorems in this study are the bases for generalizations of the multirate signal processing in the LCT domain, which can advance the filter banks theorems in the LCT domain.

Distal loop flexibility of a regulatory domain modulates dynamics and activity of C-terminal SRC kinase (csk.

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Sulyman Barkho

Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and membrane localization. While the function of interfacial segments in these multidomain kinases are well-investigated, little is known about how surface sites and long-range, allosteric coupling control protein dynamics and catalytic function. The SH2 domain of Csk is an essential component for the down-regulation of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop in a surface site far removed from kinase domain interactions. In this study, we used a combination of experimental and computational methods to probe the importance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexibility found in homologous kinase SH2 domains. Our results indicate that while the fold and function of the isolated domain and the full-length kinase are not affected by loop elongation, native protein dynamics that are essential for efficient catalysis are perturbed. We also identify key motifs and routes through which the distal SH2 site might influence catalysis at the active site. This study underscores the sensitivity of intramolecular signaling and catalysis to native protein dynamics that arise from modest changes in allosteric regions while providing a potential strategy to alter intrinsic activity and signaling modulation.

Strategic Leadership Development: An Operation Domain Application

Science.gov (United States)

1997-03-01

effectiveness. The Stratified Systems Theory Model is used to identify skills and attributes for the three leadership domains of Direct, Operation, and...tools they need to help the organization achieve its goals. In discussing leadership , it is important to distinguish between management and leadership ...Peter Drucker and Warren Bennis, two noted authors on leadership , offered the following differentiation: “ Management is doing things right

Wavefield Extrapolation in Pseudo-depth Domain

KAUST Repository

Ma, Xuxin

2011-12-11

Wave-equation based seismic migration and inversion tools are widely used by the energy industry to explore hydrocarbon and mineral resources. By design, most of these techniques simulate wave propagation in a space domain with the vertical axis being depth measured from the surface. Vertical depth is popular because it is a straightforward mapping of the subsurface space. It is, however, not computationally cost-effective because the wavelength changes with local elastic wave velocity, which in general increases with depth in the Earth. As a result, the sampling per wavelength also increases with depth. To avoid spatial aliasing in deep fast media, the seismic wave is oversampled in shallow slow media and therefore increase the total computation cost. This issue is effectively tackled by using the vertical time axis instead of vertical depth. This is because in a vertical time representation, the "wavelength" is essentially time period for vertical rays. This thesis extends the vertical time axis to the pseudo-depth axis, which features distance unit while preserving the properties of the vertical time representation. To explore the potentials of doing wave-equation based imaging in the pseudo-depth domain, a Partial Differential Equation (PDE) is derived to describe acoustic wave in this new domain. This new PDE is inherently anisotropic because the use of a constant vertical velocity to convert between depth and vertical time. Such anisotropy results in lower reflection coefficients compared with conventional space domain modeling results. This feature is helpful to suppress the low wavenumber artifacts in reverse-time migration images, which are caused by the widely used cross-correlation imaging condition. This thesis illustrates modeling acoustic waves in both conventional space domain and pseudo-depth domain. The numerical tool used to model acoustic waves is built based on the lowrank approximation of Fourier integral operators. To investigate the potential

Higher-order automatic differentiation of mathematical functions

Science.gov (United States)

Charpentier, Isabelle; Dal Cappello, Claude

2015-04-01

Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

Effective crop evapotranspiration measurement using time-domain reflectometry technique in a sub-humid region

Science.gov (United States)

Srivastava, R. K.; Panda, R. K.; Halder, Debjani

2017-08-01

The primary objective of this study was to evaluate the performance of the time-domain reflectometry (TDR) technique for daily evapotranspiration estimation of peanut and maize crop in a sub-humid region. Four independent methods were used to estimate crop evapotranspiration (ETc), namely, soil water balance budgeting approach, energy balance approach—(Bowen ratio), empirical methods approach, and Pan evaporation method. The soil water balance budgeting approach utilized the soil moisture measurement by gravimetric and TDR method. The empirical evapotranspiration methods such as combination approach (FAO-56 Penman-Monteith and Penman), temperature-based approach (Hargreaves-Samani), and radiation-based approach (Priestley-Taylor, Turc, Abetw) were used to estimate the reference evapotranspiration (ET0). The daily ETc determined by the FAO-56 Penman-Monteith, Priestley-Taylor, Turc, Pan evaporation, and Bowen ratio were found to be at par with the ET values derived from the soil water balance budget; while the methods Abetw, Penman, and Hargreaves-Samani were not found to be ideal for the determination of ETc. The study illustrates the in situ applicability of the TDR method in order to make it possible for a user to choose the best way for the optimum water consumption for a given crop in a sub-humid region. The study suggests that the FAO-56 Penman-Monteith, Turc, and Priestley-Taylor can be used for the determination of crop ETc using TDR in comparison to soil water balance budget.

A novel method for identification and quantification of consistently differentially methylated regions.

Directory of Open Access Journals (Sweden)

Ching-Lin Hsiao

Full Text Available Advances in biotechnology have resulted in large-scale studies of DNA methylation. A differentially methylated region (DMR is a genomic region with multiple adjacent CpG sites that exhibit different methylation statuses among multiple samples. Many so-called "supervised" methods have been established to identify DMRs between two or more comparison groups. Methods for the identification of DMRs without reference to phenotypic information are, however, less well studied. An alternative "unsupervised" approach was proposed, in which DMRs in studied samples were identified with consideration of nature dependence structure of methylation measurements between neighboring probes from tiling arrays. Through simulation study, we investigated effects of dependencies between neighboring probes on determining DMRs where a lot of spurious signals would be produced if the methylation data were analyzed independently of the probe. In contrast, our newly proposed method could successfully correct for this effect with a well-controlled false positive rate and a comparable sensitivity. By applying to two real datasets, we demonstrated that our method could provide a global picture of methylation variation in studied samples. R source codes to implement the proposed method were freely available at http://www.csjfann.ibms.sinica.edu.tw/eag/programlist/ICDMR/ICDMR.html.

Exploring inter-frame correlation analysis and wavelet-domain modeling for real-time caption detection in streaming video

Science.gov (United States)

Li, Jia; Tian, Yonghong; Gao, Wen

2008-01-01

In recent years, the amount of streaming video has grown rapidly on the Web. Often, retrieving these streaming videos offers the challenge of indexing and analyzing the media in real time because the streams must be treated as effectively infinite in length, thus precluding offline processing. Generally speaking, captions are important semantic clues for video indexing and retrieval. However, existing caption detection methods often have difficulties to make real-time detection for streaming video, and few of them concern on the differentiation of captions from scene texts and scrolling texts. In general, these texts have different roles in streaming video retrieval. To overcome these difficulties, this paper proposes a novel approach which explores the inter-frame correlation analysis and wavelet-domain modeling for real-time caption detection in streaming video. In our approach, the inter-frame correlation information is used to distinguish caption texts from scene texts and scrolling texts. Moreover, wavelet-domain Generalized Gaussian Models (GGMs) are utilized to automatically remove non-text regions from each frame and only keep caption regions for further processing. Experiment results show that our approach is able to offer real-time caption detection with high recall and low false alarm rate, and also can effectively discern caption texts from the other texts even in low resolutions.

A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans.

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Mariana L Coutinho

2011-12-01

Full Text Available The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3 to 8×10(5 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.

Polar Domain Discovery with Sparkler

Science.gov (United States)

Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

2017-12-01

The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

Cloning, expression, purification, and characterisation of the HEAT-repeat domain of TOR from the thermophilic eukaryote Chaetomium thermophilum.

Science.gov (United States)

Robinson, Graham C; Vegunta, Yogesh; Gabus, Caroline; Gaubitz, Christl; Thore, Stéphane

2017-05-01

The Target of Rapamycin Complex is a central controller of cell growth and differentiation in eukaryotes. Its global architecture has been described by cryoelectron microscopy, and regions of its central TOR protein have been described by X-ray crystallography. However, the N-terminal region of this protein, which consists of a series of HEAT repeats, remains uncharacterised at high resolution, most likely due to the absence of a suitable purification procedure. Here, we present a robust method for the preparation of the HEAT-repeat domain, utilizing the thermophilic fungus Chaetomium thermophilum as a source organism. We describe construct design and stable expression in insect cells. An efficient two-step purification procedure is presented, and the purified product is characterised by SEC and MALDI-TOF MS. The methods described pave the way for a complete high-resolution characterisation of this elusive region of the TOR protein. Copyright © 2017 Elsevier Inc. All rights reserved.

Precision and accuracy in CT attenuation measurement of vascular wall using region-of-interest supported by differentiation curve

International Nuclear Information System (INIS)

Suzuki, Shigeru; Kidouchi, Takashi; Kuwahara, Sadatoshi; Vembar, Mani; Takei, Ryoji; Yamamoto, Asako

2012-01-01

Objectives: To evaluate the precision and accuracy in CT attenuation measurement of vascular wall using region-of-interest (ROI) supported by differentiation curves. Study design: We used vascular models (actual attenuation value of the wall: 87 HU) with wall thicknesses of 1.5, 1.0, or 0.5 mm, filled with contrast material of 250, 348, or 436 HU. The nine vascular models were scanned with a 64-detector CT. The wall attenuation values were measured using three sizes (diameter: 0.5, 1.0, and 1.5 mm) of ROIs without differentiation curves. Sixteen measurements were repeated for each vascular model by each of two operators. Measurements supported by differentiation curves were also performed. We used analyses of variance with repeated measures for the measured attenuations for each size of the ROI. Results: Without differentiation curves, there were significant differences in the attenuation values of the wall among the three densities of contrast material, and the attenuation values tended to be overestimated more as the contrast material density increased. Operator dependencies were also found in measurements for 0.5- and 1.5-mm thickness models. With differentiation curves, measurements were not possible for 0.5- and 1.0-mm thickness models. Using differentiation curves for 1.5-mm thickness models with a ROI of 1.0- or 1.5-mm diameter, the wall attenuations were not affected by the contrast material densities and were operator independent, measuring between 75 and 103 HU. Conclusions: The use of differentiation curves can improve the precision and accuracy in wall attenuation measurement using a ROI technique, while measurements for walls of ≤1.0 mm thickness are difficult.

Detection of differentially methylated regions of irradiated fig tree selections

Energy Technology Data Exchange (ETDEWEB)

Rodrigues, Maria Gabriela Fontanetti; Soares, Murilo Racy; Gimenez, Daniele Fernanda Jovino; Fonseca, Larissa Fernanda Simielli; Torrieri, Erico; Ramos, Ester Silveira; Giuliatti, Silvana, E-mail: mariagabriela@dracena.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Dracena, SP (Brazil). Faculdade de Agricultura e Ciencias Tecnologicas; Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Dept. de Genetica; Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Jaboticabal, SP (Brazil). Faculdade de Agricultura e Ciencias Veterinarias

2017-07-15

Fig tree (Ficus carica L.) breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, 'Roxo-de-Valinhos', which had previously used methylation-sensitive amplified polymorphism (MSAP) and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP) form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes. (author)

Detection of differentially methylated regions of irradiated fig tree selections

Directory of Open Access Journals (Sweden)

Maria Gabriela Fontanetti Rodrigues

Full Text Available ABSTRACT Fig tree (Ficus carica L. breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, “Roxo-de-Valinhos”, which had previously used methylation-sensitive amplified polymorphism (MSAP and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes.

Detection of differentially methylated regions of irradiated fig tree selections

International Nuclear Information System (INIS)

Rodrigues, Maria Gabriela Fontanetti; Soares, Murilo Racy; Gimenez, Daniele Fernanda Jovino; Fonseca, Larissa Fernanda Simielli; Torrieri, Erico; Ramos, Ester Silveira; Giuliatti, Silvana; Universidade de Sao Paulo; Universidade Estadual Paulista Julio de Mesquita Filho

2017-01-01

Fig tree (Ficus carica L.) breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, 'Roxo-de-Valinhos', which had previously used methylation-sensitive amplified polymorphism (MSAP) and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP) form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes. (author)

Extending the Effective Ranging Depth of Spectral Domain Optical Coherence Tomography by Spatial Frequency Domain Multiplexing

Directory of Open Access Journals (Sweden)

Tong Wu

2016-11-01

Full Text Available We present a spatial frequency domain multiplexing method for extending the imaging depth range of a spectral domain optical coherence tomography (SDOCT system without any expensive device. This method uses two galvo scanners with different pivot-offset distances in two independent reference arms for spatial frequency modulation and multiplexing. The spatial frequency contents corresponding to different depth regions of the sample can be shifted to different frequency bands. The spatial frequency domain multiplexing SDOCT system provides an approximately 1.9-fold increase in the effective ranging depth compared with that of a conventional full-range SDOCT system. The reconstructed images of phantom and biological tissue demonstrate the expected increase in ranging depth. The parameters choice criterion for this method is discussed.

Differential morphology and image processing.

Science.gov (United States)

Maragos, P

1996-01-01

Image processing via mathematical morphology has traditionally used geometry to intuitively understand morphological signal operators and set or lattice algebra to analyze them in the space domain. We provide a unified view and analytic tools for morphological image processing that is based on ideas from differential calculus and dynamical systems. This includes ideas on using partial differential or difference equations (PDEs) to model distance propagation or nonlinear multiscale processes in images. We briefly review some nonlinear difference equations that implement discrete distance transforms and relate them to numerical solutions of the eikonal equation of optics. We also review some nonlinear PDEs that model the evolution of multiscale morphological operators and use morphological derivatives. Among the new ideas presented, we develop some general 2-D max/min-sum difference equations that model the space dynamics of 2-D morphological systems (including the distance computations) and some nonlinear signal transforms, called slope transforms, that can analyze these systems in a transform domain in ways conceptually similar to the application of Fourier transforms to linear systems. Thus, distance transforms are shown to be bandpass slope filters. We view the analysis of the multiscale morphological PDEs and of the eikonal PDE solved via weighted distance transforms as a unified area in nonlinear image processing, which we call differential morphology, and briefly discuss its potential applications to image processing and computer vision.

Going from microscopic to macroscopic on nonuniform growing domains.

Science.gov (United States)

Yates, Christian A; Baker, Ruth E; Erban, Radek; Maini, Philip K

2012-08-01

Throughout development, chemical cues are employed to guide the functional specification of underlying tissues while the spatiotemporal distributions of such chemicals can be influenced by the growth of the tissue itself. These chemicals, termed morphogens, are often modeled using partial differential equations (PDEs). The connection between discrete stochastic and deterministic continuum models of particle migration on growing domains was elucidated by Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration of individual particles was modeled as an on-lattice position-jump process. We build on this work by incorporating a more physically reasonable description of domain growth. Instead of allowing underlying lattice elements to instantaneously double in size and divide, we allow incremental element growth and splitting upon reaching a predefined threshold size. Such a description of domain growth necessitates a nonuniform partition of the domain. We first demonstrate that an individual-based stochastic model for particle diffusion on such a nonuniform domain partition is equivalent to a PDE model of the same phenomenon on a nongrowing domain, providing the transition rates (which we derive) are chosen correctly and we partition the domain in the correct manner. We extend this analysis to the case where the domain is allowed to change in size, altering the transition rates as necessary. Through application of the master equation formalism we derive a PDE for particle density on this growing domain and corroborate our findings with numerical simulations.

Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

Science.gov (United States)

Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

2016-01-01

ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

Perturbative evolution of particle orbits around Kerr black holes: time-domain calculation

Energy Technology Data Exchange (ETDEWEB)

Lopez-Aleman, Ramon [Physical Sciences Department, University of Puerto Rico-Rio Piedras, San Juan, PR 00931 (Puerto Rico); Khanna, Gaurav [Natural Science Division, Long Island University, Southampton, NY 11968 (United States); Pullin, Jorge [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States)

2003-07-21

We consider the problem of the gravitational waves produced by a particle of negligible mass orbiting a Kerr black hole. We treat the Teukolsky perturbation equation in the time domain numerically as a 2 + 1 partial differential equation. We model the particle by smearing the singularities in the source term by the use of narrow Gaussian distributions. We have been able to reproduce earlier results for equatorial circular orbits that were computed using the frequency-domain formalism. The time-domain approach is however geared for a more general evolution, for instance of nearly geodesic orbits under the effects of radiation reaction.

Perturbative evolution of particle orbits around Kerr black holes: time-domain calculation

International Nuclear Information System (INIS)

Lopez-Aleman, Ramon; Khanna, Gaurav; Pullin, Jorge

2003-01-01

We consider the problem of the gravitational waves produced by a particle of negligible mass orbiting a Kerr black hole. We treat the Teukolsky perturbation equation in the time domain numerically as a 2 + 1 partial differential equation. We model the particle by smearing the singularities in the source term by the use of narrow Gaussian distributions. We have been able to reproduce earlier results for equatorial circular orbits that were computed using the frequency-domain formalism. The time-domain approach is however geared for a more general evolution, for instance of nearly geodesic orbits under the effects of radiation reaction

Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency.

Science.gov (United States)

Leng, Lizhi; Tan, Yueqiu; Gong, Fei; Hu, Liang; Ouyang, Qi; Zhao, Yan; Lu, Guangxiu; Lin, Ge

2015-03-01

, POI2-iPS-V.1 and hEF-iPS-V.1 produced green fluorescent cells in the differentiated cultures, and the percentage of GFP-positive cells increased over the 12 days of differentiation to a maximum of 6.9 ± 0.33%, 5.3 ± 0.57% and 8.5 ± 0.29%, respectively, of the total cell population. Immunohistochemical analysis confirmed that endogenous VASA was enriched in the GFP-positive cells. Quantitative reverse transcription-PCR revealed significantly higher expression of germ cell markers [PR domain containing 1, with ZNF domain (PRDM1, BLIMP1), developmental pluripotency-associated 3 (DPPA3, STELLA), deleted in azoospermia-like (DAZL), and VASA (DDX4)] in GFP-positive cells than in GFP-negative cells. Moreover, the GFP-positive cells from POI-iPSCs had reduced expression of the family with sequence similarity 122C (FAM122C), inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), and RNA binding motif protein, X-linked (RBMX), genes located in the deleted region of the X chromosome and that are highly expressed in differentiated germ cells, compared with cells from normal iPSCs. Gene expression profiling indicated that the germ cells differentiated from POI-iPSCs were pre-meiotic. Therefore, how the differentiated primordial germ cells could progress further to meiosis and form follicles remains to be determined in the study of POI. Our results might provide an in vitro model for studying germ cell development in patients with POI. This work was supported by grants from the Major State Basic Research Development Program of China (No. 2012CB944901), the National Science Foundation of China (No. 81222007 and 81471432), the Program for New Century Excellent Talents in University and the Fundamental Research Funds for Central Universities (No. 721500003). The authors have no competing interests to declare. Not applicable. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology

A Generalized FDM for solving the Poisson's Equation on 3D Irregular Domains

Directory of Open Access Journals (Sweden)

J. Izadian

2014-01-01

Full Text Available In this paper a new method for solving the Poisson's equation with Dirichlet conditions on irregular domains is presented. For this purpose a generalized finite differences method is applied for numerical differentiation on irregular meshes. Three examples on cylindrical and spherical domains are considered. The numerical results are compared with analytical solution. These results show the performance and efficiency of the proposed method.

A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain.

Science.gov (United States)

Wu, R; Wilton, R; Cuff, M E; Endres, M; Babnigg, G; Edirisinghe, J N; Henry, C S; Joachimiak, A; Schiffer, M; Pokkuluri, P R

2017-04-01

We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from Lake Retba, in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously, and their best known function is in solute transport across membranes. PAS-like sensor domains are commonly found in signal transduction proteins. These domains are widely observed as parts of many protein architectures and complexes but have not been observed previously within the same polypeptide chain. In the structure of Dret_0059, a ketoleucine moiety is bound to the SBP, whereas a cytosine molecule is bound in the distal PAS-like domain of the tandem PAS-like domain. Differential scanning flourimetry support the binding of ligands observed in the crystal structure. There is significant interaction between the SBP and tandem PAS-like domains, and it is possible that the binding of one ligand could have an effect on the binding of the other. We uncovered three other proteins with this structural architecture in the non-redundant sequence data base, and predict that they too bind the same substrates. The genomic context of this protein did not offer any clues for its function. We did not find any biological process in which the two observed ligands are coupled. The protein Dret_0059 could be involved in either signal transduction or solute transport. © 2017 The Protein Society.

Domain wall width of lithium niobate poled during growth

CERN Document Server

Brooks, R; Hole, D E; Callejo, D; Bermudez, V; Diéguez, E

2003-01-01

Good quality crystals of periodically poled lithium niobate can be generated directly during growth. However, the temperature gradients at the zone boundaries define the width of the regions where the polarity is reversed. Hence, the region influenced the domain transition may be a significant fraction of the overall poling period for material poled during growth. Evidence for the scale of this feature is reported both by chemical etching and by the less common method of ion beam luminescence and the 'domain wall' width approximately 1 mu m for these analyses. The influence of the reversal region may differ for alternative techniques but the relevance to device design for second harmonic generation is noted.

Advanced differential quadrature methods

CERN Document Server

Zong, Zhi

2009-01-01

Modern Tools to Perform Numerical DifferentiationThe original direct differential quadrature (DQ) method has been known to fail for problems with strong nonlinearity and material discontinuity as well as for problems involving singularity, irregularity, and multiple scales. But now researchers in applied mathematics, computational mechanics, and engineering have developed a range of innovative DQ-based methods to overcome these shortcomings. Advanced Differential Quadrature Methods explores new DQ methods and uses these methods to solve problems beyond the capabilities of the direct DQ method.After a basic introduction to the direct DQ method, the book presents a number of DQ methods, including complex DQ, triangular DQ, multi-scale DQ, variable order DQ, multi-domain DQ, and localized DQ. It also provides a mathematical compendium that summarizes Gauss elimination, the Runge-Kutta method, complex analysis, and more. The final chapter contains three codes written in the FORTRAN language, enabling readers to q...

Echothymia: environmental dependency in the affective domain.

Science.gov (United States)

Marin, Robert S; Gorovoy, Ian R

2014-01-01

Echothymia is stimulus-bound affective behavior, an echophenomenon in the domain of affect. Like echolalia and echopraxia, it is a concomitant of the environmental dependency associated with dysfunction of the frontal-striatal systems that mediate so-called frontal lobe functions. The authors introduce the definition and phenomenology of echothymia, overview its differential diagnosis and clinical significance, and suggest ways in which understanding echothymia may contribute to clinical management.

PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

Science.gov (United States)

Kicka, Sébastien; Silar, Philippe

2004-03-01

MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.

Organization of functional domains in the docking protein p130Cas

International Nuclear Information System (INIS)

Nasertorabi, Fariborz; Garcia-Guzman, Miguel; Briknarova, Klara; Larsen, Elise; Havert, Marnie L.; Vuori, Kristiina; Ely, Kathryn R.

2004-01-01

The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling

Quantifying water flow and retention in an unsaturated fracture-facial domain

Science.gov (United States)

Nimmo, John R.; Malek-Mohammadi, Siamak

2015-01-01

Hydrologically significant flow and storage of water occur in macropores and fractures that are only partially filled. To accommodate such processes in flow models, we propose a three-domain framework. Two of the domains correspond to water flow and water storage in a fracture-facial region, in addition to the third domain of matrix water. The fracture-facial region, typically within a fraction of a millimeter of the fracture wall, includes a flowing phase whose fullness is determined by the availability and flux of preferentially flowing water, and a static storage portion whose fullness is determined by the local matric potential. The flow domain can be modeled with the source-responsive preferential flow model, and the roughness-storage domain can be modeled with capillary relations applied on the fracture-facial area. The matrix domain is treated using traditional unsaturated flow theory. We tested the model with application to the hydrology of the Chalk formation in southern England, coherently linking hydrologic information including recharge estimates, streamflow, water table fluctuation, imaging by electron microscopy, and surface roughness. The quantitative consistency of the three-domain matrix-microcavity-film model with this body of diverse data supports the hypothesized distinctions and active mechanisms of the three domains and establishes the usefulness of this framework.

Far- and near-field second-harmonic imaging of ferroelectric domain walls

DEFF Research Database (Denmark)

Bozhevolnyi, Sergey I.; Pedersen, K.; Skettrup, Torben

1998-01-01

Domain walls in periodically poled ferroelectric LiNbO3 crystals are observed with both far- and near-field imaging techniques that make use of second harmonic generation in the transition regions between neighbouring domains. Second harmonic images of domain walls represent bright lines of about.......5 micrometers in width (as measured with the near-field microscope) for the polarization of the second harmonic radiation perpendicular to the domain walls. Origin and selection rules for the constrast in second harmonic images of domain walls are discussed....

Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

International Nuclear Information System (INIS)

Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji

1991-01-01

A 13 C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V H , V L , and C L domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with 13 C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with [1- 13 C]Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how 13 C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule

ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.

Science.gov (United States)

Nair, Nishanth Ulhas; Sahu, Avinash Das; Bucher, Philipp; Moret, Bernard M E

2012-01-01

The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.

A 48 kDa collagen-binding phosphoprotein isolated from bovine aortic endothelial cells interacts with the collagenous domain, but not the globular domain, of collagen type IV.

Science.gov (United States)

Yannariello-Brown, J; Madri, J A

1990-01-15

We have identified collagen-binding proteins in detergent extracts of metabolically labelled bovine aortic endothelial cells (BAEC) by collagen type IV-Sepharose affinity chromatography. The major collagen type IV-binding protein identified by SDS/PAGE had a molecular mass of 48 kDa, which we term the 'collagen-binding 48 kDa protein' (CB48). The pI of CB48 was 8.0-8.3 in a two-dimensional gel system, running non-equilibrium pH gel electrophoresis in the first dimension and SDS/PAGE in the second dimension. Under these conditions CB48 separated into two major (a and b) and one minor isoform (c); a was the most basic of the three isoforms. Two-dimensional chymotryptic peptide maps derived from each individual isoform were virtually identical. The charge differences between the isoforms were due in part to differential H3(32)PO4 incorporation by the protein. CB48 bound to intact collagen type IV and the collagenous region of collagen type IV, but not to the globular NC1 domain. Cell-surface labelling and indirect immunofluorescence experiments localized the bulk of CB48 intracellularly in the endoplasmic reticulum Golgi region, with a minor population of molecules on the cell surface. A specific rabbit polyclonal anti-CB48 serum did not inhibit the attachment or spreading of BAEC to collagen type IV in an 'in vitro' adhesion assay, suggesting that the cell-surface population of CB48 is not involved in BAEC adhesion. We conclude that CB48 is a collagen-binding phosphoprotein that interacts with the collagenous domain of collagen type IV and may be involved in intracellular transport of collagen molecules.

Applicability of angular flux discontinuity factor preserving region-wise leakage for integro-differential transport equation

International Nuclear Information System (INIS)

Sakamoto, Tatsuya; Endo, Tomohiro; Yamamoto, Akio

2014-01-01

In the current core analysis, spatial homogenization is utilized to reduce the computational time. The discontinuity factor (DF) is one of the effective correction factors to reduce spatial homogenization error. The DF in diffusion equation is widely used; on the other hand the DF in transport equation has not been put to practical use although several efforts have been carried out. In this paper, the angular flux discontinuity factor (AFDF) as the DF for the integro-differential transport equation (e.g., the discrete-ordinate method, the method of characteristics) is theoretically described and its applicability is discussed. The AFDF is used to preserve the region-wise neutron leakage at each spatial mesh and defined as a ratio of heterogeneous and homogeneous angular fluxes at the homogenized region surface. In a homogeneous calculation with the AFDF, the angular flux is discontinuous at the region surface. In this paper the applicability of the AFDF to fuel pin cell homogenization is verified for one-dimensional slab geometry. As a result of this verification, it is confirmed that the AFDF has the capability to reduce the spatial homogenization error of fuel pin cell homogenization. (author)

The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer

DEFF Research Database (Denmark)

Mollenhauer, Jan; Müller, Hanna; Kollender, Gaby

2002-01-01

Deleted in malignant brain tumors 1 (DMBT1) at 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain and epithelial cancer. DMBT1 encodes a multifunctional mucin-like protein presumably involved in epithelial differentiation and protection. The gene consists of highly...... homologous and repeating exon and intron sequences. This specifically applies to the region coding for the repetitive scavenger receptor cysteine-rich (SRCR) domains and SRCR-interspersed domains (SIDs) that constitutes the major part of the gene. This particular structure may previously have interfered...... with the delineation of DMBT1 alterations in cancer. Uncovering these, however, is of mechanistic importance. By a combined approach, we conducted a detailed mutational analysis, starting from a panel of 51 tumors, including 46 tumor cell lines and five primary tumors. Alterations in the repetitive region were present...

Data compression and genomes: a two-dimensional life domain map.

Science.gov (United States)

Menconi, Giulia; Benci, Vieri; Buiatti, Marcello

2008-07-21

We define the complexity of DNA sequences as the information content per nucleotide, calculated by means of some Lempel-Ziv data compression algorithm. It is possible to use the statistics of the complexity values of the functional regions of different complete genomes to distinguish among genomes of different domains of life (Archaea, Bacteria and Eukarya). We shall focus on the distribution function of the complexity of non-coding regions. We show that the three domains may be plotted in separate regions within the two-dimensional space where the axes are the skewness coefficient and the curtosis coefficient of the aforementioned distribution. Preliminary results on 15 genomes are introduced.

The Receptor-Binding Domain in the VP1u Region of Parvovirus B19.

Science.gov (United States)

Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos

2016-02-24

Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5-80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system.

Rampant adaptive evolution in regions of proteins with unknown function in Drosophila simulans.

Directory of Open Access Journals (Sweden)

Alisha K Holloway

2007-10-01

Full Text Available Adaptive protein evolution is pervasive in Drosophila. Genomic studies, thus far, have analyzed each protein as a single entity. However, the targets of adaptive events may be localized to particular parts of proteins, such as protein domains or regions involved in protein folding. We compared the population genetic mechanisms driving sequence polymorphism and divergence in defined protein domains and non-domain regions. Interestingly, we find that non-domain regions of proteins are more frequent targets of directional selection. Protein domains are also evolving under directional selection, but appear to be under stronger purifying selection than non-domain regions. Non-domain regions of proteins clearly play a major role in adaptive protein evolution on a genomic scale and merit future investigations of their functional properties.

Longitudinal analysis of domain-level breast cancer literacy among African-American women.

Science.gov (United States)

Mabiso, Athur; Williams, Karen Patricia; Todem, David; Templin, Thomas N

2010-02-01

Functional breast cancer literacy was assessed among African-American women and measured at the domain level over time. We used the Kin Keeper(SM) Cancer Prevention Intervention to educate 161 African-American women on three domains of breast cancer literacy: (i) cancer awareness, (ii) knowledge of breast cancer screening modalities and (iii) cancer prevention and control. A breast cancer literacy assessment was administered pre- and post-educational intervention at two time points followed by another assessment 12 months after the second intervention. Generalized estimating equations were specified to predict the probability of correctly answering questions in each domain over time. Domain-level literacy differentials exist; at baseline, women had higher test scores in the breast cancer prevention and control domain than the cancer awareness domain (odds ratio = 1.67, 95% confidence interval 1.19-2.34). After Kin Keeper(SM) Cancer Prevention Intervention, African-American women consistently improved their breast cancer literacy in all domains over the five time stages (P < 0.001) though at different rates for each domain. Differences in domain-level breast cancer literacy highlight the importance of assessing literacy at the domain level. Interventions to improve African-American women's breast cancer literacy should focus on knowledge of breast cancer screening modalities and cancer awareness domains.

Power filtering of n-th order in the fractional Fourier domain

NARCIS (Netherlands)

Alieva, T.; Calvo, M.L.; Bastiaans, M.J.

2002-01-01

The main properties of the power filtering operation in the fractional Fourier domain and its relationship to the differentiation operation are considered. The application of linear power filtering for solving the phase retrieval problem from only intensity distributions is proposed. The optical

Analysis of the Sequences, Structures, and Functions of Product-Releasing Enzyme Domains in Fungal Polyketide Synthases

Directory of Open Access Journals (Sweden)

Lu Liu

2017-09-01

Full Text Available Product-releasing enzyme (PRE domains in fungal non-reducing polyketide synthases (NR-PKSs play a crucial role in catalysis and editing during polyketide biosynthesis, especially accelerating final biosynthetic reactions accompanied with product offloading. However, up to date, the systematic knowledge about PRE domains is deficient. In the present study, the relationships between sequences, structures, and functions of PRE domains were analyzed with 574 NR-PKSs of eight groups (I–VIII. It was found that the PRE domains in NR-PKSs could be mainly classified into three types, thioesterase (TE, reductase (R, and metallo-β-lactamase-type TE (MβL-TE. The widely distributed TE or TE-like domains were involved in NR-PKSs of groups I–IV, VI, and VIII. The R domains appeared in NR-PKSs of groups IV and VII, while the physically discrete MβL-TE domains were employed by most NR-PKSs of group V. The changes of catalytic sites and structural characteristics resulted in PRE functional differentiations. The phylogeny revealed that the evolution of TE domains was accompanied by complex functional divergence. The diverse sequence lengths of TE lid-loops affected substrate specificity with different chain lengths. The volume diversification of TE catalytic pockets contributed to catalytic mechanisms with functional differentiations. The above findings may help to understand the crucial catalysis of fungal aromatic polyketide biosyntheses and govern recombination of NR-PKSs to obtain unnatural target products.

Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

DEFF Research Database (Denmark)

Durkin, M E; Wewer, U M; Chung, A E

1995-01-01

of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...

Domain-enhanced analysis of microarray data using GO annotations.

Science.gov (United States)

Liu, Jiajun; Hughes-Oliver, Jacqueline M; Menius, J Alan

2007-05-15

New biological systems technologies give scientists the ability to measure thousands of bio-molecules including genes, proteins, lipids and metabolites. We use domain knowledge, e.g. the Gene Ontology, to guide analysis of such data. By focusing on domain-aggregated results at, say the molecular function level, increased interpretability is available to biological scientists beyond what is possible if results are presented at the gene level. We use a 'top-down' approach to perform domain aggregation by first combining gene expressions before testing for differentially expressed patterns. This is in contrast to the more standard 'bottom-up' approach, where genes are first tested individually then aggregated by domain knowledge. The benefits are greater sensitivity for detecting signals. Our method, domain-enhanced analysis (DEA) is assessed and compared to other methods using simulation studies and analysis of two publicly available leukemia data sets. Our DEA method uses functions available in R (http://www.r-project.org/) and SAS (http://www.sas.com/). The two experimental data sets used in our analysis are available in R as Bioconductor packages, 'ALL' and 'golubEsets' (http://www.bioconductor.org/). Supplementary data are available at Bioinformatics online.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

Science.gov (United States)

Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

2015-01-01

The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

Directory of Open Access Journals (Sweden)

Sissel B Rønning

Full Text Available The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Structure and evolution of N-domains in AAA metalloproteases.

Science.gov (United States)

Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

2015-02-27

Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

Numerical simulation of electromagnetic wave propagation using time domain meshless method

International Nuclear Information System (INIS)

Ikuno, Soichiro; Fujita, Yoshihisa; Itoh, Taku; Nakata, Susumu; Nakamura, Hiroaki; Kamitani, Atsushi

2012-01-01

The electromagnetic wave propagation in various shaped wave guide is simulated by using meshless time domain method (MTDM). Generally, Finite Differential Time Domain (FDTD) method is applied for electromagnetic wave propagation simulation. However, the numerical domain should be divided into rectangle meshes if FDTD method is applied for the simulation. On the other hand, the node disposition of MTDM can easily describe the structure of arbitrary shaped wave guide. This is the large advantage of the meshless time domain method. The results of computations show that the damping rate is stably calculated in case with R < 0.03, where R denotes a support radius of the weight function for the shape function. And the results indicate that the support radius R of the weight functions should be selected small, and monomials must be used for calculating the shape functions. (author)

Large-area formation of self-aligned crystalline domains of organic semiconductors on transistor channels using CONNECT

Science.gov (United States)

Park, Steve; Giri, Gaurav; Shaw, Leo; Pitner, Gregory; Ha, Jewook; Koo, Ja Hoon; Gu, Xiaodan; Park, Joonsuk; Lee, Tae Hoon; Nam, Ji Hyun; Hong, Yongtaek; Bao, Zhenan

2015-01-01

The electronic properties of solution-processable small-molecule organic semiconductors (OSCs) have rapidly improved in recent years, rendering them highly promising for various low-cost large-area electronic applications. However, practical applications of organic electronics require patterned and precisely registered OSC films within the transistor channel region with uniform electrical properties over a large area, a task that remains a significant challenge. Here, we present a technique termed “controlled OSC nucleation and extension for circuits” (CONNECT), which uses differential surface energy and solution shearing to simultaneously generate patterned and precisely registered OSC thin films within the channel region and with aligned crystalline domains, resulting in low device-to-device variability. We have fabricated transistor density as high as 840 dpi, with a yield of 99%. We have successfully built various logic gates and a 2-bit half-adder circuit, demonstrating the practical applicability of our technique for large-scale circuit fabrication. PMID:25902502

Recent topics in differential and analytic geometry

CERN Document Server

Ochiai, T

1990-01-01

Advanced Studies in Pure Mathematics, Volume 18-I: Recent Topics in Differential and Analytic Geometry presents the developments in the field of analytical and differential geometry. This book provides some generalities about bounded symmetric domains.Organized into two parts encompassing 12 chapters, this volume begins with an overview of harmonic mappings and holomorphic foliations. This text then discusses the global structures of a compact Kähler manifold that is locally decomposable as an isometric product of Ricci-positive, Ricci-negative, and Ricci-flat parts. Other chapters con

Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens

International Nuclear Information System (INIS)

Leeper, Thomas; Zhang, Suxin; Van Voorhis, Wesley C.; Myler, Peter J.; Varani, Gabriele

2011-01-01

NMR structures of the glutaredoxin (GLXR) domains from Br. melitensis and Ba. henselae have been determined as part of the SSGCID initiative. Comparison of the domains with known structures reveals overall structural similarity between these proteins and previously determined E. coli GLXR structures, with minor changes associated with the position of helix 1 and with regions that diverge from similar structures found in the closest related human homolog. Glutaredoxin proteins (GLXRs) are essential components of the glutathione system that reductively detoxify substances such as arsenic and peroxides and are important in the synthesis of DNA via ribonucleotide reductases. NMR solution structures of glutaredoxin domains from two Gram-negative opportunistic pathogens, Brucella melitensis and Bartonella henselae, are presented. These domains lack the N-terminal helix that is frequently present in eukaryotic GLXRs. The conserved active-site cysteines adopt canonical proline/tyrosine-stabilized geometries. A difference in the angle of α-helix 2 relative to the β-sheet surface and the presence of an extended loop in the human sequence suggests potential regulatory regions and/or protein–protein interaction motifs. This observation is consistent with mutations in this region that suppress defects in GLXR–ribonucleotide reductase interactions. These differences between the human and bacterial forms are adjacent to the dithiol active site and may permit species-selective drug design

Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation.

Science.gov (United States)

Conacci-Sorrell, Maralice; Ngouenet, Celine; Eisenman, Robert N

2010-08-06

The Myc oncoprotein family comprises transcription factors that control multiple cellular functions and are widely involved in oncogenesis. Here we report the identification of Myc-nick, a cytoplasmic form of Myc generated by calpain-dependent proteolysis at lysine 298 of full-length Myc. Myc-nick retains conserved Myc box regions but lacks nuclear localization signals and the bHLHZ domain essential for heterodimerization with Max and DNA binding. Myc-nick induces alpha-tubulin acetylation and altered cell morphology by recruiting histone acetyltransferase GCN5 to microtubules. During muscle differentiation, while the levels of full-length Myc diminish, Myc-nick and acetylated alpha-tubulin levels are increased. Ectopic expression of Myc-nick accelerates myoblast fusion, triggers the expression of myogenic markers, and permits Myc-deficient fibroblasts to transdifferentiate in response to MyoD. We propose that the cleavage of Myc by calpain abrogates the transcriptional inhibition of differentiation by full-length Myc and generates Myc-nick, a driver of cytoplasmic reorganization and differentiation. Copyright 2010 Elsevier Inc. All rights reserved.

Multiple standards of aging: gender-specific age stereotypes in different life domains.

Science.gov (United States)

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2013-12-01

Whereas it is often stated that aging might have more negative consequences for the evaluation of women compared to men, evidence for this assumption is mixed. We took a differentiated look at age stereotypes of men and women, assuming that the life domain in which older persons are rated moderates gender differences in age stereotypes. A sample of 298 participants aged 20-92 rated 65 - year-old men and women on evaluative statements in eight different life domains. Furthermore, perceptions of gender- and domain-specific age-related changes were assessed by comparing the older targets to 45 - year-old men and women, respectively. The results speak in favor of the domain specificity of evaluative asymmetries in age stereotypes for men and women, and imply that an understanding of gendered perceptions of aging requires taking into account the complexities of domain-specific views on aging.

DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

Science.gov (United States)

Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

2009-08-07

DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse

Directory of Open Access Journals (Sweden)

Michael eHeide

2015-08-01

Full Text Available Acquisition of specific neuronal identity by individual brain nuclei is a key step in brain development. However, how the mechanisms that confer neuronal identity are integrated with upstream regional specification networks is still mysterious. Expression of Sonic hedgehog (Shh, is required for hypothalamic specification and is later downregulated by Tbx3 to allow for the differentiation of the tubero-mamillary region. In this region, the mamillary body (MBO, is a large neuronal aggregate essential for memory formation. To clarify how MBO identity is acquired after regional specification, we investigated Lhx5, a transcription factor with restricted MBO expression. We first generated a hypomorph allele of Lhx5—in homozygotes, the MBO disappears after initial specification. Intriguingly, in these mutants, Tbx3 was downregulated and the Shh expression domain abnormally extended. Microarray analysis and chromatin immunoprecipitation indicated that Lhx5 appears to be involved in Shh downregulation through Tbx3 and activates several MBO-specific regulator and effector genes. Finally, by tracing the caudal hypothalamic cell lineage we show that, in the Lhx5 mutant, at least some MBO cells are present but lack characteristic marker expression. Our work shows how the Lhx5 locus contributes to integrate regional specification pathways with downstream acquisition of neuronal identity in the MBO.

Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

Energy Technology Data Exchange (ETDEWEB)

Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan))

1991-07-02

A {sup 13}C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V{sub H}, V{sub L}, and C{sub L} domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with {sup 13}C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with (1-{sup 13}C)Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how {sup 13}C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule.

Measuring regional authority

NARCIS (Netherlands)

Marks, G.W.; Hooghe, E.A.E.B.; Schakel, A.H.

2008-01-01

This article sets out a conceptual basis for measuring regional authority and engages basic measurement issues. Regional authority is disaggregated into two domains (self-rule and shared rule) and these are operationalised in eight dimensions. The article concludes by examining the robustness of

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-09-18

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+ saturating 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.

Crystal Structure of the FERM Domain of Focal Adhesion Kinase

International Nuclear Information System (INIS)

Ceccarelli, D.; Song, H.; Poy, F.; Schaller, M.; Eck, M.

2006-01-01

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment

MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

Science.gov (United States)

Shi, Lei; Zhou, Bo; Li, Pinghua; Schinckel, Allan P; Liang, Tingting; Wang, Han; Li, Huizhi; Fu, Lingling; Chu, Qingpo; Huang, Ruihua

2015-09-01

MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells. Copyright © 2015 Elsevier Inc. All rights reserved.

The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

Science.gov (United States)

Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

2000-04-01

Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

Power filtering of nth order in the fractional Fourier domain

International Nuclear Information System (INIS)

Alieva, Tatiana; Calvo, Maria Luisa; Bastiaans, Martin J.

2002-01-01

The main properties of the power filtering operation in the fractional Fourier domain and its relationship to the differentiation operation are considered. The application of linear power filtering for solving the phase retrieval problem from intensity distributions only is proposed. The optical configuration for the experimental realization of the method is discussed. (author)

Territorial differentiation of incomes adjusted for inflation

Directory of Open Access Journals (Sweden)

Marina Valeryevna, Moroshkina

2017-06-01

Full Text Available Objective to analyze and evaluate the regional disparities of socioeconomic development of the Russian regions in terms of income differentiation adjusted for the level of inflation. Methods indicator by which to measure the level of regional growth heterogeneity is Gini coefficient allowing to determine the degree of the Russian regionsrsquo deviation from absolute equality. The unique feature of the authorrsquos approach is the calculation and analysis of the Gini coefficient not only in current prices but also in comparable prices of 1991. Thus the comparison of the Gini coefficient in terms of quotper capita incomequot in the period from 1991 to 2013 in comparable and current prices allows to estimate the impact of changes in the prices level on the dynamics of regional development. Results the article states that the regions differentiation by the level of economic development determines the necessity of considering this factor in economic policy areas. In these circumstances the analysis of income differentiation of the Russian regions has to take the impact of inflation into account. The article reviews the Russian and foreign research in the sphere of the income differentiation. Significant scientific interest to the problem of regional inequality is obvious over the past several decades. Approaches and methods of assessing the level of regional disparities are systematized as well as its key performance indicators. To assess the level of differentiation of Russian regions we used the Gini coefficient which was calculated not only by current but also by comparable prices. The calculation was carried out basing on the recalculation of the per capita income using the consumer price index. In the framework of the analysis the calculated Gini coefficient for per capita income by current and integrated prices allowed to observe the differential behavior of this indicator. In terms of quotper capita incomequot by current prices there is a

Regulation of the Hsp104 middle domain activity is critical for yeast prion propagation.

Directory of Open Access Journals (Sweden)

Jennifer E Dulle

Full Text Available Molecular chaperones play a significant role in preventing protein misfolding and aggregation. Indeed, some protein conformational disorders have been linked to changes in the chaperone network. Curiously, in yeast, chaperones also play a role in promoting prion maintenance and propagation. While many amyloidogenic proteins are associated with disease in mammals, yeast prion proteins, and their ability to undergo conformational conversion into a prion state, are proposed to play a functional role in yeast biology. The chaperone Hsp104, a AAA+ ATPase, is essential for yeast prion propagation. Hsp104 fragments large prion aggregates to generate a population of smaller oligomers that can more readily convert soluble monomer and be transmitted to daughter cells. Here, we show that the middle (M domain of Hsp104, and its mobility, plays an integral part in prion propagation. We generated and characterized mutations in the M-domain of Hsp104 that are predicted to stabilize either a repressed or de-repressed conformation of the M-domain (by analogy to ClpB in bacteria. We show that the predicted stabilization of the repressed conformation inhibits general chaperone activity. Mutation to the de-repressed conformation, however, has differential effects on ATP hydrolysis and disaggregation, suggesting that the M-domain is involved in coupling these two activities. Interestingly, we show that changes in the M-domain differentially affect the propagation of different variants of the [PSI+] and [RNQ+] prions, which indicates that some prion variants are more sensitive to changes in the M-domain mobility than others. Thus, we provide evidence that regulation of the M-domain of Hsp104 is critical for efficient prion propagation. This shows the importance of elucidating the function of the M-domain in order to understand the role of Hsp104 in the propagation of different prions and prion variants.

Structure of a WW domain-containing fragment of dystrophin complexed with {beta}-dystroglycan.

Energy Technology Data Exchange (ETDEWEB)

Huang, X.; Poy, F.; Zhang, R.; Joachimiak, A.; Sudol, M.; Eck, M. J.; Biosciences Division; Dana Farber Cancer Inst.; Harvard Medical School; Mount Sinai School of Medicine

2000-08-01

Dystrophin and {beta}-dystroglycan are components of the dystrophin--glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of {beta}-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of {beta}-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in {beta}-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The {beta}-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

Functional and topological characteristics of mammalian regulatory domains

Science.gov (United States)

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project).

Science.gov (United States)

Compernolle, Sofie; De Cocker, Katrien; Roda, Célina; Oppert, Jean-Michel; Mackenbach, Joreintje D; Lakerveld, Jeroen; Glonti, Ketevan; Bardos, Helga; Rutter, Harry; Cardon, Greet; De Bourdeaudhuij, Ilse

2016-01-01

The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level. In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables. Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours. Preliminary evidence was found for

Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project.

Directory of Open Access Journals (Sweden)

Sofie Compernolle

Full Text Available The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level.In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London, a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables.Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours.Preliminary evidence was

Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects

Directory of Open Access Journals (Sweden)

Carmen L. Bayly

2017-02-01

Full Text Available Modular polyketide synthases (mPKSs build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause both unintended products and dramatically reduced activity. This limits the engineering and combinatorial potential of mPKSs, precluding access to further potential therapeutics. Different regions on a given mPKS domain determine how it interacts both with its substrate and with other domains. Within the assembly line, these interactions are crucial to the proper ordering of reactions and efficient polyketide construction. Achieving control over these domain functions, through precision engineering at key regions, would greatly expand our catalogue of accessible polyketide products. Canonical mPKS domains, given that they are among the most well-characterized, are excellent candidates for such fine-tuning. The current minireview summarizes recent advances in the mechanistic understanding and subsequent precision engineering of canonical mPKS domains, focusing largely on developments in the past year.

Consistency of differential and integral thermonuclear neutronics data

International Nuclear Information System (INIS)

Reupke, W.A.

1978-01-01

To increase the accuracy of the neutronics analysis of nuclear reactors, physicists and engineers have employed a variety of techniques, including the adjustment of multigroup differential data to improve consistency with integral data. Of the various adjustment strategies, a generalized least-squares procedure which adjusts the combined differential and integral data can significantly improve the accuracy of neutronics calculations compared to calculations employing only differential data. This investigation analyzes 14 MeV neutron-driven integral experiments, using a more extensively developed methodology and a newly developed computer code, to extend the domain of adjustment from the energy range of fission reactors to the energy range of fusion reactors

The Asia 2 specific signal peptide region and other domains in fusion protein genes characterized Asia 1 and Asia 2 canine distemper viruses

Science.gov (United States)

Sultan, Serageldeen; Charoenvisal, Nataya; Lan, Nguyen Thi; Yamaguchi, Ryoji; Maeda, Ken; Kai, Kazushige

2009-01-01

Background Although the presence of Asia 2 group of canine distemper virus (CDV) was known by the sequencing and phylogenetic analysis of hemagglutinin (H) gene, the fusion (F) protein gene sequence of Asia 2 group had not been identified. So, the sequence analysis of F gene was carried out to elucidate the genotypic varaitons among Asian isolates. Results The phylogenetic analysis of F and H gene sequences from fourteen CDV isolates obtained from diseased dogs in Japan and Thailand indicated that the F genes had a new initiation codon and extra 27 nucleotides upstream of the usual open reading frame (ORF) and the F proteins had extra 9 amino acids at the N-terminal position only in Asia 2 isolates. On the contrary, the Asia 1 isolates had three extra putative N-glycosylation sites (two sites in the signal peptide region and one site in the F1 region) except for two strains of Th12 and Ac96I (two sites in signal peptide region) adding to four putative N-glycosylation sites that were conserved among all Asian isolates and Onderstepoort strain. In addition to this difference in N-glycosylation sites, the signal peptide region had a great diversity between Asia 1 and Asia 2 isolates. Also, characteristic amino acids were detected for some strains. Conclusion Asia 2 isolates were distinguished from other CDV lineages by the extra 27 nucleotide sequence. The signal peptide region of F gene gives a remarkable differentiation between Asia 1 and Asia 2 isolates. Strains Th12 and Ac96I were differentiated from other Asia 1 strains by the F protein glycosylation sites. PMID:19807927

The PHD Domain of Np95 (mUHRF1) Is Involved in Large-Scale Reorganization of Pericentromeric Heterochromatin

Science.gov (United States)

Papait, Roberto; Pistore, Christian; Grazini, Ursula; Babbio, Federica; Cogliati, Sara; Pecoraro, Daniela; Brino, Laurent; Morand, Anne-Laure; Dechampesme, Anne-Marie; Spada, Fabio; Leonhardt, Heinrich; McBlane, Fraser; Oudet, Pierre

2008-01-01

Heterochromatic chromosomal regions undergo large-scale reorganization and progressively aggregate, forming chromocenters. These are dynamic structures that rapidly adapt to various stimuli that influence gene expression patterns, cell cycle progression, and differentiation. Np95-ICBP90 (m- and h-UHRF1) is a histone-binding protein expressed only in proliferating cells. During pericentromeric heterochromatin (PH) replication, Np95 specifically relocalizes to chromocenters where it highly concentrates in the replication factories that correspond to less compacted DNA. Np95 recruits HDAC and DNMT1 to PH and depletion of Np95 impairs PH replication. Here we show that Np95 causes large-scale modifications of chromocenters independently from the H3:K9 and H4:K20 trimethylation pathways, from the expression levels of HP1, from DNA methylation and from the cell cycle. The PHD domain is essential to induce this effect. The PHD domain is also required in vitro to increase access of a restriction enzyme to DNA packaged into nucleosomal arrays. We propose that the PHD domain of Np95-ICBP90 contributes to the opening and/or stabilization of dense chromocenter structures to support the recruitment of modifying enzymes, like HDAC and DNMT1, required for the replication and formation of PH. PMID:18508923

Distributed HUC-based modeling with SUMMA for ensemble streamflow forecasting over large regional domains.

Science.gov (United States)

Saharia, M.; Wood, A.; Clark, M. P.; Bennett, A.; Nijssen, B.; Clark, E.; Newman, A. J.

2017-12-01

Most operational streamflow forecasting systems rely on a forecaster-in-the-loop approach in which some parts of the forecast workflow require an experienced human forecaster. But this approach faces challenges surrounding process reproducibility, hindcasting capability, and extension to large domains. The operational hydrologic community is increasingly moving towards `over-the-loop' (completely automated) large-domain simulations yet recent developments indicate a widespread lack of community knowledge about the strengths and weaknesses of such systems for forecasting. A realistic representation of land surface hydrologic processes is a critical element for improving forecasts, but often comes at the substantial cost of forecast system agility and efficiency. While popular grid-based models support the distributed representation of land surface processes, intermediate-scale Hydrologic Unit Code (HUC)-based modeling could provide a more efficient and process-aligned spatial discretization, reducing the need for tradeoffs between model complexity and critical forecasting requirements such as ensemble methods and comprehensive model calibration. The National Center for Atmospheric Research is collaborating with the University of Washington, the Bureau of Reclamation and the USACE to implement, assess, and demonstrate real-time, over-the-loop distributed streamflow forecasting for several large western US river basins and regions. In this presentation, we present early results from short to medium range hydrologic and streamflow forecasts for the Pacific Northwest (PNW). We employ a real-time 1/16th degree daily ensemble model forcings as well as downscaled Global Ensemble Forecasting System (GEFS) meteorological forecasts. These datasets drive an intermediate-scale configuration of the Structure for Unifying Multiple Modeling Alternatives (SUMMA) model, which represents the PNW using over 11,700 HUCs. The system produces not only streamflow forecasts (using the Mizu

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan; Gao, Xin

2014-01-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan

2014-02-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

Dependence of the ferroelectric domain shape on the electric field of the microscope tip

International Nuclear Information System (INIS)

Starkov, Alexander S.; Starkov, Ivan A.

2015-01-01

A theory of an equilibrium shape of the domain formed in an electric field of a scanning force microscope (SFM) tip is proposed. We do not assume a priori that the domain has a fixed form. The shape of the domain is defined by the minimum of the free energy of the ferroelectric. This energy includes the energy of the depolarization field, the energy of the domain wall, and the energy of the interaction between the domain and the electric field of the SFM tip. The contributions of the apex and conical part of the tip are examined. Moreover, in the proposed approach, any narrow tip can be considered. The surface energy is determined on the basis of the Ginzburg-Landau-Devonshire theory and takes into account the curvature of the domain wall. The variation of the free energy with respect to the domain shape leads to an integro-differential equation, which must be solved numerically. Model results are illustrated for lithium tantalate ceramics

Characterization and evolution of the mitochondrial DNA control region in hornbills (Bucerotiformes).

Science.gov (United States)

Delport, Wayne; Ferguson, J Willem H; Bloomer, Paulette

2002-06-01

We determined the mitochondrial DNA control region sequences of six Bucerotiformes. Hornbills have the typical avian gene order and their control region is similar to other avian control regions in that it is partitioned into three domains: two variable domains that flank a central conserved domain. Two characteristics of the hornbill control region sequence differ from that of other birds. First, domain I is AT rich as opposed to AC rich, and second, the control region is approximately 500 bp longer than that of other birds. Both these deviations from typical avian control region sequence are explainable on the basis of repeat motifs in domain I of the hornbill control region. The repeat motifs probably originated from a duplication of CSB-1 as has been determined in chicken, quail, and snowgoose. Furthermore, the hornbill repeat motifs probably arose before the divergence of hornbills from each other but after the divergence of hornbills from other avian taxa. The mitochondrial control region of hornbills is suitable for both phylogenetic and population studies, with domains I and II probably more suited to population and phylogenetic analyses, respectively.

Multiple Shooting and Time Domain Decomposition Methods

CERN Document Server

Geiger, Michael; Körkel, Stefan; Rannacher, Rolf

2015-01-01

This book offers a comprehensive collection of the most advanced numerical techniques for the efficient and effective solution of simulation and optimization problems governed by systems of time-dependent differential equations. The contributions present various approaches to time domain decomposition, focusing on multiple shooting and parareal algorithms.  The range of topics covers theoretical analysis of the methods, as well as their algorithmic formulation and guidelines for practical implementation. Selected examples show that the discussed approaches are mandatory for the solution of challenging practical problems. The practicability and efficiency of the presented methods is illustrated by several case studies from fluid dynamics, data compression, image processing and computational biology, giving rise to possible new research topics.  This volume, resulting from the workshop Multiple Shooting and Time Domain Decomposition Methods, held in Heidelberg in May 2013, will be of great interest to applied...

E Hurter and T Pistorius THE NEW .AFRICA TOP LEVEL DOMAIN

African Journals Online (AJOL)

10332324

1997-07-01

Jul 1, 1997 ... new, private, not-for-profit corporation to take over the coordination of specific DNS ... (a) Domain names (forming a system referred to as "DNS"); ... to consumer choice, market differentiation and geographical and service- .... agreement with ICANN and must also complete a technical test to validate the.

Differential Cytotoxic Activity of Essential Oil of Lippia citriodora from Different Regions in Morocco.

Science.gov (United States)

Oukerrou, Moulay Ali; Tilaoui, Mounir; Mouse, Hassan Ait; Bouchmaa, Najat; Zyad, Abdelmajid

2017-07-01

The aim of this work was to investigate the cytotoxic effect of the essential oil of dried leaves of Lippia citriodora (H.B. & K.) harvested in different regions of Morocco. This effect was evaluated against the P815 murine mastocytoma cell line using the MTT assay. Interestingly, this work demonstrated for the first time that these essential oils exhibited a strong cytotoxic activity against the P815 cell line, with IC 50 values ranging from 7.75 to 13.25 μg/ml. This cytotoxicity began early and increased in a dose- and time-dependent manner. The chemical profile of these essential oils was analyzed by gas chromatography coupled to mass spectrometry. Importantly, the difference in terms of major components' contents was not significant suggesting probably that the differential cytotoxicity between these essential oils could be attributed to the difference in the content of these essential oils in minor compounds, which could interact with each other or with the main molecules. Finally, this study demonstrated for the first time that essential oils of L. citriodora from different regions in Morocco induced apoptosis against P815 tumor cell line. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Time-Domain Simulation of RF Couplers

International Nuclear Information System (INIS)

Smithe, David; Carlsson, Johan; Austin, Travis

2009-01-01

We have developed a finite-difference time-domain (FDTD) fluid-like approach to integrated plasma-and-coupler simulation [1], and show how it can be used to model LH and ICRF couplers in the MST and larger tokamaks.[2] This approach permits very accurate 3-D representation of coupler geometry, and easily includes non-axi-symmetry in vessel wall, magnetic equilibrium, and plasma density. The plasma is integrated with the FDTD Maxwell solver in an implicit solve that steps over electron time-scales, and permits tenuous plasma in the coupler itself, without any need to distinguish or interface between different regions of vacuum and/or plasma. The FDTD algorithm is also generalized to incorporate a time-domain sheath potential [3] on metal structures within the simulation, to look for situations where the sheath potential might generate local sputtering opportunities. Benchmarking of the time-domain sheath algorithm has been reported in the references. Finally, the time-domain software [4] permits the use of particles, either as field diagnostic (test particles) or to self-consistently compute plasma current from the applied RF power.

Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations

Directory of Open Access Journals (Sweden)

Kumar Ashwani

2007-11-01

Full Text Available Abstract Background The Plasmodium falciparum apical membrane antigen 1 (AMA1 is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR. The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates. Methods The part of the ama1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages. Results A total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands showed more haplotypes (H and nucleotide diversity π as compared to low malaria transmission areas (Uttar Pradesh and Goa. The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13 between populations. The difference between rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity. Conclusion The level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the

Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.

Directory of Open Access Journals (Sweden)

Mingshan Xue

2010-09-01

Full Text Available Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7. Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 A resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences.

Improvement in Protein Domain Identification Is Reached by Breaking Consensus, with the Agreement of Many Profiles and Domain Co-occurrence.

Directory of Open Access Journals (Sweden)

Juliana Bernardes

2016-07-01

Full Text Available Traditional protein annotation methods describe known domains with probabilistic models representing consensus among homologous domain sequences. However, when relevant signals become too weak to be identified by a global consensus, attempts for annotation fail. Here we address the fundamental question of domain identification for highly divergent proteins. By using high performance computing, we demonstrate that the limits of state-of-the-art annotation methods can be bypassed. We design a new strategy based on the observation that many structural and functional protein constraints are not globally conserved through all species but might be locally conserved in separate clades. We propose a novel exploitation of the large amount of data available: 1. for each known protein domain, several probabilistic clade-centered models are constructed from a large and differentiated panel of homologous sequences, 2. a decision-making protocol combines outcomes obtained from multiple models, 3. a multi-criteria optimization algorithm finds the most likely protein architecture. The method is evaluated for domain and architecture prediction over several datasets and statistical testing hypotheses. Its performance is compared against HMMScan and HHblits, two widely used search methods based on sequence-profile and profile-profile comparison. Due to their closeness to actual protein sequences, clade-centered models are shown to be more specific and functionally predictive than the broadly used consensus models. Based on them, we improved annotation of Plasmodium falciparum protein sequences on a scale not previously possible. We successfully predict at least one domain for 72% of P. falciparum proteins against 63% achieved previously, corresponding to 30% of improvement over the total number of Pfam domain predictions on the whole genome. The method is applicable to any genome and opens new avenues to tackle evolutionary questions such as the reconstruction of

Is Domain Highlighting Actually Helpful in Identifying Phishing Web Pages?

Science.gov (United States)

Xiong, Aiping; Proctor, Robert W; Yang, Weining; Li, Ninghui

2017-06-01

To evaluate the effectiveness of domain highlighting in helping users identify whether Web pages are legitimate or spurious. As a component of the URL, a domain name can be overlooked. Consequently, browsers highlight the domain name to help users identify which Web site they are visiting. Nevertheless, few studies have assessed the effectiveness of domain highlighting, and the only formal study confounded highlighting with instructions to look at the address bar. We conducted two phishing detection experiments. Experiment 1 was run online: Participants judged the legitimacy of Web pages in two phases. In Phase 1, participants were to judge the legitimacy based on any information on the Web page, whereas in Phase 2, they were to focus on the address bar. Whether the domain was highlighted was also varied. Experiment 2 was conducted similarly but with participants in a laboratory setting, which allowed tracking of fixations. Participants differentiated the legitimate and fraudulent Web pages better than chance. There was some benefit of attending to the address bar, but domain highlighting did not provide effective protection against phishing attacks. Analysis of eye-gaze fixation measures was in agreement with the task performance, but heat-map results revealed that participants' visual attention was attracted by the highlighted domains. Failure to detect many fraudulent Web pages even when the domain was highlighted implies that users lacked knowledge of Web page security cues or how to use those cues. Potential applications include development of phishing prevention training incorporating domain highlighting with other methods to help users identify phishing Web pages.

Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains.

Science.gov (United States)

Barlow, Paul

2018-06-01

In a new paper, the protein InvD from Yersinia pseudotuberculosis , a zoonotic pathogen, is shown to assist late-stage invasion of intestinal epithelia. Remarkably, InvD acts by binding the Fab region of IgG or IgA. It straddles adjacent light-chain and heavy-chain variable domains, but its binding is different from that of antigens in that complementarity-determining regions do not participate. Structure determination revealed that its Fab-interacting domain adopts an immunoglobulin-like fold, fused to the preceding immunoglobulin-like domain and carried on a long stalk anchored to the bacterial outer membrane. Possible roles of this unusual host-pathogen interaction include avoidance of clearance from the intestine by secretory IgA. © 2018 Barlow.

DOES IT MATTER WHERE I LIVE IN WESTERN-EUROPE - AN ANALYSIS OF REGIONAL MORTALITY DIFFERENTIALS IN BELGIUM, GERMANY AND THE NETHERLANDS

NARCIS (Netherlands)

VANDERVEEN, WJ

1994-01-01

Regional differentials in life expectancy at birth during the 1980s in Belgium, The Netherlands and some parts of the former Federal Republic of Germany are presented and commented upon. Life expectancy at birth during the 1980s was highest in The Netherlands, and lowest in some parts of southern

Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

Science.gov (United States)

McIlhinney, R A; Molnár, E

1996-04-01

To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

Abl N-terminal Cap stabilization of SH3 domain dynamics†

OpenAIRE

Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E.; Engen, John R.

2008-01-01

Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydro...

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

DEFF Research Database (Denmark)

Chen, Li; Hu, Huimin; Qiu, Weimin

2018-01-01

Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte...... differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating h...

FY1995 ultrafast photonic devices using dielectric domain superlattice; 1995 nendo yudentai domain chokoshi wo mochiita chokosoku photonic device

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-31

All optical wavelength conversion around 1550nm is of great importance for the wavelength division multiplexing optical communication system. A dielectric domain superlattice, which has a periodically domain inverted structure, has a wide potential for the various nonlinear interactions such as second harmonic generation (SHG) and difference frequency generation (DFG). The purpose of our research is to establish the theoretical bases and fabrication processes of the guided-wave wavelength converter based on the DFG by domain-inverted LiTaO{sub 3}. We have investigated basic characteristics of guided-wave DFG devices and developed the domain-inversion process by an electric field poling utilizing a liquid electrolyte consisting of LiCI in deionized water as a electrode for applying the electric field to LiTaO{sub 3} substrate. By controlling the injection current for the domain inversion precisely, we fabricated successfully uniform domain-inverted structures. 0.5mm-thick domain-inverted LiTaO{sub 3} of 7.8, 17.2 and 21.3 {mu}m periods and 0.5 duty ratio were obtained by optimizing electrode structure and the domain-inversion process. Waveguide structures can increase the conversion efficiency of DFG by several orders of magnitude over bulk interactions. We have also developed waveguide fabrication process for the domain-inverted LiTaO{sub 3} substrate. Low loss proton-exchanged waveguides were formed by annealed proton exchange technique without a degradation of the domain inversion structure. Domain-controlled nonlinear optics by designing the ferroelectric domain structure of LiTaO{sub 3} and LiNbO{sub 3} make it possible to extend all the spectral range from ultra-violet to far-infrared and THz wave region. (NEDO)

Structure and biochemical function of a prototypical Arabidopsis U-box domain

DEFF Research Database (Denmark)

Andersen, Pernille; Kragelund, Birthe B; Olsen, Addie N

2004-01-01

U-box proteins, as well as other proteins involved in regulated protein degradation, are apparently over-represented in Arabidopsis compared with other model eukaryotes. The Arabidopsis protein AtPUB14 contains a typical U-box domain followed by an Armadillo repeat region, a domain organization t...

Analytical investigation on domain of decentered parameter for self-focusing of Hermite-cosh-Gaussian laser beam in collisional plasma

Science.gov (United States)

Valkunde, Amol T.; Patil, Sandip D.; Vhanmore, Bandopant D.; Urunkar, Trupti U.; Gavade, Kusum M.; Takale, Mansing V.; Fulari, Vijay J.

2018-03-01

In the present paper, an analytically investigated domain of decentered parameter and its effect on the self-focusing of Hermit-cosh-Gaussian (HChG) laser beams in a collisional plasma have been studied theoretically. The nonlinearity in the dielectric constant of plasma arising due to the nonuniform heating of carriers along the wavefront of the laser beam has been employed in the present investigation. The nonlinear differential equation of beam width parameter for various laser modes of HChG beam is obtained by following the standard Akhamanov's parabolic equation approach under Wentzel-Kramers-Brillouin and paraxial approximations. The analytical treatment has enabled us to define three distinct regions: self-focusing, self-trapping and defocusing, which are presented graphically.

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

Science.gov (United States)

Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

2017-01-01

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

A molecular model for the differential activation of STAT3 and STAT6 by the herpesviral oncoprotein tip.

Directory of Open Access Journals (Sweden)

Eman Dey Mazumder

Full Text Available Constitutive STAT signaling provides growth promoting signals in many forms of malignancy. We performed molecular modeling and molecular dynamics studies of the interaction between the regulatory Src homology 2 (SH2 domains of STAT3 and 6 with phosphorylated peptides of the herpesviral oncoprotein Tip, which facilitates Src kinase mediated STAT-activation and T cell proliferation. The studies give insight into the ligand binding specificity of the STAT SH2 domains and provide the first model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein. The biological relevance of the modeled interactions was then confirmed by activation studies using corresponding recombinant oncoproteins, and finally by respective recombinant viruses. The functional data give experimental validation of the molecular dynamics study, and provide evidence for the involvement of STAT6 in the herpesvirus induced T cell proliferation.

B-spline Collocation with Domain Decomposition Method

International Nuclear Information System (INIS)

Hidayat, M I P; Parman, S; Ariwahjoedi, B

2013-01-01

A global B-spline collocation method has been previously developed and successfully implemented by the present authors for solving elliptic partial differential equations in arbitrary complex domains. However, the global B-spline approximation, which is simply reduced to Bezier approximation of any degree p with C 0 continuity, has led to the use of B-spline basis of high order in order to achieve high accuracy. The need for B-spline bases of high order in the global method would be more prominent in domains of large dimension. For the increased collocation points, it may also lead to the ill-conditioning problem. In this study, overlapping domain decomposition of multiplicative Schwarz algorithm is combined with the global method. Our objective is two-fold that improving the accuracy with the combination technique, and also investigating influence of the combination technique to the employed B-spline basis orders with respect to the obtained accuracy. It was shown that the combination method produced higher accuracy with the B-spline basis of much lower order than that needed in implementation of the initial method. Hence, the approximation stability of the B-spline collocation method was also increased.

Structural domains and conformational changes in nuclear chromatin: a quantitative thermodynamic approach by differential scanning calorimetry.

Science.gov (United States)

Balbi, C; Abelmoschi, M L; Gogioso, L; Parodi, S; Barboro, P; Cavazza, B; Patrone, E

1989-04-18

A good deal of information on the thermodynamic properties of chromatin was derived in the last few years from optical melting experiments. The structural domains of the polynucleosomal chain, the linker, and the core particle denature as independent units. The differential scanning calorimetry profile of isolated chromatin is made up of three endotherms, at approximately 74, 90, and 107 degrees C, having an almost Gaussian shape. Previous work on this matter, however, was mainly concerned with the dependence of the transition enthalpy on external parameters, such as the ionic strength, or with the melting of nuclei from different sources. In this paper we report the structural assignment of the transitions of rat liver nuclei, observed at 58, 66, 75, 92, and 107 degrees C. They are representative of the quiescent state of the cell. The strategy adopted in this work builds on the method developed for the investigation of complex biological macromolecules. The heat absorption profile of the nucleus was related to the denaturation of isolated nuclear components; electron microscopy and electrophoretic techniques were used for their morphological and molecular characterization. The digestion of chromatin by endogenous nuclease mimics perfectly the decondensation of the higher order structure and represented the source of several misinterpretations. This point was carefully examined in order to define unambiguously the thermal profile of native nuclei. The low-temperature transitions, centered around 58 and 66 degrees C, arise from the melting of scaffolding structures and of the proteins associated with heterogeneous nuclear RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Regionally differentiated air pollution control regulations in the installation-related emission control law of the Federal Republic of Germany

International Nuclear Information System (INIS)

Buettner, T.W.

1992-01-01

The volume treats an issue from the boundary zone between environmental law and environmental economics, namely the regionalization of air pollution control standards in installation-related emission control law. In order to examine the question of whether this proposal, which originates in the field of environmental economics, can be adopted and is purposeful, the author initially performs a complete inventorization of applicable norms, this covering emission control law, the law of regional planning, and the provisions of international law. This status quo is then reviewed using conformity and optimization criteria developed by the political sciences. The assessment comes to the conclusion that the introduction of regionally differentiated air pollution control standards is not desirable. The author further submits proposals for the streamlining of the law of installation-related air pollution control in the Federal Republic of Germany. (orig.) [de

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.

Science.gov (United States)

Fernández, Agustín F; Bayón, Gustavo F; Urdinguio, Rocío G; Toraño, Estela G; García, María G; Carella, Antonella; Petrus-Reurer, Sandra; Ferrero, Cecilia; Martinez-Camblor, Pablo; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesús; Pérez-Campo, Flor M; Riancho, José A; Bueno, Clara; Menéndez, Pablo; Mentink, Anouk; Mareschi, Katia; Claire, Fabian; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brescianini, Sonia; Moran, Sebastián; Esteller, Manel; Stolzing, Alexandra; de Boer, Jan; Nisticò, Lorenza; Stazi, Maria A; Fraga, Mario F

2015-01-01

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. © 2015 Fernández et al.; Published by Cold Spring Harbor Laboratory Press.

Polycomb domain formation depends on short and long distance regulatory cues.

Directory of Open Access Journals (Sweden)

Bernd Schuettengruber

Full Text Available BACKGROUND: Polycomb group (PcG proteins dynamically define cellular identities through the epigenetic repression of key developmental genes. In Drosophila, cis-regulatory regions termed PcG response elements (PREs act as nucleation sites for PcG proteins to create large repressive PcG domains that are marked by trimethylation of lysine 27 on histone H3 (H3K27me3. In addition to an action in cis, PREs can interact over long distances, thereby enhancing PcG dependent silencing. How PcG domains are established, which factors limit their propagation in cis, and how long range interactions of PREs in trans affect the chromatin structure is largely unknown. PRINCIPAL FINDINGS: We demonstrate that the insertion of a PRE-containing transgene in the Drosophila genome generates an artificial PcG domain and we analyze its organization by quantitative ChIP and ChIP-on-chip experiments. Intriguingly, a boundary element and known insulator proteins do not necessarily interfere with spreading of H3K27me3. Instead, domain borders correlate with the presence of promoter regions bound by RNA Polymerase II and active chromatin marks. In contrast, genes that are silent during early fly development get included within the PcG domain and this incorporation interferes with gene activation at later developmental stages. Moreover, trans-interaction of the transgenic PRE with its homologous endogenous PRE results in increased PcG binding, correlating with reinforced silencing of genes within the domain borders. CONCLUSIONS: Our results suggest that higher-order organization of PcG-bound chromatin can stabilize gene silencing within PcG domains. Further we propose that multi-protein complexes associated with active promoters are able to define the limits of PcG domains. Future work aimed to pinpoint the factors providing this barrier function will be required to understand the precise molecular mechanism by which active promoter regions can act as boundaries to stop

Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain.

Science.gov (United States)

Law, S F; Zhang, Y Z; Fashena, S J; Toby, G; Estojak, J; Golemis, E A

1999-10-10

HEF1, p130(Cas), and Efs define a family of multidomain docking proteins which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. HEF1 function has been specifically implicated in signaling pathways important for cell adhesion and differentiation in lymphoid and epithelial cells. While the SH3 domains and SH2-binding site domains (substrate domains) of HEF1 family proteins are well characterized and binding partners known, to date the highly conserved carboxy-terminal domains of the three proteins have lacked functional definition. In this study, we have determined that the carboxy-terminal domain of HEF1 contains a divergent helix-loop-helix (HLH) motif. This motif mediates HEF1 homodimerization and HEF1 heterodimerization with a recognition specificity similar to that of the transcriptional regulatory HLH proteins Id2, E12, and E47. We had previously demonstrated that the HEF1 carboxy-terminus expressed as a separate domain in yeast reprograms cell division patterns, inducing constitutive pseudohyphal growth. Here we show that pseudohyphal induction by HEF1 requires an intact HLH, further supporting the idea that this motif has an effector activity for HEF1, and implying that HEF1 pseudohyphal activity derives in part from interactions with yeast helix-loop-helix proteins. These combined results provide initial insight into the mode of function of the HEF1 carboxy-terminal domain and suggest that the HEF1 protein may interact with cellular proteins which control differentiation. Copyright 1999 Academic Press.

Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior

Science.gov (United States)

Golji, Javad; Collins, Robert; Mofrad, Mohammad R. K.

2009-01-01

α-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, α-actinin can retain conformation, function, and strength. α-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the α-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the α-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the α-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the α-actinin rod domain. PMID:19436721

Domains and domain loss

DEFF Research Database (Denmark)

Haberland, Hartmut

2005-01-01

politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

Directory of Open Access Journals (Sweden)

Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

Almost Automorphic and Pseudo-Almost Automorphic Solutions to Semilinear Evolution Equations with Nondense Domain

Directory of Open Access Journals (Sweden)

Bruno de Andrade

2009-01-01

Full Text Available We study the existence and uniqueness of almost automorphic (resp., pseudo-almost automorphic solutions to a first-order differential equation with linear part dominated by a Hille-Yosida type operator with nondense domain.

A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain: Periplasmic Ligand Binding Protein Dret_0059

Energy Technology Data Exchange (ETDEWEB)

Wu, R. [Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Wilton, R. [Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Cuff, M. E. [Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Structural Biology Center, Argonne National Laboratory, Argonne Illinois 60439; Endres, M. [Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Babnigg, G. [Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Edirisinghe, J. N. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne Illinois 60439; Computation Institute, University of Chicago, Chicago Illinois 60637; Henry, C. S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne Illinois 60439; Computation Institute, University of Chicago, Chicago Illinois 60637; Joachimiak, A. [Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Structural Biology Center, Argonne National Laboratory, Argonne Illinois 60439; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois 60637; Schiffer, M. [Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439; Pokkuluri, P. R. [Biosciences Division, Argonne National Laboratory, Argonne Illinois 60439

2017-03-06

We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from the Salt Lake Retba in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously and their best known function is in solute transport across membranes. PAS-like sensor domains are commonly found in signal transduction proteins. These domains are widely observed as parts of many protein architectures and complexes but have not been observed previously within the same polypeptide chain. In the structure of Dret_0059, a ketoleucine moiety is bound to the SBP, whereas a cytosine molecule is bound in the distal PAS-like domain of the tandem PAS-like domain. Differential scanning flourimetry support the binding of ligands observed in the crystal structure. There is significant interaction between the SBP and tandem PAS-like domains, and it is possible that the binding of one ligand could have an effect on the binding of the other. We uncovered three other proteins with this structural architecture in the non-redundant sequence data base, and predict that they too bind the same substrates. The genomic context of this protein did not offer any clues for its function. We did not find any biological process in which the two observed ligands are coupled. The protein Dret_0059 could be involved in either signal transduction or solute transport.

Major Chromosomal Breakpoint Intervals in Breast Cancer Co-Localize with Differentially Methylated Regions

Energy Technology Data Exchange (ETDEWEB)

Eric Tang, Man-Hung [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Varadan, Vinay; Kamalakaran, Sitharthan [Philips Research North America, Briarcliff Manor, NY (United States); Zhang, Michael Q. [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); The University of Texas at Dallas, Richardson, TX (United States); Tsinghua University, Beijing (China); Dimitrova, Nevenka, E-mail: nevenka.dimitrova@philips.com [Philips Research North America, Briarcliff Manor, NY (United States); Hicks, James, E-mail: hicks@cshl.edu [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States)

2012-12-27

Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple chromosomal loci (copy number variation, or CNV), and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape, the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation, but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls (Wiedswang et al., 2003), where each sample has both high-resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions (DMR), coupled with additional genomic parameters, such as repeat elements and designated “fragile sites” in the reference genome. Through this analysis, we have identified a set of 93 regional loci called breakpoint enriched DMR (BEDMRs) characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1 Mb. BEDMR loci are further associated with local hypomethylation (66%), concentrations of the Alu SINE repeats within 3 Mb (35% of the cases), and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. Furthermore, BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors, e.g., JMJD1B, which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA

Insights into amyloid-like aggregation of H2 region of the C-terminal domain of nucleophosmin.

Science.gov (United States)

Russo, Anna; Diaferia, Carlo; La Manna, Sara; Giannini, Cinzia; Sibillano, Teresa; Accardo, Antonella; Morelli, Giancarlo; Novellino, Ettore; Marasco, Daniela

2017-02-01

Nucleophosmin (NPM1) is a multifunctional protein involved in a variety of biological processes including the pathogenesis of several human malignancies and is the most frequently mutated gene in Acute Myeloid Leukemia (AML). To deepen the role of protein regions in its biological activities, lately we reported on the structural behavior of dissected C-terminal domain (CTD) helical fragments. Unexpectedly the H2 (residues 264-277) and H3 AML-mutated regions showed a remarkable tendency to form amyloid-like assemblies with fibrillar morphology and β-sheet structure that resulted as toxic when exposed to human neuroblastoma cells. More recently NPM1 was found to be highly expressed and toxic in neurons of mouse models of Huntington's disease (HD). Here we investigate the role of each residue in the β-strand aggregation process of H2 region of NPM1 by performing a systematic alanine scan of its sequence and structural and kinetic analyses of aggregation of derived peptides by means of Circular Dichorism (CD) and Thioflavin T (Th-T) assay. These solution state investigations pointed out the crucial role exerted by the basic amyloidogenic stretch of H2 (264-271) and to shed light on the initial and main interactions involved in fibril formation we performed studies on fibrils deriving from the related Ala peptides through the analysis of fibrils with birefringence of polarized optical microscopy and wide-angle X-ray scattering (WAXS). This analysis suggested that the presence of branched Ile 269 conferred preferential packing patterns that, instead, appeared geometrically hampered by the aromatic side-chain of Phe 268 . Present investigations could be useful to deepen the knowledge of AML molecular mechanisms and the role of cytoplasmatic aggregates of NPM1c+. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

Science.gov (United States)

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

Modulated Magnetic Nanowires for Controlling Domain Wall Motion: Toward 3D Magnetic Memories

KAUST Repository

Ivanov, Yurii P.; Chuvilin, Andrey; Lopatin, Sergei; Kosel, Jü rgen

2016-01-01

Cylindrical magnetic nanowires are attractive materials for next generation data storage devices owing to the theoretically achievable high domain wall velocity and their efficient fabrication in highly dense arrays. In order to obtain control over domain wall motion, reliable and well-defined pinning sites are required. Here, we show that modulated nanowires consisting of alternating nickel and cobalt sections facilitate efficient domain wall pinning at the interfaces of those sections. By combining electron holography with micromagnetic simulations, the pinning effect can be explained by the interaction of the stray fields generated at the interface and the domain wall. Utilizing a modified differential phase contrast imaging, we visualized the pinned domain wall with a high resolution, revealing its three-dimensional vortex structure with the previously predicted Bloch point at its center. These findings suggest the potential of modulated nanowires for the development of high-density, three-dimensional data storage devices. © 2016 American Chemical Society.

Modulated Magnetic Nanowires for Controlling Domain Wall Motion: Toward 3D Magnetic Memories

KAUST Repository

Ivanov, Yurii P.

2016-05-03

Cylindrical magnetic nanowires are attractive materials for next generation data storage devices owing to the theoretically achievable high domain wall velocity and their efficient fabrication in highly dense arrays. In order to obtain control over domain wall motion, reliable and well-defined pinning sites are required. Here, we show that modulated nanowires consisting of alternating nickel and cobalt sections facilitate efficient domain wall pinning at the interfaces of those sections. By combining electron holography with micromagnetic simulations, the pinning effect can be explained by the interaction of the stray fields generated at the interface and the domain wall. Utilizing a modified differential phase contrast imaging, we visualized the pinned domain wall with a high resolution, revealing its three-dimensional vortex structure with the previously predicted Bloch point at its center. These findings suggest the potential of modulated nanowires for the development of high-density, three-dimensional data storage devices. © 2016 American Chemical Society.

Electric-field domain boundary instability in weakly coupled semiconductor superlattices

Energy Technology Data Exchange (ETDEWEB)

Rasulova, G. K., E-mail: rasulova@sci.lebedev.ru [P.N. Lebedev Physical Institute of Russian Academy of Sciences, 119991 Moscow (Russian Federation); Pentin, I. V. [Moscow State Pedagogical University, 119991 Moscow (Russian Federation); Brunkov, P. N. [A. F. Ioffe Physical and Technical Institute of Russian Academy of Sciences, 194021 St. Petersburg (Russian Federation); National Research University of Information Technologies, Mechanics and Optics, 197101 St. Petersburg (Russian Federation); Egorov, A. Yu. [National Research University of Information Technologies, Mechanics and Optics, 197101 St. Petersburg (Russian Federation)

2016-05-28

Damped oscillations of the current were observed in the transient current pulse characteristics of a 30-period weakly coupled GaAs/AlGaAs superlattice (SL). The switching time of the current is exponentially decreased as the voltage is verged towards the current discontinuity region indicating that the space charge necessary for the domain boundary formation is gradually accumulated in a certain SL period in a timescale of several hundreds ns. The spectral features in the electroluminescence spectra of two connected in parallel SL mesas correspond to the energy of the intersubband transitions and the resonance detuning of subbands caused by charge trapping in the quantum wells (QWs) residing in a region of the expanded domain boundary. The obtained results support our understanding of the origin of self-oscillations as a cyclic dynamics of the subband structure in the QWs forming the expanded domain boundary.

Waggawagga-CLI: A command-line tool for predicting stable single α-helices (SAH-domains, and the SAH-domain distribution across eukaryotes.

Directory of Open Access Journals (Sweden)

Dominic Simm

Full Text Available Stable single-alpha helices (SAH-domains function as rigid connectors and constant force springs between structural domains, and can provide contact surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly consist of charged amino acids and are monomeric and stable in polar solutions, characteristics which distinguish them from coiled-coil domains and intrinsically disordered regions. Although the number of reported SAH-domains is steadily increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still missing. Here, we present Waggawagga-CLI, a command-line tool for predicting and analysing SAH-domains in protein sequence datasets. Using Waggawagga-CLI we predicted SAH-domains in 24 datasets from eukaryotes across the tree of life. SAH-domains were predicted in 0.5 to 3.5% of the protein-coding content per species. SAH-domains are particularly present in longer proteins supporting their function as structural building block in multi-domain proteins. In human, SAH-domains are mainly used as alternative building blocks not being present in all transcripts of a gene. Gene ontology analysis showed that yeast proteins with SAH-domains are particular enriched in macromolecular complex subunit organization, cellular component biogenesis and RNA metabolic processes, and that they have a strong nuclear and ribonucleoprotein complex localization and function in ribosome and nucleic acid binding. Human proteins with SAH-domains have roles in all types of RNA processing and cytoskeleton organization, and are predicted to function in RNA binding, protein binding involved in cell and cell-cell adhesion, and cytoskeletal protein binding. Waggawagga-CLI allows the user to adjust the stabilizing and destabilizing contribution of amino acid interactions in i,i+3 and i,i+4 spacings, and provides extensive flexibility for user-designed analyses.

Thermal domains in inhomogeneous current-carrying superconductors. Current-voltage characteriscs and dynamics of domain formation after current jumps

International Nuclear Information System (INIS)

Bezuglyj, A.I.; Shklovskij, V.A.

1984-01-01

The static and dynamic behavior of thermal domains in inhomogeneous superconducting films, where the inhomogeneity behaves like a portion of the film with a reduced critical current, have been studied theoretically within the framework of the phenomenological approach, using the heat balance equation and the dependence of the superconductor critical current on temperature. Depending on the size of the inhomogeneity (local or extended) and on the relative values of parameters of the homogeneous and inhomogeneous regions, different types of current-voltage characteristics are obtained. The nonstationary problem of thermal domain formation near the inhomogeneity after a current jump has been solved, and the domain boundary (kink) dynamics at a distance from the inhomogeneity has been analyzed. A combination of the results allows one to describe the whole process of normal phase formation and its spread throughout the superconducting film

Domain wall oscillation in magnetic nanowire with a geometrically confined region

Science.gov (United States)

Sbiaa, R.; Bahri, M. Al; Piramanayagam, S. N.

2018-06-01

In conventional magnetic devices such as magnetic tunnel junctions, a steady oscillation of a soft layer magnetization could find its application in various electronic systems. However, these devices suffer from their low output signal and large spectral linewidth. A more elegant scheme based on domain wall oscillation could be a solution to these issues if DW dynamics could be controlled precisely in space and time. In fact, in DW devices, the magnetic configuration of domain wall and its position are strongly dependent on the device geometry and material properties. Here we show that in a constricted device with judiciously adjusted dimensions, a DW can be trapped within the central part and keep oscillating with a single frequency f. For 200 nm by 40 nm nanowire, f was found to vary from 2 GHz to 3 GHz for a current density between 4.8 × 1012 A/m2 and 5.6 × 1012 A/m2. More interestingly, the device fabrication is simply based on two long nanowires connected by adjusting the offset in both x and y directions. This new type of devices enables the conversion of dc-current to an ac-voltage in a controllable manner opening thus the possibility of a new nano-oscillators with better performance.

C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

Science.gov (United States)

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.

Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway.

LENUS (Irish Health Repository)

Cao, Wei

2011-06-01

Emerging experimental data suggest an important role for the T-cell immunoglobulin mucin 1 (Tim-1):Tim-4 pathway in autoimmune and alloimmune responses in vivo. Using a Tim-4 ectodomain human IgG Fc fusion protein we studied the role of Tim-4 in T-cell activation, signalling and differentiation responses in vitro. We demonstrate that Tim-4Fc can inhibit naive and pre-activated T-cell activation, proliferation and cytokine secretion via a Tim-1-independent pathway. Tim-4 contains immunoglobulin variable (IgV) and mucin domains; to identify which domain accounts for the inhibitory effect novel Tim-4 fusion proteins containing either the IgV or mucin domain were generated. We demonstrate that both IgV and mucin domains are required for the inhibitory effects and that they are mediated at least in part by inhibition of extracellular signal-regulated kinase pathway activity. Given the emerging interest in the role of the Tim family in T helper type 17 (Th17) cells, which play an important role in autoimmune disease and transplantation tolerance, our data show that Tim-4Fc can prevent polarization of CD4(+) T cells to the Th17 phenotype. Collectively, our results highlight an inhibitory role for Tim-4Fc in vitro, which we propose is mediated by a receptor other than Tim-1. In addition, this study provides new insights into the role of Tim-4Fc in regulating Th17 immune responses and may open a new avenue for autoimmune therapy.

Tim-4 inhibition of T-cell activation and T helper type 17 differentiation requires both the immunoglobulin V and mucin domains and occurs via the mitogen-activated protein kinase pathway

Science.gov (United States)

Cao, Wei; Ryan, Michelle; Buckley, Deirdre; O'Connor, Rosemary; Clarkson, Michael R

2011-01-01

Emerging experimental data suggest an important role for the T-cell immunoglobulin mucin 1 (Tim-1):Tim-4 pathway in autoimmune and alloimmune responses in vivo. Using a Tim-4 ectodomain human IgG Fc fusion protein we studied the role of Tim-4 in T-cell activation, signalling and differentiation responses in vitro. We demonstrate that Tim-4Fc can inhibit naive and pre-activated T-cell activation, proliferation and cytokine secretion via a Tim-1-independent pathway. Tim-4 contains immunoglobulin variable (IgV) and mucin domains; to identify which domain accounts for the inhibitory effect novel Tim-4 fusion proteins containing either the IgV or mucin domain were generated. We demonstrate that both IgV and mucin domains are required for the inhibitory effects and that they are mediated at least in part by inhibition of extracellular signal-regulated kinase pathway activity. Given the emerging interest in the role of the Tim family in T helper type 17 (Th17) cells, which play an important role in autoimmune disease and transplantation tolerance, our data show that Tim-4Fc can prevent polarization of CD4+ T cells to the Th17 phenotype. Collectively, our results highlight an inhibitory role for Tim-4Fc in vitro, which we propose is mediated by a receptor other than Tim-1. In addition, this study provides new insights into the role of Tim-4Fc in regulating Th17 immune responses and may open a new avenue for autoimmune therapy. PMID:21463297

Multiscale Seismic Inversion in the Data and Image Domains

KAUST Repository

Zhang, Sanzong

2015-12-01

I present a general methodology for inverting seismic data in either the data or image domains. It partially overcomes one of the most serious problems with current waveform inversion methods, which is the tendency to converge to models far from the actual one. The key idea is to develop a multiscale misfit function that is composed of both a simplified version of the data and one associated with the complex part of the data. Misfit functions based on simple data are characterized by many fewer local minima so that a gradient optimization method can make quick progress in getting to the general vicinity of the actual model. Once we are near the actual model, we then use the gradient based on the more complex data. Below, we describe two implementations of this multiscale strategy: wave equation traveltime inversion in the data domain and generalized differential semblance optimization in the image domain. • Wave Equation Traveltime Inversion in the Data Domain (WT): The main difficulty with iterative waveform inversion is that it tends to get stuck in local minima associated with the waveform misfit function. To mitigate this problem and avoid the need to fit amplitudes in the data, we present a waveequation method that inverts the traveltimes of reflection events, and so is less prone to the local minima problem. Instead of a waveform misfit function, the penalty function is a crosscorrelation of the downgoing direct wave and the upgoing reflection wave at the trial image point. The time lag which maximizes the crosscorrelation amplitude represents the reflection-traveltime residual that is back-projected along the reflection wavepath to update the velocity. Shot- and angle-domain crosscorrelation functions are introduced to estimate the reflection-traveltime residual by semblance analysis and scanning. In theory, only the traveltime information is inverted and there is no need to precisely fit the amplitudes or assume a high-frequency approximation. Results

Differentially Private Event Histogram Publication on Sequences over Graphs

Institute of Scientific and Technical Information of China (English)

Ning Wang; Yu Gu; Jia Xu; Fang-Fang Li; Ge Yu

2017-01-01

The big data era is coming with strong and ever-growing demands on analyzing personal information and footprints in the cyber world. To enable such analysis without privacy leak risk, differential privacy (DP) has been quickly rising in recent years, as the first practical privacy protection model with rigorous theoretical guarantee. This paper discusses how to publish differentially private histograms on events in time series domain, with sequences of personal events over graphs with events as edges. Such individual-generated sequences commonly appear in formalized industrial workflows, online game logs, and spatial-temporal trajectories. Directly publishing the statistics of sequences may compromise personal privacy. While existing DP mechanisms mainly target at normalized domains with fixed and aligned dimensions, our problem raises new challenges when the sequences could follow arbitrary paths on the graph. To tackle the problem, we reformulate the problem with a three-step framework, which 1) carefully truncates the original sequences, trading off errors introduced by the truncation with those introduced by the noise added to guarantee privacy, 2) decomposes the event graph into path sub-domains based on a group of event pivots, and 3) employs a deeply optimized tree-based histogram construction approach for each sub-domain to benefit with less noise addition. We present a careful analysis on our framework to support thorough optimizations over each step of the framework, and verify the huge improvements of our proposals over state-of-the-art solutions.

Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning.

Science.gov (United States)

Wasser, Catherine R; Masiulis, Irene; Durakoglugil, Murat S; Lane-Donovan, Courtney; Xian, Xunde; Beffert, Uwe; Agarwala, Anandita; Hammer, Robert E; Herz, Joachim

2014-11-25

Apoer2 is an essential receptor in the central nervous system that binds to the apolipoprotein ApoE. Various splice variants of Apoer2 are produced. We showed that Apoer2 lacking exon 16, which encodes the O-linked sugar (OLS) domain, altered the proteolytic processing and abundance of Apoer2 in cells and synapse number and function in mice. In cultured cells expressing this splice variant, extracellular cleavage of OLS-deficient Apoer2 was reduced, consequently preventing γ-secretase-dependent release of the intracellular domain of Apoer2. Mice expressing Apoer2 lacking the OLS domain had increased Apoer2 abundance in the brain, hippocampal spine density, and glutamate receptor abundance, but decreased synaptic efficacy. Mice expressing a form of Apoer2 lacking the OLS domain and containing an alternatively spliced cytoplasmic tail region that promotes glutamate receptor signaling showed enhanced hippocampal long-term potentiation (LTP), a phenomenon associated with learning and memory. However, these mice did not display enhanced spatial learning in the Morris water maze, and cued fear conditioning was reduced. Reducing the expression of the mutant Apoer2 allele so that the abundance of the protein was similar to that of Apoer2 in wild-type mice normalized spine density, hippocampal LTP, and cued fear learning. These findings demonstrated a role for ApoE receptors as regulators of synaptic glutamate receptor activity and established differential receptor glycosylation as a potential regulator of synaptic function and memory. Copyright © 2014, American Association for the Advancement of Science.

Role of TRIM33 in Wnt signaling during mesendoderm differentiation.

Science.gov (United States)

Xia, Xiaojie; Zuo, Feifei; Luo, Maoguo; Sun, Ye; Bai, Jianbo; Xi, Qiaoran

2017-10-01

Tripartite motif 33 (TRIM33), a member of the transcription intermediate factor 1 (TIF1) family of transcription cofactors, mediates transforming growth factor-beta (TGF-β) signaling through its PHD-Bromo cassette in mesendoderm differentiation during early mouse embryonic development. However, the role of the TRIM33 RING domain in embryonic differentiation is less clear. Here, we report that TRIM33 mediates Wnt signaling by directly regulating the expression of a specific subset of Wnt target genes, and this action is independent of its RING domain. We show that TRIM33 interacts with β-catenin, a central player in Wnt signaling in mouse embryonic stem cells (mESCs). In contrast to previous reports in cancer cell lines, the RING domain does not appear to function as the E3 ligase for β-catenin, since neither knockout nor overexpression of TRIM33 had an effect on β-catenin protein levels in mESCs. Furthermore, we show that although TRIM33 seems to be dispensable for Wnt signaling through a reporter assay, loss of TRIM33 significantly impairs the expression of a subset of Wnt target genes, including Mixl1, in a Wnt signaling-dependent manner. Together, our results indicate that TRIM33 regulates Wnt signaling independent of the E3 ligase activity of its RING domain for β-catenin in mESCs.

Expanding the landscape of chromatin modification (CM-related functional domains and genes in human.

Directory of Open Access Journals (Sweden)

Shuye Pu

2010-11-01

Full Text Available Chromatin modification (CM plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

Directory of Open Access Journals (Sweden)

Rizwan S Akhtar

Full Text Available Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2% were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%. Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

APPLICATION OF THE POLYGONS’ METHOD FOR THE ANALYSIS OF VOLGA FEDERAL DISTRICT’S REGIONS DIFFERENTIATION IN TERMS OF POPULATION’S SOCIAL COMFORT OF LIVING

Directory of Open Access Journals (Sweden)

Marina A. Skvortsova

2014-01-01

Full Text Available The article deals with the results of the analysis of Volga federal district’s regions differentiation in terms of population’s social comfort of living using the polygons. Constructed polygons represent a graphic image position of Volga federal district’s regions on the most important criteria of social comfort of living. Calculated indexes of social comfort of living in the regions of the Volga Federal District are an integral characteristic of the object under investigation. It suggests that there is a high degree of regions’ heterogeneity in terms of the integral indicator.

Molecular markers for X-ray-insensitive differentiated cells in the Inner and outer regions of the mesenchymal space in planarian Dugesia japonica.

Science.gov (United States)

Teramoto, Machiko; Kudome-Takamatsu, Tomomi; Nishimura, Osamu; An, Yang; Kashima, Makoto; Shibata, Norito; Agata, Kiyokazu

2016-09-01

Planarian's strong regenerative ability is dependent on stem cells (called neoblasts) that are X-ray-sensitive and proliferative stem cells. In addition to neoblasts, another type of X-ray-sensitive cells was newly identified by recent research. Thus, planarian's X-ray-sensitive cells can be divided into at least two populations, Type 1 and Type 2, the latter corresponding to planarian's classically defined "neoblasts". Here, we show that Type 1 cells were distributed in the outer region (OR) immediately underneath the muscle layer at all axial levels from head to tail, while the Type 2 cells were distributed in a more internal region (IR) of the mesenchymal space at the axial levels from neck to tail. To elucidate the biological significance of these two regions, we searched for genes expressed in differentiated cells that were locate close to these X-ray-sensitive cell populations in the mesenchymal space, and identified six genes mainly expressed in the OR or IR, named OR1, OR2, OR3, IR1, IR2 and IR3. The predicted amino acid sequences of these genes suggested that differentiated cells expressing OR1, OR3, IR1, or IR2 provide Type 1 and Type 2 cells with specific extracellular matrix (ECM) environments. © 2016 Japanese Society of Developmental Biologists.

Hox gene colinear expression in the avian medulla oblongata is correlated with pseudorhombomeric domains.

Science.gov (United States)

Marín, Faustino; Aroca, Pilar; Puelles, Luis

2008-11-15

The medulla oblongata (or caudal hindbrain) is not overtly segmented, since it lacks observable interrhombomeric boundaries. However, quail-chick fate maps showed that it is formed by 5 pseudorhombomeres (r7-r11) which were empirically found to be delimited consistently at planes crossing through adjacent somites (Cambronero and Puelles, 2000). We aimed to reexamine the possible segmentation or rostrocaudal regionalisation of this brain region attending to molecular criteria. To this end, we studied the expression of Hox genes from groups 3 to 7 correlative to the differentiating nuclei of the medulla oblongata. Our results show that these genes are differentially expressed in the mature medulla oblongata, displaying instances of typical antero-posterior (3' to 5') Hox colinearity. The different sensory and motor columns, as well as the reticular formation, appear rostrocaudally regionalised according to spaced steps in their Hox expression pattern. The anterior limits of the respective expression domains largely fit boundaries defined between the experimental pseudorhombomeres. Therefore the medulla oblongata shows a Hox-related rostrocaudal molecular regionalisation comparable to that found among rhombomeres, and numerically consistent with the pseudorhombomere list. This suggests that medullary pseudorhombomeres share some AP patterning mechanisms with the rhombomeres present in the rostral, overtly-segmented hindbrain, irrespective of variant boundary properties.

General spectral flow formula for fixed maximal domain

DEFF Research Database (Denmark)

Booss-Bavnbek, Bernhelm; Zhu, Chaofeng

2005-01-01

of the resulting continuous family of (unbounded) self-adjoint Fredholm operators in terms of the Maslov index of two related curves of Lagrangian spaces. One curve is given by the varying domains, the other by the Cauchy data spaces. We provide rigorous definitions of the underlying concepts of spectral theory......We consider a continuous curve of linear elliptic formally self-adjoint differential operators of first order with smooth coefficients over a compact Riemannian manifold with boundary together with a continuous curve of global elliptic boundary value problems. We express the spectral flow...... and symplectic analysis and give a full (and surprisingly short) proof of our General Spectral Flow Formula for the case of fixed maximal domain. As a side result, we establish local stability of weak inner unique continuation property (UCP) and explain its role for parameter dependent spectral theory....

Shear at Twin Domain Boundaries in YBa2Cu3O7-x

Science.gov (United States)

Caldwell, W. A.; Tamura, N.; Celestre, R. S.; MacDowell, A. A.; Padmore, H. A.; Geballe, T. H.; Koster, G.; Batterman, B. W.; Patel, J. R.

2004-05-01

The microstructure and strain state of twin domains in YBa2Cu3O7-x are discussed based upon synchrotron white-beam x-ray microdiffraction measurements. Intensity variations of the fourfold twin splitting of Laue diffraction peaks are used to determine the twin domain structure. Strain analysis shows that interfaces between neighboring twin domains are strained in shear, whereas the interior of these domains are regions of low strain. These measurements are consistent with the orientation relationships of twin boundaries within and across domains and show that basal plane shear stresses can exceed 100MPa where twin domains meet. Our results support stress field pinning of magnetic flux vortices by twin domain boundaries.

Domain-Generality of Timing-Based Serial Order Processes in Short-Term Memory: New Insights from Musical and Verbal Domains.

Directory of Open Access Journals (Sweden)

Simon Gorin

Full Text Available Several models in the verbal domain of short-term memory (STM consider a dissociation between item and order processing. This view is supported by data demonstrating that different types of time-based interference have a greater effect on memory for the order of to-be-remembered items than on memory for the items themselves. The present study investigated the domain-generality of the item versus serial order dissociation by comparing the differential effects of time-based interfering tasks, such as rhythmic interference and articulatory suppression, on item and order processing in verbal and musical STM domains. In Experiment 1, participants had to maintain sequences of verbal or musical information in STM, followed by a probe sequence, this under different conditions of interference (no-interference, rhythmic interference, articulatory suppression. They were required to decide whether all items of the probe list matched those of the memory list (item condition or whether the order of the items in the probe sequence matched the order in the memory list (order condition. In Experiment 2, participants performed a serial order probe recognition task for verbal and musical sequences ensuring sequential maintenance processes, under no-interference or rhythmic interference conditions. For Experiment 1, serial order recognition was not significantly more impacted by interfering tasks than was item recognition, this for both verbal and musical domains. For Experiment 2, we observed selective interference of the rhythmic interference condition on both musical and verbal order STM tasks. Overall, the results suggest a similar and selective sensitivity to time-based interference for serial order STM in verbal and musical domains, but only when the STM tasks ensure sequential maintenance processes.

Domain-Generality of Timing-Based Serial Order Processes in Short-Term Memory: New Insights from Musical and Verbal Domains.

Science.gov (United States)

Gorin, Simon; Kowialiewski, Benjamin; Majerus, Steve

2016-01-01

Several models in the verbal domain of short-term memory (STM) consider a dissociation between item and order processing. This view is supported by data demonstrating that different types of time-based interference have a greater effect on memory for the order of to-be-remembered items than on memory for the items themselves. The present study investigated the domain-generality of the item versus serial order dissociation by comparing the differential effects of time-based interfering tasks, such as rhythmic interference and articulatory suppression, on item and order processing in verbal and musical STM domains. In Experiment 1, participants had to maintain sequences of verbal or musical information in STM, followed by a probe sequence, this under different conditions of interference (no-interference, rhythmic interference, articulatory suppression). They were required to decide whether all items of the probe list matched those of the memory list (item condition) or whether the order of the items in the probe sequence matched the order in the memory list (order condition). In Experiment 2, participants performed a serial order probe recognition task for verbal and musical sequences ensuring sequential maintenance processes, under no-interference or rhythmic interference conditions. For Experiment 1, serial order recognition was not significantly more impacted by interfering tasks than was item recognition, this for both verbal and musical domains. For Experiment 2, we observed selective interference of the rhythmic interference condition on both musical and verbal order STM tasks. Overall, the results suggest a similar and selective sensitivity to time-based interference for serial order STM in verbal and musical domains, but only when the STM tasks ensure sequential maintenance processes.

Interleukin 4: signalling mechanisms and control of T cell differentiation.

Science.gov (United States)

Paul, W E

1997-01-01

Interleukin 4 (IL-4) is a pleiotropic type I cytokine that controls both growth and differentiation among haemopoietic and non-haemopoietic cells. Its receptor is a heterodimer. One chain, the IL-4R alpha chain, binds IL-4 with high affinity and determines the nature of the biochemical signals that are induced. The second chain, gamma c, is required for the induction of such signals. IL-4-mediated growth depends upon activation events that involve phosphorylation of Y497 of IL-4R alpha, leading to the binding and phosphorylation of 4PS/IRS-2 in haemopoietic cells and of IRS-1 in non-haemopoietic cells. By contrast, IL-4-mediated differentiation events depend upon more distal regions of the IL-4R alpha chain that include a series of STAT-6 binding sites. The distinctive roles of these receptor domains was verified by receptor-reconstruction experiments. The 'growth' and 'differentiation' domains of the IL-4R alpha chain, independently expressed as chimeric structures with a truncated version of the IL-2R beta chain, were shown to convey their functions to the hybrid receptor. The critical role of STAT-6 in IL-4-mediated gene activation and differentiation was made clear by the finding that lymphocytes from STAT-6 knockout mice are strikingly deficient in these functions but have retained the capacity to grow, at least partially, in response to IL-4. IL-4 plays a central role in determining the phenotype of naive CD4+ T cells. In the presence of IL-4, newly primed naive T cells develop into IL-4 producers while in its absence they preferentially become gamma-interferon (IFN-gamma) producers. Recently, a specialized subpopulation of T cells, CD4+/NK1.1+ cells, has been shown to produce large amounts of IL-4 upon stimulation. Two examples of mice with deficiencies in these cells are described--beta 2-microglobulin knockout mice and SJL mice. Both show defects in the development of IL-4-producing cells and in the increase in serum IgE in response to stimulation with the

Representation of discrete Steklov-Poincare operator arising in domain decomposition methods in wavelet basis

Energy Technology Data Exchange (ETDEWEB)

Jemcov, A.; Matovic, M.D. [Queen`s Univ., Kingston, Ontario (Canada)

1996-12-31

This paper examines the sparse representation and preconditioning of a discrete Steklov-Poincare operator which arises in domain decomposition methods. A non-overlapping domain decomposition method is applied to a second order self-adjoint elliptic operator (Poisson equation), with homogeneous boundary conditions, as a model problem. It is shown that the discrete Steklov-Poincare operator allows sparse representation with a bounded condition number in wavelet basis if the transformation is followed by thresholding and resealing. These two steps combined enable the effective use of Krylov subspace methods as an iterative solution procedure for the system of linear equations. Finding the solution of an interface problem in domain decomposition methods, known as a Schur complement problem, has been shown to be equivalent to the discrete form of Steklov-Poincare operator. A common way to obtain Schur complement matrix is by ordering the matrix of discrete differential operator in subdomain node groups then block eliminating interface nodes. The result is a dense matrix which corresponds to the interface problem. This is equivalent to reducing the original problem to several smaller differential problems and one boundary integral equation problem for the subdomain interface.

Superdiffusions and positive solutions of nonlinear partial differential equations

CERN Document Server

Dynkin, E B

2004-01-01

This book is devoted to the applications of probability theory to the theory of nonlinear partial differential equations. More precisely, it is shown that all positive solutions for a class of nonlinear elliptic equations in a domain are described in terms of their traces on the boundary of the domain. The main probabilistic tool is the theory of superdiffusions, which describes a random evolution of a cloud of particles. A substantial enhancement of this theory is presented that can be of interest for everybody who works on applications of probabilistic methods to mathematical analysis.

Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change

Energy Technology Data Exchange (ETDEWEB)

Masuda, Tetsuya, E-mail: t2masuda@kais.kyoto-u.ac.jp [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Ohta, Keisuke [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Mikami, Bunzo [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Kitabatake, Naofumi [Department of Foods and Human Nutrition, Notre Dame Seishin University, Okayama 700-8516 (Japan); Tani, Fumito [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

2012-03-02

Highlights: Black-Right-Pointing-Pointer Structure of a recombinant thaumatin at pH 8.0 determined at a resolution of 1.0 A. Black-Right-Pointing-Pointer Substantial fluctuations of a loop in domain II was found in the structure at pH 8.0. Black-Right-Pointing-Pointer B-factors for Lys137, Lys163, and Lys187 were significantly affected by pH change. Black-Right-Pointing-Pointer An increase in mobility might play an important role in the heat-induced aggregation. -- Abstract: Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 Degree-Sign C for 4 h under acid conditions, it rapidly declines when heating at a pH above 6.5. To clarify the structural difference at high pH, the atomic structure of a recombinant thaumatin I at pH 8.0 was determined at a resolution of 1.0 A. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of a C{alpha} atom to be substantially greater in the large disulfide-rich region of domain II, especially residues 154-164, suggesting that a loop region in domain II to be affected by solvent conditions. Furthermore, B-factors of Lys137, Lys163, and Lys187 were significantly affected by pH change, suggesting that a striking increase in the mobility of these lysine residues, which could facilitate a reaction with a free sulfhydryl residue produced via the {beta}-elimination of disulfide bonds by heating at a pH above 7.0. The increase in mobility of lysine residues as well as a loop region in domain II might play an important role in the heat-induced aggregation of thaumatin above pH 7.0.

The interaction of process and domain in prefrontal cortex during inductive reasoning.

Science.gov (United States)

Babcock, Laura; Vallesi, Antonino

2015-01-01

Inductive reasoning is an everyday process that allows us to make sense of the world by creating rules from a series of instances. Consistent with accounts of process-based fractionations of the prefrontal cortex (PFC) along the left-right axis, inductive reasoning has been reliably localized to left PFC. However, these results may be confounded by the task domain, which is typically verbal. Indeed, some studies show that right PFC activation is seen with spatial tasks. This study used fMRI to examine the effects of process and domain on the brain regions recruited during a novel pattern discovery task. Twenty healthy young adult participants were asked to discover the rule underlying the presentation of a series of letters in varied spatial locations. The rules were either verbal (pertaining to a single semantic category) or spatial (geometric figures). Bilateral ventrolateral PFC activations were seen for the spatial domain, while the verbal domain showed only left ventrolateral PFC. A conjunction analysis revealed that the two domains recruited a common region of left ventrolateral PFC. The data support a central role of left PFC in inductive reasoning. Importantly, they also suggest that both process and domain shape the localization of reasoning in the brain. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential equations with applications in cancer diseases.

Science.gov (United States)

Ilea, M; Turnea, M; Rotariu, M

2013-01-01

Mathematical modeling is a process by which a real world problem is described by a mathematical formulation. The cancer modeling is a highly challenging problem at the frontier of applied mathematics. A variety of modeling strategies have been developed, each focusing on one or more aspects of cancer. The vast majority of mathematical models in cancer diseases biology are formulated in terms of differential equations. We propose an original mathematical model with small parameter for the interactions between these two cancer cell sub-populations and the mathematical model of a vascular tumor. We work on the assumption that, the quiescent cells' nutrient consumption is long. One the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. MATLAB simulations obtained for transition rate from the quiescent cells' nutrient consumption is long, we show a similar asymptotic behavior for two solutions of the perturbed problem. In this system, the small parameter is an asymptotic variable, different from the independent variable. The graphical output for a mathematical model of a vascular tumor shows the differences in the evolution of the tumor populations of proliferating, quiescent and necrotic cells. The nutrient concentration decreases sharply through the viable rim and tends to a constant level in the core due to the nearly complete necrosis in this region. Many mathematical models can be quantitatively characterized by ordinary differential equations or partial differential equations. The use of MATLAB in this article illustrates the important role of informatics in research in mathematical modeling. The study of avascular tumor growth cells is an exciting and important topic in cancer research and will profit considerably from theoretical input. Interpret these results to be a permanent collaboration between math's and medical oncologists.

A computational method for the coupled solution of reaction-diffusion equations on evolving domains and manifolds: Application to a model of cell migration and chemotaxis.

Science.gov (United States)

MacDonald, G; Mackenzie, J A; Nolan, M; Insall, R H

2016-03-15

In this paper, we devise a moving mesh finite element method for the approximate solution of coupled bulk-surface reaction-diffusion equations on an evolving two dimensional domain. Fundamental to the success of the method is the robust generation of bulk and surface meshes. For this purpose, we use a novel moving mesh partial differential equation (MMPDE) approach. The developed method is applied to model problems with known analytical solutions; these experiments indicate second-order spatial and temporal accuracy. Coupled bulk-surface problems occur frequently in many areas; in particular, in the modelling of eukaryotic cell migration and chemotaxis. We apply the method to a model of the two-way interaction of a migrating cell in a chemotactic field, where the bulk region corresponds to the extracellular region and the surface to the cell membrane.

An auxiliary differential equation FDTD method for anisotropic magnetized plasmas

International Nuclear Information System (INIS)

Liu Shaobin; Mo Jinjun; Yuan Naichang

2004-01-01

An auxiliary differential equation finite-difference time-domain (ADE-FDTD) methodology for anisotropic magnetized plasmas is derived. The method is based on a difference approximation of the auxiliary differential equation. A comparison with the JEC method is included. The CPU time saving by several times and accuracy of the method are confirmed by computing the reflection and transmission through a magnetized plasma layer with the direction of propagation parallel to the direction of the biasing field

Domains of psychosocial disability and mental disorders.

Science.gov (United States)

Ro, Eunyoe; Watson, David; Clark, Lee Anna

2018-06-07

This study examined relations between comprehensive domains of psychosocial disability and mental disorders to determine (1) whether differential patterns of associations exist between psychosocial disability dimensions and commonly diagnosed mental disorders and (2) whether these relations differ between self-reported and interviewer-rated psychosocial disability domains. Self-reported and interviewer-rated psychosocial functioning measures and an interviewer-rated diagnostic assessment tool were administered to 181 psychiatric outpatients. Internalizing disorders showed the strongest and most pervasive associations with psychosocial impairment across both self-reported and interviewer-rated measures, followed by thought disorder; externalizing showed the weakest associations. More specifically, logistic regression analyses indicated that lower well-being factor score significantly increased the odds of distress-disorder diagnoses, and poor basic functioning increased the odds of PTSD. Results clearly showed differences in the magnitude of associations between three dimensions of psychosocial-disability and commonly diagnosed disorders, and that these differences were similar regardless of rater type. © 2018 Wiley Periodicals, Inc.

In vitro osteosarcoma biosensing using THz time domain spectroscopy

Science.gov (United States)

Ferguson, Bradley S.; Liu, Haibo; Hay, Shelley; Findlay, David; Zhang, Xi-Cheng; Abbott, Derek

2004-03-01

Terahertz time domain spectroscopy (THz-TDS) has a wide range of applications from semiconductor diagnostics to biosensing. Recent attention has focused on bio-applications and several groups have noted the ability of THz-TDS to differentiate basal cell carcinoma tissue from healthy dermal tissue ex vivo. The contrast mechanism is unclear but has been attributed to increased interstitial water in cancerous tissue. In this work we investigate the THz response of human osteosarcoma cells and normal human bone cells grown in culture to isolate the cells' responses from other effects. A classification algorithms based on a frequency selection by genetic algorithm is used to attempt to differentiate between the cell types based on the THz spectra. Encouraging preliminary results have been obtained.

Optimal Control of Heterogeneous Systems with Endogenous Domain of Heterogeneity

International Nuclear Information System (INIS)

Belyakov, Anton O.; Tsachev, Tsvetomir; Veliov, Vladimir M.

2011-01-01

The paper deals with optimal control of heterogeneous systems, that is, families of controlled ODEs parameterized by a parameter running over a domain called domain of heterogeneity. The main novelty in the paper is that the domain of heterogeneity is endogenous: it may depend on the control and on the state of the system. This extension is crucial for several economic applications and turns out to rise interesting mathematical problems. A necessary optimality condition is derived, where one of the adjoint variables satisfies a differential inclusion (instead of equation) and the maximization of the Hamiltonian takes the form of “min-max”. As a consequence, a Pontryagin-type maximum principle is obtained under certain regularity conditions for the optimal control. A formula for the derivative of the objective function with respect to the control from L ∞ is presented together with a sufficient condition for its existence. A stylized economic example is investigated analytically and numerically.

Phase Behavior and Domain Size in Sphingomyelin-Containing Lipid Bilayers

Science.gov (United States)

Petruzielo, Robin S.; Heberle, Frederick A.; Drazba, Paul; Katsaras, John; Feigenson, Gerald W.

2013-01-01

Membrane raft size measurements are crucial to understanding the stability and functionality of rafts in cells. The challenge of accurately measuring raft size is evidenced by the disparate reports of domain sizes, which range from nanometers to microns for the ternary model membrane system sphingomyelin (SM)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol (Chol). Using Förster resonance energy transfer (FRET) and differential scanning calorimetry (DSC), we established phase diagrams for porcine brain SM (bSM)/dioleoyl-sn-glycero-3-phosphocholine (DOPC)/Chol and bSM/POPC/Chol at 15 and 25°C. By combining two techniques with different spatial sensitivities, namely FRET and small-angle neutron scattering (SANS), we have significantly narrowed the uncertainty in domain size estimates for bSM/POPC/Chol mixtures. Compositional trends in FRET data revealed coexisting domains at 15 and 25°C for both mixtures, while SANS measurements detected no domain formation for bSM/POPC/Chol. Together these results indicate that liquid domains in bSM/POPC/Chol are between 2 and 7 nm in radius at 25°C: that is, domains must be on the order of the 2–6 nm Förster distance of the FRET probes, but smaller than the ~7 nm minimum cluster size detectable with SANS. However, for palmitoyl SM (PSM)/POPC/Chol at a similar composition, SANS detected coexisting liquid domains. This increase in domain size upon replacing the natural SM component (which consists of a mixture of chain lengths) with synthetic PSM, suggests a role for SM chain length in modulating raft size in vivo. PMID:23337475

The C-terminal domain of the bacteriophage T4 terminase docks on the prohead portal clip region during DNA packaging

Science.gov (United States)

Dixit, Aparna Banerjee; Ray, Krishanu; Thomas, Julie A.; Black, Lindsay W.

2013-01-01

Bacteriophage ATP-based packaging motors translocate DNA into a pre-formed prohead through a dodecameric portal ring channel to high density. We investigated portal–terminase docking interactions at specifically localized residues within a terminase-interaction region (aa279–316) in the phage T4 portal protein gp20 equated to the clip domain of the SPP1 portal crystal structure by 3D modeling. Within this region, three residues allowed A to C mutations whereas three others did not, consistent with informatics analyses showing the tolerated residues are not strongly conserved evolutionarily. About 7.5 nm was calculated by FCS-FRET studies employing maleimide Alexa488 dye labeled A316C proheads and gp17 CT-ReAsH supporting previous work docking the C-terminal end of the T4 terminase (gp17) closer to the N-terminal GFP-labeled portal (gp20) than the N-terminal end of the terminase. Such a terminase–portal orientation fits better to a proposed “DNA crunching” compression packaging motor and to portal determined DNA headful cutting. PMID:24074593

The Role of the N-Domain in the ATPase Activity of the Mammalian AAA ATPase p97/VCP*

Science.gov (United States)

Niwa, Hajime; Ewens, Caroline A.; Tsang, Chun; Yeung, Heidi O.; Zhang, Xiaodong; Freemont, Paul S.

2012-01-01

p97/valosin-containing protein (VCP) is a type II ATPase associated with various cellular activities that forms a homohexamer with each protomer containing an N-terminal domain (N-domain); two ATPase domains, D1 and D2; and a disordered C-terminal region. Little is known about the role of the N-domain or the C-terminal region in the p97 ATPase cycle. In the p97-associated human disease inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, the majority of missense mutations are located at the N-domain D1 interface. Structure-based predictions suggest that such mutations affect the interaction of the N-domain with D1. Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97A232E, having three times higher activity. Further mutagenesis of p97A232E shows that the increase in ATPase activity is mediated through D2 and requires both the N-domain and a flexible ND1 linker. A disulfide mutation that locks the N-domain to D1 in a coplanar position reversibly abrogates ATPase activity. A cryo-EM reconstruction of p97A232E suggests that the N-domains are flexible. Removal of the C-terminal region also reduces ATPase activity. Taken together, our data suggest that the conformation of the N-domain in relation to the D1-D2 hexamer is directly linked to ATP hydrolysis and that the C-terminal region is required for hexamer stability. This leads us to propose a model where the N-domain adopts either of two conformations: a flexible conformation compatible with ATP hydrolysis or a coplanar conformation that is inactive. PMID:22270372

The role of the N-domain in the ATPase activity of the mammalian AAA ATPase p97/VCP.

Science.gov (United States)

Niwa, Hajime; Ewens, Caroline A; Tsang, Chun; Yeung, Heidi O; Zhang, Xiaodong; Freemont, Paul S

2012-03-09

p97/valosin-containing protein (VCP) is a type II ATPase associated with various cellular activities that forms a homohexamer with each protomer containing an N-terminal domain (N-domain); two ATPase domains, D1 and D2; and a disordered C-terminal region. Little is known about the role of the N-domain or the C-terminal region in the p97 ATPase cycle. In the p97-associated human disease inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, the majority of missense mutations are located at the N-domain D1 interface. Structure-based predictions suggest that such mutations affect the interaction of the N-domain with D1. Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97(A232E), having three times higher activity. Further mutagenesis of p97(A232E) shows that the increase in ATPase activity is mediated through D2 and requires both the N-domain and a flexible ND1 linker. A disulfide mutation that locks the N-domain to D1 in a coplanar position reversibly abrogates ATPase activity. A cryo-EM reconstruction of p97(A232E) suggests that the N-domains are flexible. Removal of the C-terminal region also reduces ATPase activity. Taken together, our data suggest that the conformation of the N-domain in relation to the D1-D2 hexamer is directly linked to ATP hydrolysis and that the C-terminal region is required for hexamer stability. This leads us to propose a model where the N-domain adopts either of two conformations: a flexible conformation compatible with ATP hydrolysis or a coplanar conformation that is inactive.

Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region.

Science.gov (United States)

Zhang, Yi; Lu, Yongfang; Yindee, Marnoch; Li, Kuan-Yi; Kuo, Hsiao-Yun; Ju, Yu-Ten; Ye, Shaohui; Faruque, Md Omar; Li, Qiang; Wang, Yachun; Cuong, Vu Chi; Pham, Lan Doan; Bouahom, Bounthong; Yang, Bingzhuang; Liang, Xianwei; Cai, Zhihua; Vankan, Dianne; Manatchaiworakul, Wallaya; Kowlim, Nonglid; Duangchantrasiri, Somphot; Wajjwalku, Worawidh; Colenbrander, Ben; Zhang, Yuan; Beerli, Peter; Lenstra, Johannes A; Barker, J Stuart F

2016-04-01

The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock. © 2015 John Wiley & Sons Ltd.

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

Science.gov (United States)

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

A lipid binding domain in sphingosine kinase 2

International Nuclear Information System (INIS)

Don, Anthony S.; Rosen, Hugh

2009-01-01

The lipid second messenger sphingosine 1-phosphate (S1P) is a critical mediator of cellular proliferation and survival signals, and is essential for vasculogenesis and neurogenesis. S1P formation is catalysed by sphingosine kinases 1 and 2 (Sphk1 and Sphk2). We have found that the endogenous glycolipid sulfatide (3-O-sulfogalactosylceramide) binds to and inhibits the activity of Sphk2 and the closely related ceramide kinase (Cerk), but not Sphk1. Using sulfatide as a probe, we mapped the lipid binding domain to the N-terminus of Sphk2 (residues 1-175), a region of sequence that is absent in Sphk1, but aligns with a pleckstrin homology domain in Cerk. Accordingly, Sphk2 bound to phosphatidylinositol monophosphates but not to abundant cellular phospholipids. Deleting the N-terminal domain reduced Sphk2 membrane localisation in cells. We have therefore identified a lipid binding domain in Sphk2 that is important for the enzyme's sub-cellular localisation.

Monte Carlo simulation for thermal assisted reversal process of micro-magnetic torus ring with bistable closure domain structure

Energy Technology Data Exchange (ETDEWEB)

Terashima, Kenichi; Suzuki, Kenji; Yamaguchi, Katsuhiko, E-mail: yama@sss.fukushima-u.ac.jp

2016-04-01

Monte Carlo simulations were performed for temperature dependences of closure domain parameter for a magnetic micro-torus ring cluster under magnetic field on limited temperature regions. Simulation results show that magnetic field on tiny limited temperature region can reverse magnetic closure domain structures when the magnetic field is applied at a threshold temperature corresponding to intensity of applied magnetic field. This is one of thermally assisted switching phenomena through a self-organization process. The results show the way to find non-wasteful pairs between intensity of magnetic field and temperature region for reversing closure domain structure by temperature dependence of the fluctuation of closure domain parameter. Monte Carlo method for this simulation is very valuable to optimize the design of thermally assisted switching devices.

Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

Science.gov (United States)

Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

2017-04-01

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

Structure of the USP15 N-terminal domains: a β-hairpin mediates close association between the DUSP and UBL domains.

Science.gov (United States)

Harper, Stephen; Besong, Tabot M D; Emsley, Jonas; Scott, David J; Dreveny, Ingrid

2011-09-20

Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily. © 2011 American Chemical Society

Pentamidine blocks the interaction between mutant S100A5 and RAGE V domain and inhibits the RAGE signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Cho, Ching Chang, E-mail: ccjwo@yahoo.com.tw [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Chou, Ruey Hwang, E-mail: rhchou@mail.cmu.edu.tw [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)

2016-08-19

The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia. Here, we found that pentamidine interacts with S100A5 using HSQC titration. We elucidated the interactions of S100A5 with RAGE V domain and pentamidine using fluorescence and NMR spectroscopy. We generated two binary models—the S100A5-RAGE V domain and S100A5-Pentamidine complex—and then observed that the pentamidine and RAGE V domain share a similar binding region in mS100A5. We also used the WST-1 assay to investigate the bioactivity of S100A5, RAGE V domain and pentamidine. These results indicated that pentamidine blocks the binding between S100A5 and RAGE V domain. This finding is useful for the development of new anti-proliferation drugs. - Highlights: • The interaction between mS100A5–RAGE V was investigated by fluorescence spectroscopy. • The interfacial residues on mS100A5–RAGE V and mS100A5–pentamidine contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • mS100A5–RAGE V and mS100A5–pentamidine complex models were generated from NMR restraints using HADDOCK program. • The bioactivity of the mS100A5–RAGE V and mS100A5–pentamidine complex was studied using WST-1 assay.

Scalable Domain Decomposition Preconditioners for Heterogeneous Elliptic Problems

Directory of Open Access Journals (Sweden)

Pierre Jolivet

2014-01-01

Full Text Available Domain decomposition methods are, alongside multigrid methods, one of the dominant paradigms in contemporary large-scale partial differential equation simulation. In this paper, a lightweight implementation of a theoretically and numerically scalable preconditioner is presented in the context of overlapping methods. The performance of this work is assessed by numerical simulations executed on thousands of cores, for solving various highly heterogeneous elliptic problems in both 2D and 3D with billions of degrees of freedom. Such problems arise in computational science and engineering, in solid and fluid mechanics. While focusing on overlapping domain decomposition methods might seem too restrictive, it will be shown how this work can be applied to a variety of other methods, such as non-overlapping methods and abstract deflation based preconditioners. It is also presented how multilevel preconditioners can be used to avoid communication during an iterative process such as a Krylov method.

Towards development of a high quality public domain global roads database

Directory of Open Access Journals (Sweden)

Andrew Nelson

2006-12-01

Full Text Available There is clear demand for a global spatial public domain roads data set with improved geographic and temporal coverage, consistent coding of road types, and clear documentation of sources. The currently best available global public domain product covers only one-quarter to one-third of the existing road networks, and this varies considerably by region. Applications for such a data set span multiple sectors and would be particularly valuable for the international economic development, disaster relief, and biodiversity conservation communities, not to mention national and regional agencies and organizations around the world. The building blocks for such a global product are available for many countries and regions, yet thus far there has been neither strategy nor leadership for developing it. This paper evaluates the best available public domain and commercial data sets, assesses the gaps in global coverage, and proposes a number of strategies for filling them. It also identifies stakeholder organizations with an interest in such a data set that might either provide leadership or funding for its development. It closes with a proposed set of actions to begin the process.

Direct nanoscale imaging of evolving electric field domains in quantum structures.

Science.gov (United States)

Dhar, Rudra Sankar; Razavipour, Seyed Ghasem; Dupont, Emmanuel; Xu, Chao; Laframboise, Sylvain; Wasilewski, Zbig; Hu, Qing; Ban, Dayan

2014-11-28

The external performance of quantum optoelectronic devices is governed by the spatial profiles of electrons and potentials within the active regions of these devices. For example, in quantum cascade lasers (QCLs), the electric field domain (EFD) hypothesis posits that the potential distribution might be simultaneously spatially nonuniform and temporally unstable. Unfortunately, there exists no prior means of probing the inner potential profile directly. Here we report the nanoscale measured electric potential distribution inside operating QCLs by using scanning voltage microscopy at a cryogenic temperature. We prove that, per the EFD hypothesis, the multi-quantum-well active region is indeed divided into multiple sections having distinctly different electric fields. The electric field across these serially-stacked quantum cascade modules does not continuously increase in proportion to gradual increases in the applied device bias, but rather hops between discrete values that are related to tunneling resonances. We also report the evolution of EFDs, finding that an incremental change in device bias leads to a hopping-style shift in the EFD boundary--the higher electric field domain expands at least one module each step at the expense of the lower field domain within the active region.

Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.

Science.gov (United States)

Kieken, Fabien; Loth, Karine; van Nuland, Nico; Tompa, Peter; Lenaerts, Tom

2018-04-01

Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1 H, 15 N and 13 C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains. The BMRB accession number is 27165.

The DNA binding and activation domains of Gal4p are sufficient for conveying its regulatory signals.

OpenAIRE

Ding, W V; Johnston, S A

1997-01-01

The transcriptional activation function of the Saccharomyces cerevisiae activator Gal4p is known to rely on a DNA binding activity at its amino terminus and an activation domain at its carboxy terminus. Although both domains are required for activation, truncated forms of Gal4p containing only these domains activate poorly in vivo. Also, mutations in an internal conserved region of Gal4p inactivate the protein, suggesting that this internal region has some function critical to the activity of...

The study of co-citation analysis and knowledge structure on healthcare domain

Science.gov (United States)

Chu, Kuo-Chung; Liu, Wen-I.; Tsai, Ming-Yu

2012-11-01

With the prevalence of Internet and digital archives, the online e-journal database facilitates scholars to search literature in a research domain, or to cross-search an inter-disciplined field; the key literature can be efficiently traced out. This study intends to build a Web-based citation analysis system, which consists of four modules, they are: 1) literature search module; (2) statistics module; (3) articles analysis module; and (4) co-citation analysis module. The system focuses on PubMed Central dataset that has 170,000 records. In a research domain, a specific keyword searches in terms of authors, journals, and core issues. In addition, we use data mining techniques for co-citation analysis. The results assist researchers with in-depth understanding of the domain knowledge. Having an automated system for co-citation analysis, it helps to understand changes, trends, and knowledge structure of research domain. For the best of our knowledge, the proposed system differentiates from existing online electronic retrieval database analysis function. Perhaps, the proposed system is going to be a value-added database of healthcare domain, and hope to contribute the researchers.

Differential diagnosis of regional cerebral hyperfixation of TC-99m HMPAO on SPECT imaging

Energy Technology Data Exchange (ETDEWEB)

Shirazi, P.; Konopka, L.; Crayton, J.W. [Loyola Univ. Medical Center, Maywood, IL (United States)] [and others

1994-05-01

Accurate diagnostic evaluation of patients with neurologic and neuropsychiatric disease is important because early treatment may halt disease progression and prevent impairment or disability. Cerebral hyperfixation of HMPAO has been ascribed to luxury perfusion following ischemic infarction. The present study sought to identify other conditions that also display radiotracer hyperfixation in order to develop a differential diagnosis of this finding on SPECT imaging. Two hundred fifty (n=250) successive cerebral SPECT images were reviewed for evidence of HMPAO hyperfixation. Hyperfixation was defined as enhanced focal perfusion surrounded by a zone of diminished or normal cerebral perfusion. All patients were scanned after intravenous injection of 25 mCi Tc-99m HMPAO. Volume-rendered and oblique images were obtained with a Trionix triple-head SPECT system using ultra high resolution fan beam collimators. Thirteen (13/250; 5%) of the patients exhibited regions of HMPAO hyperfixation. CT or MRI abnormalities were detected in 6/13 cases. Clinical diagnoses in these patients included intractable psychosis, post-traumatic stress disorder, alcohol and narcotic dependence, major depression, acute closed-head trauma, hypothyroidism, as well as subacute ischemic infarction. A wide variety of conditions may be associated with cerebral hyperfixation of HMPAO. These conditions include neurologic and psychiatric diagnoses, and extend the consideration of hyperfixation beyond ischemic infarction. Consequently, a differential diagnosis of HMPAO hyperfixation may be broader than originally considered, and this may suggest a fundamental role for local cerebral hyperperfusion. Elucidation of the fundamental mechanism(s) for cerebral hyperperfusion requires further investigation.

Partial differential equations in several complex variables

CERN Document Server

Chen, So-Chin

2001-01-01

This book is intended both as an introductory text and as a reference book for those interested in studying several complex variables in the context of partial differential equations. In the last few decades, significant progress has been made in the fields of Cauchy-Riemann and tangential Cauchy-Riemann operators. This book gives an up-to-date account of the theories for these equations and their applications. The background material in several complex variables is developed in the first three chapters, leading to the Levi problem. The next three chapters are devoted to the solvability and regularity of the Cauchy-Riemann equations using Hilbert space techniques. The authors provide a systematic study of the Cauchy-Riemann equations and the \\bar\\partial-Neumann problem, including L^2 existence theorems on pseudoconvex domains, \\frac 12-subelliptic estimates for the \\bar\\partial-Neumann problems on strongly pseudoconvex domains, global regularity of \\bar\\partial on more general pseudoconvex domains, boundary ...

The epigenetic regulator Smchd1 contains a functional GHKL-type ATPase domain.

Science.gov (United States)

Chen, Kelan; Dobson, Renwick C J; Lucet, Isabelle S; Young, Samuel N; Pearce, F Grant; Blewitt, Marnie E; Murphy, James M

2016-06-15

Structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is an epigenetic regulator that plays critical roles in gene regulation during development. Mutations in SMCHD1 were recently implicated in the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD), although the mechanistic basis remains of outstanding interest. We have previously shown that Smchd1 associates with chromatin via its homodimeric C-terminal hinge domain, yet little is known about the function of the putative GHKL (gyrase, Hsp90, histidine kinase, MutL)-type ATPase domain at its N-terminus. To formally assess the structure and function of Smchd1's ATPase domain, we have generated recombinant proteins encompassing the predicted ATPase domain and the adjacent region. Here, we show that the Smchd1 N-terminal region exists as a monomer and adopts a conformation resembling that of monomeric full-length heat shock protein 90 (Hsp90) protein in solution, even though the two proteins share only ∼8% overall sequence identity. Despite being monomeric, the N-terminal region of Smchd1 exhibits ATPase activity, which can be antagonized by the reaction product, ADP, or the Hsp90 inhibitor, radicicol, at a nanomolar concentration. Interestingly, introduction of an analogous mutation to that identified in SMCHD1 of an FSHD patient compromised protein stability, suggesting a possible molecular basis for loss of protein function and pathogenesis. Together, these results reveal important structure-function characteristics of Smchd1 that may underpin its mechanistic action at the chromatin level. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues adjacent to transmembrane domains.

Science.gov (United States)

Sadja, Rona; Reuveny, Eitan

2009-01-01

G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are involved in neurotransmission-mediated reduction of excitability. The gating mechanism following G protein activation of these channels likely proceeds from movement of inner transmembrane helices to allow K(+) ions movement through the pore of the channel. There is limited understanding of how the binding of G-protein betagamma subunits to cytoplasmic regions of the channel transduces the signal to the transmembrane regions. In this study, we examined the molecular basis that governs the activation kinetics of these channels, using a chimeric approach. We identified two regions as being important in determining the kinetics of activation. One region is the bottom of the outer transmembrane helix (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the second region is the bottom of the inner transmembrane helix (TM2) and the cytoplasmic domain immediately adjacent. Interestingly, both of these regions are sufficient in mediating the kinetics of fast activation gating. This result suggests that there is a cooperative movement of either one of these domains to allow fast and efficient activation gating of GIRK channels.

Interferometrically enhanced sub-terahertz picosecond imaging utilizing a miniature collapsing-field-domain source

Science.gov (United States)

Vainshtein, Sergey N.; Duan, Guoyong; Mikhnev, Valeri A.; Zemlyakov, Valery E.; Egorkin, Vladimir I.; Kalyuzhnyy, Nikolay A.; Maleev, Nikolai A.; Näpänkangas, Juha; Sequeiros, Roberto Blanco; Kostamovaara, Juha T.

2018-05-01

Progress in terahertz spectroscopy and imaging is mostly associated with femtosecond laser-driven systems, while solid-state sources, mainly sub-millimetre integrated circuits, are still in an early development phase. As simple and cost-efficient an emitter as a Gunn oscillator could cause a breakthrough in the field, provided its frequency limitations could be overcome. Proposed here is an application of the recently discovered collapsing field domains effect that permits sub-THz oscillations in sub-micron semiconductor layers thanks to nanometer-scale powerfully ionizing domains arising due to negative differential mobility in extreme fields. This shifts the frequency limit by an order of magnitude relative to the conventional Gunn effect. Our first miniature picosecond pulsed sources cover the 100-200 GHz band and promise milliwatts up to ˜500 GHz. Thanks to the method of interferometrically enhanced time-domain imaging proposed here and the low single-shot jitter of ˜1 ps, our simple imaging system provides sufficient time-domain imaging contrast for fresh-tissue terahertz histology.

The BRCT domain is a phospho-protein binding domain.

Science.gov (United States)

Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

2003-10-24

The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

Geometric differential evolution for combinatorial and programs spaces.

Science.gov (United States)

Moraglio, A; Togelius, J; Silva, S

2013-01-01

Geometric differential evolution (GDE) is a recently introduced formal generalization of traditional differential evolution (DE) that can be used to derive specific differential evolution algorithms for both continuous and combinatorial spaces retaining the same geometric interpretation of the dynamics of the DE search across representations. In this article, we first review the theory behind the GDE algorithm, then, we use this framework to formally derive specific GDE for search spaces associated with binary strings, permutations, vectors of permutations and genetic programs. The resulting algorithms are representation-specific differential evolution algorithms searching the target spaces by acting directly on their underlying representations. We present experimental results for each of the new algorithms on a number of well-known problems comprising NK-landscapes, TSP, and Sudoku, for binary strings, permutations, and vectors of permutations. We also present results for the regression, artificial ant, parity, and multiplexer problems within the genetic programming domain. Experiments show that overall the new DE algorithms are competitive with well-tuned standard search algorithms.

Essential Boundary Conditions with Straight C1 Finite Elements in Curved Domains

International Nuclear Information System (INIS)

Ferraro, N.M.; Jardin, S.C.; Luo, X.

2010-01-01

The implementation of essential boundary conditions in C1 finite element analysis requires proper treatment of both the boundary conditions on second-order differentials of the solution and the curvature of the domain boundary. A method for the imposition of essential boundary conditions using straight elements (where the elements are not deformed to approximate a curved domain) is described. It is shown that pre-multiplication of the matrix equation by the local rotation matrix at each boundary node is not the optimal transformation. The uniquely optimal transformation is found, which does not take the form of a similarity transformation due to the non-orthogonality of the transformation to curved coordinates.

Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

Energy Technology Data Exchange (ETDEWEB)

Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou; Kobe, Bostjan

2017-04-06

Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65 Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).

SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

Energy Technology Data Exchange (ETDEWEB)

Noah, Taeko K.; Kazanjian, Avedis [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Whitsett, Jeffrey [Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Neonatology and Pulmonary Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Shroyer, Noah F., E-mail: noah.shroyer@cchmc.org [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States)

2010-02-01

Background and Aims: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation. Methods: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined. Results: In LS174T colon cancer cells treated with Notch/{gamma}-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation. Conclusions: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.

Constructing Regional advantage

DEFF Research Database (Denmark)

Asheim, Bjørn T.; Boschma, Ron; Cooke, Phil

2011-01-01

This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related variety, knowledge bases and policy platforms. Related variety attaches importance to knowledge spillovers across complementary...... economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases....

Numerical models for differential problems

CERN Document Server

Quarteroni, Alfio

2017-01-01

In this text, we introduce the basic concepts for the numerical modelling of partial differential equations. We consider the classical elliptic, parabolic and hyperbolic linear equations, but also the diffusion, transport, and Navier-Stokes equations, as well as equations representing conservation laws, saddle-point problems and optimal control problems. Furthermore, we provide numerous physical examples which underline such equations. We then analyze numerical solution methods based on finite elements, finite differences, finite volumes, spectral methods and domain decomposition methods, and reduced basis methods. In particular, we discuss the algorithmic and computer implementation aspects and provide a number of easy-to-use programs. The text does not require any previous advanced mathematical knowledge of partial differential equations: the absolutely essential concepts are reported in a preliminary chapter. It is therefore suitable for students of bachelor and master courses in scientific disciplines, an...

Weak Second Order Explicit Stabilized Methods for Stiff Stochastic Differential Equations

KAUST Repository

Abdulle, Assyr; Vilmart, Gilles; Zygalakis, Konstantinos C.

2013-01-01

We introduce a new family of explicit integrators for stiff Itô stochastic differential equations (SDEs) of weak order two. These numerical methods belong to the class of one-step stabilized methods with extended stability domains and do not suffer

The urokinase receptor homolog Haldisin is a novel differentiation marker of stratum granulosum in squamous epithelia

DEFF Research Database (Denmark)

Gårdsvoll, Henrik; Kriegbaum, Mette C; Hertz, Emil P

2013-01-01

Several members of the Ly-6/uPAR (LU)-protein domain family are differentially expressed in human squamous epithelia. In some cases, they even play important roles in maintaining skin homeostasis, as exemplified by the secreted single domain member, SLURP-1, the deficiency of which is associated....... In accordance with its expression pattern, we denote this protein product, which is encoded by the LYPD5 gene, as Haldisin (human antigen with LU-domains expressed in skin). Two of the five human glycolipid-anchored membrane proteins with multiple LU-domains characterized so far are predominantly confined...

Perlindungan Merek Terdaftar Dari Kejahatan Dunia Maya Melalui Pembatasan Pendaftaran Nama Domain

Directory of Open Access Journals (Sweden)

Setia Dharma

2015-05-01

Full Text Available Abstract: The Protection of Registered Trademark of Cyber Crime Through The Restriction of The Domain Name Registration. The progress of science and technology has implications for the progress of the current trading method. It is not only done conventionally but also carried out through cyberspace. Trading in the virtual world requires the use of a domain name (cyber squatting as a differentiator between one company with other companies. Law No. 11 Year 2008 on Information and Electronic Transactions regulate the use of domain names and emphasize the element of good faith in the implementation. In practice, there is a breach of the domain name registration is a crime which is the trademark or name that has a commercial value. This paper is going to examine aspects of protection-registered trademark of cyber crime through the restriction of the domain name registration and implementation of good faith. Abstrak: Perlindungan Merek Terdaftar Dari Kejahatan Dunia Maya Melalui Pembatasan Pendaftaran Nama Domain. Kemajuan ilmu dan teknologi membawa implikasi pada kemajuan metode perdagangan yang saat ini bukan hanya dilakukan secara konvensional, namun juga dilakukan melalui dunia maya. Perdagangan dalam dunia maya mensyaratkan penggunaan nama domain (cyber squatting sebagai pembeda antara satu perusahaan dengan perusahaan yang lainnya. Undang-Undang No. 11 Tahun 2008 Tentang Informasi dan Transaksi elektronik mengatur penggunaan nama domain tersebut dan menekankan unsur iktikad baik dalam pelaksanaannya. Prakteknya, terdapat pelanggaran nama domain tersebut yang merupakan merupakan kejahatan pendaftaran merek dagang atau nama yang memiliki nilai komersial. Tulisan ini hendak mengkaji aspek perlindungan merek terdaftar dari kejahatan dunia maya melalui pembatasan pendaftaran nama domain dan pelaksanaan iktikad baik. DOI: 10.15408/jch.v1i2.1463

Evaluation of Methyl-Binding Domain Based Enrichment Approaches Revisited.

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Karolina A Aberg

Full Text Available Methyl-binding domain (MBD enrichment followed by deep sequencing (MBD-seq, is a robust and cost efficient approach for methylome-wide association studies (MWAS. MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diagenode Inc, Denville, NJ, USA, the best performing kit in that study. We find that both MethylMiner and MethylCap are two well performing MBD-enrichment kits. However, MethylMiner shows somewhat better enrichment efficiency and lower levels of background "noise". In addition, for the purpose of MWAS where we want to investigate the majority of CpGs, we find MethylMiner to be superior as it allows tailoring the enrichment to the regions where most CpGs are located. Using targeted bisulfite sequencing we confirmed that sites where methylation was detected by either MethylMiner or by MethylCap indeed were methylated.

Enrichment of short interspersed transposable elements to embryonic stem cell-specific hypomethylated gene regions.

Science.gov (United States)

Muramoto, Hiroki; Yagi, Shintaro; Hirabayashi, Keiji; Sato, Shinya; Ohgane, Jun; Tanaka, Satoshi; Shiota, Kunio

2010-08-01

Embryonic stem cells (ESCs) have a distinctive epigenome, which includes their genome-wide DNA methylation modification status, as represented by the ESC-specific hypomethylation of tissue-dependent and differentially methylated regions (T-DMRs) of Pou5f1 and Nanog. Here, we conducted a genome-wide investigation of sequence characteristics associated with T-DMRs that were differentially methylated between ESCs and somatic cells, by focusing on transposable elements including short interspersed elements (SINEs), long interspersed elements (LINEs) and long terminal repeats (LTRs). We found that hypomethylated T-DMRs were predominantly present in SINE-rich/LINE-poor genomic loci. The enrichment for SINEs spread over 300 kb in cis and there existed SINE-rich genomic domains spreading continuously over 1 Mb, which contained multiple hypomethylated T-DMRs. The characterization of sequence information showed that the enriched SINEs were relatively CpG rich and belonged to specific subfamilies. A subset of the enriched SINEs were hypomethylated T-DMRs in ESCs at Dppa3 gene locus, although SINEs are overall methylated in both ESCs and the liver. In conclusion, we propose that SINE enrichment is the genomic property of regions harboring hypomethylated T-DMRs in ESCs, which is a novel aspect of the ESC-specific epigenomic information.

The JH2 domain and SH2-JH2 linker regulate JAK2 activity: A detailed kinetic analysis of wild type and V617F mutant kinase domains.