Prefoldin–Nascent Chain Complexes in the Folding of Cytoskeletal Proteins

PubMed Central

Hansen, William J.; Cowan, Nicholas J.; Welch, William J.

1999-01-01

In vitro transcription/translation of actin cDNA and analysis of the translation products by native-PAGE was used to study the maturation pathway of actin. During the course of actin synthesis, several distinct actin-containing species were observed and the composition of each determined by immunological procedures. After synthesis of the first ∼145 amino acids, the nascent ribosome-associated actin chain binds to the recently identified heteromeric chaperone protein, prefoldin (PFD). PFD remains bound to the relatively unfolded actin polypeptide until its posttranslational delivery to cytosolic chaperonin (CCT). We show that α- and β-tubulin follow a similar maturation pathway, but to date find no evidence for an interaction between PFD and several noncytoskeletal proteins. We conclude that PFD functions by selectively targeting nascent actin and tubulin chains pending their transfer to CCT for final folding and/or assembly. PMID:10209023

Long-read sequencing of nascent RNA reveals coupling among RNA processing events.

PubMed

Herzel, Lydia; Straube, Korinna; Neugebauer, Karla M

2018-06-14

Pre-mRNA splicing is accomplished by the spliceosome, a megadalton complex that assembles de novo on each intron. Because spliceosome assembly and catalysis occur cotranscriptionally, we hypothesized that introns are removed in the order of their transcription in genomes dominated by constitutive splicing. Remarkably little is known about splicing order and the regulatory potential of nascent transcript remodeling by splicing, due to the limitations of existing methods that focus on analysis of mature splicing products (mRNAs) rather than substrates and intermediates. Here, we overcome this obstacle through long-read RNA sequencing of nascent, multi-intron transcripts in the fission yeast Schizosaccharomyces pombe Most multi-intron transcripts were fully spliced, consistent with rapid cotranscriptional splicing. However, an unexpectedly high proportion of transcripts were either fully spliced or fully unspliced, suggesting that splicing of any given intron is dependent on the splicing status of other introns in the transcript. Supporting this, mild inhibition of splicing by a temperature-sensitive mutation in prp2 , the homolog of vertebrate U2AF65, increased the frequency of fully unspliced transcripts. Importantly, fully unspliced transcripts displayed transcriptional read-through at the polyA site and were degraded cotranscriptionally by the nuclear exosome. Finally, we show that cellular mRNA levels were reduced in genes with a high number of unspliced nascent transcripts during caffeine treatment, showing regulatory significance of cotranscriptional splicing. Therefore, overall splicing of individual nascent transcripts, 3' end formation, and mRNA half-life depend on the splicing status of neighboring introns, suggesting crosstalk among spliceosomes and the polyA cleavage machinery during transcription elongation. © 2018 Herzel et al.; Published by Cold Spring Harbor Laboratory Press.

CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.

PubMed

Kostova, Kamena K; Hickey, Kelsey L; Osuna, Beatriz A; Hussmann, Jeffrey A; Frost, Adam; Weinberg, David E; Weissman, Jonathan S

2017-07-28

Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A strategy for co-translational folding studies of ribosome-bound nascent chain complexes using NMR spectroscopy.

PubMed

Cassaignau, Anaïs M E; Launay, Hélène M M; Karyadi, Maria-Evangelia; Wang, Xiaolin; Waudby, Christopher A; Deckert, Annika; Robertson, Amy L; Christodoulou, John; Cabrita, Lisa D

2016-08-01

During biosynthesis on the ribosome, an elongating nascent polypeptide chain can begin to fold, in a process that is central to all living systems. Detailed structural studies of co-translational protein folding are now beginning to emerge; such studies were previously limited, at least in part, by the inherently dynamic nature of emerging nascent chains, which precluded most structural techniques. NMR spectroscopy is able to provide atomic-resolution information for ribosome-nascent chain complexes (RNCs), but it requires large quantities (≥10 mg) of homogeneous, isotopically labeled RNCs. Further challenges include limited sample working concentration and stability of the RNC sample (which contribute to weak NMR signals) and resonance broadening caused by attachment to the large (2.4-MDa) ribosomal complex. Here, we present a strategy to generate isotopically labeled RNCs in Escherichia coli that are suitable for NMR studies. Uniform translational arrest of the nascent chains is achieved using a stalling motif, and isotopically labeled RNCs are produced at high yield using high-cell-density E. coli growth conditions. Homogeneous RNCs are isolated by combining metal affinity chromatography (to isolate ribosome-bound species) with sucrose density centrifugation (to recover intact 70S monosomes). Sensitivity-optimized NMR spectroscopy is then applied to the RNCs, combined with a suite of parallel NMR and biochemical analyses to cross-validate their integrity, including RNC-optimized NMR diffusion measurements to report on ribosome attachment in situ. Comparative NMR studies of RNCs with the analogous isolated proteins permit a high-resolution description of the structure and dynamics of a nascent chain during its progressive biosynthesis on the ribosome.

Bioorthogonal Metabolic Labeling of Nascent RNA in Neurons Improves the Sensitivity of Transcriptome-Wide Profiling.

PubMed

Zajaczkowski, Esmi L; Zhao, Qiong-Yi; Zhang, Zong Hong; Li, Xiang; Wei, Wei; Marshall, Paul R; Leighton, Laura J; Nainar, Sarah; Feng, Chao; Spitale, Robert C; Bredy, Timothy W

2018-06-15

Transcriptome-wide expression profiling of neurons has provided important insights into the underlying molecular mechanisms and gene expression patterns that transpire during learning and memory formation. However, there is a paucity of tools for profiling stimulus-induced RNA within specific neuronal cell populations. A bioorthogonal method to chemically label nascent (i.e., newly transcribed) RNA in a cell-type-specific and temporally controlled manner, which is also amenable to bioconjugation via click chemistry, was recently developed and optimized within conventional immortalized cell lines. However, its value within a more fragile and complicated cellular system such as neurons, as well as for transcriptome-wide expression profiling, has yet to be demonstrated. Here, we report the visualization and sequencing of activity-dependent nascent RNA derived from neurons using this labeling method. This work has important implications for improving transcriptome-wide expression profiling and visualization of nascent RNA in neurons, which has the potential to provide valuable insights into the mechanisms underlying neural plasticity, learning, and memory.

The recruitment of the U5 snRNP to nascent transcripts requires internal loop 1 of U5 snRNA.

PubMed

Kim, Rebecca; Paschedag, Joshua; Novikova, Natalya; Bellini, Michel

2012-12-01

In this study, we take advantage of the high spatial resolution offered by the nucleus and lampbrush chromosomes of the amphibian oocyte to investigate the mechanisms that regulate the intranuclear trafficking of the U5 snRNP and its recruitment to nascent transcripts. We monitor the fate of newly assembled fluorescent U5 snRNP in Xenopus oocytes depleted of U4 and/or U6 snRNAs and demonstrate that the U4/U6.U5 tri-snRNP is not required for the association of U5 snRNP with Cajal bodies, splicing speckles, and nascent transcripts. In addition, using a mutational analysis, we show that a non-functional U5 snRNP can associate with nascent transcripts, and we further characterize internal loop structure 1 of U5 snRNA as a critical element for licensing U5 snRNP to target both nascent transcripts and splicing speckles. Collectively, our data support the model where the recruitment of snRNPs onto pre-mRNAs is independent of spliceosome assembly and suggest that U5 snRNP may promote the association of the U4/U6.U5 tri-snRNP with nascent transcripts.

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling.

PubMed

Das, Debasis; Samanta, Dibyendu; Bhattacharya, Arpita; Basu, Arunima; Das, Anindita; Ghosh, Jaydip; Chakrabarti, Abhijit; Das Gupta, Chanchal

2017-01-01

Each cycle of translation initiation in bacterial cell requires free 50S and 30S ribosomal subunits originating from the post-translational dissociation of 70S ribosome from the previous cycle. Literature shows stable dissociation of 70S from model post-termination complexes by the concerted action of Ribosome Recycling Factor (RRF) and Elongation Factor G (EF-G) that interact with the rRNA bridge B2a/B2b joining 50S to 30S. In such experimental models, the role of full-length nascent protein was never considered seriously. We observed relatively slow release of full-length nascent protein from 50Sof post translation ribosome, and in that process, its toe prints on the rRNA in vivo and in in vitro translation with E.coli S30 extract. We reported earlier that a number of chemically unfolded proteins like bovine carbonic anhydrase (BCA), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lysozyme, ovalbumin etc., when added to free 70Sin lieu of the full length nascent proteins, also interact with identical RNA regions of the 23S rRNA. Interestingly the rRNA nucleotides that slow down release of the C-terminus of full-length unfolded protein were found in close proximity to the B2a/B2b bridge. It indicated a potentially important chemical reaction conserved throughout the evolution. Here we set out to probe that conserved role of unfolded protein conformation in splitting the free or post-termination 70S. How both the RRF-EFG dependent and the plausible nascent protein-EFG dependent ribosome recycling pathways might be relevant in bacteria is discussed here.

A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

PubMed Central

Das, Debasis; Samanta, Dibyendu; Bhattacharya, Arpita; Basu, Arunima; Das, Anindita; Ghosh, Jaydip; Chakrabarti, Abhijit; Das Gupta, Chanchal

2017-01-01

Each cycle of translation initiation in bacterial cell requires free 50S and 30S ribosomal subunits originating from the post-translational dissociation of 70S ribosome from the previous cycle. Literature shows stable dissociation of 70S from model post-termination complexes by the concerted action of Ribosome Recycling Factor (RRF) and Elongation Factor G (EF-G) that interact with the rRNA bridge B2a/B2b joining 50S to 30S. In such experimental models, the role of full-length nascent protein was never considered seriously. We observed relatively slow release of full-length nascent protein from 50Sof post translation ribosome, and in that process, its toe prints on the rRNA in vivo and in in vitro translation with E.coli S30 extract. We reported earlier that a number of chemically unfolded proteins like bovine carbonic anhydrase (BCA), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lysozyme, ovalbumin etc., when added to free 70Sin lieu of the full length nascent proteins, also interact with identical RNA regions of the 23S rRNA. Interestingly the rRNA nucleotides that slow down release of the C-terminus of full-length unfolded protein were found in close proximity to the B2a/B2b bridge. It indicated a potentially important chemical reaction conserved throughout the evolution. Here we set out to probe that conserved role of unfolded protein conformation in splitting the free or post-termination 70S. How both the RRF-EFG dependent and the plausible nascent protein–EFG dependent ribosome recycling pathways might be relevant in bacteria is discussed here. PMID:28099529

Role of the visual experience-dependent nascent proteome in neuronal plasticity

PubMed Central

Liu, Han-Hsuan; McClatchy, Daniel B; Schiapparelli, Lucio; Shen, Wanhua; Yates, John R

2018-01-01

Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor three subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity. PMID:29412139

Theory of Force Regulation by Nascent Adhesion Sites

PubMed Central

Bruinsma, Robijn

2005-01-01

The mechanical coupling of a cell with the extracellular matrix relies on adhesion sites, clusters of membrane-associated proteins that communicate forces generated along the F-Actin filaments of the cytoskeleton to connecting tissue. Nascent adhesion sites have been shown to regulate these forces in response to tissue rigidity. Force-regulation by substrate rigidity of adhesion sites with fixed area is not possible for stationary adhesion sites, according to elasticity theory. A simple model is presented to describe force regulation by dynamical adhesion sites. PMID:15849245

Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains

PubMed Central

Shen, Peter S.; Park, Joseph; Qin, Yidan; Li, Xueming; Parsawar, Krishna; Larson, Matthew H.; Cox, James; Cheng, Yifan; Lambowitz, Alan M.; Weissman, Jonathan S.; Brandman, Onn; Frost, Adam

2015-01-01

In Eukarya, stalled translation induces 40S dissociation and recruitment of the Ribosome Quality control Complex (RQC) to the 60S subunit, which mediates nascent chain degradation. Here, we report cryoEM structures revealing that the RQC components Rqc2p (YPL009C/Tae2) and Ltn1p (YMR247C/Rkr1) bind to the 60S at sites exposed after 40S dissociation, placing the Ltn1p RING domain near the exit channel and Rqc2p over the P-site tRNA. We further demonstrate that Rqc2p recruits alanine and threonine charged tRNA to the A-site and directs elongation of nascent chains independently of mRNA or 40S subunits. Our work uncovers an unexpected mechanism of protein synthesis in which a protein—not an mRNA—determines tRNA recruitment and the tagging of nascent chains with Carboxy-terminal Ala and Thr extensions (“CAT tails”). PMID:25554787

An Annotation Agnostic Algorithm for Detecting Nascent RNA Transcripts in GRO-Seq.

PubMed

Azofeifa, Joseph G; Allen, Mary A; Lladser, Manuel E; Dowell, Robin D

2017-01-01

We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA-seq, measure steady state RNA levels which are affected by transcription, post-transcriptional processing, and RNA stability. GRO-seq data, however, presents unique analysis challenges that are only beginning to be addressed. Here, we describe a new algorithm, Fast Read Stitcher (FStitch), that takes advantage of two popular machine-learning techniques, hidden Markov models and logistic regression, to classify which regions of the genome are transcribed. Given a small user-defined training set, our algorithm is accurate, robust to varying read depth, annotation agnostic, and fast. Analysis of GRO-seq data without a priori need for annotation uncovers surprising new insights into several aspects of the transcription process.

Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome

PubMed Central

Ullers, Ronald S.; Houben, Edith N.G.; Raine, Amanda; ten Hagen-Jongman, Corinne M.; Ehrenberg, Måns; Brunner, Joseph; Oudega, Bauke; Harms, Nellie; Luirink, Joen

2003-01-01

As newly synthesized polypeptides emerge from the ribosome, they interact with chaperones and targeting factors that assist in folding and targeting to the proper location in the cell. In Escherichia coli, the chaperone trigger factor (TF) binds to nascent polypeptides early in biosynthesis facilitated by its affinity for the ribosomal proteins L23 and L29 that are situated around the nascent chain exit site on the ribosome. The targeting factor signal recognition particle (SRP) interacts specifically with the signal anchor (SA) sequence in nascent inner membrane proteins (IMPs). Here, we have used photocross-linking to map interactions of the SA sequence in a short, in vitro–synthesized, nascent IMP. Both TF and SRP were found to interact with the SA with partially overlapping binding specificity. In addition, extensive contacts with L23 and L29 were detected. Both purified TF and SRP could be cross-linked to L23 on nontranslating ribosomes with a competitive advantage for SRP. The results suggest a role for L23 in the targeting of IMPs as an attachment site for TF and SRP that is close to the emerging nascent chain. PMID:12756233

Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

NASA Technical Reports Server (NTRS)

McCormick, K. M.; Schultz, E.

1992-01-01

This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another

The Fate of Nascent APP in Hippocampal Neurons: A Live Cell Imaging Study.

PubMed

DelBove, Claire E; Deng, Xian-Zhen; Zhang, Qi

2018-06-21

Amyloid precursor protein (APP) is closely associated with Alzheimer's disease (AD) because its proteolytic products form amyloid plaques and its mutations are linked to familial AD patients. As a membrane protein, APP is involved in neuronal development and plasticity. However, it remains unclear how nascent APP is distributed and transported to designated membrane compartments to execute its diverse functions. Here, we employed a dual-tagged APP fusion protein in combination with a synaptic vesicle marker to study the surface trafficking and cleavage of APP in hippocampal neurons immediately after its synthesis. Using long-term time-lapse imaging, we found that a considerable amount of nascent APP was directly transported to the somatodendritic surface, from which it propagates to distal neurites. Some APP in the plasma membrane was endocytosed and some was cleaved by α-secretase. Hence, we conclude that surface transportation of APP is a major step preceding its proteolytic processing and neuritic distribution.

RNA polymerase pausing and nascent RNA structure formation are linked through clamp domain movement

PubMed Central

Hein, Pyae P.; Kolb, Kellie E.; Windgassen, Tricia; Bellecourt, Michael J.; Darst, Seth A.; Mooney, Rachel A.; Landick, Robert

2014-01-01

The rates of RNA synthesis and nascent RNA folding into biologically active structures are linked via pausing by RNA polymerase (RNAP). Structures that form within the RNA exit channel can increase pausing by interacting with bacterial RNAP or decrease pausing by preventing backtracking. Conversely, pausing is required for proper folding of some RNAs. Opening of the RNAP clamp domain is proposed to mediate some effects of nascent RNA structures. However, the connections among RNA structure formation, clamp movement, and catalytic activity remain uncertain. We assayed exit-channel structure formation in Escherichia coli RNAP together with disulfide crosslinks that favor closed or open clamp conformations and found that clamp position directly influences RNA structure formation and catalytic activity. We report that exit-channel RNA structures slow pause escape by favoring clamp opening and through interactions with the flap that slow translocation. PMID:25108353

Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

PubMed Central

Neuhof, Andrea; Rolls, Melissa M.; Jungnickel, Berit; Kalies, Kai-Uwe; Rapoport, Tom A.

1998-01-01

Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes. PMID:9436994

Substantial Goodness and Nascent Human Life.

PubMed

Floyd, Shawn

2015-09-01

Many believe that moral value is--at least to some extent--dependent on the developmental states necessary for supporting rational activity. My paper rejects this view, but does not aim simply to register objections to it. Rather, my essay aims to answer the following question: if a human being's developmental state and occurrent capacities do not bequeath moral standing, what does? The question is intended to prompt careful consideration of what makes human beings objects of moral value, dignity, or (to employ my preferred term) goodness. Not only do I think we can answer this question, I think we can show that nascent human life possesses goodness of precisely this sort. I appeal to Aquinas's metaethics to establish the conclusion that the goodness of a human being--even if that being is an embryo or fetus--resides at the substratum of her existence. If she possesses goodness, it is because human existence is good.

Reactive uptake of HOCl to laboratory generated sea salt particles and nascent sea-spray aerosol

NASA Astrophysics Data System (ADS)

Campbell, N. R.; Ryder, O. S.; Bertram, T. H.

2013-12-01

Field observations suggest that the reactive uptake of HOCl on marine aerosol particles is an important source of chlorine radicals, particularly under low NOx conditions. However to date, laboratory measurements disagree on the magnitude of the reactive uptake coefficient for HOCl by a factor of 5 (γ(HOCl) ranges between 0.0004 and 0.0018), and there are no measurements of γ(HOCl) on nascent sea-spray aerosol. Here, we present measurements of the reactive uptake of HOCl to laboratory generated sodium chloride and sea-spray aerosol particles generated in a novel Marine Aerosol Reference Tank (MART), coupled to an entrained aerosol flow reactor and Chemical Ionization Mass Spectrometer (CIMS). Measurements of γ(HOCl) retrieved here are compared against those in the literature, and the role of organic coatings on nascent sea-spray aerosol is explored.

Rad51 recombinase prevents Mre11 nuclease-dependent degradation and excessive PrimPol-mediated elongation of nascent DNA after UV irradiation

PubMed Central

Vallerga, María Belén; Mansilla, Sabrina F.; Federico, María Belén; Bertolin, Agustina P.; Gottifredi, Vanesa

2015-01-01

After UV irradiation, DNA polymerases specialized in translesion DNA synthesis (TLS) aid DNA replication. However, it is unclear whether other mechanisms also facilitate the elongation of UV-damaged DNA. We wondered if Rad51 recombinase (Rad51), a factor that escorts replication forks, aids replication across UV lesions. We found that depletion of Rad51 impairs S-phase progression and increases cell death after UV irradiation. Interestingly, Rad51 and the TLS polymerase polη modulate the elongation of nascent DNA in different ways, suggesting that DNA elongation after UV irradiation does not exclusively rely on TLS events. In particular, Rad51 protects the DNA synthesized immediately before UV irradiation from degradation and avoids excessive elongation of nascent DNA after UV irradiation. In Rad51-depleted samples, the degradation of DNA was limited to the first minutes after UV irradiation and required the exonuclease activity of the double strand break repair nuclease (Mre11). The persistent dysregulation of nascent DNA elongation after Rad51 knockdown required Mre11, but not its exonuclease activity, and PrimPol, a DNA polymerase with primase activity. By showing a crucial contribution of Rad51 to the synthesis of nascent DNA, our results reveal an unanticipated complexity in the regulation of DNA elongation across UV-damaged templates. PMID:26627254

Nascent starbursts: a missing link in galaxy evolution

NASA Astrophysics Data System (ADS)

Roussel, Helene; Beck, Rainer; Condon, Jim; Helou, George; Smith, John-David

2005-06-01

We have identified a rare category of galaxies characterized by an extreme deficiency in synchro- tron radiation, relative to dust emission, and very high dust temperatures. We studied in detail the most extreme such object, and concluded in favor of a starburst just breaking out, less than one megayear old, in a galaxy having undergone no major star formation episode in the last 100 Myr. Such systems offer a perfect setting to study the initial conditions and early dynamics of starbursts and understand better the regulation of the infrared-radio continuum correlation in galaxies. For the prototypical nascent starburst, the mid-infrared spectrum is quite peculiar, suggesting tran- sient dust species and high optical depth; tracers of dust and molecular gas are the only indicators of unusual activity, and the active regions are likely very compact and dust-bounded, suppressing ionization. Only Spitzer data can provide the needed physical diagnostics for such regions. A sample of 25 nascent starbursts was drawn from the cross-correlation of the IRAS Faint Source Catalog and the NVSS VLA radio survey, and carefully selected based on our multi-wavelength VLA maps to span a range of infrared to radio ratios and luminosities. This sample allows a first step beyond studying prototypes toward a statistical analysis addressing systematic physical pro- perties, classification and search for starburst development sequences. We propose imaging and spectroscopic observations from 3 to 160 microns to characterize the state of the interstellar medium and the gas and dust excitation origin. Our aim is to learn from these unique systems how a star formation burst may develop in its very earliest phases, how it affects the fueling material and the host galaxy. Acquired observations of the radio continuum, cold molecular gas and tracers of shocks and HII regions will help us interpret the rich Spitzer data set and extract a coherent picture of the interstellar medium in our targets.

The Fluid Dynamics of Nascent Biofilms

NASA Astrophysics Data System (ADS)

Farthing, Nicola; Snow, Ben; Wilson, Laurence; Bees, Martin

2017-11-01

Many anti-biofilm approaches target mature biofilms with biochemical or physio-chemical interventions. We investigate the mechanics of interventions at an early stage that aim to inhibit biofilm maturation, focusing on hydrodynamics as cells transition from planktonic to surface-attached. Surface-attached cells generate flow fields that are relatively long-range compared with cells that are freely-swimming. We look at the effect of these flows on the biofilm formation. In particular, we use digital inline holographic microscopy to determine the three-dimensional flow due to a surface-attached cell and the effect this flow has on both tracers and other cells in the fluid. We compare experimental data with two models of cells on boundaries. The first approach utilizes slender body theory and captures many of the features of the experimental field. The second model develops a simple description in terms of singularity solutions of Stokes' flow, which produces qualitatively similar dynamics to both the experiments and more complex model but with significant computational savings. The range of validity of multiple cell arrangements is investigated. These two descriptions can be used to investigate the efficacy of actives developed by Unilever on nascent biofilms.

SWI/SNF Associates with Nascent Pre-mRNPs and Regulates Alternative Pre-mRNA Processing

PubMed Central

Tyagi, Anu; Ryme, Jessica; Brodin, David; Östlund Farrants, Ann Kristin; Visa, Neus

2009-01-01

The SWI/SNF chromatin remodeling complexes regulate the transcription of many genes by remodeling nucleosomes at promoter regions. In Drosophila, SWI/SNF plays an important role in ecdysone-dependent transcription regulation. Studies in human cells suggest that Brahma (Brm), the ATPase subunit of SWI/SNF, regulates alternative pre-mRNA splicing by modulating transcription elongation rates. We describe, here, experiments that study the association of Brm with transcribed genes in Chironomus tentans and Drosophila melanogaster, the purpose of which was to further elucidate the mechanisms by which Brm regulates pre-mRNA processing. We show that Brm becomes incorporated into nascent Balbiani ring pre-mRNPs co-transcriptionally and that the human Brm and Brg1 proteins are associated with RNPs. We have analyzed the expression profiles of D. melanogaster S2 cells in which the levels of individual SWI/SNF subunits have been reduced by RNA interference, and we show that depletion of SWI/SNF core subunits changes the relative abundance of alternative transcripts from a subset of genes. This observation, and the fact that a fraction of Brm is not associated with chromatin but with nascent pre-mRNPs, suggest that SWI/SNF affects pre-mRNA processing by acting at the RNA level. Ontology enrichment tests indicate that the genes that are regulated post-transcriptionally by SWI/SNF are mostly enzymes and transcription factors that regulate postembryonic developmental processes. In summary, the data suggest that SWI/SNF becomes incorporated into nascent pre-mRNPs and acts post-transcriptionally to regulate not only the amount of mRNA synthesized from a given promoter but also the type of alternative transcript produced. PMID:19424417

Probing the Role of Nascent Helicity in p27 Function as a Cell Cycle Regulator

PubMed Central

Otieno, Steve; Kriwacki, Richard

2012-01-01

p27 regulates the activity of Cdk complexes which are the principal governors of phase transitions during cell division. Members of the p27 family of proteins, which also includes p21 and p57, are called the Cip/Kip cyclin-dependent kinase regulators (CKRs). Interestingly, the Cip/Kip CKRs play critical roles in cell cycle regulation by being intrinsically unstructured, a characteristic contrary to the classical structure-function paradigm. They exhibit nascent helicity which has been localized to a segment referred to as sub-domain LH. The nascent helicity of this sub-domain is conserved and we hypothesize that it is an important determinant of their functional properties. To test this hypothesis, we successfully designed and prepared p27 variants in which domain LH was either more or less helical with respect to the wild-type protein. Thermal denaturation experiments showed that the ternary complexes of the p27 variants bound to Cdk2/Cyclin A were less stable compared to the wild-type complex. Isothermal titration calorimetry experiments showed a decrease in the enthalpy of binding for all the mutants with respect to p27. The free energies of binding varied within a much narrower range. In vitro Cdk2 inhibition assays showed that the p27 variants exhibited disparate inhibitory potencies. Furthermore, when over-expressed in NIH 3T3 mouse fibroblast cells, the less helical p27 variants were less effective in causing cell cycle arrest relative to the wild-type p27. Our results indicate that the nascent helicity of sub-domain LH plays a key role mediating the biological function of p27. PMID:23071750

Live Cell Imaging of the Nascent Inactive X Chromosome during the Early Differentiation Process of Naive ES Cells towards Epiblast Stem Cells

PubMed Central

Guyochin, Aurélia; Maenner, Sylvain; Chu, Erin Tsi-Jia; Hentati, Asma; Attia, Mikael; Avner, Philip; Clerc, Philippe

2014-01-01

Random X-chromosome inactivation ensures dosage compensation in mammals through the transcriptional silencing of one of the two X chromosomes present in each female cell. Silencing is initiated in the differentiating epiblast of the mouse female embryos through coating of the nascent inactive X chromosome by the non-coding RNA Xist, which subsequently recruits the Polycomb Complex PRC2 leading to histone H3-K27 methylation. Here we examined in mouse ES cells the early steps of the transition from naive ES cells towards epiblast stem cells as a model for inducing X chromosome inactivation in vitro. We show that these conditions efficiently induce random XCI. Importantly, in a transient phase of this differentiation pathway, both X chromosomes are coated with Xist RNA in up to 15% of the XX cells. In an attempt to determine the dynamics of this process, we designed a strategy aimed at visualizing the nascent inactive X-chromosome in live cells. We generated transgenic female XX ES cells expressing the PRC2 component Ezh2 fused to the fluorescent protein Venus. The fluorescent fusion protein was expressed at sub-physiological levels and located in nuclei of ES cells. Upon differentiation of ES cell towards epiblast stem cell fate, Venus-fluorescent territories appearing in interphase nuclei were identified as nascent inactive X chromosomes by their association with Xist RNA. Imaging of Ezh2-Venus for up to 24 hours during the differentiation process showed survival of some cells with two fluorescent domains and a surprising dynamics of the fluorescent territories across cell division and in the course of the differentiation process. Our data reveal a strategy for visualizing the nascent inactive X chromosome and suggests the possibility for a large plasticity of the nascent inactive X chromosome. PMID:25546018

A Primer on the Pathway to Scholarly Writing: Helping Nascent Writers to Unlearn Conditioned Habits

ERIC Educational Resources Information Center

McDougall, Dennis; Ornelles, Cecily; Rao, Kavita

2015-01-01

In this article, we identify eight common error patterns of nascent writers when they attempt to navigate the pathway to scholarly writing. We illustrate each error pattern via examples and counter-examples (corrections). We also describe how to identify such patterns, why those patterns might occur and persist, and why each pattern is…

A novel compound inhibits rHDL assembly and blocks nascent HDL biogenesis downstream of apoAI binding to ABCA1 expressing cells

PubMed Central

Lyssenko, Nicholas N.; Brubaker, Gregory; Smith, Bradley D.; Smith, Jonathan D.

2011-01-01

Objective Nascent high-density lipoprotein (HDL) particles form from cellular lipids and extracellular lipid-free apolipoprotein AI (apoAI) in a process mediated by ATP-binding cassette transporter A1 (ABCA1). We have sought out compounds that inhibit nascent HDL biogenesis without affecting ABCA1 activity. Methods and Results Reconstituted HDL (rHDL) formation and cellular cholesterol efflux assays were used to show that two compounds that bond via hydrogen with phospholipids inhibit rHDL and nascent HDL production. In rHDL formation assays, the inhibitory effect of compound 1 (methyl 3α-acetoxy-7α,12α-di[(phenylaminocarbonyl)amino]-5β-cholan-24-oate), the more active of the two, depended on its ability to associate with phospholipids. In cell assays, compound 1 suppressed ABCA1-mediated cholesterol efflux to apoAI, the 18A peptide, and taurocholate with high specificity, without affecting ABCA1-independent cellular cholesterol efflux to HDL and endocytosis of acetylated low-density lipoprotein (AcLDL) and transferrin. Furthermore, compound 1 did not affect ABCA1 activity adversely, as ABCA1-mediated shedding of microparticles proceeded unabated and apoAI binding to ABCA1-expressing cells increased in its presence. Conclusions The inhibitory effects of compound 1 support a three-step model of nascent HDL biogenesis: plasma membrane remodeling by ABCA1, apoAI binding to ABCA1, and lipoprotein particle assembly. The compound inhibits the final step, causing accumulation of apoAI in ABCA1-expressing cells. PMID:21836073

Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila

PubMed Central

Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.

2016-01-01

The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967

Gravitational radiation from rapidly rotating nascent neutron stars

NASA Technical Reports Server (NTRS)

Lai, Dong; Shapiro, Stuart L.

1995-01-01

We study the secular evolution and gravitational wave signature of a newly formed, rapidly rotating neutron star. The neutron star may arise from core collapse in a massive star or from the accretion-induced collapse of a white dwarf. After a brief dynamical phase, the nascent neutron star settles into an axisymmetric, secularly unstable state. Gravitational radiation drives the star to a nonaxisymmetric, stationary equilibrium configuration via the bar-mode instability. The emitted quasi-periodic gravitational waves have a unique signature: the wave frequency sweeps downward from a few hundred Hertz to zero, while the wave amplitude increase from zero to a maximum and then decays back to zero. Such a wave signal could detected by broadband gravitational wave interferometers currently being constructed. We also characterize two other types of gravitational wave signals that could arise in principle from a rapidly rotating, secularly unstable neutron star: a high-frequency (f greater than or approximately = 1000 Hz) wave which increases the pattern-speed of the star, and a wave that actually increases the angular momentum of the star.

Does Ethicality Wane with Adulthood? A Study of the Ethical Values of Entrepreneurship Students and Nascent Entrepreneurs

ERIC Educational Resources Information Center

Lourenço, Fernando; Sappleton, Natalie; Cheng, Ranis

2015-01-01

The authors examined the following questions: Does gender influence the ethicality of enterprise students to a greater extent than it does nascent entrepreneurs? If this is the case, then is it due to factors associated with adulthood such as age, work experience, marital status, and parental status? Sex-role socialization theory and moral…

Self-assembly of marine exudate particles and their impact on the CCN properties of nascent marine aerosol

NASA Astrophysics Data System (ADS)

Schill, S.; Zimmermann, K.; Ryder, O. S.; Campbell, N.; Collins, D. B.; Gianneschi, N.; Bertram, T. H.

2013-12-01

Spontaneous self-assembly of marine exudate particles has previously been observed in filtered seawater samples. The chemicophysical properties of these particles may alter the chemical composition and CCN properties of nascent marine aerosol, yet to date simultaneous measurement of seawater exudate particle formation rates and number distributions, with aerosol particle formation rates and CCN activity are lacking. Here, we use a novel Marine Aerosol Reference Tank (MART) system to experimentally mimic a phytoplankton bloom via sequential addition of biological surrogates, including sterol, galactose, lipopolysaccharide, BSA protein, and dipalmitoylphosphatidylcholine. Nascent sea-spray aerosol are generated in the MART system via a continuous plunging waterfall. Exudate particle assembly in the water is monitored via dynamic light scattering (DLS) and transmission electron microscopy (TEM) to obtain both the assembly kinetics of the particles as well as particle number distributions Simultaneous characterization of both particle production rates and super-saturated particle hygroscopicity are also discussed. This study permits analysis of the controlling role of the molecular composition of dissolved organic carbon in setting the production rates of colloidal material in the surface oceans.

The Exosome Associates Cotranscriptionally with the Nascent Pre-mRNP through Interactions with Heterogeneous Nuclear Ribonucleoproteins

PubMed Central

Hessle, Viktoria; Björk, Petra; Sokolowski, Marcus; de Valdivia, Ernesto González; Silverstein, Rebecca; Artemenko, Konstantin; Tyagi, Anu; Maddalo, Gianluca; Ilag, Leopold; Helbig, Roger; Zubarev, Roman A.

2009-01-01

Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4 is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact with nascent pre-mRNPs. Our results lead to a revised mechanistic model for cotranscriptional quality control in which the exosome is constantly recruited to newly synthesized RNAs through direct interactions with specific hnRNP proteins. PMID:19494042

Binding of transcription termination protein nun to nascent RNA and template DNA.

PubMed

Watnick, R S; Gottesman, M E

1999-12-17

The amino-terminal arginine-rich motif of coliphage HK022 Nun binds phage lambda nascent transcript, whereas the carboxyl-terminal domain interacts with RNA polymerase (RNAP) and blocks transcription elongation. RNA binding is inhibited by zinc (Zn2+) and stimulated by Escherichia coli NusA. To study these interactions, the Nun carboxyl terminus was extended by a cysteine residue conjugated to a photochemical cross-linker. The carboxyl terminus contacted NusA and made Zn2+-dependent intramolecular contacts. When Nun was added to a paused transcription elongation complex, it cross-linked to the DNA template. Nun may arrest transcription by anchoring RNAP to DNA.

Eccentricity Evolution of Extrasolar Multiple Planetary Systems Due to the Depletion of Nascent Protostellar Disks

NASA Astrophysics Data System (ADS)

Nagasawa, M.; Lin, D. N. C.; Ida, S.

2003-04-01

Most extrasolar planets are observed to have eccentricities much larger than those in the solar system. Some of these planets have sibling planets, with comparable masses, orbiting around the same host stars. In these multiple planetary systems, eccentricity is modulated by the planets' mutual secular interaction as a consequence of angular momentum exchange between them. For mature planets, the eigenfrequencies of this modulation are determined by their mass and semimajor axis ratios. However, prior to the disk depletion, self-gravity of the planets' nascent disks dominates the precession eigenfrequencies. We examine here the initial evolution of young planets' eccentricity due to the apsidal libration or circulation induced by both the secular interaction between them and the self-gravity of their nascent disks. We show that as the latter effect declines adiabatically with disk depletion, the modulation amplitude of the planets' relative phase of periapsis is approximately invariant despite the time-asymmetrical exchange of angular momentum between planets. However, as the young planets' orbits pass through a state of secular resonance, their mean eccentricities undergo systematic quantitative changes. For applications, we analyze the eccentricity evolution of planets around υ Andromedae and HD 168443 during the epoch of protostellar disk depletion. We find that the disk depletion can change the planets' eccentricity ratio. However, the relatively large amplitude of the planets' eccentricity cannot be excited if all the planets had small initial eccentricities.

A Proteomic Characterization of Factors Enriched at Nascent DNA Molecules

PubMed Central

Lopez-Contreras, Andres J.; Ruppen, Isabel; Nieto-Soler, Maria; Murga, Matilde; Rodriguez-Acebes, Sara; Remeseiro, Silvia; Rodrigo-Perez, Sara; Rojas, Ana M.; Mendez, Juan; Muñoz, Javier; Fernandez-Capetillo, Oscar

2013-01-01

SUMMARY DNA replication is facilitated by multiple factors that concentrate in the vicinity of replication forks. Here, we developed an approach that combines the isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS), allowing a comprehensive proteomic characterization of the human replisome and replisome-associated factors. In addition to known replisome components, we provide a broad list of proteins that reside in the vicinity of the replisome, some of which were not previously associated with replication. For instance, our data support a link between DNA replication and the Williams-Beuren syndrome and identify ZNF24 as a replication factor. In addition, we reveal that SUMOylation is wide-spread for factors that concentrate near replisomes, which contrasts with lower UQylation levels at these sites. This resource provides a panoramic view of the proteins that concentrate in the surroundings of the replisome, which should facilitate future investigations on DNA replication and genome maintenance. PMID:23545495

Sall1 Maintains Nephron Progenitors and Nascent Nephrons by Acting as Both an Activator and a Repressor

PubMed Central

Kanda, Shoichiro; Tanigawa, Shunsuke; Ohmori, Tomoko; Taguchi, Atsuhiro; Kudo, Kuniko; Suzuki, Yutaka; Sato, Yuki; Hino, Shinjiro; Sander, Maike; Perantoni, Alan O.; Sugano, Sumio; Nakao, Mitsuyoshi

2014-01-01

The balanced self-renewal and differentiation of nephron progenitors are critical for kidney development and controlled, in part, by the transcription factor Six2, which antagonizes canonical Wnt signaling-mediated differentiation. A nuclear factor, Sall1, is expressed in Six2-positive progenitors as well as differentiating nascent nephrons, and it is essential for kidney formation. However, the molecular functions and targets of Sall1, especially the functions and targets in the nephron progenitors, remain unknown. Here, we report that Sall1 deletion in Six2-positive nephron progenitors results in severe progenitor depletion and apoptosis of the differentiating nephrons in mice. Analysis of mice with an inducible Sall1 deletion revealed that Sall1 activates genes expressed in progenitors while repressing genes expressed in differentiating nephrons. Sall1 and Six2 co-occupied many progenitor-related gene loci, and Sall1 bound to Six2 biochemically. In contrast, Sall1 did not bind to the Wnt4 locus suppressed by Six2. Sall1-mediated repression was also independent of its binding to DNA. Thus, Sall1 maintains nephron progenitors and their derivatives by a unique mechanism, which partly overlaps but is distinct from that of Six2: Sall1 activates progenitor-related genes in Six2-positive nephron progenitors and represses gene expression in Six2-negative differentiating nascent nephrons. PMID:24744442

Simultaneous observation of nascent plasma and bubble induced by laser ablation in water with various pulse durations

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

Tamura, Ayaka, E-mail: atamura@hiroshima-u.ac.jp; Matsumoto, Ayumu; Nishi, Naoya

2015-05-07

We investigate the effects of pulse duration on the dynamics of the nascent plasma and bubble induced by laser ablation in water. To examine the relationship between the nascent plasma and the bubble without disturbed by shot-to-shot fluctuation, we observe the images of the plasma and the bubble simultaneously by using two intensified charge coupled device detectors. We successfully observe the images of the plasma and bubble during the pulsed-irradiation, when the bubble size is as small as 20 μm. The light-emitting region of the plasma during the laser irradiation seems to exceed the bubble boundary in the case of themore » short-pulse (30-ns pulse) irradiation, while the size of the plasma is significantly smaller than that of the bubble in the case of the long-pulse (100-ns pulse) irradiation. The results suggest that the extent of the plasma quenching in the initial stage significantly depends on the pulse duration. Also, we investigate how the plasma-bubble relationship in the very early stage affects the shape of the atomic spectral lines observed at the later delay time of 600 ns. The present work gives important information to obtain high quality spectra in the application of underwater laser-induced breakdown spectroscopy, as well as to clarify the mechanism of liquid-phase laser ablation.« less

A two-way street: regulatory interplay between RNA polymerase and nascent RNA structure

PubMed Central

Zhang, Jinwei; Landick, Robert

2016-01-01

The vectorial (5′-to-3′ at varying velocity) synthesis of RNA by cellular RNA polymerases creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNA polymerase and nascent RNA structure. We categorize and attempt to rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies. PMID:26822487

A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure.

PubMed

Zhang, Jinwei; Landick, Robert

2016-04-01

The vectorial (5'-to-3' at varying velocity) synthesis of RNA by cellular RNA polymerases (RNAPs) creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived, pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here, we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNAP and nascent RNA structure. We categorize and rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain

PubMed Central

Koch, Miriam; Willi, Jessica; Pradère, Ugo; Hall, Jonathan

2017-01-01

Abstract The nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and co-translational protein folding. Inducible expression of the erm resistance genes depends on ribosome stalling at specific codons of an upstream open reading frame in the presence of an exit tunnel-bound macrolide antibiotic. The molecular basis for this translation arrest is still not fully understood. Here, we used a nucleotide analog interference approach to unravel important functional groups on 23S rRNA residues in the ribosomal exit tunnel for ribosome stalling on the ErmC leader peptide. By replacing single nucleobase functional groups or even single atoms we were able to demonstrate the importance of A2062, A2503 and U2586 for drug-dependent ribosome stalling. Our data show that the universally conserved A2062 and A2503 are capable of forming a non-Watson–Crick base pair that is critical for sensing and transmitting the stalling signal from the exit tunnel back to the peptidyl transferase center of the ribosome. The nucleobases of A2062, A2503 as well as U2586 do not contribute significantly to the overall mechanism of protein biosynthesis, yet their elaborate role for co-translational monitoring of nascent peptide chains inside the exit tunnel can explain their evolutionary conservation. PMID:28369621

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain

PubMed Central

Lintner, Nathanael G.; McClure, Kim F.; Petersen, Donna; Londregan, Allyn T.; Piotrowski, David W.; Wei, Liuqing; Xiao, Jun; Bolt, Michael; Loria, Paula M.; Maguire, Bruce; Geoghegan, Kieran F.; Huang, Austin; Rolph, Tim; Liras, Spiros; Doudna, Jennifer A.; Dullea, Robert G.

2017-01-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts. PMID:28323820

Co-translational capturing of nascent ribosomal proteins by their dedicated chaperones

PubMed Central

Pausch, Patrick; Singh, Ujjwala; Ahmed, Yasar Luqman; Pillet, Benjamin; Murat, Guillaume; Altegoer, Florian; Stier, Gunter; Thoms, Matthias; Hurt, Ed; Sinning, Irmgard; Bange, Gert; Kressler, Dieter

2015-01-01

Exponentially growing yeast cells produce every minute >160,000 ribosomal proteins. Owing to their difficult physicochemical properties, the synthesis of assembly-competent ribosomal proteins represents a major challenge. Recent evidence highlights that dedicated chaperone proteins recognize the N-terminal regions of ribosomal proteins and promote their soluble expression and delivery to the assembly site. Here we explore the intuitive possibility that ribosomal proteins are captured by dedicated chaperones in a co-translational manner. Affinity purification of four chaperones (Rrb1, Syo1, Sqt1 and Yar1) selectively enriched the mRNAs encoding their specific ribosomal protein clients (Rpl3, Rpl5, Rpl10 and Rps3). X-ray crystallography reveals how the N-terminal, rRNA-binding residues of Rpl10 are shielded by Sqt1's WD-repeat β-propeller, providing mechanistic insight into the incorporation of Rpl10 into pre-60S subunits. Co-translational capturing of nascent ribosomal proteins by dedicated chaperones constitutes an elegant mechanism to prevent unspecific interactions and aggregation of ribosomal proteins on their road to incorporation. PMID:26112308

Tail-extension following the termination codon is critical for release of the nascent chain from membrane-bound ribosomes in a reticulocyte lysate cell-free system.

PubMed

Takahara, Michiyo; Sakaue, Haruka; Onishi, Yukiko; Yamagishi, Marifu; Kida, Yuichiro; Sakaguchi, Masao

2013-01-11

Nascent chain release from membrane-bound ribosomes by the termination codon was investigated using a cell-free translation system from rabbit supplemented with rough microsomal membrane vesicles. Chain release was extremely slow when mRNA ended with only the termination codon. Tail extension after the termination codon enhanced the release of the nascent chain. Release reached plateau levels with tail extension of 10 bases. This requirement was observed with all termination codons: TAA, TGA and TAG. Rapid release was also achieved by puromycin even in the absence of the extension. Efficient translation termination cannot be achieved in the presence of only a termination codon on the mRNA. Tail extension might be required for correct positioning of the termination codon in the ribosome and/or efficient recognition by release factors. Copyright © 2012. Published by Elsevier Inc.

A Numerical Study of the Plata River Plume Along the Southeastern South American Continental Shelf

DTIC Science & Technology

2005-01-01

Aires Depto. de Oceanografia, Servicio de Hidrografia Naval and Depto. CiEncias de la Atm6sfera y los Ocdanos, Buenos Aires, Argentina ABSTRACT The...descarrega no oceano Aguas de uma bacia de drenagem que cobre uma ampla Area da Amdrica do Sul. Sua pluma extende-se ao longo do norte da Argentina ...Instituto Nacional de Investigaci6n y Orlanski, I. 1976. A simple boundary condition for Desarrollo Pesquero, 109pp. unbounded hyperbolic flows. J

Selective ribosome profiling as a tool to study the interaction of chaperones and targeting factors with nascent polypeptide chains and ribosomes

PubMed Central

Becker, Annemarie H.; Oh, Eugene; Weissman, Jonathan S.; Kramer, Günter; Bukau, Bernd

2014-01-01

A plethora of factors is involved in the maturation of newly synthesized proteins, including chaperones, membrane targeting factors, and enzymes. Many factors act cotranslationally through association with ribosome-nascent chain complexes (RNCs), but their target specificities and modes of action remain poorly understood. We developed selective ribosome profiling (SeRP) to identify substrate pools and points of RNC engagement of these factors. SeRP is based on sequencing mRNA fragments covered by translating ribosomes (general ribosome profiling, RP), combined with a procedure to selectively isolate RNCs whose nascent polypeptides are associated with the factor of interest. Factor–RNC interactions are stabilized by crosslinking, the resulting factor–RNC adducts are then nuclease-treated to generate monosomes, and affinity-purified. The ribosome-extracted mRNA footprints are converted to DNA libraries for deep sequencing. The protocol is specified for general RP and SeRP in bacteria. It was first applied to the chaperone trigger factor and is readily adaptable to other cotranslationally acting factors, including eukaryotic factors. Factor–RNC purification and sequencing library preparation takes 7–8 days, sequencing and data analysis can be completed in 5–6 days. PMID:24136347

Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain.

PubMed

Koch, Miriam; Willi, Jessica; Pradère, Ugo; Hall, Jonathan; Polacek, Norbert

2017-06-20

The nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and co-translational protein folding. Inducible expression of the erm resistance genes depends on ribosome stalling at specific codons of an upstream open reading frame in the presence of an exit tunnel-bound macrolide antibiotic. The molecular basis for this translation arrest is still not fully understood. Here, we used a nucleotide analog interference approach to unravel important functional groups on 23S rRNA residues in the ribosomal exit tunnel for ribosome stalling on the ErmC leader peptide. By replacing single nucleobase functional groups or even single atoms we were able to demonstrate the importance of A2062, A2503 and U2586 for drug-dependent ribosome stalling. Our data show that the universally conserved A2062 and A2503 are capable of forming a non-Watson-Crick base pair that is critical for sensing and transmitting the stalling signal from the exit tunnel back to the peptidyl transferase center of the ribosome. The nucleobases of A2062, A2503 as well as U2586 do not contribute significantly to the overall mechanism of protein biosynthesis, yet their elaborate role for co-translational monitoring of nascent peptide chains inside the exit tunnel can explain their evolutionary conservation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Photoionization mass spectrometry for the investigation of combustion generated nascent nanoparticles and their relation to laser induced incandescence

NASA Astrophysics Data System (ADS)

Grotheer, H.-H.; Wolf, K.; Hoffmann, K.

2011-08-01

Premixed laminar flat ethylene flames were investigated for nascent nanoparticles through photoionization mass spectrometry (PIMS). Using an atmospheric McKenna burner and ethylene air flames coupled to an atmospheric sampling system, within a relatively narrow C/O range two modes of these particles were found, which can be clearly distinguished with regard to their temperature dependence, their reactivity, and their ionization behaviour. Behind a diesel engine the same particles were observed. These results were corroborated using a low pressure ethylene-O2 flame coupled to a high resolution mass spectrometer. In this case, due to a special inlet system, it was possible to operate the flame in a fairly wide C/O range without clogging of the inlet nozzles. This allowed pursuing the development of particle size distribution functions (PSDF) well into the regime of mature soot. In addition, on the low mass side of the particle spectra measurements with unity resolution were possible and this allowed gaining information concerning their growth mechanism and structure. Finally, in an attempt to mimic Laser Induced Incandescence (LII) experiments the soot-laden molecular beam was exposed to IR irradiation. This resulted in a near complete destruction of nascent particles under LII typical fluences. Small C clusters between 3 and 17 C atoms were found. In addition and with much higher intensities, clusters comprising several hundreds of C atoms were also detected, the latter even at very low fluences when small clusters were totally absent.

Nascent Transcription Affected by RNA Polymerase IV in Zea mays

PubMed Central

Erhard, Karl F.; Talbot, Joy-El R. B.; Deans, Natalie C.; McClish, Allison E.; Hollick, Jay B.

2015-01-01

All eukaryotes use three DNA-dependent RNA polymerases (RNAPs) to create cellular RNAs from DNA templates. Plants have additional RNAPs related to Pol II, but their evolutionary role(s) remain largely unknown. Zea mays (maize) RNA polymerase D1 (RPD1), the largest subunit of RNA polymerase IV (Pol IV), is required for normal plant development, paramutation, transcriptional repression of certain transposable elements (TEs), and transcriptional regulation of specific alleles. Here, we define the nascent transcriptomes of rpd1 mutant and wild-type (WT) seedlings using global run-on sequencing (GRO-seq) to identify the broader targets of RPD1-based regulation. Comparisons of WT and rpd1 mutant GRO-seq profiles indicate that Pol IV globally affects transcription at both transcriptional start sites and immediately downstream of polyadenylation addition sites. We found no evidence of divergent transcription from gene promoters as seen in mammalian GRO-seq profiles. Statistical comparisons identify genes and TEs whose transcription is affected by RPD1. Most examples of significant increases in genic antisense transcription appear to be initiated by 3ʹ-proximal long terminal repeat retrotransposons. These results indicate that maize Pol IV specifies Pol II-based transcriptional regulation for specific regions of the maize genome including genes having developmental significance. PMID:25653306

RNA editing in nascent RNA affects pre-mRNA splicing

PubMed Central

Hsiao, Yun-Hua Esther; Bahn, Jae Hoon; Yang, Yun; Lin, Xianzhi; Tran, Stephen; Yang, Ei-Wen; Quinones-Valdez, Giovanni

2018-01-01

In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A-to-I) RNA editing and its impact on alternative splicing. We observed that >95% A-to-I RNA editing events occurred in the chromatin-associated RNA prior to polyadenylation. We report about 500 editing sites in the 3′ acceptor sequences that can alter splicing of the associated exons. These exons are highly conserved during evolution and reside in genes with important cellular function. Furthermore, we identified a second class of exons whose splicing is likely modulated by RNA secondary structures that are recognized by the RNA editing machinery. The genome-wide analyses, supported by experimental validations, revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites. PMID:29724793

Structural Basis for Recognition and Sequestration of UUUOH 3 ' Temini of Nascent RNA Polymerase III Transcripts by La, a Rheumatic Disease Autoantigen

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

Teplova,M.; Yuan, Y.; Phan, A.

2006-01-01

The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUUOH 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 Angstroms crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9OH 3' end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the {beta} sheet edge,more » rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUUOH 3' ends of nascent RNA transcripts are protected during downstream processing and maturation events.« less

Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins

PubMed Central

Foulk, Michael S.; Urban, John M.; Casella, Cinzia; Gerbi, Susan A.

2015-01-01

Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand–independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo–controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na+ instead of K+ in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq. PMID:25695952

RNA editing in nascent RNA affects pre-mRNA splicing.

PubMed

Hsiao, Yun-Hua Esther; Bahn, Jae Hoon; Yang, Yun; Lin, Xianzhi; Tran, Stephen; Yang, Ei-Wen; Quinones-Valdez, Giovanni; Xiao, Xinshu

2018-06-01

In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A-to-I) RNA editing and its impact on alternative splicing. We observed that >95% A-to-I RNA editing events occurred in the chromatin-associated RNA prior to polyadenylation. We report about 500 editing sites in the 3' acceptor sequences that can alter splicing of the associated exons. These exons are highly conserved during evolution and reside in genes with important cellular function. Furthermore, we identified a second class of exons whose splicing is likely modulated by RNA secondary structures that are recognized by the RNA editing machinery. The genome-wide analyses, supported by experimental validations, revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites. © 2018 Hsiao et al.; Published by Cold Spring Harbor Laboratory Press.

A study on a nascent entomopathogenic association between caenorhabditis briggsae and serratia sp.SCBI

NASA Astrophysics Data System (ADS)

Abebe-Akele, Feseha

Life is inconceivable in the absence of interactions which could be cooperative, antagonistic or neutral. Interactions are in constant flux because on one hand it is often difficult to demarcate where one form of interaction ends and the other begins on the other hand what is cooperative at one point in time could evolve into antagonistic or neutral or vice versa. Thus, organisms, as a consequence of mutation, adaptation and natural selection would inevitably enter into natural associations from which they emerge as mutual partners, inveterate enemies or passive cohabitants. Entomopathogenic nematode (EPN) partnerships are tripartite interactions where a nematode-bacteria symbiont duo attacks a third organism -an insect or insect larva-for the mutual benefit of the attacking partners and the detriment of the insect they invade. All three participants in the interaction---the nematode worms with their symbiont bacteria and the target insect host-are among the most ancient, diverse and abundant species on earth, however, these EPN partnerships are not as common as circumstances would suggest. EPN associations, which are arguably at the peak of evolutionary co adaptations, where two primitive forms of life cooperate to take advantage of a larger species are not only fascinating but immensely important for humans. The biological and molecular mechanisms underlying entomopathogenesis have been studied in great detail for decades for their potential as biological control agents against invasive insects. In spite of intense research in The EPN field, the evolutionary history of EPN associations are largely unknown because there are no known intermediate forms. In this thesis, a nascent EPN partnership is described between Caenorhabditid nematodes and Serratia sp. SCBI. Comparative analysis of this association with other EPNs suggests that crucial aspect of EPN associations may be the ability of partners to co-exist without killing each other and that the end results of

Structural basis for recognition and sequestration of UUU(OH) 3' temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen.

PubMed

Teplova, Marianna; Yuan, Yu-Ren; Phan, Anh Tuân; Malinina, Lucy; Ilin, Serge; Teplov, Alexei; Patel, Dinshaw J

2006-01-06

The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUU(OH) 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 angstroms crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9OH 3' end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the beta sheet edge, rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUU(OH) 3' ends of nascent RNA transcripts are protected during downstream processing and maturation events.

Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins.

PubMed

Foulk, Michael S; Urban, John M; Casella, Cinzia; Gerbi, Susan A

2015-05-01

Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na(+) instead of K(+) in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq. © 2015 Foulk et al.; Published by Cold Spring Harbor Laboratory Press.

Multi-imaging analysis of nascent surface structures generated during femtosecond laser irradiation of silicon in high vacuum

NASA Astrophysics Data System (ADS)

Gesuele, F.; JJ Nivas, J.; Fittipaldi, R.; Altucci, C.; Bruzzese, R.; Maddalena, P.; Amoruso, S.

2018-02-01

We report a correlative imaging analysis of a crystalline silicon target after irradiation with a low number of 1055 nm, 850 fs laser pulses with several microscopy techniques (e.g., scanning electron microscopy, atomic force microscopy, Raman micro-imaging and confocal optical microscopy). The analysis is carried out on samples irradiated both in high vacuum and at atmospheric pressure conditions, evidencing interesting differences induced by the ambient environment. In high-vacuum conditions, the results evidence the formation of a halo, which is constituted by alternate stripes of amorphous and crystalline silicon, around the nascent ablation crater. In air, such an effect is drastically reduced, due to the significant back-deposition of nanoparticulate material induced by the larger ambient pressure.

Nascent life cycles and the emergence of higher-level individuality.

PubMed

Ratcliff, William C; Herron, Matthew; Conlin, Peter L; Libby, Eric

2017-12-05

Evolutionary transitions in individuality (ETIs) occur when formerly autonomous organisms evolve to become parts of a new, 'higher-level' organism. One of the first major hurdles that must be overcome during an ETI is the emergence of Darwinian evolvability in the higher-level entity (e.g. a multicellular group), and the loss of Darwinian autonomy in the lower-level units (e.g. individual cells). Here, we examine how simple higher-level life cycles are a key innovation during an ETI, allowing this transfer of fitness to occur 'for free'. Specifically, we show how novel life cycles can arise and lead to the origin of higher-level individuals by (i) mitigating conflicts between levels of selection, (ii) engendering the expression of heritable higher-level traits and (iii) allowing selection to efficiently act on these emergent higher-level traits. Further, we compute how canonical early life cycles vary in their ability to fix beneficial mutations via mathematical modelling. Life cycles that lack a persistent lower-level stage and develop clonally are far more likely to fix 'ratcheting' mutations that limit evolutionary reversion to the pre-ETI state. By stabilizing the fragile first steps of an evolutionary transition in individuality, nascent higher-level life cycles may play a crucial role in the origin of complex life.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate

PubMed Central

MacKinnon, Andrew L; Paavilainen, Ville O; Sharma, Ajay; Hegde, Ramanujan S; Taunton, Jack

2014-01-01

Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61α, thus revealing cotransin’s likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug. DOI: http://dx.doi.org/10.7554/eLife.01483.001 PMID:24497544

Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny.

PubMed

Crauste, Fabien; Mafille, Julien; Boucinha, Lilia; Djebali, Sophia; Gandrillon, Olivier; Marvel, Jacqueline; Arpin, Christophe

2017-03-22

Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Nascent PO(X 2Π) E,V,R,T excitations from collision-free IR laser photolysis: Specificity toward the PO(X 2Pi 1/2) spin-orbit statea)

NASA Astrophysics Data System (ADS)

Chou, Jim-Son; Sumida, David S.; Wittig, C.

1985-02-01

PO (X 2Π) is produced via the collision-free infrared multiple photon dissociation (IRMPD) of volatile organophosphorous molecules, and is detected by two-frequency two-photon ionization, using the B 2Σ+ state to provide a spectral signature from which X 2Π populations are obtained. Sequential dissociations occur during the IR laser photolysis, in which nascent fragments continue to undergo IRMPD, and PO (X 2Π) accrues from a series of bond fission reactions. Nascent vibrational, rotational, and translational excitations are in sensible accord with this mechanism, except for a few rotational states near J=19.5. Unlike the nuclear degrees of freedom, the PO (X 2Π) spin-orbit states are populated quite selectively. The 2Π3/2 state, lying only 224 cm-1 above the 2Π1/2 ground state, contains only ˜11% of the population, compared to 34% for a 300 K sample. This result is unambiguous; it persists with all precursors, laser fluences, etc., and is verified by comparisons to spectra obtained using a microwave discharge, a flame, and when thermalizing nascent excitations with an inert diluent. This result underscores the importance of the separate potential surfaces which correlate to the product spin-orbit states, and the small amount of 2Π3/2 population can be accounted for by nonadiabatic coupling during dissociation, and/or ``freezing'' the amount of S1 character in an excited precursor in which S0 and S1 are coupled nonradiatively. We note that such electronic specificity should be dealt with in the analogous recombination reactions.

Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments.

PubMed

Kolinjivadi, Arun Mouli; Sannino, Vincenzo; De Antoni, Anna; Zadorozhny, Karina; Kilkenny, Mairi; Técher, Hervé; Baldi, Giorgio; Shen, Rong; Ciccia, Alberto; Pellegrini, Luca; Krejci, Lumir; Costanzo, Vincenzo

2017-09-07

Brca2 deficiency causes Mre11-dependent degradation of nascent DNA at stalled forks, leading to cell lethality. To understand the molecular mechanisms underlying this process, we isolated Xenopus laevis Brca2. We demonstrated that Brca2 protein prevents single-stranded DNA gap accumulation at replication fork junctions and behind them by promoting Rad51 binding to replicating DNA. Without Brca2, forks with persistent gaps are converted by Smarcal1 into reversed forks, triggering extensive Mre11-dependent nascent DNA degradation. Stable Rad51 nucleofilaments, but not RPA or Rad51 T131P mutant proteins, directly prevent Mre11-dependent DNA degradation. Mre11 inhibition instead promotes reversed fork accumulation in the absence of Brca2. Rad51 directly interacts with the Pol α N-terminal domain, promoting Pol α and δ binding to stalled replication forks. This interaction likely promotes replication fork restart and gap avoidance. These results indicate that Brca2 and Rad51 prevent formation of abnormal DNA replication intermediates, whose processing by Smarcal1 and Mre11 predisposes to genome instability. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

["Anything goes"?: the implicit dialogue between Paul Feyerabend and two Brazilian researchers, Maurício da Rocha e Silva and Newton Freire-Maia].

PubMed

Bastos, Francisco Inácio

2010-03-01

The philosopher Paul Feyerabend and Brazilian scientists Maurício da Rocha e Silva and Newton Freire-Maia were contemporaries and lived surrounded by the fundamental dilemnas of science. The anarchist proposal of Feyerabend, then embryonic, was formulated in parallel by Rocha e Silva in his criticism of the scientific method. Two decades later, Feyerabend's ideas seemed implicitly to stimulate Newton Freire-Maia in his reflections on science. The web of interrelationships in the ideas of these three men - who never interacted - touches on central issues for Brazilian science from 1960 to 1980, a period in which the latter is consolidated in a dialogue with the nascent reflection on science and the scientific method in Brazil.

Isolation of nucleoli from Ehrlich ascites tumor cells and dynamics of nascent RNA within isolated nucleoli.

PubMed

Thiry, Marc; Ploton, Dominique

2008-01-01

Here we describe a new, rapid method for isolating nucleoli from Ehrlich tumor cells that preserves their morphological integrity and high transcriptional activity. Until now, methods for isolation of nucleoli were generally assumed to empty one of their three main compartments, the fibrillar center, of its contents. This new method consists of sonicating cells in an isotonic medium containing MgSO(4), spermidine, and spermine, followed by separation of nucleoli through a Percoll density gradient. Using the nonisotopic approach of labelling with BrUTP, we have further investigated the dynamics of nascent ribosomal RNAs (rRNAs) within morphologically intact isolated nucleoli at the electron microscope level. We show that ribosomal transcripts are elongated in the cortex of the fibrillar center and then enter the surrounding dense fibrillar component.

Comparative Dynamics of Retrograde Actin Flow and Focal Adhesions: Formation of Nascent Adhesions Triggers Transition from Fast to Slow Flow

PubMed Central

Alexandrova, Antonina Y.; Arnold, Katya; Schaub, Sébastien; Vasiliev, Jury M.; Meister, Jean-Jacques; Bershadsky, Alexander D.; Verkhovsky, Alexander B.

2008-01-01

Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs), and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow), and the lamellum (zone of slow flow located between the lamellipodium and the cell body). Cell migration involves expansion of both the lamellipodium and the lamellum, as well as formation of new FAs, but it is largely unknown how the position of the boundary between the two flow zones is defined, and how FAs and actin flow mutually influence each other. We investigated dynamic relationship between focal adhesions and the boundary between the two flow zones in spreading cells. Nascent FAs first appeared in the lamellipodium. Within seconds after the formation of new FAs, the rate of actin flow decreased locally, and the lamellipodium/lamellum boundary advanced towards the new FAs. Blocking fast actin flow with cytochalasin D resulted in rapid dissolution of nascent FAs. In the absence of FAs (spreading on poly-L-lysine-coated surfaces) retrograde flow was uniform and the velocity transition was not observed. We conclude that formation of FAs depends on actin dynamics, and in its turn, affects the dynamics of actin flow by triggering transition from fast to slow flow. Extension of the cell edge thus proceeds through a cycle of lamellipodium protrusion, formation of new FAs, advance of the lamellum, and protrusion of the lamellipodium from the new base. PMID:18800171

Position-specific binding of FUS to nascent RNA regulates mRNA length

PubMed Central

Masuda, Akio; Takeda, Jun-ichi; Okuno, Tatsuya; Okamoto, Takaaki; Ohkawara, Bisei; Ito, Mikako; Ishigaki, Shinsuke; Sobue, Gen

2015-01-01

More than half of all human genes produce prematurely terminated polyadenylated short mRNAs. However, the underlying mechanisms remain largely elusive. CLIP-seq (cross-linking immunoprecipitation [CLIP] combined with deep sequencing) of FUS (fused in sarcoma) in neuronal cells showed that FUS is frequently clustered around an alternative polyadenylation (APA) site of nascent RNA. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) of RNA polymerase II (RNAP II) demonstrated that FUS stalls RNAP II and prematurely terminates transcription. When an APA site is located upstream of an FUS cluster, FUS enhances polyadenylation by recruiting CPSF160 and up-regulates the alternative short transcript. In contrast, when an APA site is located downstream from an FUS cluster, polyadenylation is not activated, and the RNAP II-suppressing effect of FUS leads to down-regulation of the alternative short transcript. CAGE-seq (cap analysis of gene expression [CAGE] combined with deep sequencing) and PolyA-seq (a strand-specific and quantitative method for high-throughput sequencing of 3' ends of polyadenylated transcripts) revealed that position-specific regulation of mRNA lengths by FUS is operational in two-thirds of transcripts in neuronal cells, with enrichment in genes involved in synaptic activities. PMID:25995189

5S Ribosomal RNA Is an Essential Component of a Nascent Ribosomal Precursor Complex that Regulates the Hdm2-p53 Checkpoint

PubMed Central

Donati, Giulio; Peddigari, Suresh; Mercer, Carol A.; Thomas, George

2013-01-01

SUMMARY Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA) and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted. PMID:23831031

5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint.

PubMed

Donati, Giulio; Peddigari, Suresh; Mercer, Carol A; Thomas, George

2013-07-11

Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA) and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA-damaging therapeutic agents

PubMed Central

Liao, Hongwei; Ji, Fang; Geng, Xinwei; Xing, Meichun; Li, Wen; Chen, Zhihua; Shen, Huahao; Ying, Songmin

2017-01-01

Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability. Moreover, we show that compromised CDK1 activity dramatically increases the efficacy of chemotherapeutic agents that kill cancer cells through perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor. Our study has revealed an important role for CDK1 in the DNA replication program, and suggests that the therapeutic targeting CDK1 may be a novel approach for combination chemotherapy. PMID:29207595

Do chromatin changes around a nascent double strand DNA break spread spherically into linearly non-adjacent chromatin?

PubMed

Savic, Velibor

2013-01-01

In the last decade, a lot has been done in elucidating the sequence of events that occur at the nascent double strand DNA break. Nevertheless, the overall structure formed by the DNA damage response (DDR) factors around the break site, the repair focus, remains poorly understood. Although most of the data presented so far only address events that occur in chromatin in cis around the break, there are strong indications that in mammalian systems it may also occur in trans, analogous to the recent findings showing this if budding yeast. There have been attempts to address the issue but the final proof is still missing due to lack of a proper experimental system. If found to be true, the spatial distribution of DDR factors would have a major impact on the neighboring chromatin both in cis and in trans, significantly affecting local chromatin function; gene transcription and potentially other functions.

Do chromatin changes around a nascent double strand DNA break spread spherically into linearly non-adjacent chromatin?

PubMed Central

Savic, Velibor

2013-01-01

In the last decade, a lot has been done in elucidating the sequence of events that occur at the nascent double strand DNA break. Nevertheless, the overall structure formed by the DNA damage response (DDR) factors around the break site, the repair focus, remains poorly understood. Although most of the data presented so far only address events that occur in chromatin in cis around the break, there are strong indications that in mammalian systems it may also occur in trans, analogous to the recent findings showing this if budding yeast. There have been attempts to address the issue but the final proof is still missing due to lack of a proper experimental system. If found to be true, the spatial distribution of DDR factors would have a major impact on the neighboring chromatin both in cis and in trans, significantly affecting local chromatin function; gene transcription and potentially other functions. PMID:23882282

Decay dynamics of nascent acetonitrile and nitromethane dipole-bound anions produced by intracluster charge-transfer

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

Yandell, Margaret A.; King, Sarah B.; Neumark, Daniel M., E-mail: dneumark@berkeley.edu

2014-05-14

Decay dynamics of nascent dipole bound states of acetonitrile and nitromethane are examined using time-resolved photoelectron imaging of iodide-acetonitrile (I{sup −}·CH{sub 3}CN) and iodide-nitromethane (I{sup −}·CH{sub 3}NO{sub 2}) complexes. Dipole-bound anions are created by UV-initiated electron transfer to the molecule of interest from the associated iodide ion at energies just below the vertical detachment energy of the halide-molecule complex. The acetonitrile anion is observed to decay biexponentially with time constants in the range of 4–900 ps. In contrast, the dipole bound state of nitromethane decays rapidly over 400 fs to form the valence bound anion. The nitromethane valence anion speciesmore » then decays biexponentially with time constants of 2 ps and 1200 ps. The biexponential decay dynamics in acetonitrile are interpreted as iodine atom loss and autodetachment from the excited dipole-bound anion, followed by slower autodetachment of the relaxed metastable ion, while the dynamics of the nitromethane system suggest that a dipole-bound anion to valence anion transition proceeds via intramolecular vibrational energy redistribution to nitro group modes in the vicinity of the iodine atom.« less

Decay dynamics of nascent acetonitrile and nitromethane dipole-bound anions produced by intracluster charge-transfer.

PubMed

Yandell, Margaret A; King, Sarah B; Neumark, Daniel M

2014-05-14

Decay dynamics of nascent dipole bound states of acetonitrile and nitromethane are examined using time-resolved photoelectron imaging of iodide-acetonitrile (I(-)·CH3CN) and iodide-nitromethane (I(-)·CH3NO2) complexes. Dipole-bound anions are created by UV-initiated electron transfer to the molecule of interest from the associated iodide ion at energies just below the vertical detachment energy of the halide-molecule complex. The acetonitrile anion is observed to decay biexponentially with time constants in the range of 4-900 ps. In contrast, the dipole bound state of nitromethane decays rapidly over 400 fs to form the valence bound anion. The nitromethane valence anion species then decays biexponentially with time constants of 2 ps and 1200 ps. The biexponential decay dynamics in acetonitrile are interpreted as iodine atom loss and autodetachment from the excited dipole-bound anion, followed by slower autodetachment of the relaxed metastable ion, while the dynamics of the nitromethane system suggest that a dipole-bound anion to valence anion transition proceeds via intramolecular vibrational energy redistribution to nitro group modes in the vicinity of the iodine atom.

Mechanical Modulation of Nascent Stem Cell Lineage Commitment in Tissue Engineering Scaffolds

PubMed Central

Song, Min Jae; Dean, David; Tate, Melissa L. Knothe

2013-01-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to “map the mechanome”, defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. PMID:23660249

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

PubMed

Song, Min Jae; Dean, David; Knothe Tate, Melissa L

2013-07-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ultrafast chemical interface scattering as an additional decay channel for nascent nonthermal electrons in small metal nanoparticles.

PubMed

Bauer, Christophe; Abid, Jean-Pierre; Fermin, David; Girault, Hubert H

2004-05-15

The use of 4.2 nm gold nanoparticles wrapped in an adsorbates shell and embedded in a TiO2 metal oxide matrix gives the opportunity to investigate ultrafast electron-electron scattering dynamics in combination with electronic surface phenomena via the surface plasmon lifetimes. These gold nanoparticles (NPs) exhibit a large nonclassical broadening of the surface plasmon band, which is attributed to a chemical interface damping. The acceleration of the loss of surface plasmon phase coherence indicates that the energy and the momentum of the collective electrons can be dissipated into electronic affinity levels of adsorbates. As a result of the preparation process, gold NPs are wrapped in a shell of sulfate compounds that gives rise to a large density of interfacial molecules confined between Au and TiO2, as revealed by Fourier-transform-infrared spectroscopy. A detailed analysis of the transient absorption spectra obtained by broadband femtosecond transient absorption spectroscopy allows separating electron-electron and electron-phonon interaction. Internal thermalization times (electron-electron scattering) are determined by probing the decay of nascent nonthermal electrons (NNEs) and the build-up of the Fermi-Dirac electron distribution, giving time constants of 540 to 760 fs at 0.42 and 0.34 eV from the Fermi level, respectively. Comparison with literature data reveals that lifetimes of NNEs measured for these small gold NPs are more than four times longer than for silver NPs with similar sizes. The surprisingly long internal thermalization time is attributed to an additional decay mechanism (besides the classical e-e scattering) for the energy loss of NNEs, identified as the ultrafast chemical interface scattering process. NNEs experience an inelastic resonant scattering process into unoccupied electronic states of adsorbates, that directly act as an efficient heat bath, via the excitation of molecular vibrational modes. The two-temperature model is no longer

Sharp Transition from Nonmetallic Au246 to Metallic Au279 with Nascent Surface Plasmon Resonance.

PubMed

Higaki, Tatsuya; Zhou, Meng; Lambright, Kelly J; Kirschbaum, Kristin; Sfeir, Matthew Y; Jin, Rongchao

2018-05-02

The optical properties of metal nanoparticles have attracted wide interest. Recent progress in controlling nanoparticles with atomic precision (often called nanoclusters) provide new opportunities for investigating many fundamental questions, such as the transition from excitonic to plasmonic state, which is a central question in metal nanoparticle research because it provides insights into the origin of surface plasmon resonance (SPR) as well as the formation of metallic bond. However, this question still remains elusive because of the extreme difficulty in preparing atomically precise nanoparticles larger than 2 nm. Here we report the synthesis and optical properties of an atomically precise Au 279 (SR) 84 nanocluster. Femtosecond transient absorption spectroscopic analysis reveals that the Au 279 nanocluster shows a laser power dependence in its excited state lifetime, indicating metallic state of the particle, in contrast with the nonmetallic electronic structure of the Au 246 (SR) 80 nanocluster. Steady-state absorption spectra reveal that the nascent plasmon band of Au 279 at 506 nm shows no peak shift even down to 60 K, consistent with plasmon behavior. The sharp transition from nonmetallic Au 246 to metallic Au 279 is surprising and will stimulate future theoretical work on the transition and many other relevant issues.

Quantum-state resolved reactive scattering at the gas-liquid interface: F+squalane (C30H62) dynamics via high-resolution infrared absorption of nascent HF(v,J).

PubMed

Zolot, Alexander M; Dagdigian, Paul J; Nesbitt, David J

2008-11-21

Exothermic chemical reaction dynamics at the gas-liquid interface have been investigated by colliding a supersonic beam of F atoms [E(com)=0.7(3) kcalmol] with a continuously refreshed liquid hydrocarbon (squalane) surface under high vacuum conditions. Absolute HF(v,J) product densities are determined by infrared laser absorption spectroscopy, with velocity distributions along the probe axis derived from high resolution Dopplerimetry. Nascent HF(vNascent HF also recoils from the liquid surface with excess translational energy, resulting in Doppler broadened linewidths that increase systematically with internal HF excitation. The data are consistent with microscopic branching in HF-surface dynamics following the reactive event, with (i) a direct reactive scattering fraction of newly formed product molecules leaving the surface promptly and (ii) a trapping desorption fraction that accommodates rotationally (though still not vibrationally) with the bulk liquid. Comparison with analogous gas phase F+hydrocarbon processes reveals that the liquid acts as a partial "heat sink" for vibrational energy flow on the time scale of the chemical reaction event.

Quantum-state resolved reactive scattering at the gas-liquid interface: F +squalane (C30H62) dynamics via high-resolution infrared absorption of nascent HF(v,J)

NASA Astrophysics Data System (ADS)

Zolot, Alexander M.; Dagdigian, Paul J.; Nesbitt, David J.

2008-11-01

Exothermic chemical reaction dynamics at the gas-liquid interface have been investigated by colliding a supersonic beam of F atoms [Ecom=0.7(3)kcal/mol] with a continuously refreshed liquid hydrocarbon (squalane) surface under high vacuum conditions. Absolute HF(v,J) product densities are determined by infrared laser absorption spectroscopy, with velocity distributions along the probe axis derived from high resolution Dopplerimetry. Nascent HF(v ⩽3) products are formed in a highly nonequilibrium (inverted) vibrational distribution [⟨Evib⟩=13.2(2)kcal/mol], reflecting insufficient time for complete thermal accommodation with the surface prior to desorption. Colder, but still non-Boltzmann, rotational state populations [⟨Erot⟩=1.0(1)kcal/mol] indicate that some fraction of molecules directly scatter into the gas phase without rotationally equilibrating with the surface. Nascent HF also recoils from the liquid surface with excess translational energy, resulting in Doppler broadened linewidths that increase systematically with internal HF excitation. The data are consistent with microscopic branching in HF-surface dynamics following the reactive event, with (i) a direct reactive scattering fraction of newly formed product molecules leaving the surface promptly and (ii) a trapping desorption fraction that accommodates rotationally (though still not vibrationally) with the bulk liquid. Comparison with analogous gas phase F +hydrocarbon processes reveals that the liquid acts as a partial "heat sink" for vibrational energy flow on the time scale of the chemical reaction event.

Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs

PubMed Central

Rouvinski, Alexander; Karniely, Sharon; Kounin, Maria; Moussa, Sanaa; Goldberg, Miri D.; Warburg, Gabriela; Lyakhovetsky, Roman; Papy-Garcia, Dulce; Kutzsche, Janine; Korth, Carsten; Carlson, George A.; Godsave, Susan F.; Peters, Peter J.; Luhr, Katarina; Kristensson, Krister

2014-01-01

Mammalian prions refold host glycosylphosphatidylinositol-anchored PrPC into β-sheet–rich PrPSc. PrPSc is rapidly truncated into a C-terminal PrP27-30 core that is stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, and their subcellular locations are poorly understood; live prion visualization has not previously been achieved. A key obstacle has been the inaccessibility of PrP27-30 epitopes. We overcame this hurdle by focusing on nascent full-length PrPSc rather than on its truncated PrP27-30 product. We show that N-terminal PrPSc epitopes are exposed in their physiological context and visualize, for the first time, PrPSc in living cells. PrPSc resides for hours in unexpected cell-surface, slow moving strings and webs, sheltered from endocytosis. Prion strings observed by light and scanning electron microscopy were thin, micrometer-long structures. They were firmly cell associated, resisted phosphatidylinositol-specific phospholipase C, aligned with raft markers, fluoresced with thioflavin, and were rapidly abolished by anti-prion glycans. Prion strings and webs are the first demonstration of membrane-anchored PrPSc amyloids. PMID:24493590

Evidence for a Nascent Rift in South Sudan: Westward Extension of the East African Rift System?

NASA Astrophysics Data System (ADS)

Maceira, M.; Van Wijk, J. W.; Coblentz, D. D.; Modrak, R. T.

2013-12-01

Joint inversion of seismic and gravity data of eastern Africa reveals a low seismic wave velocity arm stretching from the southern Main Ethiopian rift westward in an east-west direction that has not been noticed in earlier work. The zone of low velocities is located in the upper mantle and is not overlain by a known structural rift expression. We analyzed the local pattern of seismicity and the stresses in the African plate to interpret this low velocity arm. The zone of low velocities is located within the Central African Fold Belt, which dissects the northern and southern portions of the African continent. It is seismically active with small to intermediate sized earthquakes occurring in the crust. Seven earthquake solutions indicate (oblique) normal faulting and low-angle normal faulting with a NS to NNW-SSE opening direction, as well as strike-slip faulting. This pattern of deformation is typically associated with rifting. The present day stress field in northeastern Africa reveals a tensional state of stress at the location of the low velocity arm with an opening direction that corresponds to the earthquake data. We propose that the South Sudan low velocity zone and seismic center are part of an undeveloped, nascent rift arm. The arm stretches from the East African Rift system westward.

Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes

PubMed Central

Chakraborty, Anirban; Tapryal, Nisha; Venkova, Tatiana; Horikoshi, Nobuo; Pandita, Raj K.; Sarker, Altaf H.; Sarkar, Partha S.; Pandita, Tej K.; Hazra, Tapas K.

2016-01-01

DNA double-strand breaks (DSBs) leading to loss of nucleotides in the transcribed region can be lethal. Classical non-homologous end-joining (C-NHEJ) is the dominant pathway for DSB repair (DSBR) in adult mammalian cells. Here we report that during such DSBR, mammalian C-NHEJ proteins form a multiprotein complex with RNA polymerase II and preferentially associate with the transcribed genes after DSB induction. Depletion of C-NHEJ factors significantly abrogates DSBR in transcribed but not in non-transcribed genes. We hypothesized that nascent RNA can serve as a template for restoring the missing sequences, thus allowing error-free DSBR. We indeed found pre-mRNA in the C-NHEJ complex. Finally, when a DSB-containing plasmid with several nucleotides deleted within the E. coli lacZ gene was allowed time to repair in lacZ-expressing mammalian cells, a functional lacZ plasmid could be recovered from control but not C-NHEJ factor-depleted cells, providing important mechanistic insights into C-NHEJ-mediated error-free DSBR of the transcribed genome. PMID:27703167

A NEW CLASS OF NASCENT ECLIPSING BINARIES WITH EXTREME MASS RATIOS

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

Moe, Maxwell; Stefano, Rosanne Di, E-mail: mmoe@cfa.harvard.edu

2015-03-10

Early B-type main-sequence (MS) stars (M {sub 1} ≈ 5-16 M {sub ☉}) with closely orbiting low-mass stellar companions (q = M {sub 2}/M {sub 1} < 0.25) can evolve to produce Type Ia supernovae, low-mass X-ray binaries, and millisecond pulsars. However, the formation mechanism and intrinsic frequency of such close extreme mass-ratio binaries have been debated, especially considering none have hitherto been detected. Utilizing observations of the Large Magellanic Cloud galaxy conducted by the Optical Gravitational Lensing Experiment, we have discovered a new class of eclipsing binaries in which a luminous B-type MS star irradiates a closely orbiting low-massmore » pre-MS companion that has not yet fully formed. The primordial pre-MS companions have large radii and discernibly reflect much of the light they intercept from the B-type MS primaries (ΔI {sub refl} ≈ 0.02-0.14 mag). For the 18 definitive MS + pre-MS eclipsing binaries in our sample with good model fits to the observed light-curves, we measure short orbital periods P = 3.0-8.5 days, young ages τ ≈ 0.6-8 Myr, and small secondary masses M {sub 2} ≈ 0.8-2.4 M {sub ☉} (q ≈ 0.07-0.36). The majority of these nascent eclipsing binaries are still associated with stellar nurseries, e.g., the system with the deepest eclipse ΔI {sub 1} = 2.8 mag and youngest age τ = 0.6 ± 0.4 Myr is embedded in the bright H II region 30 Doradus. After correcting for selection effects, we find that (2.0 ± 0.6)% of B-type MS stars have companions with short orbital periods P = 3.0-8.5 days and extreme mass ratios q ≈ 0.06-0.25. This is ≈10 times greater than that observed for solar-type MS primaries. We discuss how these new eclipsing binaries provide invaluable insights, diagnostics, and challenges for the formation and evolution of stars, binaries, and H II regions.« less

Amino acid levels in nascent metabolic syndrome: A contributor to the pro-inflammatory burden.

PubMed

Reddy, Priya; Leong, Joseph; Jialal, Ishwarlal

2018-05-01

Metabolic Syndrome (MetS) is a cluster of cardio-metabolic risk factors characterized by low-grade inflammation which confers an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Prior studies have linked elevated branched chain amino acids (BCAA) and aromatic amino acids (AAA) with T2DM and CVD. Due to the paucity of data in MetS, the aim of this study was to investigate the status of amino acids as early biomarkers of nascent MetS patients without T2DM and CVD or smoking. Healthy controls (n = 20) and MetS (n = 29) patients were recruited for the study. MetS was defined by criteria of National Cholesterol Education Program Adult Treatment Panel III of having at least 3 risk factors. Urinary amino acids were quantified by gas chromatography time-of-flight mass spectrometry at the Western NIH Metabolomics Center as expressed to urinary creatinine. Tyrosine and Isoleucine levels were significantly elevated in MetS patients. Isoleucine positively correlated with salient cardio-metabolic features and inflammatory biomarkers. Lysine and Methionine levels were decreased in MetS patients. Lysine correlated negatively with cardio-metabolic features and inflammatory bimarkers. Methionine also correlated negatively with blood pressure and certain inflammatory biomarkers. Our novel results suggest that with regards to the cardio-metabolic risk factors and pro-inflammatory features of MetS, isoleucine (BCAA) demonstrated a positive correlation while lysine demonstrated a negative correlation. Thus, increased levels of isoleucine and decreased levels of lysine could be potential early biomarkers of MetS. Copyright © 2018. Published by Elsevier Inc.

Nascent chain-monitored remodeling of the Sec machinery for salinity adaptation of marine bacteria

PubMed Central

Ishii, Eiji; Chiba, Shinobu; Hashimoto, Narimasa; Kojima, Seiji; Homma, Michio; Ito, Koreaki; Akiyama, Yoshinori; Mori, Hiroyuki

2015-01-01

SecDF interacts with the SecYEG translocon in bacteria and enhances protein export in a proton-motive-force-dependent manner. Vibrio alginolyticus, a marine-estuarine bacterium, contains two SecDF paralogs, V.SecDF1 and V.SecDF2. Here, we show that the export-enhancing function of V.SecDF1 requires Na+ instead of H+, whereas V.SecDF2 is Na+-independent, presumably requiring H+. In accord with the cation-preference difference, V.SecDF2 was only expressed under limited Na+ concentrations whereas V.SecDF1 was constitutive. However, it is not the decreased concentration of Na+ per se that the bacterium senses to up-regulate the V.SecDF2 expression, because marked up-regulation of the V.SecDF2 synthesis was observed irrespective of Na+ concentrations under certain genetic/physiological conditions: (i) when the secDF1VA gene was deleted and (ii) whenever the Sec export machinery was inhibited. VemP (Vibrio export monitoring polypeptide), a secretory polypeptide encoded by the upstream ORF of secDF2VA, plays the primary role in this regulation by undergoing regulated translational elongation arrest, which leads to unfolding of the Shine–Dalgarno sequence for translation of secDF2VA. Genetic analysis of V. alginolyticus established that the VemP-mediated regulation of SecDF2 is essential for the survival of this marine bacterium in low-salinity environments. These results reveal that a class of marine bacteria exploits nascent-chain ribosome interactions to optimize their protein export pathways to propagate efficiently under different ionic environments that they face in their life cycles. PMID:26392525

Curriculum evaluation and revision in a nascent field: the utility of the retrospective pretest--posttest model in a homeland security program of study.

PubMed

Pelfrey, William V; Pelfrey, William V

2009-02-01

Although most academic disciplines evolve at a measured pace, the emerging field of homeland security must, for reasons of safety and security, evolve rapidly. The Department of Homeland Security sponsored the establishment of a graduate educational program for key officials holding homeland security roles. Because homeland security is a nascent field, the establishment of a program curriculum was forced to draw from a variety of disciplines. Curriculum evaluation was complicated by the rapid changes occurring in the emerging discipline, producing response shift bias, and interfering with the pre-post assessments. To compensate for the validity threat associated with response shift bias, a retrospective pretest-posttest evaluative methodology was used. Data indicate the program has evolved in a significant and orderly fashion and these data support the use of this innovative evaluation approach in the development of any discipline.

Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

PubMed Central

Mansilla, Sabrina F; Bertolin, Agustina P; Bergoglio, Valérie; Pillaire, Marie-Jeanne; González Besteiro, Marina A; Luzzani, Carlos; Miriuka, Santiago G; Hoffmann, Jean-Sébastien; Gottifredi, Vanesa

2016-01-01

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis. DOI: http://dx.doi.org/10.7554/eLife.18020.001 PMID:27740454

A combined crossed-beam and theoretical study of the reaction dynamics of O(3P) + C2H3 → C2H2 + OH: Analysis of the nascent OH products with the preferential population of the Π(A') component

NASA Astrophysics Data System (ADS)

Park, Min-Jin; Jang, Su-Chan; Choi, Jong-Ho

2012-11-01

The gas-phase reaction dynamics of ground-state atomic oxygen [O(3P) from the photo-dissociation of NO2] with vinyl radicals [C2H3 from the supersonic flash pyrolysis of vinyl iodide, C2H3I] has been investigated using a combination of high-resolution laser-induced fluorescence spectroscopy in a crossed-beam configuration and ab initio calculations. Unlike the previous gas-phase bulk kinetic experiments by Baulch et al. [J. Phys. Chem. Ref. Data 34, 757 (2005)], 10.1063/1.1748524, a new exothermic channel of O(3P) + C2H3 → C2H2 + OH (X 2Π: υ″ = 0) has been identified for the first time, and the population analysis shows bimodal nascent rotational distributions of OH products with low- and high-N″ components with a ratio of 2.4:1. No spin-orbit propensities were observed, and the averaged ratios of Π(A')/Π(A″) were determined to be 1.66 ± 0.27. On the basis of computations at the CBS-QB3 theory level and comparison with prior theory, the microscopic mechanisms responsible for the nascent populations can be understood in terms of two competing dynamical pathways: a direct abstraction process in the low-N″ regime as the major pathway and an addition-complex forming process in the high-N″ regime as the minor pathway. Particularly, during the bond cleavage process of the weakly bound van der Waals complex C2H2—OH, the characteristic pathway from the low dihedral-angle geometry was consistent with the observed preferential population of the Π(A') component in the nascent OH products. A molecular-level discussion of the reactivity, mechanism, and dynamical features of the title reaction are presented together with a comparison to gas-phase oxidation reactions of a series of prototypical hydrocarbon radicals.

A combined crossed-beam and theoretical study of the reaction dynamics of O(3P) + C2H3 → C2H2 + OH: analysis of the nascent OH products with the preferential population of the Π(A') component.

PubMed

Park, Min-Jin; Jang, Su-Chan; Choi, Jong-Ho

2012-11-28

The gas-phase reaction dynamics of ground-state atomic oxygen [O((3)P) from the photo-dissociation of NO(2)] with vinyl radicals [C(2)H(3) from the supersonic flash pyrolysis of vinyl iodide, C(2)H(3)I] has been investigated using a combination of high-resolution laser-induced fluorescence spectroscopy in a crossed-beam configuration and ab initio calculations. Unlike the previous gas-phase bulk kinetic experiments by Baulch et al. [J. Phys. Chem. Ref. Data 34, 757 (2005)], a new exothermic channel of O((3)P) + C(2)H(3) → C(2)H(2) + OH (X (2)Π: υ" = 0) has been identified for the first time, and the population analysis shows bimodal nascent rotational distributions of OH products with low- and high-N" components with a ratio of 2.4:1. No spin-orbit propensities were observed, and the averaged ratios of Π(A('))∕Π(A") were determined to be 1.66 ± 0.27. On the basis of computations at the CBS-QB3 theory level and comparison with prior theory, the microscopic mechanisms responsible for the nascent populations can be understood in terms of two competing dynamical pathways: a direct abstraction process in the low-N" regime as the major pathway and an addition-complex forming process in the high-N" regime as the minor pathway. Particularly, during the bond cleavage process of the weakly bound van der Waals complex C(2)H(2)-OH, the characteristic pathway from the low dihedral-angle geometry was consistent with the observed preferential population of the Π(A') component in the nascent OH products. A molecular-level discussion of the reactivity, mechanism, and dynamical features of the title reaction are presented together with a comparison to gas-phase oxidation reactions of a series of prototypical hydrocarbon radicals.

Toward a better understanding of the mechanisms of symbiosis: a comprehensive proteome map of a nascent insect symbiont.

PubMed

Renoz, François; Champagne, Antoine; Degand, Hervé; Faber, Anne-Marie; Morsomme, Pierre; Foray, Vincent; Hance, Thierry

2017-01-01

Symbiotic bacteria are common in insects and can affect various aspects of their hosts' biology. Although the effects of insect symbionts have been clarified for various insect symbiosis models, due to the difficulty of cultivating them in vitro , there is still limited knowledge available on the molecular features that drive symbiosis. Serratia symbiotica is one of the most common symbionts found in aphids. The recent findings of free-living strains that are considered as nascent partners of aphids provide the opportunity to examine the molecular mechanisms that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic factors). In this work, a proteomic approach was used to establish a comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3 T . Most of the 720 proteins identified are related to housekeeping or primary metabolism. Of these, 76 were identified as candidate proteins possibly promoting host colonization. Our results provide strong evidence that S. symbiotica CWBI-2.3 T is well-armed for invading insect host tissues, and suggest that certain molecular features usually harbored by pathogenic bacteria are no longer present. This comprehensive proteome map provides a series of candidate genes for further studies to understand the molecular cross-talk between insects and symbiotic bacteria.

Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant

PubMed Central

Ma, Bing; Reynolds, C. Michael; Raetz, Christian R. H.

2008-01-01

The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42°C. 32Pi and [35S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42°C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42°C, consistent with a role for LptA in shuttling LPS across the periplasm. PMID:18768814

Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant.

PubMed

Ma, Bing; Reynolds, C Michael; Raetz, Christian R H

2008-09-16

The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42 degrees C. (32)P(i) and [(35)S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42 degrees C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42 degrees C, consistent with a role for LptA in shuttling LPS across the periplasm.

Time-resolved diode laser infrared absorption spectroscopy of the nascent HCl in the infrared laser chemistry of 1,2-dichloro-1,1-difluoroethane

NASA Astrophysics Data System (ADS)

Dietrich, Peter; Quack, Martin; Seyfang, George

1990-04-01

The IR multiphoton excitation and the frequency, fluence and intensity dependence of the IR-laser chemical yields of CF 2ClCH 2Cl have been studied in the fluence range of 1 to 10 J cm -2 yielding a steady-state constant k(st)/ I=0.74×10 6 s -1 MW -1 cm 2 which is approximately independent of intensity. Time-resolved IR absorption spectroscopy with diode laser sources has been used to observe the nascent HCl during the first few 100 ns indicating a population inversion between the levels ν=1, J=4 and ν=2, J=5. At low reactant pressures ( p⩽10 Pa) the time-resolved measurement gives a steady-state rate constant consistent with the theoretical result adjusted to the static yield measurements. The capability of state-selective and time-resolved IR spectroscopy is thus demonstrated, giving real-time determinations of rate constants.

Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules.

PubMed

Ma, Wenbin; Zhang, Yi; Vigneron, Nathalie; Stroobant, Vincent; Thielemans, Kris; van der Bruggen, Pierre; Van den Eynde, Benoît J

2016-02-15

Cross-presentation enables dendritic cells to present on their MHC class I molecules antigenic peptides derived from exogenous material, through a mechanism that remains partly unclear. It is particularly efficient with long peptides, which are used in cancer vaccines. We studied the mechanism of long-peptide cross-presentation using human dendritic cells and specific CTL clones against melanoma Ags gp100 and Melan-A/MART1. We found that cross-presentation of those long peptides does not depend on the proteasome or the transporter associated with Ag processing, and therefore follows a vacuolar pathway. We also observed that it makes use of newly synthesized MHC class I molecules, through peptide exchange in vesicles distinct from the endoplasmic reticulum and classical secretory pathway, in an SEC22b- and CD74-independent manner. Our results indicate a nonclassical secretion pathway followed by nascent HLA-I molecules that are used for cross-presentation of those long melanoma peptides in the vacuolar pathway. Our results may have implications for the development of vaccines based on long peptides. Copyright © 2016 by The American Association of Immunologists, Inc.

76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

Autocorrelation descriptor improvements for QSAR: 2DA_Sign and 3DA_Sign

NASA Astrophysics Data System (ADS)

Sliwoski, Gregory; Mendenhall, Jeffrey; Meiler, Jens

2016-03-01

Quantitative structure-activity relationship (QSAR) is a branch of computer aided drug discovery that relates chemical structures to biological activity. Two well established and related QSAR descriptors are two- and three-dimensional autocorrelation (2DA and 3DA). These descriptors encode the relative position of atoms or atom properties by calculating the separation between atom pairs in terms of number of bonds (2DA) or Euclidean distance (3DA). The sums of all values computed for a given small molecule are collected in a histogram. Atom properties can be added with a coefficient that is the product of atom properties for each pair. This procedure can lead to information loss when signed atom properties are considered such as partial charge. For example, the product of two positive charges is indistinguishable from the product of two equivalent negative charges. In this paper, we present variations of 2DA and 3DA called 2DA_Sign and 3DA_Sign that avoid information loss by splitting unique sign pairs into individual histograms. We evaluate these variations with models trained on nine datasets spanning a range of drug target classes. Both 2DA_Sign and 3DA_Sign significantly increase model performance across all datasets when compared with traditional 2DA and 3DA. Lastly, we find that limiting 3DA_Sign to maximum atom pair distances of 6 Å instead of 12 Å further increases model performance, suggesting that conformational flexibility may hinder performance with longer 3DA descriptors. Consistent with this finding, limiting the number of bonds in 2DA_Sign from 11 to 5 fails to improve performance.

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

The FAK–Arp2/3 interaction promotes leading edge advance and haptosensing by coupling nascent adhesions to lamellipodia actin

PubMed Central

Swaminathan, Vinay; Fischer, R. S.; Waterman, Clare M.

2016-01-01

Cell migration is initiated in response to biochemical or physical cues in the environment that promote actin-mediated lamellipodial protrusion followed by the formation of nascent integrin adhesions (NAs) within the protrusion to drive leading edge advance. Although FAK is known to be required for cell migration through effects on focal adhesions, its role in NA formation and lamellipodial dynamics is unclear. Live-cell microscopy of FAK−/− cells with expression of phosphorylation deficient or a FERM-domain mutant deficient in Arp2/3 binding revealed a requirement for FAK in promoting the dense formation, transient stabilization, and timely turnover of NA within lamellipodia to couple actin-driven protrusion to adhesion and advance of the leading edge. Phosphorylation on Y397 of FAK promotes dense NA formation but is dispensable for transient NA stabilization and leading edge advance. In contrast, transient NA stabilization and advance of the cell edge requires FAK–Arp2/3 interaction, which promotes Arp2/3 localization to NA and reduces FAK activity. Haptosensing of extracellular matrix (ECM) concentration during migration requires the interaction between FAK and Arp2/3, whereas FAK phosphorylation modulates mechanosensing of ECM stiffness during spreading. Taken together, our results show that mechanistically separable functions of FAK in NA are required for cells to distinguish distinct properties of their environment during migration. PMID:26842895

Seismic Imaging of a Nascent Batholith in the Central Andes

NASA Astrophysics Data System (ADS)

Ward, K. M.; Zandt, G.; Beck, S. L.; Christensen, D. H.; Mcfarlin, H. L.

2013-12-01

Cordilleran mountain belts, such as the modern central Andes and Mesozoic western North American Cordillera formed in regions of significant upper plate compression and were punctuated by high flux magmatic events that coalesced into large composite batholiths. Unlike the North American Cordillera, compressive mountain building is still active in the central Andes and any large modern batholith still at depth must be inferred from surface volcanics and geophysical data. In the Andes it has been suggested that a modern batholith exists beneath the Altiplano-Puna Volcanic Complex (APVC), the location of a 11-1 Ma ignimbrite flare-up, however, the magmatic underpinnings has only been geophysically investigated in a few widely spaced locations and a migmatite zone of crustal melt with minimal mantle input remains a viable competing interpretation. We present new high-resolution 3-D seismic images of the APVC crust based on a joint inversion of ambient noise surface-wave dispersion data and receiver functions from broadband stations and identify a shallow (<20 km depth) low-velocity body that we interpret as a magmatic mush zone, the Altiplano-Puna Mush Body (APMB). Below the APMB, we observe near-vertical zones of low velocity that bifurcate near the base of the crust with one arm of low velocity migrating under the main volcanic arc and a second separate arm of low velocity below the voluminous backarc volcanism. Previous attenuation tomography studies have traced these zones through the mantle where they intersect the top of the subducting Nazca slab at locations with elevated seismic activity, providing strong evidence that the deeper near-vertical zones of low velocity we are imaging are related to dewatering of the slab and associated mantle-sourced melt pathways. Based on these considerations, we suggest the ~200 km diameter and ~20 km thick body is a nascent silicic batholith compatible with the magma mush model of batholith formation. The direct imaging of this

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

hnRNP-Q1 represses nascent axon growth in cortical neurons by inhibiting Gap-43 mRNA translation

PubMed Central

Williams, Kathryn R.; McAninch, Damian S.; Stefanovic, Snezana; Xing, Lei; Allen, Megan; Li, Wenqi; Feng, Yue; Mihailescu, Mihaela Rita; Bassell, Gary J.

2016-01-01

Posttranscriptional regulation of gene expression by mRNA-binding proteins is critical for neuronal development and function. hnRNP-Q1 is an mRNA-binding protein that regulates mRNA processing events, including translational repression. hnRNP-Q1 is highly expressed in brain tissue, suggesting a function in regulating genes critical for neuronal development. In this study, we have identified Growth-associated protein 43 (Gap-43) mRNA as a novel target of hnRNP-Q1 and have demonstrated that hnRNP-Q1 represses Gap-43 mRNA translation and consequently GAP-43 function. GAP-43 is a neuronal protein that regulates actin dynamics in growth cones and facilitates axonal growth. Previous studies have identified factors that regulate Gap-43 mRNA stability and localization, but it remains unclear whether Gap-43 mRNA translation is also regulated. Our results reveal that hnRNP-Q1 knockdown increased nascent axon length, total neurite length, and neurite number in mouse embryonic cortical neurons and enhanced Neuro2a cell process extension; these phenotypes were rescued by GAP-43 knockdown. Additionally, we have identified a G-quadruplex structure in the 5′ untranslated region of Gap-43 mRNA that directly interacts with hnRNP-Q1 as a means to inhibit Gap-43 mRNA translation. Therefore hnRNP-Q1–mediated repression of Gap-43 mRNA translation provides an additional mechanism for regulating GAP-43 expression and function and may be critical for neuronal development. PMID:26658614

Electron microscopic visualization of sites of nascent DNA synthesis by streptavidin-gold binding to biotinylated nucleotides incorporated in vivo

PubMed Central

1988-01-01

Biotinylated nucleotides (bio-11-dCTP, bio-11-dUTP, and bio-7-dATP) were microinjected into unfertilized and fertilized Xenopus laevis eggs. The amounts introduced were comparable to in vivo deoxy- nucleoside triphosphate pools. At various times after microinjection, DNA was extracted from eggs or embryos and subjected to electrophoresis on agarose gels. Newly synthesized biotinylated DNA was analyzed by Southern transfer and visualized using either the BluGENE or Detek-hrp streptavidin-based nucleic acid detection systems. Quantitation of the amount of biotinylated DNA observed at various times showed that the microinjected biotinylated nucleotides were efficiently incorporated in vivo, both into replicating endogenous chromosomal DNA and into replicating microinjected exogenous plasmid DNA. At least one biotinylated nucleotide could be incorporated in vivo for every eight nucleotides of DNA synthesized. Control experiments also showed that heavily biotinylated DNA was not subjected to detectable DNA repair during early embryogenesis (for at least 5 h after activation of the eggs). The incorporated biotinylated nucleotides were visualized by electron microscopy by using streptavidin-colloidal gold or streptavidin-ferritin conjugates to bind specifically to the biotin groups projecting from the newly replicated DNA. The incorporated biotinylated nucleotides were thus made visible as electron-dense spots on the underlying DNA molecules. Biotinylated nucleotides separated by 20-50 bases could be resolved. We conclude that nascent DNA synthesized in vivo in Xenopus laevis eggs can be visualized efficiently and specifically using the techniques described. PMID:3392102

A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA.

PubMed

Yordanova, Martina M; Wu, Cheng; Andreev, Dmitry E; Sachs, Matthew S; Atkins, John F

2015-07-17

The protein antizyme is a negative regulator of cellular polyamine concentrations from yeast to mammals. Synthesis of functional antizyme requires programmed +1 ribosomal frameshifting at the 3' end of the first of two partially overlapping ORFs. The frameshift is the sensor and effector in an autoregulatory circuit. Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only supports low levels of frameshifting. The high levels usually observed depend on the presence of cis-acting stimulatory elements located 5' and 3' of the frameshift site. Antizyme genes from different evolutionary branches have evolved different stimulatory elements. Prior and new multiple alignments of fungal antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a distinct pattern of conservation 5' of the frameshift site consistent with a function at the amino acid level. As shown here when tested in Schizosaccharomyces pombe and mammalian HEK293T cells, the 5' part of this conserved sequence acts at the nascent peptide level to stimulate the frameshifting, without involving stalling detectable by toe-printing. However, the peptide is only part of the signal. The 3' part of the stimulator functions largely independently and acts at least mostly at the nucleotide level. When polyamine levels were varied, the stimulatory effect was seen to be especially responsive in the endogenous polyamine concentration range, and this effect may be more general. A conserved RNA secondary structure 3' of the frameshift site has weaker stimulatory and polyamine sensitizing effects on frameshifting. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

The FAK-Arp2/3 interaction promotes leading edge advance and haptosensing by coupling nascent adhesions to lamellipodia actin.

PubMed

Swaminathan, Vinay; Fischer, R S; Waterman, Clare M

2016-04-01

Cell migration is initiated in response to biochemical or physical cues in the environment that promote actin-mediated lamellipodial protrusion followed by the formation of nascent integrin adhesions (NAs) within the protrusion to drive leading edge advance. Although FAK is known to be required for cell migration through effects on focal adhesions, its role in NA formation and lamellipodial dynamics is unclear. Live-cell microscopy of FAK(-/-)cells with expression of phosphorylation deficient or a FERM-domain mutant deficient in Arp2/3 binding revealed a requirement for FAK in promoting the dense formation, transient stabilization, and timely turnover of NA within lamellipodia to couple actin-driven protrusion to adhesion and advance of the leading edge. Phosphorylation on Y397 of FAK promotes dense NA formation but is dispensable for transient NA stabilization and leading edge advance. In contrast, transient NA stabilization and advance of the cell edge requires FAK-Arp2/3 interaction, which promotes Arp2/3 localization to NA and reduces FAK activity. Haptosensing of extracellular matrix (ECM) concentration during migration requires the interaction between FAK and Arp2/3, whereas FAK phosphorylation modulates mechanosensing of ECM stiffness during spreading. Taken together, our results show that mechanistically separable functions of FAK in NA are required for cells to distinguish distinct properties of their environment during migration. © 2016 Swaminathan et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

75 FR 75868 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal... of the Thielert Engine Owners Group commented that the Model DA 42 has the same door design and the same unsafe condition. He recommended that the AD also apply to the Model DA 42. The FAA has discussed...

Nascent Leadership Behaviors

ERIC Educational Resources Information Center

Payette, Dennis L.; Libertella, Anthony F.

2011-01-01

This paper is a compendium of leadership behaviors that emerging or aspirant leaders could choose to enhance their management and leadership skills. These behaviors were drawn directly from the experience of the authors, both of whom have held senior leadership and management positions in business, law, and higher education. This paper is an…

da Vinci decoded: does da Vinci stereopsis rely on disparity?

PubMed

Tsirlin, Inna; Wilcox, Laurie M; Allison, Robert S

2012-11-01

In conventional stereopsis, the depth between two objects is computed based on the retinal disparity in the position of matching points in the two eyes. When an object is occluded by another object in the scene, so that it is visible only in one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990) found that a precept of quantitative depth between the two objects could still be established for such stimuli and proposed that this precept is based on the constraints imposed by occlusion geometry. They named this and other occlusion-based depth phenomena "da Vinci stereopsis." Subsequent research found quantitative depth based on occlusion geometry in several other classes of stimuli grouped under the term da Vinci stereopsis. However, Nakayama and Shimojo's findings were later brought into question by Gillam, Cook, and Blackburn (2003), who suggested that quantitative depth in their stimuli was perceived based on conventional disparity. In order to understand whether da Vinci stereopsis relies on one type of mechanism or whether its function is stimulus dependent we examine the nature and source of depth in the class of stimuli used by Nakayama and Shimojo (1990). We use three different psychophysical and computational methods to show that the most likely source for depth in these stimuli is occlusion geometry. Based on these experiments and previous data we discuss the potential mechanisms responsible for processing depth from monocular features in da Vinci stereopsis.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Ab initio prediction of fast non-equilibrium transport of nascent polarons in SrI2: a key to high-performance scintillation

NASA Astrophysics Data System (ADS)

Zhou, Fei; Sadigh, Babak; Erhart, Paul; Åberg, Daniel

2016-08-01

The excellent light yield proportionality of europium-doped strontium iodide (SrI2:Eu) has resulted in state-of-the-art γ-ray detectors with remarkably high-energy resolution, far exceeding that of most halide compounds. In this class of materials, the formation of self-trapped hole polarons is very common. However, polaron formation is usually expected to limit carrier mobilities and has been associated with poor scintillator light-yield proportionality and resolution. Here using a recently developed first-principles method, we perform an unprecedented study of polaron transport in SrI2, both for equilibrium polarons, as well as nascent polarons immediately following a self-trapping event. We propose a rationale for the unexpected high-energy resolution of SrI2. We identify nine stable hole polaron configurations, which consist of dimerised iodine pairs with polaron-binding energies of up to 0.5 eV. They are connected by a complex potential energy landscape that comprises 66 unique nearest-neighbour migration paths. Ab initio molecular dynamics simulations reveal that a large fraction of polarons is born into configurations that migrate practically barrier free at room temperature. Consequently, carriers created during γ-irradiation can quickly diffuse away reducing the chance for non-linear recombination, the primary culprit for non-proportionality and resolution reduction. We conclude that the flat, albeit complex, landscape for polaron migration in SrI2 is a key for understanding its outstanding performance. This insight provides important guidance not only for the future development of high-performance scintillators but also of other materials, for which large polaron mobilities are crucial such as batteries and solid-state ionic conductors.

Fault block kinematics at a releasing stepover of the Eastern California shear zone: Partitioning of rotation style in and around the Coso geothermal area and nascent metamorphic core complex

NASA Astrophysics Data System (ADS)

Pluhar, Christopher J.; Coe, Robert S.; Lewis, Jonathan C.; Monastero, Francis C.; Glen, Jonathan M. G.

2006-10-01

, K. Richards-Dinger, The Coso geothermal field: a nascent metamorphic core complex, Geol. Soc. Amer. Bull. 117 (2005) 1534-1553.] characterize as a nascent metamorphic core complex. Consistent with upper plate disruption above a detachment, surface rocks (i.e. the upper plate of the detachment system) at the Coso geothermal area are tilted westward. However they appear to exhibit no detectable rotation. Thus, the style of block rotation may be partitioned: with clockwise vertical-axis rotation dominating in the Wild Horse Mesa and horizontal axis rotation (tilting) in the geothermal area.

The da Vinci robot.

PubMed

Moran, Michael E

2006-12-01

One might assume from the title of this paper that the nuances of a complex mechanical robot will be discussed, and this would be correct. On the other hand, the date of the design and possible construction of this robot was 1495, a little more than five centuries ago. The key point in the title is the lack of a trademarked name, as Leonardo was the designer of this sophisticated system. His notes from the Codex Altanticus represent the foundation of this report. English translations of da Vinci's notebooks are currently available. Beginning in the 1950s, investigators at the University of California began to ponder the significance of some of da Vinci's markings on what appeared to be technical drawings. Such markings also occur in his Codex Atlanticus (the largest single collection of da Vinci's sheets, consisting of 1119 separate pages and 481 folios) along with a large number of other mechanical devices. Continuing research at the Instituto e Museo di Storia della Scienza in Florence has yielded a great deal of information about Leonardo's intentions with regard to his mechanical knight. It is now known that da Vinci's robot would have had the outer appearance of a Germanic knight. It had a complex core of mechanical devices that probably was human powered. The robot had two independent operating systems. The first had three degree-of-freedom legs, ankles, knees, and hips. The second had four degrees of freedom in the arms with articulated shoulders, elbows, wrists, and hands. A mechanical analog-programmable controller within the chest provided the power and control for the arms. The legs were powered by an external crank arrangement driving the cable, which connected to key locations near each lower extremity's joints. Da Vinci also is known to have devised a programmable front-wheel-drive automobile with rack-and-pinion suspension mechanisms at age 26. He would recall this device again, when, at age 40, he is thought to have built a programmable automated

PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

PubMed

Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

2016-05-27

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Trace Gas Measurements in Nascent, Aged and Cloud-processed Smoke from Africa Savanna Fires by Airborne Fourier Transform Infrared Spectroscopy (AFTIR)

NASA Technical Reports Server (NTRS)

Yokelson, Robert J.; Bertschi, Isaac T.; Christian, Ted J.; Hobbs, Peter V.; Ward, Darold E.; Hao, Wei Min

2003-01-01

We measured stable and reactive trace gases with an airborne Fourier transform infrared spectrometer (AFTIR) on the University of Washington Convair-580 research aircraft in August/September 2000 during the SAFARI 2000 dry season campaign in Southern Africa. The measurements included vertical profiles of C02, CO, H20, and CH4 up to 5.5 km on six occasions above instrumented ground sites and below the TERRA satellite and ER-2 high-flying research aircraft. We also measured the trace gas emissions from 10 African savanna fires. Five of these fires featured extensive ground-based fuel characterization, and two were in the humid savanna ecosystem that accounts for most African biomass burning. The major constituents we detected in nascent CH3OOH, HCHO, CH30H, HCN, NH3, HCOOH, and C2H2. These are the first quantitative measurements of the initial emissions of oxygenated volatile organic compounds (OVOC), NH3, and HCN from African savanna fires. On average, we measured 5.3 g/kg of OVOC and 3.6 g/kg of hydrocarbons (including CH4) in the initial emissions from the fires. Thus, the OVOC will have profound, largely unexplored effects on tropical tropospheric chemistry. The HCN emission factor was only weakly dependent on fire type; the average value (0.53 g/kg) is about 20 times that of a previous recommendation. HCN may be useful as a tracer for savanna fires. Delta O3/Delta CO and Delta CH3COO/Delta CO increased to as much as 9% in <1 h of photochemical processing downwind of fires. Direct measurements showed that cloud processing of smoke greatly reduced CH30H, NH3, CH3COOH, SO2, and NO2 levels, but significantly increased HCHO and NO.

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2...

Beyond Donor-Acceptor (D-A) Approach: Structure-Optoelectronic Properties-Organic Photovoltaic Performance Correlation in New D-A1 -D-A2 Low-Bandgap Conjugated Polymers.

PubMed

Chochos, Christos L; Drakopoulou, Sofia; Katsouras, Athanasios; Squeo, Benedetta M; Sprau, Christian; Colsmann, Alexander; Gregoriou, Vasilis G; Cando, Alex-Palma; Allard, Sybille; Scherf, Ullrich; Gasparini, Nicola; Kazerouni, Negar; Ameri, Tayebeh; Brabec, Christoph J; Avgeropoulos, Apostolos

2017-04-01

Low-bandgap near-infrared polymers are usually synthesized using the common donor-acceptor (D-A) approach. However, recently polymer chemists are introducing more complex chemical concepts for better fine tuning of their optoelectronic properties. Usually these studies are limited to one or two polymer examples in each case study so far, though. In this study, the dependence of optoelectronic and macroscopic (device performance) properties in a series of six new D-A 1 -D-A 2 low bandgap semiconducting polymers is reported for the first time. Correlation between the chemical structure of single-component polymer films and their optoelectronic properties has been achieved in terms of absorption maxima, optical bandgap, ionization potential, and electron affinity. Preliminary organic photovoltaic results based on blends of the D-A 1 -D-A 2 polymers as the electron donor mixed with the fullerene derivative [6,6]-phenyl-C 71 -butyric acid methyl ester demonstrate power conversion efficiencies close to 4% with short-circuit current densities (J sc ) of around 11 mA cm -2 , high fill factors up to 0.70, and high open-circuit voltages (V oc s) of 0.70 V. All the devices are fabricated in an inverted architecture with the photoactive layer processed in air with doctor blade technique, showing the compatibility with roll-to-roll large-scale manufacturing processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis[C][W

PubMed Central

Xia, Tian; Li, Na; Dumenil, Jack; Li, Jie; Kamenski, Andrei; Bevan, Michael W.; Gao, Fan; Li, Yunhai

2013-01-01

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement. PMID:24045020

Estimativas de possiveis recursos de petroleo e gas na America Central e na America do Sul [Estimates of possible petroleum and gas resources in Central American and South America

USGS Publications Warehouse

Schenk, C.S.

2001-01-01

O U.S. Geological Survey recentemente completou estimativas de possíveis recursos de petróleo e gás em 130 áreas petrolíferas pré-determinadas no mundo (USGS, 2000). Vinte e três destas áreas ficam na América do Sul, na América Central, e no Caribe (fig. 1). Os resultados estão apresentados na tabela 1. Nas 23 áreas, estimamos um total de 105 BBO e um total de 487 TCFG. A região composta de América Central mais América do Sul ficou em terceiro lugar no mundo em termos de possíveis recursos de petróleo e gás. No primeiro lugar ficou o Oriente Médio e no segundo lugar ficou a antiga União Soviética (USGS, 2000). As áreas com maiores probabilidades de encontrar depósitos gigantes de petróleo e gás se localizam nas áreas do Oceano Atlântico começando com a Bacia de Santos no sul até a Bacia Guyana-Suriname no norte. As possibilidades de existirem depósitos gigantes são maiores nas áreas submersas do mar até profundidades de 3,600 m. Diversos depósitos gigantes de petróleo foram descobertos no mar na Bacia de Campos e ainda podem serem encontrados depósitos similares na Bacia de Campos e suas imediações.

Leonardo da Vinci and the Downburst.

NASA Astrophysics Data System (ADS)

Gedzelman, Stanley David

1990-05-01

Evidence from the drawings, experiments, and writings of Leonardo da Vinci are presented to demonstrate that da Vinci recognized and, possibly, discovered the downburst and understood its associated airflow. Other early references to vortex flows resembling downbursts are mentioned.

Test Review: TestDaF

ERIC Educational Resources Information Center

Norris, John; Drackert, Anastasia

2018-01-01

The Test of German as a Foreign Language (TestDaF) plays a critical role as a standardized test of German language proficiency. Developed and administered by the Society for Academic Study Preparation and Test Development (g.a.s.t.), TestDaF was launched in 2001 and has experienced persistent annual growth, with more than 44,000 test takers in…

Overview of ATLAS PanDA Workload Management

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Wenaus, T.; Nilsson, P.; Stewart, G. A.; Walker, R.; Stradling, A.; Caballero, J.; Potekhin, M.; Smith, D.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in addition to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.

Overview of ATLAS PanDA Workload Management

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

Maeno T.; De K.; Wenaus T.

2011-01-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in additionmore » to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.« less

Vi-da: vitiligo diagnostic assistance mobile application

NASA Astrophysics Data System (ADS)

Nugraha, G. A.; Nurhudatiana, A.; Bahana, R.

2018-03-01

Vitiligo is a skin disorder in which white patches of depigmentation appear on different parts of the body. Usually, patients come to hospitals or clinics to have their vitiligo conditions assessed. This can be very tiring to the patients, as vitiligo treatments usually take a relatively long period of time, which can range from months to years. To address this challenge, we present in this paper a prototype of an Android-based mobile application called Vi-DA, which stands for Vitiligo Diagnostic Assistance. Vi-DA consists of three subsystems, which are user sign-up subsystem, camera and image analysis subsystem, and progress report subsystem. The mobile application was developed in Java programming language and uses MySQL as the database system. Vi-DA adopts a vitiligo segmentation algorithm to segment input image into normal skin area, vitiligo skin area, and non-skin area. Results showed that Vi-DA gave comparable results to the previous system implemented in Matlab. User acceptance testing results also showed that all respondents agreed on the usefulness of the system and agreed to use Vi-DA again in the future. Vi-DA benefits both dermatologists and patients as not only a computer-aided diagnosis (CAD) tool but also as a smart application that can be used for self-assessment at home.

Transfer of subduction fluids into the deforming mantle wedge during nascent subduction: Evidence from trace elements and boron isotopes (Semail ophiolite, Oman)

NASA Astrophysics Data System (ADS)

Prigent, C.; Guillot, S.; Agard, P.; Lemarchand, D.; Soret, M.; Ulrich, M.

2018-02-01

The basal part of the Semail ophiolitic mantle was (de)formed at relatively low temperature (LT) directly above the plate interface during "nascent subduction" (the prelude to ophiolite obduction). This subduction-related LT deformation was associated with progressive strain localization and cooling, resulting in the formation of porphyroclastic to ultramylonitic shear zones prior to serpentinization. Using petrological and geochemical analyses (trace elements and B isotopes), we show that these basal peridotites interacted with hydrous fluids percolating by porous flow during mylonitic deformation (from ∼850 down to 650 °C). This process resulted in 1) high-T amphibole crystallization, 2) striking enrichments of minerals in fluid mobile elements (FME; particularly B, Li and Cs with concentrations up to 400 times those of the depleted mantle) and 3) peridotites with an elevated δ11B of up to +25‰. These features indicate that the metasomatic hydrous fluids are most likely derived from the dehydration of subducting crustal amphibolitic materials (i.e., the present-day high-T sole). The rapid decrease in metasomatized peridotite δ11B with increasing distance to the contact with the HT sole (to depleted mantle isotopic values in <1 km) suggests an intense interaction between peridotites and rapid migrating fluids (∼1-25 m.y-1), erasing the initial high-δ11B subduction fluid signature within a short distance. The increase of peridotite δ11B with increasing deformation furthermore indicates that the flow of subduction fluids was progressively channelized in actively deforming shear zones parallel to the contact. Taken together, these results also suggest that the migration of subduction fluids/melts by porous flow through the subsolidus mantle wedge (i.e., above the plate interface at sub-arc depths) is unlikely to be an effective mechanism to transport slab-derived elements to the locus of partial melting in subduction zones.

Metaproteomics of Microbiota in Naturally Fermented Soybean Paste, Da-jiang.

PubMed

Zhang, Ping; Zhang, Pengfei; Xie, Mengxi; An, Feiyu; Qiu, Boshu; Wu, Rina

2018-05-01

Da-jiang is a typical traditional fermented soybean product in China. At present, the proteins in da-jiang are needed to be explored. The composition and species of microbial proteins in traditional fermented da-jiang were analyzed by metaproteomics based on sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that the number and variety of microbial proteins in the traditional fermented da-jiang from different regions were different. The production site influences the fermentation in da-jiang. Then we analyzed the functions of the microbial proteins identified in da-jiang, and found that they were mainly involved in the process of protein synthesis, glycometabolism and nucleic acid synthesis. In addtion, we compared the proteins composition in different da-jiang. There are 51 common proteins of naturally fermented da-jiang, and 25 common microbial sources. The main commonly microbial sources of fungal proteins are Saccharomyces cerevisiae and Schizosaccharomyces; the main commonly microbial sources of bacterial proteins are Enterococcus faecalis, Leuconostoc mesenteroides, Acinetobacter baumannii, and Bacillus subtilis. These common microbes play the predominant role in da-jiang fermentation. The present results help us to understand the fermentation of da-jiang and improve the quality and safety of final products in the future. The study illustrated metaproteome of microbiota in traditional fermented soybean paste, da-jiang, by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A method of extracting metaproteome from microbiota in da-jiang was attempted. The findings help to understand the fermentation of da-jiang and improve the quality and safety of da-jiang in fermented industry. © 2018 Institute of Food Technologists®.

Molecular mechanism and structure of Trigger Factor bound to the translating ribosome

PubMed Central

Merz, Frieder; Boehringer, Daniel; Schaffitzel, Christiane; Preissler, Steffen; Hoffmann, Anja; Maier, Timm; Rutkowska, Anna; Lozza, Jasmin; Ban, Nenad; Bukau, Bernd; Deuerling, Elke

2008-01-01

Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome–nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors. PMID:18497744

Nascent Genomic Evolution and Allopatric Speciation of Myroides profundi D25 in Its Transition from Land to Ocean.

PubMed

Zhang, Yu-Zhong; Li, Yi; Xie, Bin-Bin; Chen, Xiu-Lan; Yao, Qiong-Qiong; Zhang, Xi-Ying; Kempher, Megan L; Zhou, Jizhong; Oren, Aharon; Qin, Qi-Long

2016-01-12

A large amount of bacterial biomass is transferred from land to ocean annually. Most transferred bacteria should not survive, but undoubtedly some do. It is unclear what mechanisms these bacteria use in order to survive and even thrive in a new marine environment. Myroides profundi D25(T), a member of the Bacteroidetes phylum, was isolated from deep-sea sediment of the southern Okinawa Trough near the China mainland and had high genomic sequence identity to and synteny with the human opportunistic pathogen Myroides odoratimimus. Phylogenetic and physiological analyses suggested that M. profundi recently transitioned from land to the ocean. This provided an opportunity to explore how a bacterial genome evolved to survive in a novel environment. Changes in the transcriptome were evaluated when both species were cultured under low-salinity conditions and then transferred to high-salinity conditions. Comparative genomic and transcriptomic analyses showed that M. profundi altered transcription regulation in the early stages of survival. In these stages, vertically inherited genes played a key role in the survival of M. profundi. The contribution of M. profundi unique genes, some possibly acquired by horizontal gene transfer (HGT), appeared relatively small, and expression levels of unique genes were diminished under the high-salinity conditions. We postulate that HGT genes might play an important role in longer-term adaptation. These results suggested that some human pathogens might have the ability to survive in and adapt to the marine environment, which may have important implications for public health control in coastal regions. Horizontal gene transfer (HGT) is considered to be important for bacteria to adapt to a different microhabitat. However, our results showed that vertically inherited genes might play more important roles than HGT genes in the nascent adaptation to the marine environment in the bacterium Myroides profundi, which has recently been

[Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

VerSeDa: vertebrate secretome database

PubMed Central

Cortazar, Ana R.; Oguiza, José A.

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. Database URL: VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php PMID:28365718

VerSeDa: vertebrate secretome database.

PubMed

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

Raven surgical robot training in preparation for da vinci.

PubMed

Glassman, Deanna; White, Lee; Lewis, Andrew; King, Hawkeye; Clarke, Alicia; Glassman, Thomas; Comstock, Bryan; Hannaford, Blake; Lendvay, Thomas S

2014-01-01

The rapid adoption of robotic assisted surgery challenges the pace at which adequate robotic training can occur due to access limitations to the da Vinci robot. Thirty medical students completed a randomized controlled trial evaluating whether the Raven robot could be used as an alternative training tool for the Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci robot. Two groups, one trained on the da Vinci and one trained on the Raven, were tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS block transfer proficiency training there was no statistically significant difference between path length (p=0.39) and economy of motion scores (p=0.06) between the two groups, but those trained on the da Vinci did have faster task times (p=0.01). These results provide evidence for the value of using the Raven robot for training prior to using the da Vinci surgical system for similar tasks.

Construção de um catálogo de aglomerados abertos para estudo da dinâmica da estrutura espiral da Galáxia

NASA Astrophysics Data System (ADS)

Carlos, I. M.; Lépine, J. R. D.

2003-08-01

Os aglomerados abertos são objetos de grande valor para o estudo da dinâmica da Galáxia devido esses objetos terem uma faixa de idade relativamente ampla. O trabalho visa estudar a dinâmica da estrutura espiral da Galáxia principalmente através do uso desses aglomerados, uma vez que o estudo da cinemática desses objetos é fundamental para esse objetivo. Nosso grupo trabalha no sentido de construir uma base de dados de aglomerados abertos contendo coordenadas, distância, idade, movimentos próprios e velocidades radiais e já disponibiliza uma nova versão do catálogo de aglomerados abertos o qual é uma compilação de edições anteriores, principalmente Lynga (1987), Mermilliod (1995) e ESO-B (Lauberts 1982). Nossa amostra possui cerca de 1630 aglomerados, mas nem todos os parâmetros acima citados foram determinados em sua totalidade. Para determinarmos esses parâmetros, derivamos as cores intrínsecas das estrelas membro de cada aglomerado a partir de seus tipos espectrais (busca feita no SIMBAD) obtendo assim o excesso de cor individual. A distribuição dos excessos de cor foi então utilizada para derivarmos o avermelhamento médio para cada aglomerado. De maneira similar, os tipos espectrais foram usados para estimar as magnitudes absolutas, e com as magnitudes absolutas e aparentes determinamos a respectiva distribuição do módulo de distância e finalmente a distância. Para determinar as idades foram confeccionados os diagramas cor-magnitude das estrelas de cada aglomerado onde foram superpostas a Seqüência Principal de Idade Zero (ZAMS). Superpomos a ZAMS de Schmidt-Kaler e isócronas de composição solar. Essas isócronas foram usadas para determinação das idades dos aglomerados. Uma vez que não temos ainda resultados finais, apresentamos então alguns diagramas cor-magnitude os quais foram usados para determinação, principalmente, da distância e idade dos aglomerados.

Tristan da Cunha Island

NASA Image and Video Library

2018-05-25

Tristan da Cunha is both a remote group of volcanic islands in the south Atlantic, and the main island. It is the most remote inhabited island group in the world, 2400 km from the nearest inhabited land. Tristan has a population of about 250 inhabitants, and is part of the British overseas territory of Saint Helena, Ascension and Tristan da Cunha. In 1961 the eruption of Queen Mary's Peak forced the evacuation of the entire population for two years. The image was acquired October 7, 2017, and is located at 37.1 degrees south, 12.3 degrees west. https://photojournal.jpl.nasa.gov/catalog/PIA22506

WRS2 UPA DA Removal

NASA Image and Video Library

2009-11-23

ISS021-E-032275 (23 Nov. 2009) --- NASA astronaut Leland Melvin, STS-129 mission specialist, holds the failed Urine Processor Assembly / Distillation Assembly (UPA DA) in the Destiny laboratory of the International Space Station while space shuttle Atlantis remains docked with the station. Melvin and European Space Agency astronaut Frank De Winne (out of frame), Expedition 21 commander, removed and packed the UPA DA, then transferred it from the Water Recovery System 2 (WRS-2) rack to Atlantis for stowage on the middeck.

Possibility of the transformation of eEF-2 (100 kDa) to eEF-2 (65 kDa) in the peptide elongation process in vitro.

PubMed

Gajko, A; Sredzińska, K; Galasiński, W; Gindzieński, A

1999-02-16

Two active eEF-2 polypeptides of approximately 100 and 65 kDa were copurified from rat liver cells and separated. The fate of eEF-2 (100 kDa) during its binding to ribosomes and in the translocation step of the peptide elongation process was investigated. It was shown that eEF-2 (100 kDa) did not change its form during the process of binding to the ribosomes. In the postribosomal supernatant, obtained from the postincubation mixture of the elongation process, only eEF-2 (65 kDa) was found. These results suggest that the form of eEF-2 (100 kDa), when bound to the ribosome during the elongation process, is transformed to eEF-2 (65 kDa). Copyright 1999 Academic Press.

[Clinical application of Da Vinci surgical system in China].

PubMed

Jin, Zhenyu

2014-01-01

Da Vinci robotic surgical system leads the development of minimally invasive surgical techniques. By using Da Vinci surgical robot for minimally invasive surgery, it brings a lot of advantages to the surgeons. Since 2008, Da Vinci surgeries have been performed in 14 hospitals in domestic cities such as Beijing and Shanghai. Until the end of 2012, 3 551 cases of Da Vinci robotic surgery have been performed, covering various procedures of various surgical departments including the department of general surgery, urology, cardiovascular surgery, thoracic surgery, gynecology, and etc. Robotic surgical technique has made remarkable achievements.

WRS2 UPA DA Removal

NASA Image and Video Library

2009-11-23

ISS021-E-032273 (23 Nov. 2009) --- European Space Agency astronaut Frank De Winne, Expedition 21 commander, holds the failed Urine Processor Assembly / Distillation Assembly (UPA DA) in the Destiny laboratory of the International Space Station while space shuttle Atlantis remains docked with the station. De Winne and NASA astronaut Leland Melvin (out of frame), STS-129 mission specialist, removed and packed the UPA DA, then transferred it from the Water Recovery System 2 (WRS-2) rack to Atlantis for stowage on the middeck.

[da Vinci surgical system].

PubMed

Watanabe, Gou; Ishikawa, Norihiro

2014-07-01

The da Vinci surgical system was developed by Intuitive Surgical Inc. in the United States as an endoscopic surgical device to assist remote control surgeries. In 1998, the Da Vinci system was first used for cardiothoracic procedures. Currently a combination of robot-assisted internal thoracic artery harvest together with coronary artery bypass grafting (CABG) through a mini-incision (ThoraCAB) or totally endoscopic procedures including anastomoses under robotic assistance (TECAB) are being conducted for the treatment of coronary artery diseases. With the recent advances in catheter interventions, hybrid procedures combining catheter intervention with ThoraCAB or TECAB are anticipated in the future.On the other hand, with the decrease in number of coronary artery bypass surgeries, the share of valvular surgeries is expected to increase in the future. Among them, mitral valvuloplasty for mitral regurgitation is anticipated to be conducted mainly by low-invasive procedures, represented by minimally invasive cardiac surgery( MICS) and robot-assisted surgery. Apart from the intrinsic good surgical view, robotic-assisted systems offer additional advantages of the availability of an amplified view and the easy to observe the mitral valve in the physiological position. Thus, robotic surgical surgeries that make complicated procedures easier are expected to accomplish further developments in the future. Furthermore, while the number of surgeries for atrial septal defects has decreased dramatically following the widespread use of Amplatzer septal occluder, robotic surgery may become a good indication for cases in which the Amplatzer device is not indicated. In Japan, clinical trial of the da Vinci robotic system for heart surgeries has been completed. Statutory approval of the da Vinci system for mitral regurgitation and atrial septal defects is anticipated in the next few years.

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits.

PubMed Central

Fearnley, I M; Finel, M; Skehel, J M; Walker, J E

1991-01-01

The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit. Images Fig. 1. PMID:1832859

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

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

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

DaCHS: Data Center Helper Suite

NASA Astrophysics Data System (ADS)

Demleitner, Markus

2018-04-01

DaCHS, the Data Center Helper Suite, is an integrated package for publishing astronomical data sets to the Virtual Observatory. Network-facing, it speaks the major VO protocols (SCS, SIAP, SSAP, TAP, Datalink, etc). Operator-facing, many input formats, including FITS/WCS, ASCII files, and VOTable, can be processed to publication-ready data. DaCHS puts particular emphasis on integrated metadata handling, which facilitates a tight integration with the VO's Registry

Respostas religiosas à aids no Brasil: impressões de pesquisa acerca da Pastoral de DST/Aids da Igreja Católica1

PubMed Central

Seffner, Fernando; Silva, Cristiane Gonçalves Meireles da; Maksud, Ívia; Garcia, Jonathan; Rios, Luís Felipe; Natividade, Marcelo; Borges, Priscila Rodrigues; Parker, Richard; Terto, Veriano

2009-01-01

O texto encontra-se estruturado em quatro partes. Na primeira delas, apresentamos um conjunto de considerações e informações acerca da situação da aids no Brasil, das relações entre religião, sexualidade, aids e estado laico, bem como uma descrição mais clara do Projeto Respostas Religiosas ao HIV/Aids no Brasil, do qual este texto apresenta algumas impressões de pesquisa preliminares. A seguir, dedicamos um item a apresentação da Pastoral de DST/Aids, sua história, estrutura e objetivos. No item seguinte problematizamos diversas questões em particular no âmbito das relações Estado e Igreja, relações entre agentes de pastoral e hierarquia da Igreja, e questões ligadas mais diretamente à sexualidade e aids, todas referenciadas ao trabalho da Pastoral de DST/Aids. Ao final, apresentamos a bibliografia e fontes consultadas. PMID:20442806

PCA as a practical indicator of OPLS-DA model reliability.

PubMed

Worley, Bradley; Powers, Robert

Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) are powerful statistical modeling tools that provide insights into separations between experimental groups based on high-dimensional spectral measurements from NMR, MS or other analytical instrumentation. However, when used without validation, these tools may lead investigators to statistically unreliable conclusions. This danger is especially real for Partial Least Squares (PLS) and OPLS, which aggressively force separations between experimental groups. As a result, OPLS-DA is often used as an alternative method when PCA fails to expose group separation, but this practice is highly dangerous. Without rigorous validation, OPLS-DA can easily yield statistically unreliable group separation. A Monte Carlo analysis of PCA group separations and OPLS-DA cross-validation metrics was performed on NMR datasets with statistically significant separations in scores-space. A linearly increasing amount of Gaussian noise was added to each data matrix followed by the construction and validation of PCA and OPLS-DA models. With increasing added noise, the PCA scores-space distance between groups rapidly decreased and the OPLS-DA cross-validation statistics simultaneously deteriorated. A decrease in correlation between the estimated loadings (added noise) and the true (original) loadings was also observed. While the validity of the OPLS-DA model diminished with increasing added noise, the group separation in scores-space remained basically unaffected. Supported by the results of Monte Carlo analyses of PCA group separations and OPLS-DA cross-validation metrics, we provide practical guidelines and cross-validatory recommendations for reliable inference from PCA and OPLS-DA models.

DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.

PubMed

Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min

2014-04-01

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

A Influência da Escola e da Mídia na Obtenção dos Conhecimentos Astronômicos

NASA Astrophysics Data System (ADS)

da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.

2006-08-01

O universo em que vivemos possui segredos jamais imaginados pelo homem, fruto da pequena proporção que ocupamos diante de um cosmos infinito. A astronomia funciona como um instrumento que sacia a sede humana em desvendar esses segredos, estudando as galáxias, quasares, pulsares além da existência de todos os elementos que preenchem o espaço cósmico, o vácuo, não mais vazio como se pensou em outros tempos. A mídia explora esse campo de forma mística e também científica. A difusão adequada e dentro dos padrões educacionais vigentes, de conceitos astronômicos, se faz necessária, devido sua presença nos conteúdos escolares, centros de ciência e na mídia, de modo geral. A reforma do Currículo Básico da Escola Pública da maioria dos Estados brasileiros introduziu conceitos astronômicos desde a pré-escola até o Ensino Médio. Num estudo realizado com 1.032 alunos do Ensino Médio de seis escolas estaduais, revelou-se através da aplicação de um questionário que abordava conheciment os básicos em astronomia, como estes foram adquiridos e qual era a infra-estrutura oferecida pela escola: para 66,2% dos entrevistados o professor já fez alguma apresentação a respeito de astronomia. O presente estudo revelou também que 44,5% dos alunos entrevistados adquiriram seus conhecimentos astronômicos na escola, 28,1% através da televisão e 27,4% afirmaram que seus conhecimentos foram obtidos através de outros tipos de mídia (internet, filmes e revistas). Embora o estudo revele claramente que há certo equilíbrio na forma em que os alunos obtiveram seus conhecimentos astronômicos, a mídia ainda explora e muitas vezes desperta o interesse pela astronomia com assuntos que não fazem parte de nosso cotidiano como, por exemplo, o homem na Lua, os projetos espaciais e a primeira viagem de um astronauta brasileiro no espaço. Porém, em certos casos, a mídia pode promover conhecimentos incompletos ou mesmo equivocados sobre os conceitos que envolvam

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC... attached to a properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 3 2014-07-01 2014-07-01 false DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC... attached to a properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS... properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b) Preparation at...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS... properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b) Preparation at...

DA1 receptors modulation in rat isolated trachea.

PubMed

Cabezas, Gloria A; Velasco, Manuel

2010-01-01

We have previously demonstrated that low dose of inhaled dopamine (0.5-2 microg kg(-1) min(-1)) induces broncodilatacion in patients with acute asthma attack, suggesting that this dopamine effect is mediated by dopaminergic rather than by adrenergic receptors. To understand better these dopamine effect, rat tracheal smooth muscle was used as a model to evaluate the responses of beta2-, alpha1-, alpha2-adrenergic and DA1 and DA2 dopaminergic antagonists. Tracheal rings from male Sprague-Dawley rats (n = 90) were excised and placed in an organ bath containing modified Krebs-Ringer bicarbonate buffer at 37 degrees C, and gassed with O2 (95%) and CO2 (5%). Contractile responses were recorded with an isometric transducer in a polygraph (Letica, Spain). Contraction was induced by accumulative doses of acetylcholine (0.1, 0.3, 1, 3, 10 mM) or by electric field stimulation (10 Hz at 2 milliseconds), and accumulative doses of dopamine were added to the bath. Low concentration (0.1-0.3 mM) elicited a small initial contraction, followed by a marked relaxation. Cholinergic contraction was completely reversed at 6 mM of dopamine. This biphasic dopaminergic response was not blocked by incubation with beta2-adrenergic antagonist propranolol (0.1 microM), alpha1-antagonist, terazosin (0.1 mM), alpha2-antagonist, yohimbine (0.1 mM), or by DA2 antagonist metoclopramide (1-8 mM); DA1 antagonist SCH23390 (0.1 microM) produced a sustained increase of basal tone but did not block initial dopaminergic contraction and partially inhibited bronchodilator effect of dopamine. Dopaminergic relaxation in rat trachea is mediated by DA1 rather than by DA2 receptors; and adrenergic receptors are not involved in such dopamine-induced response. Finally, DA1 antagonist SCH23390 exerts intrinsic contractile activity on airway smooth muscle that deserves further research.

Tree Branching: Leonardo da Vinci's Rule versus Biomechanical Models

PubMed Central

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule. PMID:24714065

Tree branching: Leonardo da Vinci's rule versus biomechanical models.

PubMed

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule.

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

The role of transparency in da Vinci stereopsis.

PubMed

Zannoli, Marina; Mamassian, Pascal

2011-10-15

The majority of natural scenes contains zones that are visible to one eye only. Past studies have shown that these monocular regions can be seen at a precise depth even though there are no binocular disparities that uniquely constrain their locations in depth. In the so-called da Vinci stereopsis configuration, the monocular region is a vertical line placed next to a binocular rectangular occluder. The opacity of the occluder has been mentioned to be a necessary condition to obtain da Vinci stereopsis. However, this opacity constraint has never been empirically tested. In the present study, we tested whether da Vinci stereopsis and perceptual transparency can interact using a classical da Vinci configuration in which the opacity of the occluder varied. We used two different monocular objects: a line and a disk. We found no effect of the opacity of the occluder on the perceived depth of the monocular object. A careful analysis of the distribution of perceived depth revealed that the monocular object was perceived at a depth that increased with the distance between the object and the occluder. The analysis of the skewness of the distributions was not consistent with a double fusion explanation, favoring an implication of occlusion geometry in da Vinci stereopsis. A simple model that includes the geometry of the scene could account for the results. In summary, the mechanism responsible to locate monocular regions in depth is not sensitive to the material properties of objects, suggesting that da Vinci stereopsis is solved at relatively early stages of disparity processing. Copyright © 2011 Elsevier Ltd. All rights reserved.

Natural Product Inspired Hsp90 N-Terminal Inhibitors for the Treatment of Cancer: From Bench to Bedside

PubMed Central

Blagg, Brian S. J.

2015-01-01

The 90 kDa heat shock proteins (Hsp90) are responsible for the conformational maturation of nascent polypeptides and the rematuration of denatured proteins. Proteins dependent upon Hsp90 are associated with all six hallmarks of cancer. Upon Hsp90 inhibition, protein substrates are degraded via the ubiquitin-proteasome pathway. Consequentially, inhibition of Hsp90 offers a therapeutic opportunity for the treatment of cancer. Natural product inhibitors of Hsp90 have been identified in vitro, which have served as leads for the development of more efficacious inhibitors and analogs that have entered clinical trials. This review highlights the development of natural product analogs, as well as the development of clinically important inhibitors that arose from natural products. PMID:26010985

Effect of shorter dark adaptation on ISCEV standard DA 0.01 and DA 3 skin ERGs in healthy adults.

PubMed

Hamilton, R; Graham, K

2016-08-01

To quantify dark-adapted (DA) skin ERG changes during 20 min of dark adaptation. Sixteen healthy adult subjects were dark-adapted for 20 min during which ISCEV standard dim (0.01 phot cd s m(-2)) white flash ERGs were recorded at 1, 2, 3, 4, 5, 10, 15 and 20 min, and bright (3 phot cd s m(-2)) white ERGs were recorded at 2, 5, 10, 15 and 20 min without mydriasis and using skin electrodes. Amplitudes and peak times were normalised to 20 min values. Halving dark adaptation from 20 to 10 min had no measureable effect on the DA 3 ERG and caused a 10 % amplitude loss (range 0-23 %) only for the DA 0.01 ERG b-wave amplitude. No significant peak time changes resulted, nor increased parameter variability. Reducing dark adaptation from 20 to 10 min or even less has an effect on only DA 0.01 ERGs. Shorter dark adaptation than 20 min may not compromise the clinical utility of the ERG providing clinics adhere to the usual standards of adequate reference data.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Myelin management by the 18.5–kDa and 21.5–kDa classic myelin basic protein isoforms

PubMed Central

Harauz, George; Boggs, Joan M.

2013-01-01

The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly and membrane extension, binding to SH3-domains, participation in Fyn-mediated signaling pathways, sequestration of phosphoinositides, and maintenance of calcium homeostasis. Of the diverse post-translational modifications of this isoform, phosphorylation is the most dynamic, and modulates 18.5-kDa MBP’s protein-membrane and protein-protein interactions, indicative of a rich repertoire of functions. In developing and mature myelin, phosphorylation can result in microdomain or even nuclear targeting of the protein, supporting the conclusion that 18.5-kDa MBP has significant roles beyond membrane adhesion. The full-length, early-developmental 21.5-kDa splice isoform is predominantly karyophilic due to a non-traditional P-Y nuclear localization signal, with effects such as promotion of oligodendrocyte proliferation. We discuss in vitro and recent in vivo evidence for multifunctionality of these classic basic proteins of myelin, and argue for a systematic evaluation of the temporal and spatial distributions of these protein isoforms, and their modified variants, during oligodendrocyte differentiation. PMID:23398367

Experience with ATLAS MySQL PanDA database service

NASA Astrophysics Data System (ADS)

Smirnov, Y.; Wlodek, T.; De, K.; Hover, J.; Ozturk, N.; Smith, J.; Wenaus, T.; Yu, D.

2010-04-01

The PanDA distributed production and analysis system has been in production use for ATLAS data processing and analysis since late 2005 in the US, and globally throughout ATLAS since early 2008. Its core architecture is based on a set of stateless web services served by Apache and backed by a suite of MySQL databases that are the repository for all PanDA information: active and archival job queues, dataset and file catalogs, site configuration information, monitoring information, system control parameters, and so on. This database system is one of the most critical components of PanDA, and has successfully delivered the functional and scaling performance required by PanDA, currently operating at a scale of half a million jobs per week, with much growth still to come. In this paper we describe the design and implementation of the PanDA database system, its architecture of MySQL servers deployed at BNL and CERN, backup strategy and monitoring tools. The system has been developed, thoroughly tested, and brought to production to provide highly reliable, scalable, flexible and available database services for ATLAS Monte Carlo production, reconstruction and physics analysis.

Technical review of the da Vinci surgical telemanipulator.

PubMed

Freschi, C; Ferrari, V; Melfi, F; Ferrari, M; Mosca, F; Cuschieri, A

2013-12-01

The da Vinci robotic surgical telemanipulator has been utilized in several surgical specialties for varied procedures, and the users' experiences have been widely published. To date, no detailed system technical analyses have been performed. A detailed review was performed of all publications and patents about the technical aspects of the da Vinci robotic system. Published technical literature on the da Vinci system highlight strengths and weaknesses of the robot design. While the system facilitates complex surgical operations and has a low malfunction rate, the lack of haptic (especially tactile) feedback and collisions between the robotic arms remain the major limitations of the system. Accurate, preplanned positioning of access ports is essential. Knowledge of the technical aspects of the da Vinci robot is important for optimal use. We confirmed the excellent system functionality and ease of use for surgeons without an engineering background. Research and development of the surgical robot has been predominant in the literature. Future trends address robot miniaturization and intelligent control design. Copyright © 2012 John Wiley & Sons, Ltd.

SINTERING OF NASCENT CALCIUM OXIDE

EPA Science Inventory

The paper discusses the measurement of the sintering rate of CaO in a nitrogen atmosphere at temperatures of 700-1100 C. CaO prepared from ultrapure CaCO3 was compared with an impure CaO derived from limestone. Both materials yielded an initial surface area of 104 sq m/g. The rat...

Perfil dos Professores de Ciências Naturais do Recôncavo da Bahia - Alunos da Disciplina Terra e Universo no Curso de Ciências Naturais do Parfor

NASA Astrophysics Data System (ADS)

Lima, S. R.; Cerqueira Júnior, W.; Dutra, G.

2011-12-01

Este trabalho foi desenvolvido pelo projeto Astronomia no Recôncavo da Bahia, no Centro de Formação de Professores da Universidade Federal do Recôncavo da Bahia. Traçamos o perfil de um grupo de professores que lecionam conteúdos de Ciências Naturais no recôncavo, alunos do curso de Licenciatura em Ciências Naturais, oferecido dentro do Plano Nacional de Formação de Professores da Educação Básica. Nosso objetivo era avaliar se eles estão preparados para trabalhar conteúdos de Astronomia e identificar suas dificuldades. Os resultados serviram para orientar o professor da disciplina “Terra e Universo”, oferecida no segundo semestre de 2010. Durante a primeira aula da disciplina Terra e Universo, os alunos responderam a um questionário contendo questões abertas e fechadas, divididas em duas partes. A primeira procurando caracterizar profissionalmente os alunos enquanto professores da rede pública da região do Recôncavo Sul da Bahia e uma segunda parte procurando identificar conhecimentos básicos em Astronomia. Os resultados indicam uma predominância de professores do sexo feminino, com idade superior aos 40 anos, pardos e sem formação específica para o ensino de ciências. A maioria leciona há mais de 15 anos para turmas do 1º ao 5º ano, alguns lecionam para turmas de 6º ao 9º ano. Quase todos nunca participaram de um curso de formação continuada em Astronomia. Além disso, não estão habituados a ler revistas especializadas e nem livros com esta temática. Os que procuram ensinar temas voltados para a Astronomia têm, no livro didático, a maior fonte de informação sobre o assunto. As respostas também indicam uma deficiência em conteúdos básicos como a compreensão da esfericidade da Terra, noções de verticalidade e gravidade, incapacidade de identificar a Terra como um planeta, no Sistema Solar, em uma galáxia, no Universo. Estes resultados ressaltam a importância de disciplinas de Astronomia básica na formação dos

The Case: Bunche-Da Vinci Learning Partnership Academy

ERIC Educational Resources Information Center

Eisenberg, Nicole; Winters, Lynn; Alkin, Marvin C.

2005-01-01

The Bunche-Da Vinci case described in this article presents a situation at Bunche Elementary School that four theorists were asked to address in their evaluation designs (see EJ791771, EJ719772, EJ791773, and EJ792694). The Bunche-Da Vinci Learning Partnership Academy, an elementary school located between an urban port city and a historically…

Thermodynamics and kinetics of protein folding on the ribosome: Alteration in energy landscapes, denatured state, and transition state ensembles

NASA Astrophysics Data System (ADS)

O'Brien, Edward; Vendruscolo, Michele; Dobson, Christopher

2010-03-01

In vitro experiments examining cotranslational folding utilize ribosome-nascent chain complexes (RNCs) in which the nascent chain is stalled at different points of its biosynthesis on the ribosome. We investigate the thermodynamics, kinetics, and structural properties of RNCs containing five different globular and repeat proteins stalled at ten different nascent chain lengths using coarse grained replica exchange simulations. We find that when the proteins are stalled near the ribosome exit tunnel opening they exhibit altered folding coopserativity, quantified by the van't Hoff enthalpy criterion; a significantly altered denatured state ensemble, in terms of Rg and shape parameters (Rg tensor); and the appearance of partially folded intermediates during cotranslation, evidenced by the appearance of a third basin in the free energy profile. These trends are due in part to excluded volume (crowding) interactions between the ribosome and nascent chain. We perform in silico temperature-jump experiments on the RNCs and examine nascent chain folding kinetics and structural changes in the transition state ensemble at various stall lengths.

The future of PanDA in ATLAS distributed computing

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

ECTA/DaSy Framework Self-Assessment Comparison Tool

ERIC Educational Resources Information Center

Center for IDEA Early Childhood Data Systems (DaSy), 2016

2016-01-01

The Self-Assessment Comparison (SAC) Tool is for state Part C and Section 619/Preschool programs to use to assess changes in the implementation of one or more components of the ECTA System Framework and/or subcomponenets of the DaSy Data System Framework. It is a companion to the ECTA/DaSy Framework Self-Assessment. Key features of the SAC are…

The ATLAS PanDA Monitoring System and its Evolution

NASA Astrophysics Data System (ADS)

Klimentov, A.; Nevski, P.; Potekhin, M.; Wenaus, T.

2011-12-01

The PanDA (Production and Distributed Analysis) Workload Management System is used for ATLAS distributed production and analysis worldwide. The needs of ATLAS global computing imposed challenging requirements on the design of PanDA in areas such as scalability, robustness, automation, diagnostics, and usability for both production shifters and analysis users. Through a system-wide job database, the PanDA monitor provides a comprehensive and coherent view of the system and job execution, from high level summaries to detailed drill-down job diagnostics. It is (like the rest of PanDA) an Apache-based Python application backed by Oracle. The presentation layer is HTML code generated on the fly in the Python application which is also responsible for managing database queries. However, this approach is lacking in user interface flexibility, simplicity of communication with external systems, and ease of maintenance. A decision was therefore made to migrate the PanDA monitor server to Django Web Application Framework and apply JSON/AJAX technology in the browser front end. This allows us to greatly reduce the amount of application code, separate data preparation from presentation, leverage open source for tools such as authentication and authorization mechanisms, and provide a richer and more dynamic user experience. We describe our approach, design and initial experience with the migration process.

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

32 CFR 643.121 - Private organizations on DA installations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Private organizations on DA installations. 643.121 Section 643.121 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY... DA installations. (a) AR 210-1 defines and classifies private organizations, such as thrift shops and...

Use of the new da Vinci Xi® during robotic rectal resection for cancer: a pilot matched-case comparison with the da Vinci Si®.

PubMed

Morelli, Luca; Guadagni, Simone; Di Franco, Gregorio; Palmeri, Matteo; Caprili, Giovanni; D'Isidoro, Cristiano; Cobuccio, Luigi; Marciano, Emanuele; Di Candio, Giulio; Mosca, Franco

2017-03-01

The aim of this study was to compare the short-term outcomes of robotic rectal resection with total mesorectal excision (TME) for rectal cancer, with the use of the new da Vinci Xi® (Xi-RobTME group) and the da Vinci Si® (Si-RobTME group). Ten patients with histologically confirmed rectal cancer underwent robot-assisted TME with the use of the new da Vinci Xi. The outcomes of Xi-RobTME group were compared with a Si-RobTME group selected using a case-matched methodology. Overall operative times and mean hospital stays were shorter in the Xi-RobTME group. Surgeries were fully robotic with a complete take-down of the splenic flexure in all Xi-RobTME cases, while only four cases of the Si-RobTME group were fully robotic, with two cases of complete take-down of the splenic flexure. The new da Vinci Xi could offer some advantages with respect to the da Vinci Si in rectal resection for cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A 32 kDa viral attachment protein of lymphocystis disease virus (LCDV) specifically interacts with a 27.8 kDa cellular receptor from flounder (Paralichthys olivaceus).

PubMed

Zhong, Ying; Fei, Chenjie; Tang, Xiaoqian; Zhan, Wenbin; Sheng, Xiuzhen

2017-06-01

The 27.8 kDa protein in flounder gill (FG) cells was previously proved to be a receptor specific for lymphocystis disease virus (LCDV) entry and infection. In this paper, a 32 kDa viral attachment protein (VAP) of LCDV specifically binding to the 27.8 kDa receptor (27.8R) was found by far-Western blotting coupled with monoclonal antibodies (MAbs) against 27.8R. The 32 kDa protein was confirmed to be encoded by the open reading frame (ORF) 038 gene in LCDV-C, and predicted to contain a putative transmembrane region, multiple N-myristoylation and glycosylation sites and phosphorylation motifs. The expression plasmid of pET-32a-ORF038 was constructed and the recombinant VAP (rVAP) was obtained. Rabbit polyclonal antibodies against the rVAP were prepared and could recognize the rVAP and 32 kDa protein in LCDV. Immunogold electron microscopy showed that the 32 kDa protein was located on the surface of LCDV particles. Immunofluorescence assay demonstrated that the rVAP could bind to the 27.8R on the cell membrane of the FG monolayer and the anti-27.8R MAbs could block the rVAP binding. Pre-incubation of the rVAP with FG cells before LCDV infection, or pre-incubation of LCDV with the antibodies against the rVAP, could significantly decrease the LCDV copy numbers (P<0.05) and delay the emergence of cytopathic effects in FG cells in a dose-dependent manner. These results indicated for the first time that the 32 kDa protein functioned as an attachment protein for the initial attachment and entry of LCDV, and the interaction of the 32 kDa VAP with the 27.8R-initiated LCDV infection.

Virtual reality training improves da Vinci performance: a prospective trial.

PubMed

Cho, Jae Sung; Hahn, Koo Yong; Kwak, Jung Myun; Kim, Jin; Baek, Se Jin; Shin, Jae Won; Kim, Seon Hahn

2013-12-01

The DV-Trainer™ (a virtual reality [VR] simulator) (Mimic Technologies, Inc., Seattle, WA) is one of several different robotic surgical training methods. We designed a prospective study to determine whether VR training could improve da Vinci(®) Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) performance. Surgeons (n=12) were enrolled using a randomized protocol. Groups 1 (VR training) and 2 (control) participated in VR and da Vinci exercises. Participants' time and moving distance were combined to determine a composite score: VR index=1000/(time×moving distance). The da Vinci exercises included needle control and suturing. Procedure time and error were measured. A composite index (DV index) was computed and used to measure da Vinci competency. After the initial trial with both the VR and da Vinci exercises, only Group 1 was trained with the VR simulator following our institutional curriculum for 3 weeks. All members of both groups then participated in the second trial of the VR and da Vinci exercises and were scored in the same way as in the initial trial. In the initial trial, there was no difference in the VR index (Group 1 versus Group 2, 8.9 ± 3.3 versus 9.4 ± 3.7; P=.832) and the DV index (Group 1 versus Group 2, 3.85 ± 0.73 versus 3.66 ± 0.65; P=.584) scores between the two groups. At the second time point, Group 1 showed increased VR index scores in comparison with Group 2 (19.3 ± 4.5 versus 9.7 ± 4.1, respectively; P=.001) and improved da Vinci performance skills as measured by the DV index (5.80 ± 1.13 versus 4.05 ± 1.03, respectively; P=.028) and by suturing time (7.1 ± 1.54 minutes versus 10.55 ± 1.93 minutes, respectively; P=.018). We found that VR simulator training can improve da Vinci performance. VR practice can result in an early plateau in the learning curve for robotic practice under controlled circumstances.

The ATLAS PanDA Pilot in Operation

NASA Astrophysics Data System (ADS)

Nilsson, P.; Caballero, J.; De, K.; Maeno, T.; Stradling, A.; Wenaus, T.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis system (PanDA) [1-2] was designed to meet ATLAS [3] requirements for a data-driven workload management system capable of operating at LHC data processing scale. Submitted jobs are executed on worker nodes by pilot jobs sent to the grid sites by pilot factories. This paper provides an overview of the PanDA pilot [4] system and presents major features added in light of recent operational experience, including multi-job processing, advanced job recovery for jobs with output storage failures, gLExec [5-6] based identity switching from the generic pilot to the actual user, and other security measures. The PanDA system serves all ATLAS distributed processing and is the primary system for distributed analysis; it is currently used at over 100 sites worldwide. We analyze the performance of the pilot system in processing real LHC data on the OSG [7], EGI [8] and Nordugrid [9-10] infrastructures used by ATLAS, and describe plans for its evolution.

Yarkovsky-driven Impact Predictions: Apophis and 1950 DA

NASA Astrophysics Data System (ADS)

Chesley, Steven R.; Farnocchia, D.; Chodas, P. W.; Milani, A.

2013-10-01

Orbit determination for Near-Earth Asteroids presents unique technical challenges due to the imperative of early detection and careful assessment of the risk posed by specific Earth close approaches. The occurrence of an Earth impact can be decisively driven by the Yarkovsky effect, which is the most important nongravitational perturbation as it causes asteroids to undergo a secular variation in semimajor axis resulting in a quadratic effect in anomaly. We discuss the cases of (99942) Apophis and (29075) 1950 DA. The relevance of the Yarkovsky effect for Apophis is due to a scattering close approach in 2029 with minimum geocentric distance ~38000 km. For 1950 DA the influence of the Yarkovsky effect in 2880 is due to the long time interval preceding the impact. We use the available information from the astrometry and the asteroids' physical models and dynamical evolution as a starting point for a Monte Carlo method that allows us to measure how the Yarkovsky effect affects orbital predictions. We also find that 1950 DA has a 98% likelihood of being a retrograde rotator. For Apophis we map onto the 2029 close approach b-plane and analyze the keyholes corresponding to resonant close approaches. For 1950 DA we use the b-plane corresponding to the possible impact in 2880. We finally compute the impact probability from the mapped probability density function on the considered b-plane. For Apophis we have 4 in a million chances of an impact in 2068, while the probability of Earth impact in 2880 for 1950 DA is 0.04%.

Da Vinci robot-assisted system for thymectomy: experience of 55 patients in China.

PubMed

Jun, Yi; Hao, Li; Demin, Li; Guohua, Dong; Hua, Jing; Yi, Shen

2014-09-01

Da Vinci robot-assisted thymectomy has been used in the past several years in China, however, practical experience in performing this approach in China remains limited. Thus, the study aimed to evaluate the experience of da Vinci robot-assisted thymectomy in China. From June 2010 to December 2012, 55 patients with diseases of the thymus underwent thymectomy using the da Vinci surgical HD robotic system. The clinical data of the da Vinci robot-assisted thymectomies were compared with the data of video-assisted thoracoscopic thymectomies in the same period. All da Vinci robot operations were successful. This is a retrospective analysis which demonstrated that compared with video-assisted thoracoscopic thymectomy in the same period, the clinical outcomes of da Vinci robot-assisted thymectomy were not significantly different. The da Vinci robot-assisted thymectomy is a safe, minimally invasive, and convenient operation, and shows promise for general thoracic surgery in China. Copyright © 2014 John Wiley & Sons, Ltd.

JCoDA: a tool for detecting evolutionary selection.

PubMed

Steinway, Steven N; Dannenfelser, Ruth; Laucius, Christopher D; Hayes, James E; Nayak, Sudhir

2010-05-27

The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding

JCoDA: a tool for detecting evolutionary selection

PubMed Central

2010-01-01

Background The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. Results JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. Conclusions JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary

High resolution structure of cleaved Serpin 42 Da from Drosophila melanogaster.

PubMed

Ellisdon, Andrew M; Zhang, Qingwei; Henstridge, Michelle A; Johnson, Travis K; Warr, Coral G; Law, Ruby Hp; Whisstock, James C

2014-04-24

The Drosophila melanogaster Serpin 42 Da gene (previously Serpin 4) encodes a serine protease inhibitor that is capable of remarkable functional diversity through the alternative splicing of four different reactive centre loop exons. Eight protein isoforms of Serpin 42 Da have been identified to date, targeting the protease inhibitor to both different proteases and cellular locations. Biochemical and genetic studies suggest that Serpin 42 Da inhibits target proteases through the classical serpin 'suicide' inhibition mechanism, however the crystal structure of a representative Serpin 42 Da isoform remains to be determined. We report two high-resolution crystal structures of Serpin 42 Da representing the A/B isoforms in the cleaved conformation, belonging to two different space-groups and diffracting to 1.7 Å and 1.8 Å. Structural analysis reveals the archetypal serpin fold, with the major elements of secondary structure displaying significant homology to the vertebrate serpin, neuroserpin. Key residues known to have central roles in the serpin inhibitory mechanism are conserved in both the hinge and shutter regions of Serpin 42 Da. Furthermore, these structures identify important conserved interactions that appear to be of crucial importance in allowing the Serpin 42 Da fold to act as a versatile template for multiple reactive centre loops that have different sequences and protease specificities. In combination with previous biochemical and genetic studies, these structures confirm for the first time that the Serpin 42 Da isoforms are typical inhibitory serpin family members with the conserved serpin fold and inhibitory mechanism. Additionally, these data reveal the remarkable structural plasticity of serpins, whereby the basic fold is harnessed as a template for inhibition of a large spectrum of proteases by reactive centre loop exon 'switching'. This is the first structure of a Drosophila serpin reported to date, and will provide a platform for future mutational

Qual o Papel da Escola e da Mídia na Obtenção dos Conhecimentos Astronômicos?

NASA Astrophysics Data System (ADS)

da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.

2007-08-01

É amplamente reconhecido que as pessoas em geral têm grande fascínio e interesse pela Astronomia. Por outro lado, o conteúdo dessa área incluído no ensino formal está longe de ser abrangente e suficiente para suprir a demanda. Esse interesse permite aperfeiçoar a divulgação e o ensino não formal de Astronomia através da mídia aliando a adequação do conteúdo à expectativa das pessoas. A reforma do Currículo Básico da Escola Pública da maioria dos Estados brasileiros tem introduzido Astronomia desde a pré-escola até o Ensino Médio. Num estudo realizado com 1180 alunos do Ensino Médio de seis escolas estaduais, revelou-se através da aplicação de um formulário contendo questões que abordavam conhecimentos básicos em Astronomia, como foram adquiridos tais conhecimentos e à infra-estrutura da escola. Para 66,1% dos entrevistados o professor já fez alguma apresentação a respeito de Astronomia. O presente estudo revelou também que 54,4% dos alunos entrevistados adquiriram seus conhecimentos astronômicos na escola, 18,4% através da televisão e 27,1% afirmaram que seus conhecimentos foram obtidos através de outros tipos de mídia (internet, livros didáticos, filmes e revistas). Embora o estudo revele claramente que há certo equilíbrio no meio em que os alunos obtiveram seus conhecimentos astronômicos, a mídia busca não somente sua difusão, mas a disponibilização desse conhecimento de maneira correta, que às vezes, não é atingido, apresentando conceitos sem fundamentação e incorretos. Por outro lado, no dia-a-dia escolar, é comum encontrar professores que vêm para as aulas com concepções prévias, que podem diferir substancialmente das idéias a serem ensinadas, dificultando o aprendizado de futuros conceitos científicos. Uma avaliação criteriosa, avaliando as dificuldades dos professores em determinar o sentido correto dos conceitos e observando a metodologia que utilizam no ensino, poderá proporcionar uma melhor

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

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

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Contribution of DA Signaling to Appetitive Odor Perception in a Drosophila Model.

PubMed

Pu, Yuhan; Palombo, Melissa Megan Masserant; Shen, Ping

2018-04-13

Understanding cognitive processes that translate chemically diverse olfactory stimuli to specific appetitive drives remains challenging. We have shown that food-related odors arouse impulsive-like feeding of food media that are palatable and readily accessible in well-nourished Drosophila larvae. Here we provide evidence that two assemblies of four dopamine (DA) neurons, one per brain hemisphere, contribute to perceptual processing of the qualitative and quantitative attributes of food scents. These DA neurons receive neural representations of chemically diverse food-related odors, and their combined neuronal activities become increasingly important as the chemical complexity of an appetizing odor stimulus increases. Furthermore, in each assembly of DA neurons, integrated odor signals are transformed to one-dimensional DA outputs that have no intrinsic reward values. Finally, a genetic analysis has revealed a D1-type DA receptor (Dop1R1)-gated mechanism in neuropeptide Y-like neurons that assigns appetitive significance to selected DA outputs. Our findings suggest that fly larvae provide a useful platform for elucidation of molecular and circuit mechanisms underlying cognitive processing of olfactory and possibly other sensory cues.

PanDA for COMPASS at JINR

NASA Astrophysics Data System (ADS)

Petrosyan, A. Sh.

2016-09-01

PanDA (Production and Distributed Analysis System) is a workload management system, widely used for data processing at experiments on Large Hadron Collider and others. COMPASS is a high-energy physics experiment at the Super Proton Synchrotron. Data processing for COMPASS runs locally at CERN, on lxbatch, the data itself stored in CASTOR. In 2014 an idea to start running COMPASS production through PanDA arose. Such transformation in experiment's data processing will allow COMPASS community to use not only CERN resources, but also Grid resources worldwide. During the spring and summer of 2015 installation, validation and migration work is being performed at JINR. Details and results of this process are presented in this paper.

DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

PubMed

Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

2015-01-01

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Multiquadrant robotic colorectal surgery: the da Vinci Xi vs Si comparison.

PubMed

Protyniak, Bogdan; Jorden, Jeffrey; Farmer, Russell

2018-03-01

The newly introduced da Vinci Xi Surgical System hopes to address the shortcomings of its predecessor, specifically robotic arm restrictions and difficulty working in multiple quadrants. We compare the two robot platforms in multiquadrant surgery at a major colorectal referral center. Forty-four patients in the da Vinci Si group and 26 patients in the Xi group underwent sigmoidectomy or low anterior resection between 2014 and 2016. Patient demographics, operative variables, and postoperative outcomes were compared using descriptive statistics. Both groups were similar in age, sex, BMI, pelvic surgeries, and ASA class. Splenic flexure was mobilized in more (p = 0.045) da Vinci Xi cases compared to da Vinci Si both for sigmoidectomy (50 vs 15.4%) and low anterior resection (60 vs 29%). There was no significant difference in operative time (219.9 vs 224.7 min; p = 0.640), blood loss (170.0 vs 188.1 mL; p = 0.289), length of stay (5.7 vs 6 days; p = 0.851), or overall complications (26.9 vs 22.7%; p = 0.692) between the da Vinci Xi and Si groups, respectively. Single-dock multiquadrant robotic surgery, measured by splenic flexure mobilization with concomitant pelvic dissection, was more frequently performed using the da Vinci Xi platform with no increase in operative time, bleeding, or postoperative complications. The new platform provides surgeons an easier alternative to the da Vinci Si dual docking or combined robotic/laparoscopic multiquadrant surgery.

Output control of da Vinci surgical system's surgical graspers.

PubMed

Johnson, Paul J; Schmidt, David E; Duvvuri, Umamaheswar

2014-01-01

The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors. Copyright © 2014 Elsevier Inc. All rights reserved.

Mevalocidin: a novel, phloem mobile phytotoxin from Fusarium DA056446 and Rosellinia DA092917.

PubMed

Gerwick, B Clifford; Brewster, William K; Deboer, Gerrit J; Fields, Steve C; Graupner, Paul R; Hahn, Donald R; Pearce, Cedric J; Schmitzer, Paul R; Webster, Jeffery D

2013-02-01

A multiyear effort to identify new natural products was built on a hypothesis that both phytotoxins from plant pathogens and antimicrobial compounds might demonstrate herbicidal activity. The discovery of one such compound, mevalocidin, is described in the current report. Mevalocidin was discovered from static cultures of two unrelated fungal isolates designated Rosellinia DA092917 and Fusarium DA056446. The chemical structure was confirmed by independent synthesis. Mevalocidin demonstrated broad spectrum post-emergence activity on grasses and broadleaves and produced a unique set of visual symptoms on treated plants suggesting a novel mode of action. Mevalocidin was rapidly absorbed in a representative grass and broadleaf plant. Translocation occurred from the treated leaf to other plant parts including roots confirming phloem as well as xylem mobility. By 24 hr after application, over 20 % had been redistributed through-out the plant. Mevalocidin is a unique phytotoxin based on its chemistry, with the uncommon attribute of demonstrating both xylem and phloem mobility in grass and broadleaf plants.

Da Vinci Xi Robot–Assisted Penetrating Keratoplasty

PubMed Central

Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-01-01

Purpose This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Methods Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Results Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5–61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. Conclusions We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Translational Relevance Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use. PMID:28660096

Da Vinci Xi Robot-Assisted Penetrating Keratoplasty.

PubMed

Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-06-01

This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5-61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use.

Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.

PubMed

Pagnier, Guillaume J; Kastanenka, Ksenia V; Sohn, Miwon; Choi, Sangzin; Choi, Song-Hyen; Soh, HyeYeon; Bacskai, Brian J

2018-01-29

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging. We examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid deposits and intracellular calcium in neurons with multiphoton microscopy was performed. Chronic administration of DA-9803 restored behavioral deficits in 5XFAD mice and reduced amyloid-β levels. DA-9803 also prevented progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected in a subset of neurons before the treatment, was restored and served as a functional indicator of treatment efficacy in addition to the behavioral readout. In contrast, mice treated with vehicle alone continued to progressively accumulate amyloid plaques and calcium overload. In summary, treatment with DA-9803 prevented structural and functional outcome measures in mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach for Alzheimer's disease.

Load evaluation of the da Vinci surgical system for transoral robotic surgery.

PubMed

Fujiwara, Kazunori; Fukuhara, Takahiro; Niimi, Koji; Sato, Takahiro; Kitano, Hiroya

2015-12-01

Transoral robotic surgery, performed with the da Vinci surgical system (da Vinci), is a surgical approach for benign and malignant lesions of the oral cavity and laryngopharynx. It provides several unique advantages, which include a 3-dimensional magnified view and ability to see and work around curves or angles. However, the current da Vinci surgical system does not provide haptic feedback. This is problematic because the potential risks specific to the transoral use of the da Vinci include tooth injury, mucosal laceration, ocular injury and mandibular fracture. To assess the potential for intraoperative injuries, we measured the load of the endoscope and the instrument of the da Vinci Si surgical system. We pressed the endoscope and instrument of the da Vinci Si against Load cell six times each and measured the dynamic load and the time-to-maximum load. We also struck the da Vinci Si endoscope and instrument against the Load cell six times each and measured the impact load. The maximum dynamic load was 7.27 ± 1.31 kg for the endoscope and 1.90 ± 0.72 for the instrument. The corresponding time-to-maximum loads were 1.72 ± 0.22 and 1.29 ± 0.34 s, but the impact loads were significantly lower than the dynamic load. It remains possible that a major load is exerted on adjacent structures by continuous contact with the endoscope and instrument of da Vinci Si. However, there is a minor delay in reaching the maximum load. Careful monitoring by an on-site assistant may, therefore, help prevent contiguous injury.

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

2016-09-01

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

PubMed

Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Sobre a largura da última superfície de espalhamento

NASA Astrophysics Data System (ADS)

Nobre, M. A. S.; Pires, N.; Lima, J. A. S.

2003-08-01

De acordo com o modelo do "Big-Bang", no universo primordial a matéria estava em equilíbrio térmico com a radiação. Com a expansão a temperatura da radiação cai. Quando a temperatura chega em torno dos 4.000K, os espalhamentos diminuem, começando a recombinação dos prótons e elétrons em Hidrogênio neutro (era conhecida como da recombinação). Ao final da recombinação, os fótons se propagam livremente sofrendo, em princípio, somente os efeitos do "redshift" cosmológico. Esses fótons nos alcançam hoje como a radiação cósmica de fundo (RCF), e parecem vir de uma superfície esférica ao nosso redor, tal que o raio dela é a distância que ele viajou desde seu último espalhamento na época da recombinação. Naturalmente, esse processo não ocorreu abruptamente, implicando na existência de uma largura no espaço dos "redshifts" que deve depender do modelo cosmológico específico e dos processos físicos considerados. Neste trabalho analisamos os efeitos de diferentes modelos - a saber, aqueles com decaimento do vácuo L(t), criação de matéria, quintessência e gás de Chaplygin - sobre a última superfície de espalhamento da RCF, em particular sua largura e a função visibilidade, que determina a probabilidade de um fóton ter tido seu último espalhamento num "redshift" z. No caso particular dos modelos com decaimento do vácuo, existe uma forte dependência da função visibilidade com L(t). Tais efeitos poderão ser testados através da análise dos resultados de experimentos mais precisos que estão atualmente em andamento, como por exemplo, o WMAP.

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

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

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

PD2P: PanDA Dynamic Data Placement for ATLAS

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

Maeno, T.; De, K.; Panitkin, S.

2012-12-13

The PanDA (Production and Distributed Analysis) system plays a key role in the ATLAS distributed computing infrastructure. PanDA is the ATLAS workload management system for processing all Monte-Carlo (MC) simulation and data reprocessing jobs in addition to user and group analysis jobs. The PanDA Dynamic Data Placement (PD2P) system has been developed to cope with difficulties of data placement for ATLAS. We will describe the design of the new system, its performance during the past year of data taking, dramatic improvements it has brought about in the efficient use of storage and processing resources, and plans for the future.

The Da Vinci European BioBank: A Metabolomics-Driven Infrastructure

PubMed Central

Carotenuto, Dario; Luchinat, Claudio; Marcon, Giordana; Rosato, Antonio; Turano, Paola

2015-01-01

We present here the organization of the recently-constituted da Vinci European BioBank (daVEB, https://www.davincieuropeanbiobank.org/it). The biobank was created as an infrastructure to support the activities of the Fiorgen Foundation (http://www.fiorgen.net/), a nonprofit organization that promotes research in the field of pharmacogenomics and personalized medicine. The way operating procedures concerning samples and data have been developed at daVEB largely stems from the strong metabolomics connotation of Fiorgen and from the involvement of the scientific collaborators of the foundation in international/European projects aimed to tackle the standardization of pre-analytical procedures and the promotion of data standards in metabolomics. PMID:25913579

Performances on simulator and da Vinci robot on subjects with and without surgical background.

PubMed

Moglia, Andrea; Ferrari, Vincenzo; Melfi, Franca; Ferrari, Mauro; Mosca, Franco; Cuschieri, Alfred; Morelli, Luca

2017-08-17

To assess whether previous training in surgery influences performance on da Vinci Skills Simulator and da Vinci robot. In this prospective study, thirty-seven participants (11 medical students, 17 residents, and 9 attending surgeons) without previous experience in laparoscopy and robotic surgery performed 26 exercises at da Vinci Skills Simulator. Thirty-five then executed a suture using a da Vinci robot. The overall scores on the exercises at the da Vinci Skills Simulator show a similar performance among the groups with no statistically significant pair-wise differences (p < .05). The quality of the suturing based on the unedited videos of the test run was similar for the intermediate (7 (4, 10)) and expert group (6.5 (4.5, 10)), and poor for the untrained groups (5 (3.5, 9)), without statistically significant difference (p < .05). This study showed, for subjects new to laparoscopy and robotic surgery, insignificant differences in the scores at the da Vinci Skills Simulator and at the da Vinci robot on inanimate models.

Ecological Carrying Capacity of Land Use Changes in Da'an City

NASA Astrophysics Data System (ADS)

Wang, H.; Zhang, J.; Li, B.

2018-04-01

Based on GIS and RS technology, this paper analyzed the land use change in Da'an city from 1995 to 2010. land-use ecological evaluation index was constructed to evaluate the land-use ecological risk of Da 'an city dynamically, and the land-use ecological risk level map was made, and then the distribution and change of the land-use ecological carrying capacity pattern of Da'an city were analyzed qualitatively. According to the evaluation results of ecological carrying capacity, the ecological environment of Da'an city has deteriorated in fifteen years. in 1995, the poor ecological environment area is mainly distributed in the northeast area of Da'an city, and the area is small, while the area of the central and southern areas is large; In 2010, the western region also appeared environmental degradation, the northeast environment deterioration is serious, the dominant area is reduced, and a small amount of deterioration in the central and southern regions. According to the study of this paper, in the future, we should strengthen the comprehensive management of this part of the area, strengthen vegetation coverage, reduce soil erosion, ensure the effective improvement of ecological environment.

The real code of leonardo da vinci.

PubMed

Ose, Leiv

2008-02-01

Leonardo da Vinci was born in Italy. Among the researchers and scientists, he is favourably known for his remarkable efforts in scientific work. His investigations of atherosclerosis judiciously combine three separate fields of research. In 1506, he finished his masterpiece, painting of Mona Lisa. A careful clinical examination of the famous painting reveals a yellow irregular leather-like spot at the inner end of the left upper eyelid and a soft bumpy well-defined swelling of the dorsum of the right hand beneath the index finger about 3 cm long. This is probably the first case of familial hypercholesterolemia (FH). The FH code of Leonardo da Vinci was given immense consideration by scientists like Carl Muller, who described the xanthomas tuberosum and angina pectoris. On the contrary, Akira Endo searched for microbial metabolites that would inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol and finally, Michael Brown and Joseph Goldstein published a remarkable series of elegant and insightful papers in the 70s and 80s. They established that the cellular uptake of low-density lipoprotein (LDL) essentially requires the LDL receptor. this was the real Code of Leonardo da Vinci.

Leonardo da Vinci's studies of the heart.

PubMed

Shoja, Mohammadali M; Agutter, Paul S; Loukas, Marios; Benninger, Brion; Shokouhi, Ghaffar; Namdar, Husain; Ghabili, Kamyar; Khalili, Majid; Tubbs, R Shane

2013-08-20

Leonardo da Vinci's detailed drawings are justly celebrated; however, less well known are his accounts of the structures and functions of the organs. In this paper, we focus on his illustrations of the heart, his conjectures about heart and blood vessel function, his experiments on model systems to test those conjectures, and his unprecedented conclusions about the way in which the cardiovascular system operates. In particular, da Vinci seems to have been the first to recognize that the heart is a muscle and that systole is the active phase of the pump. He also seems to have understood the functions of the auricles and pulmonary veins, identified the relationship between the cardiac cycle and the pulse, and explained the hemodynamic mechanism of valve opening and closure. He also described anatomical variations and changes in structure and function that occurred with age. We outline da Vinci's varied career and suggest ways in which his personality, experience, skills and intellectual heritage contributed to these advances in understanding. We also consider his influence on later studies in anatomy and physiology. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

PubMed

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

Is da Vinci Xi Better than da Vinci Si in Robotic Rectal Cancer Surgery? Comparison of the 2 Generations of da Vinci Systems.

PubMed

Ozben, Volkan; Cengiz, Turgut B; Atasoy, Deniz; Bayraktar, Onur; Aghayeva, Afag; Erguner, Ilknur; Baca, Bilgi; Hamzaoglu, Ismail; Karahasanoglu, Tayfun

2016-10-01

We aimed to compare perioperative outcomes for procedures using the latest generation of da Vinci robot versus its previous version in rectal cancer surgery. Fifty-three patients undergoing robotic rectal cancer surgery between January 2010 and March 2015 were included. Patients were classified into 2 groups (Xi, n=28 vs. Si, n=25) and perioperative outcomes were analyzed. The groups had significant differences including operative procedure, hybrid technique and redocking (P>0.05). In univariate analysis, the Xi group had shorter console times (265.7 vs. 317.1 min, P=0.006) and total operative times (321.6 vs. 360.4 min, P=0.04) and higher number of lymph nodes harvested (27.5 vs. 17.0, P=0.008). In multivariate analysis, Xi robot was associated with a shorter console time (odds ratio: 0.09, P=0.004) with no significant differences regarding other outcomes. Both generations of da Vinci robot led to similar short-term outcomes in rectal cancer surgery, but the Xi robot allowed shorter console times.

OpenDA-WFLOW framework for improving hydrologic predictions using distributed hydrologic models

NASA Astrophysics Data System (ADS)

Weerts, Albrecht; Schellekens, Jaap; Kockx, Arno; Hummel, Stef

2017-04-01

Data assimilation (DA) holds considerable potential for improving hydrologic predictions (Liu et al., 2012) and increase the potential for early warning and/or smart water management. However, advances in hydrologic DA research have not yet been adequately or timely implemented in operational forecast systems to improve the skill of forecasts for better informed real-world decision making. The objective of this work is to highlight the development of a generic linkage of the open source OpenDA package and the open source community hydrologic modeling framework Openstreams/WFLOW and its application in operational hydrological forecasting on various spatial scales. The coupling between OpenDA and Openstreams/wflow framework is based on the emerging standard Basic Model Interface (BMI) as advocated by CSDMS using cross-platform webservices (i.e. Apache Thrift) developed by Hut et al. (2016). The potential application of the OpenDA-WFLOW for operational hydrologic forecasting including its integration with Delft-FEWS (used by more than 40 operational forecast centers around the world (Werner et al., 2013)) is demonstrated by the presented case studies. We will also highlight the possibility to give real-time insight into the working of the DA methods applied for supporting the forecaster as mentioned as one of the burning issues by Liu et al., (2012).

32 CFR 644.512 - DA-SBA joint set-aside determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true DA-SBA joint set-aside determination. 644.512 Section 644.512 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL... Stone § 644.512 DA-SBA joint set-aside determination. Section 15 of the Small Business Act (15 U.S.C...

Leonardo da Vinci's foot: historical evidence of concept.

PubMed

Jastifer, James R; Toledo-Pereyra, Luis H

2012-10-01

Leonardo da Vinci (1452-1519), world-renowned Italian renaissance master, is known for his contributions to, and broad interests in science and art. The objective of this work is to demonstrate the extent of his science by applying the use of his concepts to current models of foot and ankle mechanics. The art and science of Leonardo Da Vinci were extensively analyzed by reviewing his original drawings and hand written notebooks as well as their English translation. Current medical journals including the topics of foot, ankle, and biomechanics were reviewed for modern evidence and application of his concepts. The library of Michigan State University and the electronic library of the Royal Library at Windsor Castle were extensively utilized. From the depths of Santa Maria Nuova Hospital in Florence and Santo Spirito Hospital in Rome, through his commentary and anatomical drawings of around 30 cadaver dissections he performed, Leonardo da Vinci expressed his concept of foot and ankle anatomy and mechanics. He laid forth concepts, which vary little from current theories including those of proportion, statics and joint stability, sesamoid biomechanics, and structural support of the foot. Leonardo da Vinci, by combining an interest in anatomy and a gift of genius and artistic ability laid a foundation of foot and ankle anatomy and mechanics that have been applied in modern clinical sciences. Leonardo in this way made important contributions to the practice of foot and ankle orthopedics.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model

PubMed Central

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-01-01

Background/Aims DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Methods Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. Results In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. Conclusions The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity. PMID:25071903

Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

PubMed

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-07-01

DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

Fluorescence growth of self-polymerized fluorescence polydopamine for ratiometric visual detection of DA.

PubMed

Yu, Miao; Lu, Yang; Tan, Zhenjiang

2017-06-01

In this work, a novel and facile ratiometric fluorescence probe was prepared for the visual detection of dopamine (DA). In this detection system, red-emission CdTe@SiO 2 (r-QDs@SiO 2 ) was used as steady core of the probe and inverse microemulsion method was applied to synthesize uniform r-QDs@SiO 2 , this step could protect CdTe from contacting with human skin directly. Polydopamine (PDA) acted as response signal to detect DA, a very handy method which just combined polyethyleneimine (PEI) with DA together to synthesize PDA, this way for synthesis of PDA was much time-saving and non-toxic than any other methods. Differently from traditional analysis processes, the products of this experiment were also the analysis substances in final. Under optimum measurement conditions, the dual-emission ratiometric fluorescence probe was used for detections of DA in a concentration ranged from 10μM to 80μM with a detection limit of 0.12μM, with addition of DA the color of the probe changed from red to green watched by naked eyes. In addition, the developed probe was also used for detections of DA in human serum samples successfully. This study provides a simple, time-saving and non-toxic approach for detections of DA without the requirement of complex equipment. Copyright © 2017 Elsevier B.V. All rights reserved.

Thinking like Leonardo da Vinci and its implications for the modern doctor.

PubMed

Baum, Neil

2013-01-01

Most people when asked to name the most creative, innovative, and multidimensional people in history would agree that Leonardo da Vinci is either at the top or very close to the number one position on that list. Wouldn't it be nice to think like da Vinci? This article shares the seven unique principles of thinking that da Vinci used that enabled him to be the greatest painter, sculptor, architect, musician, mathematician, engineer, inventor, anatomist, geologist, cartographer, botanist, and writer of his (if not of all) time. This article will take you deep into the notebooks and codices of da Vinci, and suggest ways his ideas can be used by anyone in the healthcare profession to make them a better healthcare provider.

76 FR 31457 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation... reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance... DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance. Depending on...

Reflections on protein splicing: structures, functions and mechanisms

PubMed Central

Anraku, Yasuhiro; Satow, Yoshinori

2009-01-01

Twenty years ago, evidence that one gene produces two enzymes via protein splicing emerged from structural and expression studies of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and contains two independent genetic information for Vma1p (a catalytic 70-kDa subunit of the vacuolar H+-ATPase) and VDE (a 50-kDa DNA endonuclease) as an in-frame spliced insert in the gene. Protein splicing is a posttranslational cellular process, in which an intervening polypeptide termed as the VMA1 intein is self-catalytically excised out from a nascent 120-kDa VMA1 precursor and two flanking polypeptides of the N- and C-exteins are ligated to produce the mature Vma1p. Subsequent studies have demonstrated that protein splicing is not unique to the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its structure-directed chemical mechanisms, a series of biochemical and crystal structural studies has been carried out with the use of various VMA1 recombinants. This article summarizes a VDE-mediated self-catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation. PMID:19907126

Leonardo Da Vinci and stroke - vegetarian diet as a possible cause.

PubMed

Oztürk, Serefnur; Altieri, Marta; Troisi, Pina

2010-01-01

Leonardo da Vinci (April 15, 1452 to May 2, 1519) was an Italian Renaissance architect, musician, anatomist, inventor, engineer, sculptor, geometer, and painter. It has been gleaned from the many available historical documents that da Vinci was a vegetarian who respected and loved animals, and that he suffered from right hemiparesis in the last 5 years of his life. A vegetarian diet has both positive and negative influences on the cerebrovascular system. In this report, a possible relation between a vegetarian diet and stroke is discussed from various perspectives as related to Leonardo da Vinci's stroke. Copyright (c) 2010 S. Karger AG, Basel.

Early clinical experience with the da Vinci Xi Surgical System in general surgery.

PubMed

Hagen, Monika E; Jung, Minoa K; Ris, Frederic; Fakhro, Jassim; Buchs, Nicolas C; Buehler, Leo; Morel, Philippe

2017-09-01

The da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2014 to facilitate minimally invasive surgery. Novel features are targeted towards facilitating complex multi-quadrant procedures, but data is scarce so far. Perioperative data of patients who underwent robotic general surgery with the da Vinci Xi system within the first 6 month after installation were collected and analyzed. The gastric bypass procedures performed with the da Vinci Xi Surgical System were compared to an equal amount of the last procedures with the da Vinci Si Surgical System. Thirty-one foregut (28 Roux-en-Y gastric bypasses), 6 colorectal procedures and 1 revisional biliary procedure were performed. The mean operating room (OR) time was 221.8 (±69.0) minutes for gastric bypasses and 306.5 (±48.8) for colorectal procedures with mean docking time of 9.4 (±3.8) minutes. The gastric bypass procedure was transitioned from a hybrid to a fully robotic approach. In comparison to the last 28 gastric bypass procedures performed with the da Vinci Si Surgical System, the OR time was comparable (226.9 versus 230.6 min, p = 0.8094), but the docking time significantly longer with the da Vinci Xi Surgical System (8.5 versus 6.1 min, p = 0.0415). All colorectal procedures were performed with a single robotic docking. No intraoperative and two postoperative complications occurred. The da Vinci Xi might facilitate single-setups of totally robotic gastric bypass and colorectal surgeries. However, further comparable research is needed to clearly determine the significance of this latest version of the da Vinci Surgical System.

76 FR 14346 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... been reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard... condition for the specified products. The MCAI states: Cracks have been reportedly found on DA 42 Main...

[Diagnostic Accuracy of the LiSe-DaZ for Children with Specific Language Impairment].

PubMed

Stephan, T; Keilmann, A

2015-12-01

Currently, only few tests for the development of speech and language exist for bi- or multilingual children in Germany. One of those, the LiSe-DaZ (Linguistic performance measurement - German as a second language), was examined in a prospective study regarding its practicability and the sensitivity to detect children with specific language impairment in a group of children aged 5 to 7 who suffered from a severe language impairment according to clinical tests. 74 children (mean age: 60 months; 46% monolingual German-speaking; 54% bi- or multilingual) with severe specific language impairment were examined with the LiSe-DaZ in addition to the clinical established diagnostic during their in-patient stay in the hospital. The children, on average, showed in the receptive language abilities (LiSe-DaZ vs. TROG-D), the expressive vocabulary (LiSe-DaZ vs. AWST-R or WWT) and in the use of prepositions (LiSe-DaZ vs. Ravensburger Dysgrammatical clinical trial) significantly (p<0,0005) better results in the LiSe-DaZ. Thus, the majority of children were diagnosed as language impaired by clinically established tests whereas the LiSe-DaZ considered the children's language development to be normal. This difference was consistently more prominent for children with German as a second language. Compared with the clinically established tests, the informative value of the LiSe-DaZ turned out to be insufficient. The LiSe-DaZ does not detect children with the need of language therapy. Nevertheless, a norming of the established speech tests for bi- or multilingual children would be desirable to avoid unfounded judgements. © Georg Thieme Verlag KG Stuttgart · New York.

Leonardo da Vinci (1452-1519) and his depictions of the human spine.

PubMed

Bowen, Garvin; Gonzales, Jocelyn; Iwanaga, Joe; Fisahn, Christian; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

2017-12-01

Few individuals in history have exerted so great an influence and made such extensive contributions to so many disciplines as Leonardo da Vinci. Da Vinci's inquisitive, experimental mentality led him to many discoveries, such as spinal cord function and the proper anatomy of several organ systems. Respected not only as an artist but also as an anatomist, he made many significant contributions to the field. This article explores da Vinci's drawings, in relation to the anatomy of the human spine.

The Real Code of Leonardo da Vinci

PubMed Central

Ose, Leiv

2008-01-01

Leonardo da Vinci was born in Italy. Among the researchers and scientists, he is favourably known for his remarkable efforts in scientific work. His investigations of atherosclerosis judiciously combine three separate fields of research. In 1506, he finished his masterpiece, painting of Mona Lisa. A careful clinical examination of the famous painting reveals a yellow irregular leather-like spot at the inner end of the left upper eyelid and a soft bumpy well-defined swelling of the dorsum of the right hand beneath the index finger about 3 cm long. This is probably the first case of familial hypercholesterolemia (FH). The FH code of Leonardo da Vinci was given immense consideration by scientists like Carl Muller, who described the xanthomas tuberosum and angina pectoris. On the contrary, Akira Endo searched for microbial metabolites that would inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol and finally, Michael Brown and Joseph Goldstein published a remarkable series of elegant and insightful papers in the 70s and 80s. They established that the cellular uptake of low-density lipoprotein (LDL) essentially requires the LDL receptor. In conclusion: this was the real Code of Leonardo da Vinci. PMID:19924278

[The rational application of Da Vinci surgical system in thyroidectomy].

PubMed

He, Q Q

2017-08-01

Da Vinci surgical system is the most advanced minimally invasive surgical platform in the world, and this system has been widely used in cardiac surgery, urology surgery, gynecologic surgery and general surgery. Although the application of this system was relatively late in thyroid surgery, the number of thyroidectomy with Da Vinci surgical system is increasing quickly. Having reviewed recent studies and summarized clinical experience, compared with traditional open operation, the robotic thyroidectomy has the same surgical safety and effectiveness in selective patients with thyroid cancer. In this paper, several aspects on this novel operation were demonstrated, including surgical indications and contraindications, the approaches, surgical procedures and postoperative complications, in order to promote the rational application of Da Vinci surgical system in thyroidectomy.

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

Desenvolvimento de modelo clínico para predição da possibilidade de identificação da artéria de Adamkiewicz por angiotomografia

PubMed Central

Amato, Alexandre Campos Moraes; Parga, José Rodrigues; Stolf, Noedir Antônio Groppo

2018-01-01

Resumo Contexto Diferenças morfológicas da artéria de Adamkiewicz (AKA) entre a população portadora e não portadora de doença aórtica têm importância clínica, influenciando as complicações neuroisquêmicas da medula espinhal em procedimentos operatórios. Ainda não é conhecida a correlação entre parâmetros clínicos e a previsibilidade da identificação dessa artéria pela angiotomografia. Objetivo Desenvolver um modelo matemático que, através de parâmetros clínicos correlacionados com aterosclerose, possa prever a probabilidade de identificação da AKA em pacientes submetidos a angiotomografias. Método Estudo observacional transversal utilizando banco de imagens e dados de pacientes. Foi feita análise estatística multivariada e criado modelo matemático logit de predição para identificação da AKA. Variáveis significativas foram utilizadas na montagem da fórmula para cálculo da probabilidade de identificação. O modelo foi calibrado, e a discriminação foi avaliada pela curva receiver operating characteristic (ROC). A seleção das variáveis explanatórias foi guiada pela maior área na curva ROC (p = 0,041) e pela significância combinada das variáveis. Resultados Foram avaliados 110 casos (54,5% do sexo masculino, com idade média de 60,97 anos e etnia com coeficiente B -2,471, M -1,297, N -0,971), com AKA identificada em 60,9%. Índice de massa corporal: 27,06 ± 0,98 (coef. -0,101); fumantes: 55,5% (coef. -1,614/-1,439); diabéticos: 13,6%; hipertensos: 65,5% (coef. -1,469); dislipidêmicos: 58,2%; aneurisma aórtico: 38,2%; dissecção aórtica: 12,7%; e trombo mural: 24,5%. Constante de 6,262. Fórmula para cálculo da probabilidade de detecção: (e−(Coef. Etnia+(Coef. IMC×IMC)+Coef.fumante+Coef.HAS+Coef.dislip+Constante)+1)−1 . O modelo de predição foi criado e disponibilizado no link https://vascular.pro/aka-model . Conclusão Com as covariáveis etnia, índice de massa corporal, tabagismo, hipertens

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Biofortification of soybean meal: immunological properties of the 27 kDa γ-zein.

PubMed

Krishnan, Hari B; Jang, Sungchan; Kim, Won-Seok; Kerley, Monty S; Oliver, Melvin J; Trick, Harold N

2011-02-23

Legumes, including soybeans ( Glycine max ), are deficient in sulfur-containing amino acids, which are required for the optimal growth of monogastric animals. This deficiency can be overcome by expressing heterologous proteins rich in sulfur-containing amino acids in soybean seeds. A maize 27 kDa γ-zein, a cysteine-rich protein, has been successfully expressed in several crops including soybean, barley, and alfalfa with the intent to biofortify these crops for animal feed. Previous work has shown that the maize 27 kDa zein can withstand digestion by pepsin and elicit an immunogenic response in young pigs. By use of sera from patients who tested positive by ImmunoCAP assay for elevated IgE to maize proteins, specific IgE binding to the 27 kDa γ-zein is demonstrated. Bioinformatic analysis using the full-length and 80 amino acid sliding window FASTA searches identified significant sequence homology of the 27 kDa γ-zein with several known allergens. Immunoblot analysis using human serum that cross-reacts with maize seed proteins also revealed specific IgE-binding to the 27 kDa γ-zein in soybean seed protein extracts containing the 27 kDa zein. This study demonstrates for the first time the allergenicity potential of the 27 kDa γ-zein and the potential that this protein has to limit livestock performance when used in soybeans that serve as a biofortified feed supplement.

Quasi-Langrangian models of nascent thermals

NASA Technical Reports Server (NTRS)

Rambaldi, S.; Randall, D. A.

1981-01-01

The motions in and around an isolated thermal were studied and rising motion in the core, and sinking motion on the outside were found; while the circulation resembled that of a vortex ring. In an entity cloud model, cloudy thermal is tracked, in a Lagrangian fashion, as a discrete entity; the field of motion in and around the thermal is not explicitly simulated. Field of motion cloud models, in which the equations of motion are numerically integrated on an Eulerian grid were developed. It is shown that the great potential of a hybrid cloud model can combine the simplicity of the entity models with the generality and flexibility of the field-of-motion models. A key problem to be overcome in the development of a hybrid model is the formulation of a mathematical framework within which the cloud dynamics can be represented.

Nascent Function Concepts in Nova Scientia

ERIC Educational Resources Information Center

Groetsch, C. W.

2004-01-01

The origin of the function concept is usually traced to Galileo's work on motion. We argue that specific proto-function concepts appeared in the work of Tartaglia a century before the publication of Galileo's Two New Sciences. The study of Tartaglia's ideas can be used in the classroom as a historical introduction to various function concepts,…

Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors.

PubMed

Kajiwara, Naohiro; Taira, Masahiro; Yoshida, Koichi; Hagiwara, Masaru; Kakihana, Masatoshi; Usuda, Jitsuo; Uchida, Osamu; Ohira, Tatsuo; Kawate, Norihiko; Ikeda, Norihiko

2011-10-01

The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy.

Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis)

PubMed Central

Xu, Min-jie; Zhang, Cong; Yang, Zhigang

2018-01-01

Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light

DaMab-2: Anti-Human DGKα Monoclonal Antibody for Immunocytochemistry.

PubMed

Nakano, Tomoyuki; Ogasawara, Satoshi; Tanaka, Toshiaki; Hozumi, Yasukazu; Mizuno, Satoru; Satoh, Eri; Sakane, Fumio; Okada, Naoki; Taketomi, Akinobu; Honma, Ryusuke; Nakamura, Takuro; Saidoh, Noriko; Yanaka, Miyuki; Itai, Shunsuke; Handa, Saori; Chang, Yao-Wen; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari; Goto, Kaoru

2017-08-01

Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic acid serve as signaling molecules, DGK is regarded as a hub between diacylglycerol-mediated and phosphatidic acid-mediated signaling. One of the 10 DGK isozymes, DGKα, is shown to be involved in T cell function. Transfection studies using tagged expression vectors revealed that DGKα localizes to the cytoplasm and nucleus and translocates to the plasma membrane in response to T cell receptor stimulation. However, a limited number of studies reported the localization of native protein of DGKα in tissues and cells. In this study, we immunized mice with recombinant DGKα and developed several anti-DGKα monoclonal antibodies (mAbs). One of the established anti-DGKα mAbs is a clone DaMab-2 (mouse IgG 1 , kappa). In enzyme-linked immunosorbent assay, DaMab-2 recognized only DGKα, and did not react with the other isozymes, such as DGKγ, DGKζ, DGKη, and DGKδ. Importantly, DaMab-2 is very useful in immunocytochemical analysis of human cultured cells, indicating that DaMab-2 is advantageous to analyze the localization and function of DGKα.

DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia

PubMed Central

Kwon, Yong Sam; Son, Miwon

2013-01-01

Motilitone® (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments. PMID:24265862

DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Shin, Cheol Min; Lee, Yoon Jin; Kim, Jong-Min; Lee, Jee Young; Kim, Kyung-Joon; Choi, Yoon Jin; Kim, Nayoung; Lee, Dong Ho

2018-04-21

To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). Copyright © 2018 Elsevier Ltd. All rights reserved.

PanDA Pilot Submission using Condor-G: Experience and Improvements

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

Zhao X.; Hover John; Wlodek Tomasz

2011-01-01

PanDA (Production and Distributed Analysis) is the workload management system of the ATLAS experiment, used to run managed production and user analysis jobs on the grid. As a late-binding, pilot-based system, the maintenance of a smooth and steady stream of pilot jobs to all grid sites is critical for PanDA operation. The ATLAS Computing Facility (ACF) at BNL, as the ATLAS Tier1 center in the US, operates the pilot submission systems for the US. This is done using the PanDA 'AutoPilot' scheduler component which submits pilot jobs via Condor-G, a grid job scheduling system developed at the University of Wisconsin-Madison.more » In this paper, we discuss the operation and performance of the Condor-G pilot submission at BNL, with emphasis on the challenges and issues encountered in the real grid production environment. With the close collaboration of Condor and PanDA teams, the scalability and stability of the overall system has been greatly improved over the last year. We review improvements made to Condor-G resulting from this collaboration, including isolation of site-based issues by running a separate Gridmanager for each remote site, introduction of the 'Nonessential' job attribute to allow Condor to optimize its behavior for the specific character of pilot jobs, better understanding and handling of the Gridmonitor process, as well as better scheduling in the PanDA pilot scheduler component. We will also cover the monitoring of the health of the system.« less

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

PubMed

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

Cloning, expression and activation of a truncated 92-kDa gelatinase minienzyme.

PubMed

Kröger, M; Tschesche, H

1997-09-01

The matrix metalloproteinases (MMPs) are a family of highly homologous zinc-endopeptidases that degrade extracellular matrix components. Human 92-kDa gelatinase (MMP-9) represents one of the MMPs that cleaves native collagen type IV. As a basis for structural investigations, the short form (catalytic domain, amino acid residues 113-450) of the 92-kDa gelatinase cDNA was cloned and expressed in E. coli as a minienzyme. By combination of reverse transcription (RT) and polymerase chain reaction (PCR), the truncated 92-kDa gelatinase-cDNA was amplified from the corresponding mRNA derived from ovarian carcinoma cells. The cDNA fragment obtained was cloned in E. coli and sequenced. With the exception of one nucleotide inversion at position 745 (gt-->tg) the cDNA sequence was identical to the nucleotide sequence of the 92-kDa gelatinase as has been previously reported. The protein was expressed in E. coli using the vector pET-12b. The recombinant protein was stored in inclusion bodies and extracted as a 38 kDa species from the inclusion bodies by solubilization in 8 M urea. The product was purified by affinity chromatography and gel filtration. Amino-terminal sequence analysis confirmed the identity with the catalytic domain of 92-kDa gelatinase. The recombinant protein was refolded in the presence of Ca2+ and Zn2+ and yielded an active minienzyme with gelatinolytic activity. It degrades the native substrate collagen type IV and the synthetic substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 x AcOH like the full-length 92-kDa gelatinase. The catalytic activity could be inhibited by the specific MMP inhibitors TIMP-1 and TIMP-2.

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron

PubMed Central

Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry. PMID:27163287

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron.

PubMed

Shen, Hung-Chang; Wei, Jia-Yi; Chu, Sao-Yu; Chung, Pei-Chi; Hsu, Tsai-Chi; Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

Revisiting shape selectivity in liquid chromatography for polycyclic aromatic hydrocarbons (PAHs) - six-ring and seven-ring Cata-condensed PAH isomers of molecular mass 328 Da and 378 Da.

PubMed

Oña-Ruales, Jorge O; Sander, Lane C; Wilson, Walter B; Wise, Stephen A

2018-01-01

The relationship of reversed-phase liquid chromatography (RPLC) retention on a polymeric C 18 stationary phase and the shape of polycyclic aromatic hydrocarbons (PAHs) was investigated for three-ring to seven-ring cata-condensed isomers. We report the first RPLC separation for six-ring and seven-ring cata-condensed PAH isomers. Correlations of LC retention and shape parameters (length-to-breath ratio, L/B and thickness, T) were investigated for 2 three-ring isomers (molecular mass 178 Da), 5 four-ring isomers (molecular mass 228 Da), 11 five-ring isomers (molecular mass 278 Da), 17 six-ring isomers (molecular mass 328 Da), and 20 seven-ring isomers (molecular mass 378 Da). Significant linear correlations were found for all isomer groups (r = 0.71 to 0.94). Nonplanarity of the PAH isomers was found to influence retention (i.e., nonplanar isomers eluting earlier than expected based on L/B) and linear correlations of retention vs. T for isomer groups containing nonplanar isomers were significant (r = 0.71 to 0.86). Graphical abstract.

Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

PubMed

Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

2014-09-01

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

A relevant IgE-reactive 28kDa protein identified from Salsola kali pollen extract by proteomics is a natural degradation product of an integral 47kDa polygalaturonase.

PubMed

Mas, Salvador; Oeo-Santos, Carmen; Cuesta-Herranz, Javier; Díaz-Perales, Araceli; Colás, Carlos; Fernández, Javier; Barber, Domingo; Rodríguez, Rosalía; de Los Ríos, Vivian; Barderas, Rodrigo; Villalba, Mayte

2017-08-01

A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola kali pollen extract is incubated with individual sera from Amaranthaceae pollen sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we identified this protein band as an allergenic polygalacturonase enzyme. The allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of 39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae allergenic polygalacturonases. cDNA-encoding sequence was subcloned into the pET41b vector and produced in bacteria as a His-tag fusion recombinant protein. The far-UV CD spectrum determined that rSal k 6 was folded. Immunostaining of the S. kali pollen protein extract with a rSal k 6-specific pAb and LC-MS/MS proteomic analyses confirmed the co-existence of the 28kDa band together with an allergenic band of about 47kDa in the pollen extract. Therefore, the 28kDa was assigned as a natural degradation product of the 47kDa integral polygalacturonase. The IgE-binding inhibition to S. kali pollen extract using rSal k 6 as inhibitor showed that signals directed to both protein bands of 28 and 47kDa were completely abrogated. The average prevalence of rSal k 6 among the three populations analyzed was 30%, with values correlating well with the levels of grains/m 3 of Amaranthaceae pollen. Sal k 6 shares IgE epitopes with Oleaceae members (Fraxinus excelsior, Olea europaea and Syringa vulgaris), with IgE-inhibition values ranging from 20% to 60%, respectively. No IgE-inhibition was observed with plant-derived food extracts. Copyright © 2017 Elsevier B.V. All rights reserved.

Geomagnetic observations on tristan da cunha, south atlantic ocean

USGS Publications Warehouse

Matzka, J.; Olsen, N.; Maule, C.F.; Pedersen, L.W.; Berarducci, A.M.; Macmillan, S.

2009-01-01

Few geomagnetic ground observations exist of the Earth's strongest core field anomaly, the South Atlantic Anomaly (SAA). The geomagnetic repeat station on the island Tristan da Cunha, located half-way between South Africa and South America at 37?? 05' S, 12?? 18' W, is therefore of crucial importance. We have conducted several sets of repeat station measurements during magnetically quiet conditions (Kp 2o or less) in 2004. The procedures are described and the results are compared to those from earlier campaigns and to the predictions of various global field models. Features of the local crustal bias field and the solar quiet daily variation are discussed. We also evaluate the benefit of continuous magnetic field recordings from Tristan da Cunha, and argue that such a data set is a very valuable addition to geomagnetic satellite data. Recently, funds were set up to establish and operate a magnetometer station on Tristan da Cunha during the Swarm magnetic satellite mission (2011-2014).

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.

PubMed

Lee, Joo H; Bae, Soo K; Kwon, Jong W; Kim, Won B; Lee, Myung G

2005-12-01

The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Septal membrane localization by C-terminal amphipathic α-helices of MinD in Bacillus subtilis mutant cells lacking MinJ or DivIVA.

PubMed

Ishikawa, Kazuki; Matsuoka, Satoshi; Hara, Hiroshi; Matsumoto, Kouji

2017-10-18

The Min system, which inhibits assembly of the cytokinetic protein FtsZ, is largely responsible for positioning the division site in rod-shaped bacteria. It has been reported that MinJ, which bridges DivIVA and MinD, is targeted to the cell poles by an interaction with DivIVA, and that MinJ in turn recruits MinCD to the cell poles. MinC, however, is located primarily at active division sites at mid-cell when expressed from its native promoter. Surprisingly, we found that Bacillus subtilis MinD is located at nascent septal membranes and at an asymmetric site on lateral membranes between nascent septal membranes in filamentous cells lacking MinJ or DivIVA. Bacillus subtilis MinD has two amphipathic α-helices rich in basic amino acid residues at its C-terminus; one of these, named MTS1 here, is the counterpart of the membrane targeting sequence (MTS) in Escherichia coli MinD while the other, named MTS-like sequence (MTSL), is the nearest helix to MTS1. These amphipathic helices were located independently at nascent septal membranes in cells lacking MinJ or DivIVA, whereas elimination of the helices from the wild type protein reduced its localization considerably. MinD variants with altered MTS1 and MTSL, in which basic amino acid residues were replaced with proline or acidic residues, were not located at nascent septal membranes, indicating that the binding to the nascent septal membranes requires basic residues and a helical structure. The septal localization of MTSL, but not of MTS1, was dependent on host cell MinD. These results suggest that MinD is targeted to nascent septal membranes via its C-terminal amphipathic α-helices in B. subtilis cells lacking MinJ or DivIVA. Moreover, the diffuse distribution of MinD lacking both MTSs suggests that only a small fraction of MinD depends on MinJ for its localization to nascent septal membranes.

Seeking 'energy' vs. pain relief in spas in Brazil (Caldas da Imperatriz) and Portugal (Termas da Sulfurea).

PubMed

Quintela, Maria Manuel

2011-04-01

This paper is a comparative ethnography of the therapeutic practices at two different spa locations: Caldas da Imperatriz, SC, Brazil, and Termas da Sulfurea in Cabeco de Vide, Portugal. The comparison reveals the existence of contrasting 'explanatory models' held by the spa-goers as well as by the official medical systems. In the Portuguese context this model is highly medicalized; in the Brazilian case, spa treatments are viewed as 'alternative' or 'complementary' therapy and are also related to religious philosophies. Each model corresponds to a different idiom expressing certain experiences and world views, one focusing on 'pains' (dores) and the other on 'energy' (energia), the former leading to the rationale of 'curing', the latter to the notion of 'energizing'. In this paper the author intends to analyze and contrast the categories found in these models, which originate from different conceptions of health, illness and healing for Brazilian and Portuguese spa-goers.

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

PubMed

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Influence of 120 kDa Pyruvate:Ferredoxin Oxidoreductase on Pathogenicity of Trichomonas vaginalis.

PubMed

Song, Hyun-Ouk

2016-02-01

Trichomonas vaginalis is a flagellate protozoan parasite and commonly infected the lower genital tract in women and men. Iron is a known nutrient for growth of various pathogens, and also reported to be involved in establishment of trichomoniasis. However, the exact mechanism was not clarified. In this study, the author investigated whether the 120 kDa protein of T. vaginalis may be involved in pathogenicity of trichomonads. Antibodies against 120 kDa protein of T. vaginalis, which was identified as pyruvate:ferredoxin oxidoreductase (PFOR) by peptide analysis of MALDI-TOF-MS, were prepared in rabbits. Pretreatment of T. vaginalis with anti-120 kDa Ab decreased the proliferation and adherence to vaginal epithelial cells (MS74) of T. vaginalis. Subcutaneous tissue abscess in anti-120 kDa Ab-treated T. vaginalis-injected mice was smaller in size than that of untreated T. vaginalis-infected mice. Collectively, the 120 kDa protein expressed by iron may be involved in proliferation, adhesion to host cells, and abscess formation, thereby may influence on the pathogenicity of T. vaginalis.

Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

USDA-ARS?s Scientific Manuscript database

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

PubMed

Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

2015-01-01

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

PubMed

McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

1990-01-01

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Color constrains depth in da Vinci stereopsis for camouflage but not occlusion.

PubMed

Wardle, Susan G; Gillam, Barbara J

2013-12-01

Monocular regions that occur with binocular viewing of natural scenes can produce a strong perception of depth--"da Vinci stereopsis." They occur either when part of the background is occluded in one eye, or when a nearer object is camouflaged against a background surface in one eye's view. There has been some controversy over whether da Vinci depth is constrained by geometric or ecological factors. Here we show that the color of the monocular region constrains the depth perceived from camouflage, but not occlusion, as predicted by ecological considerations. Quantitative depth was found in both cases, but for camouflage only when the color of the monocular region matched the binocular background. Unlike previous reports, depth failed even when nonmatching colors satisfied conditions for perceptual transparency. We show that placing a colored line at the boundary between the binocular and monocular regions is sufficient to eliminate depth from camouflage. When both the background and the monocular region contained vertical contours that could be fused, some observers appeared to use fusion, and others da Vinci constraints, supporting the existence of a separate da Vinci mechanism. The results show that da Vinci stereopsis incorporates color constraints and is more complex than previously assumed.

Ultrasonic irradiation enhanced the ability of Fluorescein-DA-Fe(III) on sonodynamic and sonocatalytic damages of DNA molecules.

PubMed

Wu, Qiong; Chen, Xia; Jia, Lizhen; Wang, Yi; Sun, Ying; Huang, Xingjun; Shen, Yuxiang; Wang, Jun

2017-11-01

The interaction of DNA with Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein-Ferrous(III) (Fluorescein-DA-Fe(III)) with dual functional (sonodynamic and sonocatalytic) activity was studied by UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. And then, the damage of DNA caused by Fluorescein-DA-Fe(III) under ultrasonic irradiation (US) was researched by agarose gel electrophoresis and cytotoxicity assay. Meanwhile, some influenced factors such as ultrasonic irradiation time and Fluorescein-DA-Fe(III) concentration on the damage degree of DNA molecules were also examined. As a control, for Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein (Fluorescein-DA), the same experiments were carried out. The results showed that both Fluorescein-DA-Fe(III) and Fluorescein-DA can interact with DNA molecules. Under ultrasonic irradiation, Fluorescein-DA shows sonodynamic activity, which can damage DNA molecules. While, in the presence of Fe(III) ion, the Fluorescein-DA-Fe(III) displays not only sonodynamic activity but also sonocatalytic activity under ultrasonic irradiation, which injures DNA more serious than Fluorescein-DA. The researches confirmed the dual function (sonodynamic activity and sonocatalytic activity) of Fluorescein-DA-Fe(III) and expanded the usage of Fluorescein-DA-Fe(III) as a sonosensitizer in sonodynamic therapy (SDT). Copyright © 2017 Elsevier B.V. All rights reserved.

The Indicative and Subjunctive "da"-complements in Serbian A Syntactic-Semantic Approach

ERIC Educational Resources Information Center

Todorovic, Natasa

2012-01-01

A syntactic-semantic investigation of subjunctive and indicative "da"-complements in Serbian is conducted in this project. After a careful comparison of Serbian sentence constructions with "da"-complements to the equivalent sentence structures in languages of the Balkans as well as other Slavic languages, it is clearly…

The coolest DA white dwarfs detected at soft X-ray wavelengths

NASA Technical Reports Server (NTRS)

Kidder, K. M.; Holberg, J. B.; Barstow, M. A.; Tweedy, R. W.; Wesemael, F.

1992-01-01

New soft X-ray/EUV photometric observations of the DA white dwarfs KPD 0631 + 1043 = WD 0631 + 107 and PG 1113 + 413 = WD 1113 + 413 are analyzed. Previously reported soft X-ray detections of three other DAs and the failure to detect a fourth DA in deep Exosat observations are investigated. New ground-based spectra are presented for all of the objects, with IUE Ly-alpha spectra for some. These data are used to constrain the effective temperatures and surface gravities. The improved estimates of these parameters are employed to refer a photospheric He abundance for the hotter objects and to elucidate an effective observational low-temperature threshold for the detection of pure hydrogen DA white dwarfs at soft X-ray wavelengths.

Complete daVinci versus laparoscopic pyeloplasty: cost analysis.

PubMed

Bhayani, Sam B; Link, Richard E; Varkarakis, John M; Kavoussi, Louis R

2005-04-01

Computer-assisted pyeloplasty with the daVinci system is an emerging technique to treat ureteropelvic junction (UPJ) obstruction. A relative cost analysis was performed assessing this technology in comparison with purely laparoscopic pyeloplasty. Eight patients underwent computer-assisted (daVinci) dismembered pyeloplasty (CP) via a transperitoneal four-port approach. They were compared with 13 patients who underwent purely laparoscopic pyeloplasty (LP). All patients had a primary UPJ obstruction and were matched for age, sex, and body mass index. The cost of equipment and capital depreciation for both procedures, as well as assessment of room set-up time, takedown time, and personnel were analyzed. Surgeons and nursing staff for both groups were experienced in both laparoscopy and daVinci procedures. One- and two-way financial analysis was performed to assess relative costs. The mean set-up and takedown time was 71 minutes for CP and 49 minutes for LP. The mean length of stay was 2.3 days for CP and 2.5 days for LP. The mean operating room (OR) times for CP and LP were 176 and 210 minutes, respectively. There were no complications in either group. One-way cost analysis with an economic model showed that LP is more cost effective than CP at our hospital if LP OR time is <338 minutes. With adjustment to a volume of 500 daVinci cases/year, CP is still not as cost effective as LP. Two-way sensitivity analysis shows that in-room time must still be <130 minutes and yearly cases must be >500 to obtain cost equivalence for CP. Perioperative parameters for CP are encouraging. However, the costs are a clear disadvantage. In our hospital, it is more cost effective to teach and perform LP than to perform CP.

Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex

PubMed Central

Lyumkis, Dmitry; Oliveira dos Passos, Dario; Tahara, Erich B.; Webb, Kristofor; Bennett, Eric J.; Vinterbo, Staal; Potter, Clinton S.; Carragher, Bridget; Joazeiro, Claudio A. P.

2014-01-01

All organisms have evolved mechanisms to manage the stalling of ribosomes upon translation of aberrant mRNA. In eukaryotes, the large ribosomal subunit-associated quality control complex (RQC), composed of the listerin/Ltn1 E3 ubiquitin ligase and cofactors, mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. How RQC recognizes stalled ribosomes and performs its functions has not been understood. Using single-particle cryoelectron microscopy, we have determined the structure of the RQC complex bound to stalled 60S ribosomal subunits. The structure establishes how Ltn1 associates with the large ribosomal subunit and properly positions its E3-catalytic RING domain to mediate nascent chain ubiquitylation. The structure also reveals that a distinguishing feature of stalled 60S particles is an exposed, nascent chain-conjugated tRNA, and that the Tae2 subunit of RQC, which facilitates Ltn1 binding, is responsible for selective recognition of stalled 60S subunits. RQC components are engaged in interactions across a large span of the 60S subunit surface, connecting the tRNA in the peptidyl transferase center to the distally located nascent chain tunnel exit. This work provides insights into a mechanism linking translation and protein degradation that targets defective proteins immediately after synthesis, while ignoring nascent chains in normally translating ribosomes. PMID:25349383

dK/da effects on the SCC growth rates of nickel base alloys in high-temperature water

NASA Astrophysics Data System (ADS)

Chen, Kai; Wang, Jiamei; Du, Donghai; Andresen, Peter L.; Zhang, Lefu

2018-05-01

The effect of dK/da on crack growth behavior of nickel base alloys has been studied by conducting stress corrosion cracking tests under positive and negative dK/da loading conditions on Alloys 690, 600 and X-750 in high temperature water. Results indicate that positive dK/da accelerates the SCC growth rates, and the accelerating effect increases with dK/da and the initial CGR. The FRI model was found to underestimate the dK/da effect by ∼100X, especially for strain hardening materials, and this underscores the need for improved insight and models for crack tip strain rate. The effect of crack tip strain rate and dK/dt in particular can explain the dK/da accelerating effect.

[Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].

PubMed

Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.

[First experience in the thyroid and parathyroid surgery using the da Vinci® system].

PubMed

Al Kadah, B; Siemer, S; Schick, B

2014-01-01

Endoscopic surgery for the treatment of thyroid and parathyroid pathologies is gaining increasing attention. The da Vinci® system has been already widely used in different fields of medicine including recently thyroid and parathyroid surgery. Herein we report our first experiences in endoscopic surgery of thyroid and parathyroid pathologies using the da Vinci® system. 8 patients presenting with struma nodosa in 6 cases and parathyroid adenomas in 2 cases have been treated using the da Vinci® system at the ENT department of Homburg/Saar University. The skin incision to introduce the instruments with the da Vinci® system were axilar or at the lateral segment of the clavicle. The neurovascular structures like inferior laryngeal nerve as well as the pathologies were clearly 3-dimensional visualized in all 8 cases. No paralysis of the vocal cord was observed. All patients had in histological examination a benign pathology. The endoscopic surgery of the thyroid and parathyroid gland can be performed using the da Vinci® system and offers an excellent, intraoperative, 3-dimensional visualization of the neurovascular structures. Additionally the da Vinci® system enables skin incisions within considerable distance from the thyroid and parathyroid gland. © Georg Thieme Verlag KG Stuttgart · New York.

DA-Raf, a dominant-negative antagonist of the Ras-ERK pathway, is a putative tumor suppressor.

PubMed

Kanno, Emiri; Kawasaki, Osamu; Takahashi, Kazuya; Takano, Kazunori; Endo, Takeshi

2018-01-01

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Análise da aplicação e dos resultados do modelo OPM3® para a área da saúde

PubMed Central

Augusto dos Santos, Luis; de Fátima Marin, Heimar

2015-01-01

Esta pesquisa procurou analisar se um modelo de questionário criado por uma comunidade internacional de gerenciamento de projetos e se é aplicavél a organizações voltadas a área de saúde. O modelo OPM3® (Organizational Project Management Maturity Model) foi criado para que organizações de qualquer área ou porte pudessem identificar a presença, ou ausência, de boas práticas de gerenciamento. O objetivo da aplicação desse modelo é avaliar sempre a organização e não o entrevistado. No presente artigo, são apresentados os resultados da aplicação desse modelo em uma organização que possuía produtos e serviços de tecnologia da informação aplicados à área de saúde. Este estudo verificou que o modelo é aplicável de forma rápida e que a organização analisada possuía um número expressivo de boas práticas. PMID:26924862

ATLAS WORLD-cloud and networking in PanDA

NASA Astrophysics Data System (ADS)

Barreiro Megino, F.; De, K.; Di Girolamo, A.; Maeno, T.; Walker, R.; ATLAS Collaboration

2017-10-01

The ATLAS computing model was originally designed as static clouds (usually national or geographical groupings of sites) around the Tier 1 centres, which confined tasks and most of the data traffic. Since those early days, the sites’ network bandwidth has increased at 0(1000) and the difference in functionalities between Tier 1s and Tier 2s has reduced. After years of manual, intermediate solutions, we have now ramped up to full usage of World-cloud, the latest step in the PanDA Workload Management System to increase resource utilization on the ATLAS Grid, for all workflows (MC production, data (re)processing, etc.). We have based the development on two new site concepts. Nuclei sites are the Tier 1s and large Tier 2s, where tasks will be assigned and the output aggregated, and satellites are the sites that will execute the jobs and send the output to their nucleus. PanDA dynamically pairs nuclei and satellite sites for each task based on the input data availability, capability matching, site load and network connectivity. This contribution will introduce the conceptual changes for World-cloud, the development necessary in PanDA, an insight into the network model and the first half-year of operational experience.

Yarkovsky-driven Impact Predictions: Apophis and 1950 DA

NASA Astrophysics Data System (ADS)

Farnocchia, Davide; Chesley, S. R.; Chodas, P.; Milani, A.

2013-05-01

Abstract (2,250 Maximum Characters): Orbit determination for Near-Earth Asteroids presents unique technical challenges due to the imperative of early detection and careful assessment of the risk posed by specific Earth close approaches. The occurrence of an Earth impact can be decisively driven by the Yarkovsky effect, which is the most important nongravitational perturbation as it causes asteroids to undergo a secular variation in semimajor axis resulting in a quadratic effect in anomaly. We discuss the cases of (99942) Apophis and (29075) 1950 DA. The relevance of the Yarkovsky effect for Apophis is due to a scattering close approach in 2029 with minimum geocentric distance ~38000 km. For 1950 DA the influence of the Yarkovsky effect in 2880 is due to the long time interval preceding the impact. We use the available information on the asteroids' physical models as a starting point for a Monte Carlo method that allow us to measure how the Yarkovsky effect affects orbital predictions. For Apophis we map onto the 2029 close approach b-plane and analyze the keyholes corresponding to resonant close approaches. For 1950 DA we use the b-plane corresponding to the possible impact in 2880. We finally compute the impact probability from the mapped probability density function on the considered b-plane.

[Anesthesia experiences on laparoscopic nephrectomy with da Vinci S robotics].

PubMed

Mou, Ling; Lan, Zhixun

2015-09-01

To summarize the clinical anesthesia experiences in 20 patients who underwent laparoscopic nephrectomy with da Vinci S robotics.
 Anesthesia data of 20 patients from Sichuan Provincial People's Hospital, who underwent laparoscopic nephrectomy with da Vinci S robotics from August 2014 to November 2014, were analyzed and summarized. The anesthesia time, operation time, CO(2) pneumoperitoneum time, PaCO(2) and PETCO(2) were recorded.
 All patients were anesthetized and underwent surgery with da Vinci S robotics. The anesthesia time was (220±14) min, the operation time was (187±11) min, and the CO(2) pneumoperitoneum time was (180±13) min. The PaCO(2) and PETCO(2) were significantly elevated at 1.5 h after operation compared with those at the baseline (before pneumoperitoneum) (P<0.05). The pH value was significantly decreased at 2.5 h after operation compared to that at the baseline (P<0.05). The peak airway pressure of inspiration was significantly elevated at 0.5 h after the beginning of pneumoperitoneum compared to that at the baseline (P<0.05).
 The hemodynamics is stable during the laparoscopic nephrectomy with da vinci S robotics. However, the duration of CO(2) pneumoperitoneum is significantly increased compared to that of other surgical procedures, resulting in high airway resistance and acid-base disturbance.

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

PubMed

Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-09-01

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Maize 27 kDa gamma-zein is a potential allergen for early weaned pigs.

PubMed

Krishnan, Hari B; Kerley, Monty S; Allee, Gary L; Jang, Sungchan; Kim, Won-Seok; Fu, Chunjiang J

2010-06-23

Soybean and maize are extensively used in animal feed, primarily in poultry, swine, and cattle diets. Soybean meal can affect pig performance in the first few weeks following weaning and elicit specific antibodies in weaned piglets. Though maize is a major component of pig feed, it is not known if any of the maize proteins can elicit immunological response in young pigs. In this study, we have identified a prominent 27 kDa protein from maize as an immunodominant protein in young pigs. This protein, like some known allergens, exhibited resistance to pepsin digestion in vitro. Several lines of evidence identify the immunodominant 27 kDa protein as a gamma-zein, a maize seed storage protein. First, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of different solubility classes of maize seed proteins revealed the presence of an abundant 27 kDa protein in the prolamin (zein) fraction. Antibodies raised against the purified maize 27 kDa gamma-zein also reacted against the same protein recognized by the young pig serum. Additionally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the peptides generated by trypsin digestion of the immunodominant 27 kDa protein showed significant homology to the maize 27 kDa gamma-zein. Since eliminating the allergenic protein will have a great impact on the nutritive value of the maize meal and expand its use in the livestock industry, it will be highly desirable to develop maize cultivars completely lacking the 27 kDa allergenic protein.

The da Vinci robotic surgical assisted anterior lumbar interbody fusion: technical development and case report.

PubMed

Beutler, William J; Peppelman, Walter C; DiMarco, Luciano A

2013-02-15

Technique development to use the da Vince Robotic Surgical System for anterior lumbar interbody fusion at L5-S1 is detailed. A case report is also presented. To evaluate and develop the da Vinci robotic assisted laparoscopic anterior lumbar stand-alone interbody fusion procedure. Anterior lumbar interbody fusion is a common procedure associated with potential morbidity related to the surgical approach. The da Vinci robot provides intra-abdominal dissection and visualization advantages compared with the traditional open and laparoscopic approach. The surgical techniques for approach to the anterior lumbar spine using the da Vinci robot were developed and modified progressively beginning with operative models followed by placement of an interbody fusion cage in the living porcine model. Development continued to progress with placement of fusion cage in a human cadaver, completed first in the laboratory setting and then in the operating room. Finally, the first patient with fusion completed using the da Vinci robot-assisted approach is presented. The anterior transperitoneal approach to the lumbar spine is accomplished with enhanced visualization and dissection capability, with maintenance of pneumoperitoneum using the da Vinci robot. Blood loss is minimal. The visualization inside the disc space and surrounding structures was considered better than current open and laparoscopic techniques. The da Vinci robot Surgical System technique continues to develop and is now described for the transperitoneal approach to the anterior lumbar spine. 4.

Specific cytoarchitectureal changes in hippocampal subareas in daDREAM mice.

PubMed

Mellström, Britt; Kastanauskaite, Asta; Knafo, Shira; Gonzalez, Paz; Dopazo, Xose M; Ruiz-Nuño, Ana; Jefferys, John G R; Zhuo, Min; Bliss, Tim V P; Naranjo, Jose R; DeFelipe, Javier

2016-02-29

Transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a Ca(2+)-binding protein that regulates Ca(2+) homeostasis through gene regulation and protein-protein interactions. It has been shown that a dominant active form (daDREAM) is implicated in learning-related synaptic plasticity such as LTP and LTD in the hippocampus. Neuronal spines are reported to play important roles in plasticity and memory. However, the possible role of DREAM in spine plasticity has not been reported. Here we show that potentiating DREAM activity, by overexpressing daDREAM, reduced dendritic basal arborization and spine density in CA1 pyramidal neurons and increased spine density in dendrites in dentate gyrus granule cells. These microanatomical changes are accompanied by significant modifications in the expression of specific genes encoding the cytoskeletal proteins Arc, Formin 1 and Gelsolin in daDREAM hippocampus. Our results strongly suggest that DREAM plays an important role in structural plasticity in the hippocampus.

Role of DNA polymerase I-associated 5'-exonuclease in replication of coliphage M13 replicative-form DNA

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

Dasgupta, S.; Mitra, S.

The conversion of both parental- and progeny-nascent open circular M13 RF DNA into covalently closed RF I is drastically reduced in an E. coli mutant deficient in the 5' ..-->.. 3' exonuclease associated with DNA polymerase I. The nascent progeny RF DNA also contains a significant proportion of fragments of smaller than unit length.

Estudo de não gaussianidade nas anisotropias da RCF medidas Wmap

NASA Astrophysics Data System (ADS)

Andrade, A. P. A.; Wuensche, C. A.; Ribeiro, A. L. B.

2003-08-01

A investigação do campo de flutuações da Radiação Cósmica de Fundo (RCF) pode oferecer um importante teste para os modelos cosmológicos que descrevem a origem e a evolução das flutuações primordiais. De um lado, apresenta-se o modelo inflacionário que prevê um espectro de flutuações adiabáticas distribuídas segundo uma gaussiana e, de outro, os modelos de defeitos topológicos (dentre outros) que descrevem um mecanismo para a geração de flutuações de isocurvatura que obedecem a uma distribuição não gaussiana. Este trabalho tem como objetivo caracterizar traços do modelo não gaussiano de campo misto (entre flutuações adiabáticas e de isocurvatura) nos mapas do Wilkinson Microwave Anisotropy Probe (WMAP). Simulações das anisotropias da RCF no contexto de mistura indicam traços marcantes na distribuição das flutuações de temperatura, mesmo quando consideradas pequenas contribuições do campo de isocurvatura (da ordem de 0.001). O efeito da mistura entre os campos resulta na transferência de potência de flutuações em escalas angulares intermediárias para flutuações em pequenas escalas angulares. Este efeito pode ser caracterizado pela relação entre as amplitudes dos primeiros picos acústicos no espectro de potência da RCF. Neste trabalho, investigamos a contribuição do campo de isocurvatura, no contexto de mistura, sobre as observações recentes da RCF realizadas pelo WMAP. As previsões do modelo de campo misto, uma vez confrontadas com as observações em pequenas escalas angulares, podem ajudar a revelar a natureza das flutuações primordiais.

Integration of PanDA workload management system with Titan supercomputer at OLCF

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

The PanDA (Production and Distributed Analysis) workload management system (WMS) was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. While PanDA currently distributes jobs to more than 100,000 cores at well over 100 Grid sites, the future LHC data taking runs will require more resources than Grid computing can possibly provide. To alleviate these challenges, ATLAS is engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF). The current approach utilizes a modified PanDA pilot framework for job submission to Titan's batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on Titan's multicore worker nodes. It also gives PanDA new capability to collect, in real time, information about unused worker nodes on Titan, which allows precise definition of the size and duration of jobs submitted to Titan according to available free resources. This capability significantly reduces PanDA job wait time while improving Titan's utilization efficiency. This implementation was tested with a variety of Monte-Carlo workloads on Titan and is being tested on several other supercomputing platforms. Notice: This manuscript has been authored, by employees of Brookhaven Science Associates, LLC under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy. The publisher by accepting the manuscript for publication acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

A Creative Approach to the Common Core Standards: The Da Vinci Curriculum

ERIC Educational Resources Information Center

Chaucer, Harry

2012-01-01

"A Creative Approach to the Common Core Standards: The Da Vinci Curriculum" challenges educators to design programs that boldly embrace the Common Core State Standards by imaginatively drawing from the genius of great men and women such as Leonardo da Vinci. A central figure in the High Renaissance, Leonardo made extraordinary contributions as a…

Low strain, long life creep fatigue of AF2-1DA and INCO 718

NASA Technical Reports Server (NTRS)

Thakker, A. B.; Cowles, B. A.

1983-01-01

Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation.

PubMed

Sapountzi, Vasileia; Logan, Ian R; Nelson, Glyn; Cook, Susan; Robson, Craig N

2008-01-01

Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat-interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function.

[The Arabic influence in the "Colóquios dos simples e drogas da India" of Garcia da Orta].

PubMed

Ricordel, Joëlle

2015-09-01

The "Colóquios dos simples e drogas he cousas medicinais de Índia" (Conversations on the simples, drugs and medicinal substances of India) (1563) of Garcia da Orta is a botanical and pharmacognosy book. The author is a Portuguese physician who studied in the Spanish universities and practiced medicine mainly in India. He studies in short chapters presented in the form of dialogues about sixty simples. Sources to which he refers are indicative of a "classical" training, but also the mark of a curious and open mind to different cultures. The Arabic sources are numerous and mainly concern the identification of substances by abundant synonyms of their names in foreign languages and different medicinal uses that may have been done by the ancient physicians. However, Da Orta is critical with respect to these sources, seeking contradictions and differences of opinion among authors. He confronts them with the oral information collected thanks to a wide network of contacts.

A Value-Engaged Approach for Evaluating the Bunche-Da Vinci Learning Academy

ERIC Educational Resources Information Center

Greene, Jennifer C.

2005-01-01

In 2001, the Bunche Academy was chosen by its district to join in partnership with the Da Vinci Learning Corporation to embark on an ambitious whole-school reform initiative, especially designed by the corporation for low-performing schools. In this chapter, the author describes how, as illustrated in the Bunche-Da Vinci Learning Academy context,…

Comparison of Abbott and Da-an real-time PCR for quantitating serum HBV DNA.

PubMed

Qiu, Ning; Li, Rui; Yu, Jian-Guo; Yang, Wen; Zhang, Wei; An, Yong; Li, Tong; Liu, Xue-En; Zhuang, Hui

2014-09-07

To compare the performance of the Da-an real-time hepatitis B virus (HBV) DNA assay and Abbott RealTime HBV assay. HBV DNA standards as well as a total of 180 clinical serum samples from patients with chronic hepatitis B were measured using the Abbott and Da-an real-time polymerase chain reaction (PCR) assays. Correlation and Bland-Altman plot analysis was used to compare the performance of the Abbott and Da-an assays. The HBV DNA levels were logarithmically transformed for analysis. All statistical analyses were performed using SPSS for Windows version 18.0. The correlation between the two assays was analyzed by Pearson's correlation and linear regression. The Bland-Altman plots were used for the analysis of agreement between the two assays. A P value of < 0.05 was considered statistically significant. The HBV DNA values measured by the Abbott or Da-an assay were significantly correlated with the expected values of HBV DNA standards (r = 0.999, for Abbott; r = 0.987, for Da-an, P < 0.001). A Bland-Altman plot showed good agreement between these two assays in detecting HBV DNA standards. Among the 180 clinical serum samples, 126 were quantifiable by both assays. Fifty-two samples were detectable by the Abbott assay but below the detection limit of the Da-an assay. Moreover, HBV DNA levels measured by the Abbott assay were significantly higher than those of the Da-an assay (6.23 ± 1.76 log IU/mL vs 5.46 ± 1.55 log IU/mL, P < 0.001). A positive correlation was observed between HBV DNA concentrations determined by the two assays in 126 paired samples (r = 0.648, P < 0.001). One hundred and fifteen of 126 (91.3%) specimens tested with both assays were within mean difference ± 1.96 SD of HBV DNA levels. The Da-an assay presented lower sensitivity and a narrower linear range as compared to the Abbott assay, suggesting the need to be improved.

Lessons learned - MO&DA at JPL. [Mission Operations and Data Analysis cost reduction of planetary exploration

NASA Technical Reports Server (NTRS)

Handley, Thomas H., Jr.

1993-01-01

The issues of how to avoid future surprise growth in Mission Operations and Data Analysis (MO&DA) costs and how to minimize total MO&DA costs for planetary missions are discussed within the context of JPL mission operations support. It is argued that there is no simple, single solution: the entire Project life-cycle must be addressed. It is concluded that cost models that can predict both MO&DA cost as well as Ground System development costs are needed. The first year MO&DA budget plotted against the total of ground and flight systems developments is shown. In order to better recognize changes and control costs in general, a modified funding line item breakdown is recommended to distinguish between development costs (prelaunch and postlaunch) and MO&DA costs.

Trichinella spiralis: strong antibody response to a 49 kDa newborn larva antigen in infected rats.

PubMed

Salinas-Tobon, Maria Del Rosario; Navarrete-Leon, Anaid; Mendez-Loredo, Blanca Esther; Esquivel-Aguirre, Dalia; Martínez-Abrajan, Dulce Maria; Hernandez-Sanchez, Javier

2007-02-01

In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000 muscle larvae (ML) and bled at different time intervals up to day 31 post infection (p.i.). Ab production was higher with 2000 ML dose and decreased with 8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on day 19 and remained high until the end of the study. Abs bound strongly at least to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97 kDa (described previously as TSL-1 antigens) occurred late in the infection. A follow-up of antigen recognition up to day 61 with the optimal immunization dose (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days p.i., which suggested antigenic differences with the previously reported 43 kDa ML antigen strongly recognized late in the infection. To analyze the stage-specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa NBL component in NBL total soluble extract but no reactivity was observed with soluble antigen of the other T. spiralis stages. Albeit with less intensity, the 49 kDa component was also recognized by PoAb together with other antigens of 53, 97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results reveal

Isoform composition and stoichiometry of the approx. 90-kDa heat shock protein associated with glucocorticoid receptors

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

Mendel, D.B.; Orti, E.

1988-05-15

The authors observed that the approx. 90-kDa non-steroid-binding component of nonactivated glucocorticoid receptors purified from WEHI-7 mouse thymoma cells (which has been identified as the approx. 90-kDa heat shock protein) consistently migrates as a doublet during polyacrylamide gel electrophoresis under denaturing and reducing conditions. It has recently been reported that murine Meth A cells contain a tumor-specific transplantation antigen (TSTA) which is related or identical to the approx. 90-kDa heat shock protein. The observation that TSTA and the approx. 90-kDa heat shock protein isolated from these cells exists as two isoforms of similar molecular mass and charge has suggested thatmore » the doublet observed is also due to the existence of two isoforms. They have therefore conducted this study to determine whether TSTA and the approx. 90-kDa component of glucocorticoid receptors are indeed related, to establish whether the receptor preferentially binds one isoform of the approx. 90-kDa heat shock protein, and to investigate the stoichiometry of the nonactivated receptor complex. They used the BuGr1 and AC88 monoclonal antibodies to purify, respectively, receptor-associated and free approx. 90-kDa heat shock protein from WEHI-7 cells grown for 48 h with (/sup 35/S)methionine to metabolically label proteins to steady state. The long-term metabolic labeling approach has also enabled them to directly determine that the purified non-activated glucocorticoid receptor contains a single steroid-binding protein and two approx. 90-kDa non-steroid-binding subunits. The consistency with which a approx. 1:2 stoichiometric ratio of steroid binding to approx. 90-kDa protein is observed supports the view that the approx. 90-kDa heat shock protein is a true component of nonactivated glucocorticoid-receptor complexes.« less

40 CFR 60.48Da - Compliance provisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 60.48Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... extensions shall be granted by the relevant air division or office director of the appropriate Regional... Protection Agency (U.S. EPA); Office of Air Quality Planning and Standards; Sector Policies and Programs...

40 CFR 60.48Da - Compliance provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 60.48Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... extensions shall be granted by the relevant air division or office director of the appropriate Regional... Protection Agency (U.S. EPA); Office of Air Quality Planning and Standards; Sector Policies and Programs...

Ab initio prediction of fast non-equilibrium transport of nascent polarons in SrI 2: a key to high-performance scintillation [First-principles study of hole polaron formation and migration in strontium iodide

DOE PAGES

Zhou, Fei; Sadigh, Babak; Aberg, Daniel; ...

2016-08-12

The excellent light yield proportionality of europium-doped strontium iodide (SrI 2:Eu) has resulted in state-of-the-art γ-ray detectors with remarkably high-energy resolution, far exceeding that of most halide compounds. In this class of materials, the formation of self-trapped hole polarons is very common. However, polaron formation is usually expected to limit carrier mobilities and has been associated with poor scintillator light-yield proportionality and resolution. Here using a recently developed first-principles method, we perform an unprecedented study of polaron transport in SrI 2, both for equilibrium polarons, as well as nascent polarons immediately following a self-trapping event. We propose a rationale formore » the unexpected high-energy resolution of SrI 2. We identify nine stable hole polaron configurations, which consist of dimerised iodine pairs with polaron-binding energies of up to 0.5 eV. They are connected by a complex potential energy landscape that comprises 66 unique nearest-neighbour migration paths. Ab initio molecular dynamics simulations reveal that a large fraction of polarons is born into configurations that migrate practically barrier free at room temperature. Consequently, carriers created during γ-irradiation can quickly diffuse away reducing the chance for nonlinear recombination, the primary culprit for non-proportionality and resolution reduction. We conclude that the flat, albeit complex, landscape for polaron migration in SrI 2 is a key for understanding its outstanding performance. This insight provides important guidance not only for the future development of high-performance scintillators but also of other materials, for which large polaron mobilities are crucial such as batteries and solid-state ionic conductors.« less

Origins of the Mechanochemical Coupling of Peptide Bond Formation to Protein Synthesis.

PubMed

Fritch, Benjamin; Kosolapov, Andrey; Hudson, Phillip; Nissley, Daniel A; Woodcock, H Lee; Deutsch, Carol; O'Brien, Edward P

2018-04-18

Mechanical forces acting on the ribosome can alter the speed of protein synthesis, indicating that mechanochemistry can contribute to translation control of gene expression. The naturally occurring sources of these mechanical forces, the mechanism by which they are transmitted 10 nm to the ribosome's catalytic core, and how they influence peptide bond formation rates are largely unknown. Here, we identify a new source of mechanical force acting on the ribosome by using in situ experimental measurements of changes in nascent-chain extension in the exit tunnel in conjunction with all-atom and coarse-grained computer simulations. We demonstrate that when the number of residues composing a nascent chain increases, its unstructured segments outside the ribosome exit tunnel generate piconewtons of force that are fully transmitted to the ribosome's P-site. The route of force transmission is shown to be through the nascent polypetide's backbone, not through the wall of the ribosome's exit tunnel. Utilizing quantum mechanical calculations we find that a consequence of such a pulling force is to decrease the transition state free energy barrier to peptide bond formation, indicating that the elongation of a nascent chain can accelerate translation. Since nascent protein segments can start out as largely unfolded structural ensembles, these results suggest a pulling force is present during protein synthesis that can modulate translation speed. The mechanism of force transmission we have identified and its consequences for peptide bond formation should be relevant regardless of the source of the pulling force.

Da-KGM based GO-reinforced FMBO-loaded aerogels for efficient arsenic removal in aqueous solution.

PubMed

Ye, Shuxin; Jin, Weiping; Huang, Qing; Hu, Ying; Li, Yan; Li, Jing; Li, Bin

2017-01-01

Composites based on deacetylated konjac glucomannan (Da-KGM) and graphene oxide (GO) aerogels with iron and manganese oxides (FMBO) for effective removal of arsenic from contaminated water. Da-KGM, which was used as supporting composite matrix here, were firstly treated with GO and loaded FMBO. The obtained Da-KGM/GO/FMBO composite aerogels were characterized by compression test, thermo gravimetric analysis (TGA), X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The characteristic results showed that addition of GO exhibited enhanced mechanical properties towards Da-KGM aerogels. What's more, results of FTIR indicated the strong intermolecular hydrogen bond interaction between KGM and GO. Batch adsorption tests were used to evaluate arsenic removal capacity. Da-KGM/GO loaded FMBO composite aerogels exhibited high adsorption ability for arsenite [As(III)] and arsenate [As(V)]. The adsorption results showed that the arsenic for both arsenite [As(III)] and arsenate [As(V)] removal process followed a pseudo-second-order rate equation and Langmuir monolayer adsorption. The maximum As(III) and As(V) uptake capacity of Da-KGM/GO(10%)/FMBO composite aerogels reached 30.21mgg -1 and 12.08mgg -1 respectively according to Langmuir isotherm at pH 7 and 323K. Copyright © 2016 Elsevier B.V. All rights reserved.

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion.

PubMed

Khaldy, Hoda; Escames, Germaine; León, Josefa; Bikjdaouene, Leila; Acuña-Castroviejo, Darío

2003-01-01

Previous studies showed a synergistic effect of melatonin and deprenyl against dopamine (DA) autoxidation in vitro. Since oxidative stress is implicated in Parkinson's disease (PD), we explored the effects of melatonin plus deprenyl administration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in C57/Bl6 mice. Melatonin, but not deprenyl prevents the inhibition of mitochondrial complex I and the oxidative damage in nigrostriatal neurons induced by MPTP. With the dose used deprenyl recovers 50% DA levels and tyrosine hydroxylase activity depressed by the neurotoxin, normalizing locomotor activity of mice. Melatonin, which was unable to counteract MPTP-induced DA depletion and inhibition of tyrosine hydroxylase activity, potentiates the effect of deprenyl on catecholamine turnover and mice ambulatory activity. These results suggest a dissociation of complex I inhibition from DA depletion in this model of Parkinson's disease. The data also support that a combination of melatonin, which improves mitochondrial electron transport chain and reduces oxidative damage, and deprenyl, which promotes the specific function of the rescued neurons, i.e. DA turnover, may be a promising strategy for the treatment of PD.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

PubMed

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Usefulness of 8 kDa protein of Fasciola hepatica in diagnosis of fascioliasis

PubMed Central

Kim, Kwangsig; Yang, Hyun Jong

2003-01-01

This study was designed to detect and evaluate an antigenicity of low molecular weight proteins of Fasciola hepatica in fascioliasis. Low molecular weight protein of F. hepatica was purified by ammonium sulfate precipitation and Sephacryl S-100 HR gel filtration. The protein obtained was estimated to be 8 kDa on 7.5-15% gradient sodium dodecyl sulfate gel electrophoresis. Immunoblotting studies showed that the 8 kDa protein reacted with human fascioliasis sera, but not other trematodiasis sera. This result suggests that the 8 kDa protein of F. hepatica is one of diagnostic antigens in human fascioliasis without cross-reaction with other human trematodiasis. PMID:12815325

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

PubMed

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-04-30

DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats

PubMed Central

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-01-01

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

Solving da Vinci stereopsis with depth-edge-selective V2 cells

PubMed Central

Assee, Andrew; Qian, Ning

2007-01-01

We propose a new model for da Vinci stereopsis based on a coarse-to-fine disparity-energy computation in V1 and disparity-boundary-selective units in V2. Unlike previous work, our model contains only binocular cells, relies on distributed representations of disparity, and has a simple V1-to-V2 feedforward structure. We demonstrate with random dot stereograms that the V2 stage of our model is able to determine the location and the eye-of-origin of monocularly occluded regions and improve disparity map computation. We also examine a few related issues. First, we argue that since monocular regions are binocularly defined, they cannot generally be detected by monocular cells. Second, we show that our coarse-to-fine V1 model for conventional stereopsis explains double matching in Panum’s limiting case. This provides computational support to the notion that the perceived depth of a monocular bar next to a binocular rectangle may not be da Vinci stereopsis per se (Gillam et al., 2003). Third, we demonstrate that some stimuli previously deemed invalid have simple, valid geometric interpretations. Our work suggests that studies of da Vinci stereopsis should focus on stimuli more general than the bar-and-rectangle type and that disparity-boundary-selective V2 cells may provide a simple physiological mechanism for da Vinci stereopsis. PMID:17698163

Direct voltammetric specific recognition of dopamine using AlIII-DA complexes at the hanging mercury drop electrode.

PubMed

Zhang, Fuping; Zhang, Min; Cheng, Jiongjia; Yang, Li; Ji, Ming; Bi, Shuping

2007-11-01

In this paper, we firstly report the direct voltammetric recognition and determination of dopamine (DA) by using Al(III)-DA complexes at the hanging mercury drop electrode (HMDE). A new sensitive cathodic peak of Al(III)-DA can be detected at -900 mV (vs. SCE) in 0.1 M NH(4)Cl-NH(3).H(2)O-0.1 M KCl buffer solution at pH 8.5. This unique -900 mV cathodic peak arises from the specific interaction between Al(III) and DA on the HMDE, whereas other substances with similar structures, such as L-dopa, epinephrine (EP), norepinephrine (NE), catechols, caffeic acid (CA), trihydric phenols and tiron, do not yield any new peak on the voltammograms in the potential range from -100 to -1200 mV when Al(III) is added. The distinct voltammetric characteristic of the recognition of DA can effectively inhibit the interferences of both ascorbic acid and uric acid in the DA determination by the direct electrochemistry, which is a major difficulty when a solid electrode is used. The proposed method can be anticipated as an effective means for the recognition of DA in the elucidation of the mechanisms of Parkinson's disease (PD) and Alzheimer's disease (AD) in the presence of Al(III).

SAGES TAVAC safety and effectiveness analysis: da Vinci ® Surgical System (Intuitive Surgical, Sunnyvale, CA).

PubMed

Tsuda, Shawn; Oleynikov, Dmitry; Gould, Jon; Azagury, Dan; Sandler, Bryan; Hutter, Matthew; Ross, Sharona; Haas, Eric; Brody, Fred; Satava, Richard

2015-10-01

The da Vinci(®) Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is a computer-assisted (robotic) surgical system designed to enable and enhance minimally invasive surgery. The Food and Drug Administration (FDA) has cleared computer-assisted surgical systems for use by trained physicians in an operating room environment for laparoscopic surgical procedures in general, cardiac, colorectal, gynecologic, head and neck, thoracic and urologic surgical procedures. There are substantial numbers of peer-reviewed papers regarding the da Vinci(®) Surgical System, and a thoughtful assessment of evidence framed by clinical opinion is warranted. The SAGES da Vinci(®) TAVAC sub-committee performed a literature review of the da Vinci(®) Surgical System regarding gastrointestinal surgery. Conclusions by the sub-committee were vetted by the SAGES TAVAC Committee and SAGES Executive Board. Following revisions, the document was evaluated by the TAVAC Committee and Executive Board again for final approval. Several conclusions were drawn based on expert opinion organized by safety, efficacy, and cost for robotic foregut, bariatric, hepatobiliary/pancreatic, colorectal surgery, and single-incision cholecystectomy. Gastrointestinal surgery with the da Vinci(®) Surgical System is safe and comparable, but not superior to standard laparoscopic approaches. Although clinically acceptable, its use may be costly for select gastrointestinal procedures. Current data are limited to the da Vinci(®) Surgical System; further analyses are needed.

32 CFR 516.14 - Service of process on DA or Secretary of Army.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Service of process on DA or Secretary of Army. 516.14 Section 516.14 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Service of Process § 516.14 Service of process on DA...

The analysis Arabidopsis thaliana overexpressing a 14kDa self-folding protein [abstract

USDA-ARS?s Scientific Manuscript database

A recent study in banana identified a 14kDa protein that has been hypothesized to function in regulating the nucleation and growth of the needle-shaped crystals of calcium oxalate that accumulate within the tissues of this plant. To gain further insight in to the functional role of this 14 kDa prote...

32 CFR 516.14 - Service of process on DA or Secretary of Army.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Service of process on DA or Secretary of Army. 516.14 Section 516.14 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Service of Process § 516.14 Service of process on DA...

[La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

Petrogenesis of meta-volcanic rocks from the Maimón Formation (Dominican Republic): Geochemical record of the nascent Greater Antilles paleo-arc

NASA Astrophysics Data System (ADS)

Torró, Lisard; Proenza, Joaquín A.; Marchesi, Claudio; Garcia-Casco, Antonio; Lewis, John F.

2017-05-01

stages transitional between FAB and first-island arc magmatism, whereas Group 2 boninitic lavas resulted from focused flux melting and higher degrees of melt extraction in a more mature stage of subduction. Group 3 basalts probably represent magmatism taking place immediately before the establishment of a steady-state subduction regime. The relatively high extents of flux melting and slab input recorded in the Maimón lavas support a scenario of hot subduction beneath the nascent Greater Antilles paleo-arc. Paleotectonic reconstructions and the markedly depleted, though heterogeneous character of the mantle source, indicate the rise of shallow asthenosphere which had sourced mid-ocean ridge basalts (MORB) and/or back-arc basin basalts (BABB) in the proto-Caribbean domain prior to the inception of SW-dipping subduction. Relative to the neighbouring Aptian-Albian Los Ranchos Formation, we suggest that Maimón volcanic rocks extruded more proximal to the vertical projection of the subducting proto-Caribbean spreading ridge.

Hidden sketches by Leonardo da Vinci revealed

NASA Astrophysics Data System (ADS)

Dumé, Belle

2009-02-01

Three drawings on the back of Leonardo da Vinci's The Virgin and Child with St Anne (circa 1508) have been discovered by researchers led by Michel Menu from the Centre de Recherche et de Restauration des Musées de France (C2RMF) and the Louvre Museum in Paris.

[Leonardo da Vinci--a dyslectic genius?].

PubMed

Røsstad, Anna

2002-12-10

Leonardo da Vinci's texts consist almost exclusively of scientific notes. Working on a book on Leonardo's art, I studied all Leonardo's published texts carefully for any new information. In some prefaces I came to suspect that Leonardo might have suffered from dyslexia. This article considers the question of whether it is possible to find indications of dyslexia in Leonardo's texts and in the accounts of his life.

The spin evolution of nascent neutron stars

NASA Astrophysics Data System (ADS)

Watts, Anna L.; Andersson, Nils

2002-07-01

The loss of angular momentum owing to unstable r-modes in hot young neutron stars has been proposed as a mechanism for achieving the spin rates inferred for young pulsars. One factor that could have a significant effect on the action of the r-mode instability is fallback of supernova remnant material. The associated accretion torque could potentially counteract any gravitational-wave-induced spin-down, and accretion heating could affect the viscous damping rates and hence the instability. We discuss the effects of various external agents on the r-mode instability scenario within a simple model of supernova fallback on to a hot young magnetized neutron star. We find that the outcome depends strongly on the strength of the magnetic field of the star. Our model is capable of generating spin rates for young neutron stars that accord well with initial spin rates inferred from pulsar observations. The combined action of r-mode instability and fallback appears to cause the spin rates of neutron stars born with very different spin rates to converge, on a time-scale of approximately 1 year. The results suggest that stars with magnetic fields <=1013G could emit a detectable gravitational wave signal for perhaps several years after the supernova event. Stars with higher fields (magnetars) are unlikely to emit a detectable gravitational wave signal via the r-mode instability. The model also suggests that the r-mode instability could be extremely effective in preventing young neutron stars from going dynamically unstable to the bar-mode.

Formation of the 67-kDa laminin receptor by acylation of the precursor.

PubMed

Butò, S; Tagliabue, E; Ardini, E; Magnifico, A; Ghirelli, C; van den Brûle, F; Castronovo, V; Colnaghi, M I; Sobel, M E; Ménard, S

1998-06-01

Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor invasiveness has been clearly demonstrated, its molecular structure remains an open problem, since only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated so far. A pool of recently obtained monoclonal antibodies directed against the recombinant 37LRP molecule was used to investigate the processing that leads to the formation of the 67-kDa molecule. In soluble extracts of A431 human carcinoma cells, these reagents recognize the precursor molecule as well as the mature 67LR and a 120-kDa molecule. The recovery of these proteins was found to be strikingly dependent upon the cell solubilization conditions: the 67LR is soluble in NP-40-lysis buffer whereas the 37LRP is NP-40-insoluble. Inhibition of 67LR formation by cerulenin indicates that acylation is involved in the processing of the receptor. It is likely a palmitoylation process, as indicated by sensitivity of NP-40-soluble extracts to hydroxylamine treatment. Immunoblotting assays performed with a polyclonal serum directed against galectin3 showed that both the 67- and the 120-kDa proteins carry galectin3 epitopes whereas the 37LRP does not. These data suggest that the 67LR is a heterodimer stabilized by strong intramolecular hydrophobic interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross-reacting molecule.

PanDA: Exascale Federation of Resources for the ATLAS Experiment at the LHC

NASA Astrophysics Data System (ADS)

Barreiro Megino, Fernando; Caballero Bejar, Jose; De, Kaushik; Hover, John; Klimentov, Alexei; Maeno, Tadashi; Nilsson, Paul; Oleynik, Danila; Padolski, Siarhei; Panitkin, Sergey; Petrosyan, Artem; Wenaus, Torre

2016-02-01

After a scheduled maintenance and upgrade period, the world's largest and most powerful machine - the Large Hadron Collider(LHC) - is about to enter its second run at unprecedented energies. In order to exploit the scientific potential of the machine, the experiments at the LHC face computational challenges with enormous data volumes that need to be analysed by thousand of physics users and compared to simulated data. Given diverse funding constraints, the computational resources for the LHC have been deployed in a worldwide mesh of data centres, connected to each other through Grid technologies. The PanDA (Production and Distributed Analysis) system was developed in 2005 for the ATLAS experiment on top of this heterogeneous infrastructure to seamlessly integrate the computational resources and give the users the feeling of a unique system. Since its origins, PanDA has evolved together with upcoming computing paradigms in and outside HEP, such as changes in the networking model, Cloud Computing and HPC. It is currently running steadily up to 200 thousand simultaneous cores (limited by the available resources for ATLAS), up to two million aggregated jobs per day and processes over an exabyte of data per year. The success of PanDA in ATLAS is triggering the widespread adoption and testing by other experiments. In this contribution we will give an overview of the PanDA components and focus on the new features and upcoming challenges that are relevant to the next decade of distributed computing workload management using PanDA.

Local classification: Locally weighted-partial least squares-discriminant analysis (LW-PLS-DA).

PubMed

Bevilacqua, Marta; Marini, Federico

2014-08-01

The possibility of devising a simple, flexible and accurate non-linear classification method, by extending the locally weighted partial least squares (LW-PLS) approach to the cases where the algorithm is used in a discriminant way (partial least squares discriminant analysis, PLS-DA), is presented. In particular, to assess which category an unknown sample belongs to, the proposed algorithm operates by identifying which training objects are most similar to the one to be predicted and building a PLS-DA model using these calibration samples only. Moreover, the influence of the selected training samples on the local model can be further modulated by adopting a not uniform distance-based weighting scheme which allows the farthest calibration objects to have less impact than the closest ones. The performances of the proposed locally weighted-partial least squares-discriminant analysis (LW-PLS-DA) algorithm have been tested on three simulated data sets characterized by a varying degree of non-linearity: in all cases, a classification accuracy higher than 99% on external validation samples was achieved. Moreover, when also applied to a real data set (classification of rice varieties), characterized by a high extent of non-linearity, the proposed method provided an average correct classification rate of about 93% on the test set. By the preliminary results, showed in this paper, the performances of the proposed LW-PLS-DA approach have proved to be comparable and in some cases better than those obtained by other non-linear methods (k nearest neighbors, kernel-PLS-DA and, in the case of rice, counterpropagation neural networks). Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of porcine 25 kDa amelogenin and its proteolytic derivatives on bone sialoprotein expression.

PubMed

Nakayama, Y; Yang, L; Mezawa, M; Araki, S; Li, Z; Wang, Z; Sasaki, Y; Takai, H; Nakao, S; Fukae, M; Ogata, Y

2010-10-01

Amelogenins are hydrophobic proteins that are the major component of developing enamel. Enamel matrix derivative has been used for periodontal regeneration. Bone sialoprotein is an early phenotypic marker of osteoblast differentiation. In this study, we examined the ability of porcine amelogenins to regulate bone sialoprotein transcription. To determine the molecular basis of the transcriptional regulation of the bone sialoprotein gene by amelogenins, we conducted northern hybridization, transient transfection analyses and gel mobility shift assays using the osteoblast-like ROS 17/2.8 cells. Amelogenins (100 ng/mL) up-regulated bone sialoprotein mRNA at 3 h, with maximal mRNA expression occurring at 12 h (25 and 20 kDa) and 6 h (13 and 6 kDa). Amelogenins (100 ng/mL, 12 h) increased luciferase activities in pLUC3 (nucleotides -116 to +60), and 6 kDa amelogenin up-regulated pLUC4 (nucleotides -425 to +60) activity. The tyrosine kinase inhibitor inhibited amelogenin-induced luciferase activities, whereas the protein kinase A inhibitor abolished 25 kDa amelogenin-induced bone sialoprotein transcription. The effects of amelogenins were abrogated by 2-bp mutations in the fibroblast growth factor 2 response element (FRE). Gel-shift assays with radiolabeled FRE, homeodomain-protein binding site (HOX) and transforming growth factor-beta1 activation element (TAE) double-strand oligonucleotides revealed increased binding of nuclear proteins from amelogenin-stimulated ROS 17/2.8 cells at 3 h (25 and 13 kDa) and 6 h (20 and 6 kDa). These results demonstrate that porcine 25 kDa amelogenin and its proteolytic derivatives stimulate bone sialoprotein transcription by targeting FRE, HOX and TAE in the bone sialoprotein gene promoter, and that full-length amelogenin and amelogenin cleavage products are able to regulate bone sialoprotein transcription via different signaling pathways. (c) 2010 John Wiley & Sons A/S.

Complexity of VTA DA neural activities in response to PFC transection in nicotine treated rats.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin M; Akay, Metin

2011-02-27

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction between VTA and PFC. The complexity of the recorded neural firing was subsequently assessed using a method based on the Lempel-Ziv estimator. The results were compared with those obtained when computing the entropy of neural firing. Exposure to nicotine triggered a significant increase in VTA DA neurons firing complexity when communication between PFC and VTA was present, while transection obliterated the effect of nicotine. Similar results were obtained when entropy values were estimated. Our findings suggest that PFC plays a vital role in mediating VTA activity. We speculate that increased firing complexity with acute nicotine administration in PFC intact subjects is due to the close functional coupling between PFC and VTA. This hypothesis is supported by the fact that deletion of PFC results in minor alterations of VTA DA neural firing when nicotine is acutely administered.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

PubMed

Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

2017-01-01

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

The da Vinci telerobotic surgical system: the virtual operative field and telepresence surgery.

PubMed

Ballantyne, Garth H; Moll, Fred

2003-12-01

The United States Department of Defense developed the telepresence surgery concept to meet battlefield demands. The da Vinci telerobotic surgery system evolved from these efforts. In this article, the authors describe the components of the da Vinci system and explain how the surgeon sits at a computer console, views a three-dimensional virtual operative field, and performs the operation by controlling robotic arms that hold the stereoscopic video telescope and surgical instruments that simulate hand motions with seven degrees of freedom. The three-dimensional imaging and handlike motions of the system facilitate advanced minimally invasive thoracic, cardiac, and abdominal procedures. da Vinci has recently released a second generation of telerobots with four arms and will continue to meet the evolving challenges of surgery.

Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis.

PubMed Central

Mukherjee, T; Basu, D; Mahapatra, S; Goffin, C; van Beeumen, J; Basu, J

1996-01-01

The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin. PMID:8947487

Sequence and expression variations suggest an adaptive role for the DA1-like gene family in the evolution of soybeans.

PubMed

Zhao, Man; Gu, Yongzhe; He, Lingli; Chen, Qingshan; He, Chaoying

2015-05-15

The DA1 gene family is plant-specific and Arabidopsis DA1 regulates seed and organ size, but the functions in soybeans are unknown. The cultivated soybean (Glycine max) is believed to be domesticated from the annual wild soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the evolution of soybeans, we compared variation at both sequence and expression levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). Sequence identities were extremely high between the orthologous pairs between soybeans, while the paralogous copies in a soybean species showed a relatively high divergence. Moreover, the expression variation of DA1-like paralogous genes in soybean was much greater than the orthologous gene pairs between the wild and cultivated soybeans during development and challenging abiotic stresses such as salinity. We further found that overexpressing GsoDA1 genes did not affect seed size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed germination sensitivity to salt stress. Moreover, most of these genes could improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a detection of expression variation of several key genes in the salt-tolerance pathways. Our work suggested that expression diversification of DA1-like genes is functionally associated with adaptive radiation of soybeans, reinforcing that the plant-specific DA1 gene family might have contributed to the successful adaption to complex environments and radiation of the plants.

Aerodynamic design of the Cal Poly Da Vinci Human-Powered Helicopter

NASA Technical Reports Server (NTRS)

Larwood, Scott; Saiki, Neal

1990-01-01

This paper will discuss the methodology used in designing the rotor and drive propellers for the third generation Cal Poly Da Vinci Human-Powered Helicopter. The rotor was designed using a lifting surface, uniform inflow hover analysis code and the propeller was designed using a minimum induced-loss method. Construction, geometry, and operating considerations are discussed as they impact the designs. Optimization of the design performance is also explained. The propellers were tested in a wind tunnel and results are compared with theoretical data. Successful flight tests of the Da Vinci III are discussed.

Left lower lobe sleeve lobectomy for lung cancer using the Da Vinci surgical system.

PubMed

Zhao, Yandong; Jiao, Wenjie; Ren, Xiaoyang; Zhang, Liangdong; Qiu, Tong; Fu, Bo; Wang, Lei

2016-04-12

Despite the robotic surgery is widely applied, sleeve lobectomy for lung cancer using the Da Vinci surgical system is still less performed. We described a sleeve lobectomy for adenocarcinoma located at the left lower lobe using the Da Vinci surgical system. A case of 57-year old female referred to our hospital. Computed tomography scan showed an occupation located at the left lower lobe and adenocarcinoma project from the lobe bronchus was diagnosed by bronchoscope examination. A sleeve lobectomy was performed using the Da Vinci surgical system and the postoperative recovery was uneventful. Robotic thoracic surgery is feasible to perform sleeve lobectomy inspite of inadequate experience.

The Battle of RNA Synthesis: Virus versus Host.

PubMed

Harwig, Alex; Landick, Robert; Berkhout, Ben

2017-10-21

Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage.

Oligosaccharyltransferase directly binds to ribosome at a location near the translocon-binding site

PubMed Central

Harada, Yoichiro; Li, Hua; Li, Huilin; Lennarz, William J.

2009-01-01

Oligosaccharyltransferase (OT) transfers high mannose-type glycans to the nascent polypeptides that are translated by the membrane-bound ribosome and translocated into the lumen of the endoplasmic reticulum through the Sec61 translocon complex. In this article, we show that purified ribosomes and OT can form a binary complex with a stoichiometry of ≈1 to 1 in the presence of detergent. We present evidence that OT may bind to the large ribosomal subunit near the site where nascent polypeptides exit. We further show that OT and the Sec61 complex can simultaneously bind to ribosomes in vitro. Based on existing data and our findings, we propose that cotranslational translocation and N-glycosylation of nascent polypeptides are mediated by a ternary supramolecular complex consisting of OT, the Sec61 complex, and ribosomes. PMID:19365066

Translocation of an 89-kDa periplasmic protein is associated with Holospora infection

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

Iwatani, Koichi; Dohra, Hideo; Lang, B. Franz

2005-12-02

The symbiotic bacterium Holospora obtusa infects the macronucleus of the ciliate Paramecium caudatum. After ingestion by its host, an infectious form of Holospora with an electron-translucent tip passes through the host digestive vacuole and penetrates the macronuclear envelope with this tip. To investigate the underlying molecular mechanism of this process, we raised a monoclonal antibody against the tip-specific 89-kDa protein, sequenced this partially, and identified the corresponding complete gene. The deduced protein sequence carries two actin-binding motifs. Indirect immunofluorescence microscopy shows that during escape from the host digestive vacuole, the 89-kDa proteins translocates from the inside to the outside ofmore » the tip. When the bacterium invades the macronucleus, the 89-kDa protein is left behind at the entry point of the nuclear envelope. Transmission electron microscopy shows the formation of fine fibrous structures that co-localize with the antibody-labeled regions of the bacterium. Our findings suggest that the 89-kDa protein plays a role in Holospora's escape from the host digestive vacuole, the migration through the host cytoplasm, and the invasion into the macronucleus.« less

Effects of acute amphetamine (AMPH) treatment on rat striatal dopamine (DA) receptor activity

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

Roseboom, P.H.; Iwaniec, L.M.; Ackerman, J.M.

1986-03-05

Upon administration of AMPH rats display a complex series of dose and time dependent behaviors and changes in dopaminergic activity. They found a decrease in D1 DA receptor-stimulated adenylate cyclase (DA-AC) activity in rat striatal membranes after acute in vivo AMPH at a dose and time of intense stereotyped behavior. The Ka for D1-AC activity increased and the Vmax decreased in striatal membranes from rats given 7.5 mg/kg AMPH i.p. and killed 1 hr later as compared to saline (SAL) controls. They examined whether the decrease of DA-AC was due to a change in receptor number or activation of GTP-bindingmore » protein, Ns. Female Holtzman rats were injected with SAL or 7.5 mg/kg AMPH and killed 1 hr later. A 27,000 x g striatal particulate fraction was prepared for AC assay or (/sup 3/H)DA binding with 10 nM spiroperidol. They found no difference in stimulation of AC by NaF, GTP or GppNHp at any dose tested in membranes from SAL- and AMPH-treated rats. Calmodulin-stimulated AC was also unchanged after AMPH. Specific binding at a saturating concentration of (/sup 3/H)DA was 191 +/- 31 and 117 +/- 14 fmol/mg prot in membranes from SAL- and AMPH-treated rats, respectively. This suggests an alteration is occurring at the level of the D1 receptor rather than at coupling of Ns with the AC catalytic subunit.« less

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Recombinant expression, isolation, and proteolysis of extracellular matrix-secreted phosphoprotein-24 kDa.

PubMed

Murray, Elsa J Brochmann; Murray, Samuel S; Simon, Robert; Behnam, Keyvan

2007-01-01

Secreted phosphoprotein-24 kDa (spp24) is an extracellular matrix protein first cloned from bone. Bovine spp24 is transcribed as a 203 amino acid residue protein that undergoes cleavage of a secretory peptide to form the mature protein (spp24, residues 24 to 203). While not osteogenic itself, spp24 is degraded to a pro-osteogenic protein, spp18.5, in bone. Both spp18.5 and spp24 contain a cyclic TRH1 (TGF-beta receptor II homology-1) domain similar to that found in the receptor itself and in fetuin. A synthetic peptide corresponding to the TRH1 domain of spp18.5 and spp24 specifically binds BMP-2 and enhances the rate and magnitude of BMP-2-induced ectopic bone formation in vivo. The parental protein, spp24, exhibits a high affinity for bone and mineral complexes, but its abundance there is low, suggesting that it is rapidly degraded. The availability of recombinant spp24 and its degradation products would facilitate the elucidation of their structure:function relationships. We describe here the expression of His(6)-tagged bovine spp24 (residues 24 to 203) in E. coli, its purification by high-resolution IMAC (immobilized metal affinity chromatography), and the characterization of the full-length recombinant 21.5 kDa protein and its two major 16 kDa and 14.5 kDa degradation products (spp24, residues 24 to 157, and spp24, residues 24 to 143) by mass spectroscopy. The recombinant spp24 protein was resistant to proteolysis by MC3T3-E1 osteoblastic cell extracts in the absence of calcium; however, in the presence of 4 mM Ca, it can undergo essentially complete proteolysis to small peptides, bypassing the 16 kDa and 14.5 kDa intermediates. This confirms the proteolytic susceptibility of spp24. It also suggests that the levels of spp24 in bone may be regulated, in part, by calcium-dependent proteolysis mediated by osteoblastic cells.

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Hypothalamic interaction with the mesolimbic DA system in the control of the maternal and sexual behaviors in rats.

PubMed

Stolzenberg, Danielle S; Numan, Michael

2011-01-01

The medial preoptic area (MPOA) of the hypothalamus regulates maternal behavior, male sexual behavior, and female sexual behavior. Functional neuroanatomical evidence indicates that the appetitive aspects of maternal behavior are regulated through MPOA interactions with the mesolimbic dopamine (DA) system; a major focus of this review is to explore whether or not the MPOA participates in the appetitive aspects of sexual behavior via its interaction with the mesolimbic DA system. A second focus of this review is to examine the extent to which estradiol interactions with DA within this circuit regulate all three reproductive behaviors. One mechanism through which estradiol activates male sexual behavior is through the potentiation of DA activity in the MPOA. In the hypothalamus, estradiol has also been found to act in concert with DA, through the activation of similar intracellular signaling pathways, in order to stimulate female sexual behavior. Finally, recent evidence suggests that some effects of estradiol are mediated by direct action of estradiol on the mesolimbic DA system. Copyright © 2010 Elsevier Ltd. All rights reserved.

The neuroanatomic complexity of the CRF and DA systems and their interface: What we still don't know.

PubMed

Kelly, E A; Fudge, J L

2018-07-01

Corticotropin-releasing factor (CRF) is a neuropeptide that mediates the stress response. Long known to contribute to regulation of the adrenal stress response initiated in the hypothalamic-pituitary axis (HPA), a complex pattern of extrahypothalamic CRF expression is also described in rodents and primates. Cross-talk between the CRF and midbrain dopamine (DA) systems links the stress response to DA regulation. Classically CRF + cells in the extended amygdala and paraventricular nucleus (PVN) are considered the main source of this input, principally targeting the ventral tegmental area (VTA). However, the anatomic complexity of both the DA and CRF system has been increasingly elaborated in the last decade. The DA neurons are now recognized as having diverse molecular, connectional and physiologic properties, predicted by their anatomic location. At the same time, the broad distribution of CRF cells in the brain has been increasingly delineated using different species and techniques. Here, we review updated information on both CRF localization and newer conceptualizations of the DA system to reconsider the CRF-DA interface. Copyright © 2018 Elsevier Ltd. All rights reserved.

PanDaTox: A tool for accelerated metabolic engineering

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

Amitai, Gil; Sorek, Rotem

2012-07-18

Metabolic engineering is often facilitated by cloning of genes encoding enzymes from various heterologous organisms into E. coli. Such engineering efforts are frequently hampered by foreign genes that are toxic to the E. coli host. We have developed PanDaTox (www.weizmann.ac.il/pandatox), a web-based resource that provides experimental toxicity information for more than 1.5 million genes from hundreds of different microbial genomes. The toxicity predictions, which were extensively experimentally verified, are based on serial cloning of genes into E. coli as part of the Sanger whole genome shotgun sequencing process. PanDaTox can accelerate metabolic engineering projects by allowing researchers to exclude toxicmore » genes from the engineering plan and verify the clonability of selected genes before the actual metabolic engineering experiments are conducted.« less

gLExec and MyProxy integration in the ATLAS/OSG PanDA workload management system

NASA Astrophysics Data System (ADS)

Caballero, J.; Hover, J.; Litmaath, M.; Maeno, T.; Nilsson, P.; Potekhin, M.; Wenaus, T.; Zhao, X.

2010-04-01

Worker nodes on the grid exhibit great diversity, making it difficult to offer uniform processing resources. A pilot job architecture, which probes the environment on the remote worker node before pulling down a payload job, can help. Pilot jobs become smart wrappers, preparing an appropriate environment for job execution and providing logging and monitoring capabilities. PanDA (Production and Distributed Analysis), an ATLAS and OSG workload management system, follows this design. However, in the simplest (and most efficient) pilot submission approach of identical pilots carrying the same identifying grid proxy, end-user accounting by the site can only be done with application-level information (PanDA maintains its own end-user accounting), and end-user jobs run with the identity and privileges of the proxy carried by the pilots, which may be seen as a security risk. To address these issues, we have enabled PanDA to use gLExec, a tool provided by EGEE which runs payload jobs under an end-user's identity. End-user proxies are pre-staged in a credential caching service, MyProxy, and the information needed by the pilots to access them is stored in the PanDA DB. gLExec then extracts from the user's proxy the proper identity under which to run. We describe the deployment, installation, and configuration of gLExec, and how PanDA components have been augmented to use it. We describe how difficulties were overcome, and how security risks have been mitigated. Results are presented from OSG and EGEE Grid environments performing ATLAS analysis using PanDA and gLExec.

Effects of DA-6034 on aqueous tear fluid secretion and conjunctival goblet cell proliferation.

PubMed

Choi, Seul Min; Lee, Yeong Geon; Seo, Mi Jung; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-06-01

This study was conducted to evaluate the effect of DA-6034, a potent secretagogue, on aqueous tear fluid secretion and its quality in normal rabbit. We also evaluated, in animal models of experimentally induced dry eye disease, its effectiveness over time to stimulate aqueous tear production by ocular ferning test and goblet cell proliferation. Aqueous tear production, total protein levels, and glycoprotein levels in normal rabbits were evaluated after topical application of DA-6034 (0.3, 1, and 3%). Moreover, time course aqueous tear volume measurement and ocular ferning test in tear fluid were performed in dry eyes of rabbits that had been given 1% atropine sulfate, topically. Altogether, tear fluid production and conjunctival goblet cell numbers were measured in dry eyes of mice that had been given topical scopolamine. Topical application of DA-6034 (0.3, 1, and 3%) significantly increased (P < 0.05) aqueous tear production in a concentration-dependent manner in normal rabbits. There was no change in total protein levels while glycoprotein levels were significantly increased (P < 0.05) at 3% DA-6034. The increase in aqueous tear fluid was significant (P < 0.05) and lasted for 2 h post-instillation in dry eyes of rabbits that had been given 1% atropine sulfate; 10-day repeated instillation of the drug in this model resulted in large and homogeneous fern-like tear patterns. In a mouse model, DA-6034 given as a 3% eyedrop solution significantly increased (P < 0.05) tear fluid production and conjunctival goblet cell number. These results suggest that DA-6034 accelerates not only tear secretion but also mucin production and may be a potential therapeutic agent for the treatment of dry eye disease.

Does transition from the da Vinci Si to Xi robotic platform impact single-docking technique for robot-assisted laparoscopic nephroureterectomy?

PubMed

Patel, Manish N; Aboumohamed, Ahmed; Hemal, Ashok

2015-12-01

To describe our robot-assisted nephroureterectomy (RNU) technique for benign indications and RNU with en bloc excision of bladder cuff (BCE) and lymphadenectomy (LND) for malignant indications using the da Vinci Si and da Vinci Xi robotic platform, with its pros and cons. The port placement described for Si can be used for standard and S robotic systems. This is the first report in the literature on the use of the da Vinci Xi robotic platform for RNU. After a substantial experience of RNU using different da Vinci robots from the standard to the Si platform in a single-docking fashion for benign and malignant conditions, we started using the newly released da Vinci Xi robot since 2014. The most important differences are in port placement and effective use of the features of da Vinci Xi robot while performing simultaneous upper and lower tract surgery. Patient positioning, port placement, step-by-step technique of single docking RNU-LND-BCE using the da Vinci Si and da Vinci Xi robot are shown in an accompanying video with the goal that centres using either robotic system benefit from the hints and tips. The first segment of video describes RNU-LND-BCE using the da Vinci Si followed by the da Vinci Xi to highlight differences. There was no need for patient repositioning or robot re-docking with the new da Vinci Xi robotic platform. We have experience of using different robotic systems for single docking RNU in 70 cases for benign (15) and malignant (55) conditions. The da Vinci Xi robotic platform helps operating room personnel in its easy movement, allows easier patient side-docking with the help of its boom feature, in addition to easy and swift movements of the robotic arms. The patient clearance feature can be used to avoid collision with the robotic arms or the patient's body. In patients with challenging body habitus and in situations where bladder cuff management is difficult, modifications can be made through reassigning the camera to a different port with

Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages.

PubMed

Rabe, Shahrzad Zamani Taghizadeh; Ghazanfari, Tooba; Siadat, Zahra; Rastin, Maryam; Rabe, Shahin Zamani Taghizadeh; Mahmoudi, Mahmoud

2015-04-01

Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. J774A.1 macrophages were treated with 14-kDa protein (5-30 μg/ml) with/without LPS (1 μg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1β released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1β in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.

Selective increase of in vivo firing frequencies in DA SN neurons after proteasome inhibition in the ventral midbrain.

PubMed

Subramaniam, Mahalakshmi; Kern, Beatrice; Vogel, Simone; Klose, Verena; Schneider, Gaby; Roeper, Jochen

2014-09-01

The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

DaVinci's Mona Lisa entering the next dimension.

PubMed

Carbon, Claus-Christian; Hesslinger, Vera M

2013-01-01

For several of Leonardo da Vinci's paintings, such as The Virgin and Child with St Anne or the Mona Lisa, there exist copies produced by his own studio. In case of the Mona Lisa, a quite exceptional, rediscovered studio copy was presented to the public in 2012 by the Prado Museum in Madrid. Not only does it mirror its famous counterpart superficially; it also features the very same corrections to the lower layers, which indicates that da Vinci and the 'copyist' must have elaborated their panels simultaneously. On the basis of subjective (thirty-two participants estimated painter-model constellations) as well as objective data (analysis of trajectories between landmarks of both paintings), we revealed that both versions differ slightly in perspective. We reconstructed the original studio setting and found evidence that the disparity between both paintings mimics human binocular disparity. This points to the possibility that the two Giocondas together might represent the first stereoscopic image in world history.

A Proposal to Build Evaluation Capacity at the Bunche-Da Vinci Learning Partnership Academy

ERIC Educational Resources Information Center

King, Jean A.

2005-01-01

The author describes potential evaluation capacity-building activities in contrast to the specifics of an evaluation design. Her response to the case of the Bunche-Da Vinci Learning Partnership Academy is developed in three parts: (1) an initial framing of the Bunche-Da Vinci situation; (2) what should be done before signing a contract; and (3)…

32 CFR Appendix E to Part 623 - Surety Bond (DA Form 4881-3-R)

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Surety Bond (DA Form 4881-3-R) E Appendix E to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY SUPPLIES AND EQUIPMENT LOAN OF ARMY MATERIEL Pt. 623, App. E Appendix E to Part 623—Surety Bond (DA Form 4881-3-R...

How to Think Like Leonardo da Vinci

ERIC Educational Resources Information Center

Caouette, Ralph

2008-01-01

To be effective and relevant in twenty-first-century learning, art needs to be more inclusive. In this article, the author discusses how teachers can find a good example in Leonardo da Vinci for building an art program. His art, design, and curiosity are the perfect foundation for any art program, at any level. (Contains 3 resources and 3 online…

Robotic resections in hepatobiliary oncology - initial experience with Xi da Vinci system in India.

PubMed

Chandarana, M; Patkar, S; Tamhankar, A; Garg, S; Bhandare, M; Goel, M

2017-01-01

Minimal invasive surgery has proven its advantages over open surgeries in the perioperative period. Food and Drug Administration approved da Vinci robot in 2000. The latest version, da Vinci Xi system has a mobile tower-based robot with several modifications to improve the functionality, versatility, and operative ease. None of the centers have reported exclusively on hepatobiliary oncology using the da Vinci Xi system. We report our initial experience. To study the feasibility, advantages, and discuss the operative technique of da Vinci Xi system in hepatobiliary oncology. Data were analyzed retrospectively from a prospectively maintained database from June 2015 to October 2016. Twenty-five patients with suspected or proven hepatobiliary malignancies were operated. Total robotic technique using da Vinci Xi system was used. Demographic details and perioperative outcomes were noted. Of the 25 surgeries, 14 patients had a suspected gallbladder malignancy, 11 patients had primary or metastatic liver tumor. Median age was 53 years. The average duration of surgery was 225 min with a median blood loss 150 ml. The median postoperative stay was 4 days. The median nodal yield for radical cholecystectomy was seven. Five patients required conversion. Two of these developed postoperative morbidity. Robotic surgery for hepatobiliary oncology is feasible and can be performed safely in experienced hands. Increasing experience in this field may equal or even prove advantageous over conventional or laparoscopic approach in future. A cautious approach with judicious patient selection is the key to establishing robotic surgery as a standard surgical approach.

Efficacy of DA-9701 (Motilitone) in Functional Dyspepsia Compared to Pantoprazole: A Multicenter, Randomized, Double-blind, Non-inferiority Study.

PubMed

Jung, Hye-Kyung; Lee, Kwang Jae; Choi, Myung-Gyu; Park, Hyojin; Lee, Joon Seong; Rhee, Poong-Lyul; Kim, Nayoung; Park, KyungSik; Choi, Suck Chei; Lee, Oh Young; Huh, Kyu Chan; Song, Geun Am; Hong, Su Jin; Sohn, Chong Il; Jung, Hwoon-Yong; Lee, Yong Chan; Rew, Jong Sun; Jee, Sam Ryong; Kwon, Joong Goo

2016-04-30

The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Westerncountries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. Theprimary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptomimprovement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups.Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes anddyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacyof DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 andpantoprazole in patients with FD.

Integration Of PanDA Workload Management System With Supercomputers for ATLAS and Data Intensive Science

NASA Astrophysics Data System (ADS)

Klimentov, A.; De, K.; Jha, S.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Wells, J.; Wenaus, T.

2016-10-01

The.LHC, operating at CERN, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than grid can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility. Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This implementation was tested with a variety of Monte-Carlo workloads on several supercomputing platforms for ALICE and ATLAS experiments and it is in full pro duction for the ATLAS since September 2015. We will present our current accomplishments with running PanDA at supercomputers and demonstrate our ability to use PanDA as a portal independent of the

Long-term evolution of 1991 DA: A dynamically evolved extinct Halley-type comet

NASA Technical Reports Server (NTRS)

Hahn, Gerhard; Bailey, M. E.

1992-01-01

The long-term dynamical evolution of 21 variational orbits for the intermediate-period asteroid 1991 DA was followed for up to +/-10(exp 5) years from the present. 1991 DA is close to the 2:7 resonance with Jupiter; it has avoided close encounters, within 1 AU, with this planet for at least the past 30,000 years, even at the node crossing. The future evolution typically shows no close encounters with Jupiter within at least 50,000 years. This corresponds to the mean time between node crossings with either Jupiter or Saturn. Close encounters with Saturn and Jupiter lead to a chaotic evolution for the whole ensemble, while secular perturbations cause large-amplitude swings in eccentricity and inclination (the latter covering the range 15 deg approximately less than i approximately less than 85 deg) which correlate with deep excursions of the perihelion distance to values much less than 1 AU. These variations are similar to those found in P/Machholz and a variety of other high-inclination orbits, e.g., P/Hartley-IRAS. We emphasize the connection between the orbital evolution of 1991 DA and that of Halley-type comets. If 1991 DA was once a comet, it is not surprising that it is now extinct.

Cloning and sequencing of a gene encoding the 69-kDa extracellular chitinase of Janthinobacterium lividum.

PubMed

Gleave, A P; Taylor, R K; Morris, B A; Greenwood, D R

1995-09-15

Janthinobacterium lividum secretes a major 56-kDa chitinase and a minor 69-kDa chitinase. A chitinase gene was defined on a 3-kb fragment of clone pRKT10, by virtue of fluorescent colonies in the presence of 4-methylumbelliferyl-beta-D-N,N',N"-chitotrioside. Nucleotide sequencing revealed an 1998-bp open reading frame with the potential to encode a 69,716-Da protein with amino acid sequences similar to those in other chitinases, suggesting it encodes the minor chitinase (Chi69). Chitinase activity of Escherichia coli (pRKT10) lysates was detected mainly in the periplasmic fraction and immunoblotting detected a 70-kDa protein in this fraction. Chi69 has an N-terminal secretory leader peptide preceding two probable chitin-binding domains and a catalytic domain. These functional domains are separated by linker regions of proline-threonine repeats. Amino acid sequencing of cyanogen bromide cleavage-derived peptides from the major 56-kDa chitinase suggested that Chi69 may be a precursor of Chi56. In addition, an N-terminally truncated version of Chi69 retained chitinase activity as expected if in vivo processing of Chi69 generates Chi56.

Battle of the bots: a comparison of the standard da Vinci and the da Vinci Surgical Skills Simulator in surgical skills acquisition.

PubMed

Brown, Kevin; Mosley, Natalie; Tierney, James

2017-06-01

Virtual reality simulators are increasingly used to gain robotic surgical skills. This study compared use of the da Vinci Surgical Skills Simulator (dVSSS) to the standard da Vinci (SdV) robot for skills acquisition in a prospective randomized study. Residents from urology, gynecology, and general surgery programs performed three virtual reality tasks (thread the ring, ring rail, and tubes) on the dvSSS. Participants were then randomized to one of the two study groups (dVSSS and SdV). Each participant then practiced on either the dVSSS or the SdV (depending on randomization) for 30 min per week over a 4-week time period. The dVSSS arm was not permitted to practice ring rail (due to no similar practice scenario available for the SdV group). Following 4 weeks of practice, participants performed the same three virtual reality tasks and the results were recorded and compared to baseline. Overall and percent improvement were recorded for all participants from pre-test to post-test. Two-way ANOVA analyses were used to compare the dVSSS and SdV groups and three tasks. Initially, 30 participants were identified and enrolled in the study. Randomization resulted in 15 participants in each arm. During the course of the study, four participants were unable to complete all tasks and practice sessions and were, therefore, excluded. This resulted in a total of 26 participants (15 in the dVSSS group and 11 in the SdV group) who completed the study. Overall total improvement score was found to be 23.23 and 23.48 for the SdV and dVSSS groups, respectively (p = 0.9245). The percent improvement was 60 and 47 % for the SdV and dVSSS groups respectively, which was a statistically significant difference between the two groups and three tasks. Practicing on the standard da Vinci is comparable to practicing on the da Vinci simulator for acquiring robotic surgical skills. In spite of several potential advantages, the dVSSS arm performed no better than the SdV arm in the final

Increasing protein production rates can decrease the rate at which functional protein is produced

NASA Astrophysics Data System (ADS)

Sharma, Ajeet; O'Brien, Edward

The rate at which soluble, functional protein is produced by the ribosome has recently been found to vary in complex and unexplained ways as various translation-associated rates are altered through synonymous codon substitutions. We combine a well-established ribosome-traffic model with a master-equation model of co-translational domain folding to explore the scenarios that are possible for the protein production rate, J, and the functional-nascent protein production rate, F, as the rates associated with translation are altered. We find that while J monotonically increases as the rates of translation-initiation, -elongation and -termination increase, F can either increase or decrease. F exhibits non-monotonic behavior because increasing these rates can cause a protein to be synthesized more rapidly but provide less time for nascent-protein domains to co-translationally fold thereby producing less functional nascent protein immediately after synthesis. We further demonstrate that these non-monotonic changes in Faffect the post-translational, steady-state levels of functional protein in a similar manner. Our results provide a possible explanation for recent experimental observations that the specific activity of enzymatic proteins can decrease with increased synthesis rates and can in principle be used to rationally-design transcripts to maximize the production of functional nascent protein.

Oligosaccharyltransferase directly binds to ribosome at a location near the translocon-binding site

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

Harada, Y.; Li, H.; Li, Hua

2009-04-28

Oligosaccharyltransferase (OT) transfers high mannose-type glycans to the nascent polypeptides that are translated by the membrane-bound ribosome and translocated into the lumen of the endoplasmic reticulum through the Sec61 translocon complex. In this article, we show that purified ribosomes and OT can form a binary complex with a stoichiometry of {approx}1 to 1 in the presence of detergent. We present evidence that OT may bind to the large ribosomal subunit near the site where nascent polypeptides exit. We further show that OT and the Sec61 complex can simultaneously bind to ribosomes in vitro. Based on existing data and our findings,more » we propose that cotranslational translocation and N-glycosylation of nascent polypeptides are mediated by a ternary supramolecular complex consisting of OT, the Sec61 complex, and ribosomes.« less

Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Lee, Yeong Geon; Lee, Min Jung; Jeon, Hyung Jun; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-01-01

This study was designed to assess whether DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone monohydrate), a new synthetic derivative of eupatilin, increases secretion of mucin-like glycoprotein and some mucins species in conjunctiva and cornea, and contributes to the preservation of ocular surface integrity. Human conjunctival and corneal epithelial cells were incubated with DA-6034 (1-250 microM). To investigate mucin secreting activity more directly, isolated rat conjunctival goblet cells were also used. Corneal protection was investigated using a desiccation-induced rabbit model of dry eye syndrome. It was found that DA-6034 increased mucin-like glycoprotein levels of both conjunctival and corneal epithelial cells at concentrations above 100 microM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 microM) significantly increased production of some mucins species including MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16. DA-6034 also significantly increased MUC5AC production from conjunctival goblet cells isolated from rats. In the rabbit desiccation model, an ophthalmic suspension containing 3% DA-6034 significantly reduced corneal damage induced by desiccation. These results suggest that DA-6034 is a good candidate for treatment of dry eye through maintaining ocular surface integrity, which might be related to mucin secretion.

The Role of Hsp70 in the Regulation of Autophagy in Gametogenesis, Pregnancy, and Parturition.

PubMed

Witkin, Steven S; Kanninen, Tomi T; Sisti, Giovanni

2017-01-01

Induction of the 70 kDa heat shock protein (hsp70) and autophagy are two major mechanisms that promote cell homeostasis during the rapid cell growth and differentiation characteristic of reproduction. Hsp70 insures proper assembly, conformation, and intracellular transport of nascent proteins. Autophagy removes from the cytoplasm proteins, other macromolecules, and organelles that are no longer functional or needed and recycles their components for synthesis of new products under nutritionally limiting conditions. Hsp70 inhibits autophagy and so a proper balance between these two processes is essential for optimal germ cell production and survival and pregnancy progression. A marked inhibition in autophagy and a concomitant increase in hsp70 at term is a trigger for parturition. Excessive external or endogenous stress that induces a high level of hsp70 production can lead to a non-physiological inhibition of autophagy, resulting in altered spermatogenesis, premature ovarian failure, and complications of pregnancy including preeclampsia, intrauterine growth restriction, and preterm birth.

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-09-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

Biogenic manganese oxide nanoparticle formation by a multimeric multicopper oxidase Mnx

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

Romano, Christine A.; Zhou, Mowei; Song, Yang

Bacteria that produce Mn oxides are extraordinarily skilled engineers of nanomaterials that contribute significantly to global biogeochemical cycles. Their enzyme-based reaction mechanisms may be genetically tailored for environmental remediation applications or bioenergy production. However, significant challenges exist for structural characterization of the enzymes responsible for biomineralization. The active Mn oxidase, Mnx, in Bacillus sp. PL-12 is a complex composed of a multicopper oxidase (MCO), MnxG, and two accessory proteins MnxE and MnxF. MnxG shares sequence similarity with other, structurally characterized MCOs. However, MnxE and MnxF have no similarity to any characterized proteins. The ~200 kDa complex has been recalcitrant tomore » crystallization, so its structure is unknown. In this study, native mass spectrometry defines the subunit topology and copper binding of the Mnx complex, while high resolution electron microscopy visualizes the protein and nascent Mn oxide minerals. These data provide critical structural information for conceptualizing how Mnx produces nanoparticulate Mn oxides.« less

Chaperonin Polymers in Archaea: The Cytoskeleton of Prokaryotes?

DOE R&D Accomplishments Database

Trent, J. D.; Kagawa, H. K.; Zaluzec, N. J.

1997-07-01

Chaperonins are protein complexes that play a critical role in folding nascent polypeptides under normal conditions and refolding damaged proteins under stress conditions. In all organisms these complexes are composed of evolutionarily conserved 60-kDa proteins arranged in double-ring structures with between 7 and 9 protein subunits per ring. These double ring structures are assumed to be the functional units in vivo, although they have never been observed inside cells. Here the authors show that the purified chaperonin from the hyperthermophilic archaeon Sulfolobus shibatae, which is closely related to chaperonins in eukaryotes, has a double ring structure at low concentrations (0.1 mg/ml), but at more physiological concentrations, the rings stack end to end to form polymers. The polymers are stable at physiological temperatures (75 C) and closely resemble structures observed inside unfixed S. shibatae cells. The authors suggest that in vivo chaperonin activity may be regulated by polymerization and that chaperonin polymers may act as a cytoskeleton-like structure in archaea and bacteria.

Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.

PubMed

Herrera-Mundo, Nieves; Sitges, María

2013-01-01

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

P2X1 Receptor-Mediated Ca2+ Influx Triggered by DA-9801 Potentiates Nerve Growth Factor-Induced Neurite Outgrowth.

PubMed

Back, Moon Jung; Lee, Hae Kyung; Lee, Joo Hyun; Fu, Zhicheng; Son, Mi Won; Choi, Sang Zin; Go, Hyo Sang; Yoo, Sungjae; Hwang, Sun Wook; Kim, Dae Kyong

2016-11-16

Nerve growth factor (NGF)-induced neuronal regeneration has emerged as a strategy to treat neuronal degeneration-associated disorders. However, direct NGF administration is limited by the occurrence of adverse effects at high doses of NGF. Therefore, development of a therapeutic strategy to promote the NGF trophic effect is required. In view of the lack of understanding of the mechanism for potentiating the NGF effect, this study investigated molecular targets of DA-9801, a well-standardized Dioscorea rhizome extract, which has a promoting effect on NGF. An increase in intracellular calcium ion level was induced by DA-9801, and chelation of extracellular calcium ions with ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) suppressed the potentiating effect of DA-9801 on NGF-induced neurite outgrowth. In addition, EGTA treatment reduced the DA-9801-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), the major mediators of neurite outgrowth. To find which calcium ion-permeable channel contributes to the calcium ion influx induced by DA-9801, we treated PC12 cells with various inhibitors of calcium ion-permeable channels. NF449, a P2X1 receptor selective antagonist, significantly abolished the potentiating effect of DA-9801 on NGF-induced neurite outgrowth and abrogated the DA-9801-induced ERK1/2 phosphorylation. In addition, transfection with siRNA of P2X1 receptor significantly reduced the DA-9801-enhanced neurite outgrowth. In conclusion, calcium ion influx through P2X1 receptor mediated the promoting effect of DA-9801 on NGF-induced neurite outgrowth via ERK1/2 phosphorylation.

Whole-Genome Sequences of DA and F344 Rats with Different Susceptibilities to Arthritis, Autoimmunity, Inflammation and Cancer

PubMed Central

Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A.; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S.

2013-01-01

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease. PMID:23695301

Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer.

PubMed

Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S

2013-08-01

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.

New Members in the Galaxy Group Around Giant Radio Galaxy DA 240

NASA Astrophysics Data System (ADS)

Chen, Ru-Rong; Peng, Bo; Strom, Richard

2018-05-01

With new spectroscopic observations of group candidates around the giant radio galaxy DA 240, we have identified five new group members, increasing the number to twenty-five. While all the new members are located some distance from the host galaxy, two of them lie in one of the radio lobes, and the rest are found at a distance from the radio components. The new group members reinforce our earlier conclusion that the distribution of the DA 240 group with respect to the radio lobes is unusual among giant radio galaxy host environments.

Evolution of robots throughout history from Hephaestus to Da Vinci Robot.

PubMed

Iavazzo, Christos; Gkegke, Xanthi-Ekaterini D; Iavazzo, Paraskevi-Evangelia; Gkegkes, Ioannis D

2014-01-01

Da Vinci robot is increasingly used for operations adding the advantages of robots to the favor of medicine. This is a historical article with the aim to present the evolution of robots in the medical area from the time of ancient myths to Renaissance and finally to the current revolutionary applications. We endeavored to collect several elegant narratives on the topic. The use of imagination could help the reader to find similarities. A trip from the Greek myths of Hephaestus through Aristotle and Leonardo Da Vinci to the robots of Karel Capek and Isaac Asimov and finally the invention of the medical robots is presented.

An endogenous 55 kDa TNF receptor mediates cell death in a neural cell line.

PubMed

Sipe, K J; Srisawasdi, D; Dantzer, R; Kelley, K W; Weyhenmeyer, J A

1996-06-01

Tumor necrosis factor-alpha (TNF) is associated with developmental and injury-related events in the central nervous system (CNS). In the present study, we have examined the role of TNF on neurons using the clonal murine neuroblastoma line, N1E-115 (N1E). N1E cells represent a well-defined model for studying neuronal development since they can be maintained as either undifferentiated, mitotically active neuroblasts or as differentiated, mature neurons. Northern and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that both undifferentiated and differentiated N1Es express transcripts for the 55 kDa TNF receptor (TNFR), but not the 75 kDa TNFR. The biological activity of the expressed TNF receptor was demonstrated by a dose dependent cytotoxicity to either recombinant murine or human TNF when the cells were incubated with the transcriptional inhibitor actinomycin D. The lack of the 75 kDa receptor mRNA expression and the dose dependent response to rHuTNF, an agonist specific for the murine 55 kDa receptor, suggest that the TNF induced cytotoxicity is mediated through the 55 kDa receptor in both the undifferentiated and differentiated N1Es. Light microscopic observations, flow cytometric analysis of hypodiploid DNA, and electrophoretic analysis of nucleosomal DNA fragmentation of N1Es treated with actinomycin D and TNF revealed features characteristic of both necrotic and apoptotic cell death. These findings demonstrate that blast and mature N1E cells express the 55 kDa TNF receptor which is responsible for inducing both necrotic and apoptotic death in these cells. The observation that actinomycin D renders N1E cells susceptible to the cytotoxic effects of TNF indicates that a sensitization step, such as removal of an endogenous protective factor or viral-mediated inhibition of transcription, may be necessary for TNF cytotoxicity in neurons.

Extraction of Features from High-resolution 3D LiDaR Point-cloud Data

NASA Astrophysics Data System (ADS)

Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

2008-12-01

Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the Geo

Modifications of transaxillary approach in endoscopic da Vinci-assisted thyroid and parathyroid gland surgery.

PubMed

Al Kadah, Basel; Piccoli, Micaela; Mullineris, Barbara; Colli, Giovanni; Janssen, Martin; Siemer, Stephan; Schick, Bernhard

2015-03-01

Endoscopic surgery for treatment of thyroid and parathyroid pathologies is increasingly gaining attention. The da Vinci system has already been widely used in different fields of medicine and quite recently in thyroid and parathyroid surgery. Herein, we report about modifications of the transaxillary approach in endoscopic surgery of thyroid and parathyroid gland pathologies using the da Vinci system. 16 patients suffering from struma nodosa in 14 cases and parathyroid adenomas in two cases were treated using the da Vinci system at the ENT Department of Homburg/Saar University and in cooperation with the Department of General Surgery in New Sant'Agostino Hospital, Modena/Italy. Two different retractors, endoscopic preparation of the access and three different incision modalities were used. The endoscopic preparation of the access allowed us to have a better view during preparation and reduced surgical time compared to the use of a headlamp. To introduce the da Vinci instruments at the end of the access preparation, the skin incisions were over the axilla with one incision in eight patients, two incisions in four patients and three incisions in a further four patients. The two and three skin incisions modality allowed introduction of the da Vinci instruments without arm conflicts. The use of a new retractor (Modena retractor) compared to a self-developed retractor made it easier during the endoscopic preparation of the access and the reposition of the retractor. The scar was hidden in the axilla and independent of the incisions selected, the cosmetic findings were judged by the patients to be excellent. The neurovascular structures such as inferior laryngeal nerve, superior laryngeal nerve and vessels, as well as the different pathologies, were clearly 3D visualized in all 16 cases. No paralysis of the vocal cord was observed. All patients had a benign pathology in their histological examination. The endoscopic surgery of the thyroid and parathyroid gland can be

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

PubMed Central

Lissek, Silke; Glaubitz, Benjamin; Wolf, Oliver T.; Tegenthoff, Martin

2015-01-01

Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling. PMID:26388752

DA+ data acquisition and analysis software at the Swiss Light Source macromolecular crystallography beamlines.

PubMed

Wojdyla, Justyna Aleksandra; Kaminski, Jakub W; Panepucci, Ezequiel; Ebner, Simon; Wang, Xiaoqiang; Gabadinho, Jose; Wang, Meitian

2018-01-01

Data acquisition software is an essential component of modern macromolecular crystallography (MX) beamlines, enabling efficient use of beam time at synchrotron facilities. Developed at the Paul Scherrer Institute, the DA+ data acquisition software is implemented at all three Swiss Light Source (SLS) MX beamlines. DA+ consists of distributed services and components written in Python and Java, which communicate via messaging and streaming technologies. The major components of DA+ are the user interface, acquisition engine, online processing and database. Immediate data quality feedback is achieved with distributed automatic data analysis routines. The software architecture enables exploration of the full potential of the latest instrumentation at the SLS MX beamlines, such as the SmarGon goniometer and the EIGER X 16M detector, and development of new data collection methods.

DA+ data acquisition and analysis software at the Swiss Light Source macromolecular crystallography beamlines

PubMed Central

Wojdyla, Justyna Aleksandra; Kaminski, Jakub W.; Ebner, Simon; Wang, Xiaoqiang; Gabadinho, Jose; Wang, Meitian

2018-01-01

Data acquisition software is an essential component of modern macromolecular crystallography (MX) beamlines, enabling efficient use of beam time at synchrotron facilities. Developed at the Paul Scherrer Institute, the DA+ data acquisition software is implemented at all three Swiss Light Source (SLS) MX beamlines. DA+ consists of distributed services and components written in Python and Java, which communicate via messaging and streaming technologies. The major components of DA+ are the user interface, acquisition engine, online processing and database. Immediate data quality feedback is achieved with distributed automatic data analysis routines. The software architecture enables exploration of the full potential of the latest instrumentation at the SLS MX beamlines, such as the SmarGon goniometer and the EIGER X 16M detector, and development of new data collection methods. PMID:29271779

Thorascopic resection of an apical paraspinal schwannoma using the da Vinci surgical system.

PubMed

Finley, David; Sherman, Jonathan H; Avila, Edward; Bilsky, Mark

2014-01-01

Posterior mediastinal neurogenic tumors have traditionally been resected via an open posterolateral thoracotomy. Video-assisted thorascopic surgery has emerged as an alternative technique allowing for improved morbidity with decreased blood loss, less postoperative pain, and a shorter recovery period, among others. The da Vinci surgical system, as first described for urologic procedures, has recently been reported for lung lobectomy. This technique provides the advantages of instrumentation with 6 degrees of freedom, stable operating arms, and improved visualization with the three-dimensional high-definition camera. We describe the technique for thorascopic resection of an apical paraspinal schwannoma of the T1 nerve root with the da Vinci surgical system. This technique used a specialized intraoperative neuromonitoring probe for free-running electromyography (EMG) and triggered EMG. We demonstrate successful resection of a posterior paraspinal schwannoma with the da Vinci surgical system while preserving neurologic function. The patient displayed stable intraoperative monitoring of the T1 nerve root and full intrinsic hand strength postoperatively. The technique described in this article introduces robotic system accuracy and precludes the need for an open thoracotomy. In addition, this approach demonstrates the ability of the da Vinci surgical system to safely dissect tumors from their neural attachments and is applicable to other such lesions of similar size and location. Georg Thieme Verlag KG Stuttgart · New York.

[Trattamento della dipendenza da alcol. Alcol e giovani: punto di vista sociale].

PubMed

Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Lombardo, Giuseppe; De Rosa, Francesca; Messina, Marisa Patrizia; Vitali, Mario; Pisciotta, Fabiola; Nanut, Miriana; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Gli adolescenti rappresentano la fascia di età più vulnerabile ai danni causati dall'abuso di alcol, in quanto iniziare a bere in giovane età è associato a un aumento del rischio di dipendenza da alcolici in età adulta. I giovani tendono a bere grandi quantità di alcolici al fine di ricercare forti emozioni e nel tentativo di raggiungere il divertimento a ogni costo, tramite le proprietà psicotrope degli alcolici. Le cause che li inducono ad assumere questi comportamenti sono da ricercare nella non conoscenza degli effetti dannosi dell'alcol, nel rito di convivialità sociale (evenienza per la quale si attribuisce all'alcol la funzione di facilitatore dell'aggregazione tra giovani), nella mancanza di interessi personali, nella scarsità dei controlli e nelle abitudini familiari. Le azioni da intraprendere per limitare o arrestare il consumo nocivo di alcol nei giovani si devono basare su interventi finalizzati a ritardare l'età del primo contatto con le bevande alcoliche, mediante la realizzazione di campagne educazionali rivolte ai giovani stessi, ai loro familiari e alla società intera.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

PubMed

Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

2014-09-01

Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to

Analyzing the relation between the microbial diversity of DaQu and the turbidity spoilage of traditional Chinese vinegar.

PubMed

Li, Pan; Li, Sha; Cheng, Lili; Luo, Lixin

2014-07-01

Vinegar is a traditional fermented condiment, and the microbial diversity of DaQu makes the quality of vinegar products. Recently, turbidity spoilage of vinegar sharply tampered with the quality of vinegar. In this study, the relation between the microbial diversity of DaQu and turbidity spoilage of vinegar was analyzed by plating technique, PCR-denaturing gradient gel electrophoresis (DGGE), and high-performance liquid chromatography (HPLC). The 16S rRNA sequencing and DGGE analysis indicated that Bacillus (Bacillus subtilis, Bacillus amyloliquefaciens, and Bacillus thuringiensis) and Lactobacillus (including Lactobacillus acidipiscis and Lactobacillus pobuzihii) species were the dominant contaminants in vinegar products. Meanwhile, DGGE analysis showed that the dominant bacteria in DaQu belonged to genera Bacillus, Lactobacillus, Pseudomonas, Weissella, Saccharopolyspora, Enterobacter, and Pantoea. However, only two yeast species (Pichia kudriavzevii and Saccharomycopsis fibuligera) and seven mold species including Aspergillus oryzae, Aspergillus niger, Aspergillus candidus, Rhizopus microspores, Eurotium herbariorum, Absidia corymbifera, and Eupenicillium javanicum were detected in the DaQu. The population level of fungi was below 5 log CFU/g in DaQu. The chemical and physical properties of vinegar and sediments were also determined. On the basis of a combined microbial diversity-chemical analysis, we demonstrated that turbidity spoilage of vinegar was a result of cooperation among the low population level and abundance of fungal species in DaQu, the suitable climate conditions, and the contaminants in vinegar. This is the first report to analyze the relation between the microbial diversity of DaQu and turbidity spoilage of vinegar.

Da Vinci robot-assisted anatomic left hemihepatectomy and biliary reconstruction.

PubMed

Wang, Zhifei; Liu, Quanda; Chen, Junzhou; Duan, Weihong; Zhou, Ningxin

2013-06-01

Since the introduction of Da Vinci robotic surgery, more and more complicated surgeries can now be performed robotically, yet there have been very few on robotic hepatectomy, especially when billiary reconstruction is involved. The video shows our initial experience with an anatomic hepatectomy using Da Vinci surgical robot. In this case, we also conducted billiary reconstruction due to the anatomic abnormality of bile duct, while applying the choledochoscopy. The preoperative diagnosis is primary liver carcinoma, tumor thrombi in bile duct, and hepatitis B. First, the gallbladder was resected, and cystic artery and duct were identified. After opening of the common bile duct above the junction, the choledochoscopy was performed. Tumor thrombi were found in common bile duct and left hepatic duct, and they were all removed. Left branches hepatic artery and portal vein were dissected, ligated, and divided. Thrombi in the left hepatic duct were removed also. After marking the cutting line along the ischemic boarder, liver parenchyma was transected using robotic harmonic scalpel. Branches of ducts were encountered and managed by either direct coagulating or dividing after clipping. The left hepatic vein was visualized, exposed, and divided during hepatectomy. Two T tubes were placed into common hepatic duct and the proximal cutting end of right anterior bile duct which was found to join the left hepatic duct, respectively. The operation went on successfully. The operation time was 410 minutes, the blood loss was 200 mL. The pathologic diagnosis was introductal papillary adenocarcinoma of left hepatic duct. The patient went on well postoperatively and was followed up for 22 months till now. Postoperative computed tomography examination showed no recurrence. Da Vinci-assisted robotic hepatectomy can be performed safely in the hands of experienced hepatobilliary surgeons, and choledochoscopy can be combined for bile duct exploration. With the advantages of Da Vinci robot

PanDA for ATLAS distributed computing in the next decade

NASA Astrophysics Data System (ADS)

Barreiro Megino, F. H.; De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Padolski, S.; Panitkin, S.; Wenaus, T.; ATLAS Collaboration

2017-10-01

The Production and Distributed Analysis (PanDA) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at the Large Hadron Collider (LHC) data processing scale. Heterogeneous resources used by the ATLAS experiment are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, dozens of scientific applications are supported, while data processing requires more than a few billion hours of computing usage per year. PanDA performed very well over the last decade including the LHC Run 1 data taking period. However, it was decided to upgrade the whole system concurrently with the LHC’s first long shutdown in order to cope with rapidly changing computing infrastructure. After two years of reengineering efforts, PanDA has embedded capabilities for fully dynamic and flexible workload management. The static batch job paradigm was discarded in favor of a more automated and scalable model. Workloads are dynamically tailored for optimal usage of resources, with the brokerage taking network traffic and forecasts into account. Computing resources are partitioned based on dynamic knowledge of their status and characteristics. The pilot has been re-factored around a plugin structure for easier development and deployment. Bookkeeping is handled with both coarse and fine granularities for efficient utilization of pledged or opportunistic resources. An in-house security mechanism authenticates the pilot and data management services in off-grid environments such as volunteer computing and private local clusters. The PanDA monitor has been extensively optimized for performance and extended with analytics to provide aggregated summaries of the system as well as drill-down to operational details. There are as well many other challenges planned or recently implemented, and adoption by non-LHC experiments such

The influence of ancient Greek thought on fifteenth century anatomy: Galenic influence and Leonardo da Vinci.

PubMed

Tubbs, Richard Isaiah; Gonzales, Jocelyn; Iwanaga, Joe; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

2018-06-01

Leonardo da Vinci (1452-1519) can be called one of the earliest contributors to the history of anatomy and, by extension, the study of medicine. He may have even overshadowed Andreas Vesalius (1514-1564), the so-called founder of human anatomy, if his works had been published within his lifetime. While some of the best illustrations of their time, with our modern knowledge of anatomy, it is clear that many of da Vinci's depictions of human anatomy are inaccurate. However, he also made significant discoveries in anatomy and remarkable predictions of facts he could not yet discover with the technology available to him. Additionally, da Vinci was largely influenced by Greek anatomists, as indicated from his ideas about anatomical structure. In this historical review, we describe da Vinci's history, influences, and discoveries in anatomical research and his depictions and errors with regards to the musculoskeletal system, cardiovascular system, nervous system, and other organs.

STRESS AND FAILURE ANALYSIS OF RAPIDLY ROTATING ASTEROID (29075) 1950 DA

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

Hirabayashi, Masatoshi; Scheeres, Daniel J., E-mail: masatoshi.hirabayashi@colorado.edu

Rozitis et al. recently reported that near-Earth asteroid (29075) 1950 DA, whose bulk density ranges from 1.0 g cm{sup –3} to 2.4 g cm{sup –3}, is a rubble pile and requires a cohesive strength of at least 44-76 Pa to keep from failing due to its fast spin period. Since their technique for giving failure conditions required the averaged stress over the whole volume, it discarded information about the asteroid's failure mode and internal stress condition. This paper develops a finite element model and revisits the stress and failure analysis of 1950 DA. For the modeling, we do not consider material hardening andmore » softening. Under the assumption of an associated flow rule and uniform material distribution, we identify the deformation process of 1950 DA when its constant cohesion reaches the lowest value that keeps its current shape. The results show that to avoid structural failure the internal core requires a cohesive strength of at least 75-85 Pa. It suggests that for the failure mode of this body, the internal core first fails structurally, followed by the surface region. This implies that if cohesion is constant over the whole volume, the equatorial ridge of 1950 DA results from a material flow going outward along the equatorial plane in the internal core, but not from a landslide as has been hypothesized. This has additional implications for the likely density of the interior of the body.« less

The Potential da Vinci in All of Us

ERIC Educational Resources Information Center

Petto, Sarah; Petto, Andrew

2009-01-01

The study of the human form is fundamental to both science and art curricula. For vertebrates, perhaps no feature is more important than the skeleton to determine observable form and function. As Leonard da Vinci's famous Proportions of the Human Figure (Virtruvian Man) illustrates, the size, shape, and proportions of the human body are defined by…

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling.

PubMed

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-05-30

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50-55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome.

Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

PubMed

Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

2015-01-01

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

The aqueous phase of Alzheimer's disease brain contains assemblies built from ∼4 and ∼7 kDa Aβ species.

PubMed

Mc Donald, Jessica M; O'Malley, Tiernan T; Liu, Wen; Mably, Alexandra J; Brinkmalm, Gunnar; Portelius, Erik; Wittbold, William M; Frosch, Matthew P; Walsh, Dominic M

2015-11-01

Much knowledge about amyloid β (Aβ) aggregation and toxicity has been acquired using synthetic peptides and mouse models, whereas less is known about soluble Aβ in human brain. We analyzed aqueous extracts from multiple AD brains using an array of techniques. Brains can contain at least four different Aβ assembly forms including: (i) monomers, (ii) a ∼7 kDa Aβ species, and larger species (iii) from ∼30-150 kDa, and (iv) >160 kDa. High molecular weight species are by far the most prevalent and appear to be built from ∼7 kDa Aβ species. The ∼7 kDa Aβ species resist denaturation by chaotropic agents and have a higher Aβ42/Aβ40 ratio than monomers, and are unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1. Further analysis of brain-derived ∼7 kDa Aβ species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Settings, Pros and Cons of the New Surgical Robot da Vinci Xi System for Transoral Robotic Surgery (TORS): A Comparison With the Popular da Vinci Si System.

PubMed

Kim, Da Hee; Kim, Hwan; Kwak, Sanghyun; Baek, Kwangha; Na, Gina; Kim, Ji Hoon; Kim, Se Heon

2016-10-01

The da Vinci system (da Vinci Surgical System; Intuitive Surgical Inc.) has rapidly developed in several years from the S system to the Si system and now the Xi System. To investigate the surgical feasibility and to provide workflow guidance for the newly released system, we used the new da Vinci Xi system for transoral robotic surgery (TORS) on a cadaveric specimen. Bilateral supraglottic partial laryngectomy, hypopharyngectomy, lateral oropharyngectomy, and base of the tongue resection were serially performed in search of the optimal procedures with the new system. The new surgical robotic system has been upgraded in all respects. The telescope and camera were incorporated into one system, with a digital end-mounted camera. Overhead boom rotation allows multiquadrant access without axis limitation, the arms are now thinner and longer with grabbing movements for easy adjustments. The patient clearance button dramatically reduces external collisions. The new surgical robotic system has been optimized for improved anatomic access, with better-equipped appurtenances. This cadaveric study of TORS offers guidance on the best protocol for surgical workflow with the new Xi system leading to improvements in the functional results of TORS.

32 CFR Appendix F to Part 623 - Power of Attorney (DA Form 4881-4-R)

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Power of Attorney (DA Form 4881-4-R) F Appendix F to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY SUPPLIES AND EQUIPMENT LOAN OF ARMY MATERIEL Pt. 623, App. F Appendix F to Part 623—Power of Attorney (DA Form 4881-4-R...

40 CFR 60.45Da - Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 7 2013-07-01 2013-07-01 false Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO). 60.45Da Section 60.45Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for...

40 CFR 60.45Da - Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 7 2012-07-01 2012-07-01 false Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO). 60.45Da Section 60.45Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for...

40 CFR 60.45Da - Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 7 2014-07-01 2014-07-01 false Alternative standards for combined nitrogen oxides (NOX) and carbon monoxide (CO). 60.45Da Section 60.45Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for...

Trombose induzida pelo calor endovenoso: relato de dois casos tratados com rivaroxabana e revisão da literatura

PubMed Central

de Araujo, Walter Junior Boim; Timi, Jorge Rufino Ribas; Erzinger, Fabiano Luiz; Caron, Filipe Carlos

2016-01-01

Resumo Define-se trombose induzida pelo calor endovenoso como a propagação do trombo a partir de uma veia superficial em direção a uma veia mais profunda. Em geral, é considerada clinicamente insignificante quando não há propagação do trombo para o sistema venoso profundo. Essa condição pode ser tratada com terapia anticoagulante, embora a observação pareça ser suficiente, principalmente para graus menores. Neste estudo, relatamos dois casos de trombose induzida pelo calor endovenoso que teriam indicação de heparina de baixo peso molecular até a resolução do quadro. Porém, optou-se pelo uso da rivaroxabana (15 mg de 12 em 12h), com resolução completa do trombo em 4 semanas (caso 1) e em 7 dias (caso 2). A rivaroxabana pode ser uma alternativa promissora no tratamento da trombose induzida pelo calor endovenoso avançada, pela simplicidade da posologia, sem comprometimento da eficácia ou da segurança. São necessários estudos prospectivos, randomizados e controlados que possibilitem melhor entendimento da condição e o desenvolvimento de recomendações mais definitivas sobre opções de prevenção e tratamento.

Gene cloning and biochemical characterization of a catalase from Gluconobacter oxydans.

PubMed

Yamaguchi, Haruhiko; Sugiyama, Keigo; Hosoya, Miho; Takahashi, Seiji; Nakayama, Toru

2011-05-01

Gluconobacter oxydans has a large number of membrane-bound dehydrogenases linked to the respiratory chain that catalyze incomplete oxidation of a wide range of organic compounds by oxidative fermentation. Because the respiratory chain is a primary site of reactive oxygen species (ROS) production, the bacterium is expected to have a high capacity to detoxify nascent ROS. In the present study, a gene that encodes a catalase of G. oxydans, which might act as a potential scavenger of H(2)O(2), was cloned, and the expression product (termed rGoxCat) was characterized biochemically. rGoxCat is a heme b-containing tetrameric protein (molecular mass, 320 kDa) consisting of identical subunits. The recombinant enzyme displayed a strong catalase activity with a k(cat) of 6.28×10(4) s(-1) and a K(m) for H(2)O(2) of 61 mM; however, rGoxCat exhibited no peroxidase activity. These results, along with the phylogenetic position of the enzyme, provide conclusive evidence that rGoxCat is a monofunctional, large-subunit catalase. The enzyme was most stable in the pH range of 4-9, and greater than 60% of the original activity was retained after treatment at pH 3.0 and 40°C for 1h. Moreover, the enzyme exhibited excellent thermostability for a catalase from a mesophilic organism, retaining full activity after incubation for 30 min at 70°C. The observed catalytic properties of rGoxCat, as well as its stability in a slightly acidic environment, are consistent with its role in the elimination of nascent H(2)O(2) in a bacterium that produces a large amount of organic acid via oxidative fermentation. Copyright © 2010. Published by Elsevier B.V.

THERMAL FATIGUE OF INCONEL ALLOY DA718

DTIC Science & Technology

2016-10-27

this material meets the required improvement and offers a low cost alternative to powder metallurgy Rene’95. However, its thermal fatigue resistance ...remains to be fully clarified. Its nominal chemical composition is shown in Table B-1. In the fully heat treated condition, DA718 consists of a γ...chromel-alumel thermocouple , spot-welded to the mid-length of the specimen. The thermal strain, induced by the expansion and contraction of the

Nitrergic Pathway Is the Major Mechanism for the Effect of DA-9701 on the Rat Gastric Fundus Relaxation.

PubMed

Min, Yang Won; Ko, Eun-Ju; Lee, Ji Yeon; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J; Rhee, Poong-Lyul

2014-07-31

DA-9701 significantly improved gastric accommodation by increasing the postprandial gastric volume. In this study, we investigated how DA-9701 affects the rat gastric fundus relaxation. Gastric fundus muscle strips (9 longitudinal and 7 circular muscles) were obtained from rats. Electrical field stimulation (EFS) was performed at various frequencies (1, 5, 10 and 20 Hz) and train durations (1, 5, 10 and 20 seconds) to select optimal condition for experiments. Isometric force measurements were performed in response to EFS. Peak and nadir were observed during the first 1 minute after initiation of EFS in control state and after sequential addition of atropine (1 μM), DA-9701 (0.5, 5, 25 and 50 μg), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM) and tetrodotoxin (TTX, 1 μM) to the organ bath. The optimal frequency and duration of EFS to evoke nerve-mediated relaxation was determined as 5 Hz for 10 seconds. Addition of L-NNA in the presence of atropine and DA-9701 (50 μg) decreased nadir by inhibiting relaxation from -0.054 ± 0.021 g to -0.022 ± 0.015 g (P = 0.026) in longitudinal muscles. However, subsequent application of MRS2500 in the presence of atropine, DA-9701 (50 μg) and L-NNA did not affect nadir. In circular muscles, subsequent addition of L-NNA and MRS2500 in the presence of atropine and DA-9701 (50 μg) did not show significant change of nadir. Our data suggest that the effect of DA-9701 on the rat gastric fundus relaxation is mainly mediated by nitrergic rather than purinergic pathway.

Choosing sides--asymmetric centriole and basal body assembly.

PubMed

Pearson, Chad G

2014-07-01

Centrioles and basal bodies (CBBs) are microtubule-rich cylindrical structures that nucleate and organize centrosomes and cilia, respectively. Despite their apparent ninefold rotational symmetry, the nine sets of triplet microtubules in CBBs possess asymmetries in their morphology and in the structures that associate with them. These asymmetries define the position of nascent CBB assembly, the orientation of ciliary beating, the orientation of spindle poles and the maintenance of cellular geometry. For some of these functions, the orientation of CBBs is first established during new CBB biogenesis when the daughter structure is positioned adjacent to the mother. The mother CBB organizes the surrounding environment that nascent CBBs are born into, thereby providing a nest for the new CBB to develop. Protists, including ciliates and algae, highlight the importance of this environment with the formation of asymmetrically placed scaffolds onto which new basal bodies assemble and are positioned. Recent studies illuminate the positioning of nascent centrioles relative to a modular pericentriolar material (PCM) environment and suggest that, like ciliates, centrosomes organize an immediate environment surrounding centrioles for their biogenesis and positioning. In this Commentary, I will explore the positioning of nascent CBB assembly as the first event in building cellular asymmetries and describe how the environment surrounding both basal bodies and centrioles may define asymmetric assembly. © 2014. Published by The Company of Biologists Ltd.

Choosing sides – asymmetric centriole and basal body assembly

PubMed Central

Pearson, Chad G.

2014-01-01

ABSTRACT Centrioles and basal bodies (CBBs) are microtubule-rich cylindrical structures that nucleate and organize centrosomes and cilia, respectively. Despite their apparent ninefold rotational symmetry, the nine sets of triplet microtubules in CBBs possess asymmetries in their morphology and in the structures that associate with them. These asymmetries define the position of nascent CBB assembly, the orientation of ciliary beating, the orientation of spindle poles and the maintenance of cellular geometry. For some of these functions, the orientation of CBBs is first established during new CBB biogenesis when the daughter structure is positioned adjacent to the mother. The mother CBB organizes the surrounding environment that nascent CBBs are born into, thereby providing a nest for the new CBB to develop. Protists, including ciliates and algae, highlight the importance of this environment with the formation of asymmetrically placed scaffolds onto which new basal bodies assemble and are positioned. Recent studies illuminate the positioning of nascent centrioles relative to a modular pericentriolar material (PCM) environment and suggest that, like ciliates, centrosomes organize an immediate environment surrounding centrioles for their biogenesis and positioning. In this Commentary, I will explore the positioning of nascent CBB assembly as the first event in building cellular asymmetries and describe how the environment surrounding both basal bodies and centrioles may define asymmetric assembly. PMID:24895399

Novas determinações dos parâmetros atmosféricos das estrelas anãs brancas DA

NASA Astrophysics Data System (ADS)

Giovannini, O.; Costa, A. F. M.; Kepler, S. O.

2003-08-01

Nós temos selecionado uma amostra de estrelas anãs brancas DA (atmosfera de hidrogênio) a partir dos índices de Strömgren cujos valores estão próximos a região de instabilidade das estrelas anãs brancas DA variáveis, as chamadas estrelas DAV ou ZZ Ceti. O objetivo é determinar os parâmetros fundamentais (temperatura efetiva, Teff, aceleração da gravidade, log g, e massa) destas estrelas para verificar quais os parâmetros estelares estão envolvidos com o mecanismo de pulsação das estrelas DAV. Nós obtemos, até agora, mais de 120 espectros óticos de estrelas DA. Entre as estrelas selecionadas há 20 estrelas variáveis (DAV). Assim, podemos verificar se existem ou não estrelas não variáveis dentro da faixa de instabilidade das estrelas ZZ Ceti. Neste trabalho nós apresentamos a determinação dos parâmetros atmosféricos (temperatura efetiva, Teff, e aceleração da gravidade, log g) das estrelas anãs brancas DA usando os novos modelos de atmosfera ML2/a = 0.6. Estes modelos têm sido utilizados recentemente por fornecerem uma excelente consistência interna na determinação das temperaturas nas regiões do ultra-violeta e ótico. Os parâmetros atmosféricos são determinados espectroscopicamente através da comparação do fluxo de energia das linhas de Balmer (Hb à H9) entre os espectros observados e sintéticos (gerados pelos modelos de atmosfera). As temperaturas obtidas com os novos modelos são, em geral, menores (~ 1000 K menos) que as temperaturas determinadas anteriormente, com modelos ML1. Os valores de log g não mudaram significativamente (menos de 10%). A faixa de instabilidade das DAVs está entre 11000 e 13000 K, consistente com dados de outros autores.

A distância e o conteúdo estelar da região HII gigante G333.1-0.4 - vínculos para a taxa de formação estelar da galáxia

NASA Astrophysics Data System (ADS)

Figuerêdo, E.; Damineli, A.; Blum, R.; Conti, P.

2003-08-01

Neste trabalho apresentamos imagens de alta resolução angular da região HII gigante G333.1-0.4 obtidas através dos filtros J, H e K no telescópio de 4-m do CTIO. Este trabalho faz parte de um estudo de regiões HII gigantes no infravermelho próximo que tem por objetivo estudar a natureza da formação de estrelas massivas e traçar a estrutura espiral de nossa galáxia. Nossa determinação da distância é baseada no método da paralaxe espectroscópica de estrelas OB localizadas na seqüência principal de idade zero (ZAMS) do Diagrama HR. No caso de G333.1-0.4, a magnitude aparente das estrelas localizadas na ZAMS indica que a distância não pode ser maior do que o limite inferior determinado por técnica rádio (2,8 kpc). Resultados semelhantes foram encontrados para regiões estudadas anteriormente, reforçando a idéia de que a taxa de formação estelar na Via Láctea é menor do que o determinado a partir de dados rádio. Nossos resultados mais recentes sobre o conteúdo estelar de G333.1-0.4 revelaram vários objetos que possuem cores bastante avermelhadas (H-K > 2,0). Nós identificamos estes objetos usando os diagramas cor-cor e cor-magnitude dos aglomerados. Estes objetos apresentam um forte excesso em emissão na banda K e possivelmente se tratam de estrelas do tipo OB envolvidas por um disco/envelope circumestelar espesso. O estudo da função de massa inical desta região, em conjunto com resultados de nossos trabalhos anteriores, aponta para uma IMF independente da posição galática. A contagem de estrelas nos fornece um valor para o número de fótons no contínuo de Lyman que corrobora com a afirmação de que G333.1-0.4 se encontra mais próxima da menor distância determinada por rádio.

Training and Health. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs in the fields of health and medicine that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) CYTOTRAIN (a transnational vocational training program in cervical cancer screening); (2) Apollo (a program of open and distance learning for paramedical…

Common commercial cosmetic products induce arthritis in the DA rat.

PubMed Central

Sverdrup, B; Klareskog, L; Kleinau, S

1998-01-01

Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9417771

Expression, purification, and characterization of a bifunctional 99-kDa peptidoglycan hydrolase from Pediococcus acidilactici ATCC 8042.

PubMed

García-Cano, Israel; Campos-Gómez, Manuel; Contreras-Cruz, Mariana; Serrano-Maldonado, Carlos Eduardo; González-Canto, Augusto; Peña-Montes, Carolina; Rodríguez-Sanoja, Romina; Sánchez, Sergio; Farrés, Amelia

2015-10-01

Pediococcus acidilactici ATCC 8042 is a lactic acid bacteria that inhibits pathogenic microorganisms such as Staphylococcus aureus through the production of two proteins with lytic activity, one of 110 kDa and the other of 99 kDa. The 99-kDa one has high homology to a putative peptidoglycan hydrolase (PGH) enzyme reported in the genome of P. acidilactici 7_4, where two different lytic domains have been identified but not characterized. The aim of this work was the biochemical characterization of the recombinant enzyme of 99 kDa. The enzyme was cloned and expressed successfully and retains its activity against Micrococcus lysodeikticus. It has a higher N-acetylglucosaminidase activity, but the N-acetylmuramoyl-L-alanine amidase can also be detected spectrophotometrically. The protein was then purified using gel filtration chromatography. Antibacterial activity showed an optimal pH of 6.0 and was stable between 5.0 and 7.0. The optimal temperature for activity was 60 °C, and all activity was lost after 1 h of incubation at 70 °C. The number of strains susceptible to the recombinant 99-kDa enzyme was lower than that susceptible to the mixture of the 110- and 99-kDa PGHs of P. acidilactici, a result that suggests synergy between these two enzymes. This is the first PGH from LAB that has been shown to possess two lytic sites. The results of this study will aid in the design of new antibacterial agents from natural origin that can combat foodborne disease and improve hygienic practices in the industrial sector.

Operative technique and early experience for robotic-assisted laparoscopic nephroureterectomy (RALNU) using da Vinci Xi.

PubMed

Darwiche, Fadi; Swain, Sanjaya; Kallingal, George; Punnen, Sanoj; Manoharan, Murugesan; Parekh, Dipen J; Gonzalgo, Mark L

2015-01-01

Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform. A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU. Robotic-assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra-operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days). The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.

Carboxyl methylation of 21-23 kDa membrane proteins in intact neuroblastoma cells is increased with differentiation.

PubMed

Haklai, R; Kloog, Y

1990-01-01

Evidence is presented for specific enzymatic methylation of 21-23 kDa membrane proteins in intact neuroblastoma N1E 115 cells, which is increased in dimethylsulfoxide-induced differentiated cells. Methylation of these proteins has characteristics typical of enzymatic reactions in which base labile volatile methyl groups are incorporated into proteins, consistent with the formation of protein carboxyl methylesters. However, these methylesters of the 21-23 kDa proteins are relatively stable compared to other protein carboxyl methylesters. The 3-fold increase in methylated 21-23 kDa proteins in the differentiated cells suggest biological significance in differentiation of the cell membranes.

Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

PubMed

Jung, Ji Won; Kim, Ju Myung; Jeong, Jin Seok; Son, Miwon; Lee, Hye Suk; Lee, Myung Gull; Kang, Hee Eun

2014-07-01

1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

RISING FROM THE ASHES: MID-INFRARED RE-BRIGHTENING OF THE IMPOSTOR SN 2010da IN NGC 300

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

Lau, Ryan M.; Ressler, Michael E.; Kasliwal, Mansi M.

2016-10-20

We present multi-epoch mid-infrared (IR) photometry and the optical discovery observations of the “impostor” supernova (SN) 2010da in NGC 300 using new and archival Spitzer Space Telescope images and ground-based observatories. The mid-infrared counterpart of SN 2010da was detected as Spitzer Infrared Intensive Transient Survey (SPIRITS) 14bme in the SPIRITS, an ongoing systematic search for IR transients. Before erupting on 2010 May 24, the SN 2010da progenitor exhibited a constant mid-IR flux at 3.6 and only a slight ∼10% decrease at 4.5 μ m between 2003 November and 2007 December. A sharp increase in the 3.6 μ m flux followedmore » by a rapid decrease measured ∼150 days before and ∼80 days after the initial outburst, respectively, reveal a mid-IR counterpart to the coincident optical and high luminosity X-ray outbursts. At late times, after the outburst (∼2000 days), the 3.6 and 4.5 μ m emission increased to over a factor of two times the progenitor flux and is currently observed (as of 2016 Feb) to be fading, but still above the progenitor flux. We attribute the re-brightening mid-IR emission to continued dust production and increasing luminosity of the surviving system associated with SN 2010da. We analyze the evolution of the dust temperature ( T {sub d} ∼ 700–1000 K), mass ( M {sub d} ∼ 0.5–3.8 × 10{sup −7} M {sub ⊙}), luminosity ( L {sub IR} ∼ 1.3–3.5 × 10{sup 4} L {sub ⊙}), and the equilibrium temperature radius ( R {sub eq} ∼ 6.4–12.2 au) in order to resolve the nature of SN 2010da. We address the leading interpretation of SN 2010da as an eruption from a luminous blue variable high-mass X-ray binary (HMXB) system. We propose that SN 2010da is instead a supergiant (sg)B[e]-HMXB based on similar luminosities and dust masses exhibited by two other known sgB[e]-HMXB systems. Additionally, the SN 2010da progenitor occupies a similar region on a mid-IR color–magnitude diagram (CMD) with known sgB[e] stars in the Large

Um estudo espectrofotométrico da variável cataclísmica V3885 Sgr

NASA Astrophysics Data System (ADS)

Ribeiro, F. M. A.; Diaz, M. P.

2003-08-01

Variáveis Cataclísmicas são sistemas binários cerrados compostos de uma anã vermelha que transfere matéria para uma anã branca, em sistemas não magnéticos ocorre a formação de um disco de acresção em torno da anã branca. V3885 Sgr é uma variável cataclísmica classificada como sendo do tipo nova-like. É apresentado um estudo espectrofotométrico de V3885 Sgr de alta resolução temporal feito na região do visível. A região observada é centrada em Ha e abrange também a linha de HeI 6678. O primeiro resultado obtido neste estudo é a determinação do período orbital a partir de medidas da velocidade radial da linha de Ha como sendo 0,20716071(22) dias, resolvendo inconsistências quanto a esse valor na literatura e definindo uma efeméride a longo prazo para o sistema. Com este período e as medidas de velocidade radial do perfil de linha de Ha foi construído um diagrama de massas, através do qual restringimos as massas das componentes estelares do sistema e limitamos a inclinação orbital do sistema. Foram construídos diagramas de Greenstein para as linhas de Ha e HeI, onde os espectros médios em cada intervalo de fase são representados lado a lado em escala de cinza, indicando a existência de uma emissão intensa proveniente da parte posterior do disco. A partir da tomografia Doppler obtivemos perfis de emissividade radial para o disco tanto para a linha de Ha como para HeI. Os resultados obtidos são comparados com os de outros sistemas estudados com a mesma técnica. Serão apresentados também resultados da tomografia de flickering para o sistema.

Automatic localization of the da Vinci surgical instrument tips in 3-D transrectal ultrasound.

PubMed

Mohareri, Omid; Ramezani, Mahdi; Adebar, Troy K; Abolmaesumi, Purang; Salcudean, Septimiu E

2013-09-01

Robot-assisted laparoscopic radical prostatectomy (RALRP) using the da Vinci surgical system is the current state-of-the-art treatment option for clinically confined prostate cancer. Given the limited field of view of the surgical site in RALRP, several groups have proposed the integration of transrectal ultrasound (TRUS) imaging in the surgical workflow to assist with accurate resection of the prostate and the sparing of the neurovascular bundles (NVBs). We previously introduced a robotic TRUS manipulator and a method for automatically tracking da Vinci surgical instruments with the TRUS imaging plane, in order to facilitate the integration of intraoperative TRUS in RALRP. Rapid and automatic registration of the kinematic frames of the da Vinci surgical system and the robotic TRUS probe manipulator is a critical component of the instrument tracking system. In this paper, we propose a fully automatic registration technique based on automatic 3-D TRUS localization of robot instrument tips pressed against the air-tissue boundary anterior to the prostate. The detection approach uses a multiscale filtering technique to identify and localize surgical instrument tips in the TRUS volume, and could also be used to detect other surface fiducials in 3-D ultrasound. Experiments have been performed using a tissue phantom and two ex vivo tissue samples to show the feasibility of the proposed methods. Also, an initial in vivo evaluation of the system has been carried out on a live anaesthetized dog with a da Vinci Si surgical system and a target registration error (defined as the root mean square distance of corresponding points after registration) of 2.68 mm has been achieved. Results show this method's accuracy and consistency for automatic registration of TRUS images to the da Vinci surgical system.

Integration Of PanDA Workload Management System With Supercomputers for ATLAS and Data Intensive Science

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

De, K; Jha, S; Klimentov, A

2016-01-01

The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS, one of the largest collaborations ever assembled in the sciences, is at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, the ATLAS experiment is relying on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Managementmore » System for managing the workflow for all data processing on over 150 data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. While PanDA currently uses more than 250,000 cores with a peak performance of 0.3 petaFLOPS, LHC data taking runs require more resources than Grid computing can possibly provide. To alleviate these challenges, LHC experiments are engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with supercomputers in United States, Europe and Russia (in particular with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF), MIRA supercomputer at Argonne Leadership Computing Facilities (ALCF), Supercomputer at the National Research Center Kurchatov Institute , IT4 in Ostrava and others). Current approach utilizes modified PanDA pilot framework for job submission to the supercomputers batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on LCFs multi-core worker nodes. This

Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.

PubMed

Radford, N B; Fina, M; Benjamin, I J; Moreadith, R W; Graves, K H; Zhao, P; Gavva, S; Wiethoff, A; Sherry, A D; Malloy, C R; Williams, R S

1996-03-19

Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

PubMed

Gökce, Mehmet I; Wang, Xuemei; Frost, Jacqueline; Roberson, Pamela; Volk, Robert J; Brooks, Durado; Canfield, Steven E; Pettaway, Curtis A

2017-02-15

The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society. © 2016 American Cancer Society.

Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

PubMed

Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

2011-08-01

To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (P<0.05), and the GABA concentration and Glu utilization rate in the mPFC also decreased (P<0.05). Compared with the chronic medication model group, the DA concentration of the mPFC in the SZ developmental group decreased (P<0.05), and the DOPAC concentration and the utility rate of DA in the hippocampus also decreased (P<0.01, P<0.05, respectively). The activities of DA, Glu and GABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

Facilitating Employees' and Students' Process towards Nascent Entrepreneurship

ERIC Educational Resources Information Center

Hietanen, Lenita

2015-01-01

Purpose: The purpose of this paper is to investigate a model for facilitating employees' and full-time, non-business students' entrepreneurial capabilities during their optional entrepreneurship studies at one Finnish Open University. Design/methodology/approach: The case study investigates the course in which transitions from employees or…

Exploring Nascent Entrepreneurial Learning: A Mixed Method Study

ERIC Educational Resources Information Center

Post, Ernie

2014-01-01

One purpose of this study was to add insight to help Small Business Development Center (SBDC) entrepreneurial educators understand why over 40% of their adult learners discontinue their learning program prematurely. In addition, this study explored how the comprehensive Self-Directed Learning (SDL) model might inform our understanding of attrition…

Automated Support for da Vinci Surgical System

DTIC Science & Technology

2011-05-01

MScore, which provides objective assessment measuring robotic surgery skills across all computed metrics (Figure 7). In addition to viewing single ...holding an object. Data Collection & Analysis (Task 5)  Preliminary Experiments  During the first phase of data collection, a single performance of...a single task (anastomosis) trial was recorded from six different users – three each for the da Vinci and the dV-Trainer platforms. On each platform

DA white dwarfs in Sloan Digital Sky Survey Data Release 7 and a search for infrared excess emission

NASA Astrophysics Data System (ADS)

Girven, J.; Gänsicke, B. T.; Steeghs, D.; Koester, D.

2011-10-01

We present a method which uses colour-colour cuts on the Sloan Digital Sky Survey (SDSS) photometry to select white dwarfs with hydrogen-rich (DA) atmospheres without the recourse to spectroscopy. This method results in a sample of DA white dwarfs that is 95 per cent complete at an efficiency of returning a true DA white dwarf of 62 per cent. The approach was applied to SDSS Data Release 7 for objects with and without SDSS spectroscopy. This led to 4636 spectroscopicially confirmed DA white dwarfs with g≤ 19; a ˜70 per cent increase compared to Eisenstein et al.'s 2006 sample. Including the photometric-only objects, we estimate a factor of 3 increase in DA white dwarfs. We find that the SDSS spectroscopic follow-up is 44 per cent complete for DA white dwarfs with Teff≳ 8000 K. We further cross-correlated the SDSS sample with Data Release 8 of the UKIRT (United Kingdom Infrared Telescope) Infrared Deep Sky Survey (UKIDSS) Large Area Survey. The spectral energy distributions (SED) of both subsets, with and without SDSS spectroscopy, were fitted with white dwarf models to determine the fraction of DA white dwarfs with low-mass stellar companions or dusty debris discs via the detection of excess near-infrared emission. From the spectroscopic sample we find that 2.0 per cent of white dwarfs have an excess consistent with a brown dwarf type companion, with a firm lower limit of 0.8 per cent. From the white dwarfs with photometry only, we find that 1.8 per cent are candidates for having brown dwarf companions. Similarly, both samples show that ˜1 per cent of white dwarfs are candidates for having a dusty debris disc.

'2A-Like' Signal Sequences Mediating Translational Recoding: A Novel Form of Dual Protein Targeting.

PubMed

Roulston, Claire; Luke, Garry A; de Felipe, Pablo; Ruan, Lin; Cope, Jonathan; Nicholson, John; Sukhodub, Andriy; Tilsner, Jens; Ryan, Martin D

2016-08-01

We report the initial characterization of an N-terminal oligopeptide '2A-like' sequence that is able to function both as a signal sequence and as a translational recoding element. Owing to this translational recoding activity, two forms of nascent polypeptide are synthesized: (i) when 2A-mediated translational recoding has not occurred: the nascent polypeptide is fused to the 2A-like N-terminal signal sequence and the fusion translation product is targeted to the exocytic pathway, and, (ii) a translation product where 2A-mediated translational recoding has occurred: the 2A-like signal sequence is synthesized as a separate translation product and, therefore, the nascent (downstream) polypeptide lacks the 2A-like signal sequence and is localized to the cytoplasm. This type of dual-functional signal sequence results, therefore, in the partitioning of the translation products between the two sub-cellular sites and represents a newly described form of dual protein targeting. © 2016 The Authors. Traffic published by John Wiley & Sons Ltd.

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

PubMed Central

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-01-01

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50–55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.25642.001 PMID:28556777

Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

PubMed

Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

2014-07-15

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

PubMed Central

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-01-01

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

PubMed

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-04-13

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA

[History of robotics: from archytas of tarentum until Da Vinci robot. (Part II)].

PubMed

Sánchez-Martín, F M; Jiménez Schlegl, P; Millán Rodríguez, F; Salvador-Bayarri, J; Monllau Font, V; Palou Redorta, J; Villavicencio Mavrich, H

2007-03-01

Robotic surgery is a reality. In order to to understand how new robots work is interesting to know the history of ancient (see part i) and modern robotics. The desire to design automatic machines imitating humans continued for more than 4000 years. Archytas of Tarentum (at around 400 a.C.), Heron of Alexandria, Hsieh-Fec, Al-Jazari, Bacon, Turriano, Leonardo da Vinci, Vaucanson o von Kempelen were robot inventors. At 1942 Asimov published the three robotics laws. Mechanics, electronics and informatics advances at XXth century developed robots to be able to do very complex self governing works. At 1985 the robot PUMA 560 was employed to introduce a needle inside the brain. Later on, they were designed surgical robots like World First, Robodoc, Gaspar o Acrobot, Zeus, AESOP, Probot o PAKI-RCP. At 2000 the FDA approved the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale, CA, USA), a very sophisticated robot to assist surgeons. Currently urological procedures like prostatectomy, cystectomy and nephrectomy are performed with the da Vinci, so urology has become a very suitable speciality to robotic surgery.

Robotic right colectomy using the Da Vinci Single-Site® platform: case report.

PubMed

Morelli, Luca; Guadagni, Simone; Caprili, Giovanni; Di Candio, Giulio; Boggi, Ugo; Mosca, Franco

2013-09-01

While single-port laparoscopy for abdominal surgery is technically challenging, the Da Vinci Single-Site® robotic surgery platform may help to overcome some of the difficulties of this rapidly evolving technique. The authors of this article present a case of single-incision, robotic right colectomy using this device. A 74-year-old female with malignant polyp of caecum was operated on with a single-site approach using the Da Vinci Single-Site® robotic surgery device. Resection and anastomosis were performed extra-corporeally after undocking the robot. The procedure was successfully completed in 200 min. No surgical complications occurred during the intervention and the post-operative stay and no conversion to laparotomy or additional trocars were required. To the best of our knowledge, this is the first case of right colectomy using the Da Vinci Single-Site® robotic surgery platform to be reported. The procedure is feasible and safe and its main advantages are restoration of triangulation and reduced instrument clashes. Copyright © 2013 John Wiley & Sons, Ltd.

The DaVinci Project: Multimedia in Art and Chemistry.

ERIC Educational Resources Information Center

Simonson, Michael; Schlosser, Charles

1998-01-01

Provides an overview of the DaVinci Project, a collaboration of students, teachers, and researchers in chemistry and art to develop multimedia materials for grades 3-12 visualizing basic concepts in chemistry and visual art. Topics addressed include standards in art and science; the conceptual framework for the project; and project goals,…

In vivo exposure to ozone produces an increase in a 72-kDa heat shock protein in guinea pigs.

PubMed

Su, W Y; Gordon, T

1997-09-01

Although several lines of evidence have suggested that oxidizing agents can induce heat shock proteins (HSPs) in vitro, little is known about the induction of HSPs during in vivo exposure to oxidants. Guinea pigs were exposed to ozone for 6 h and euthanized up to 72 h later. Proteins from lavage cells and lung tissue were characterized by immunoblotting with 72- and 73/72-kDa HSP monoclonal antibodies. Although 73-kDa HSP was expressed constituitively in lung tissue, it was not affected by ozone. In contrast, 72-kDa HSP was significantly increased in lavage cells and lung tissue of animals exposed to 0.4 and 0.66 parts/million of ozone. Both heat treatment and arsenite induced 72-kDa HSP in cultured alveolar macrophages. The increase in 72-kDa HSP in the lavage cell pellet peaked at 24 h after ozone, whereas the influx of polymorphonuclear leukocytes peaked at 4 h. Examination of the induction of HSPs by ozone may provide clues to the development of ozone tolerance in humans and animals.

Evolution of the ATLAS PanDA Production and Distributed Analysis System

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

Maeno, T.; De, K.; Wenaus, T.

2012-12-13

Evolution of the ATLAS PanDA Production and Distributed Analysis System T Maeno1,5, K De2, T Wenaus1, P Nilsson2, R Walker3, A Stradling2, V Fine1, M Potekhin1, S Panitkin1 and G Compostella4 Published under licence by IOP Publishing Ltd Journal of Physics: Conference Series, Volume 396, Part 3 Article PDF References Citations Metrics 101 Total downloads Cited by 8 articles Turn on MathJax Share this article Article information Abstract The PanDA (Production and Distributed Analysis) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at LHC data processing scale. PanDAmore » has performed well with high reliability and robustness during the two years of LHC data-taking, while being actively evolved to meet the rapidly changing requirements for analysis use cases. We will present an overview of system evolution including automatic rebrokerage and reattempt for analysis jobs, adaptation for the CernVM File System, support for the multi-cloud model through which Tier-2 sites act as members of multiple clouds, pledged resource management and preferential brokerage, and monitoring improvements. We will also describe results from the analysis of two years of PanDA usage statistics, current issues, and plans for the future.« less

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia.

PubMed

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-07-30

Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia

PubMed Central

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-01-01

Background/Aims Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Methods Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients’ quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. Results We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. Conclusions DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety. PMID:26130637

Asteroid 2012 DA14 as Seen from Siding Spring, Australia

NASA Image and Video Library

2013-02-15

An animated set of images, from the telescope known as the iTelescope.net Siding Spring Observatory, shows asteroid 2012 DA14 as the streak moving from top to bottom in the field of view. The animation is available in the Planetary Photojournal.

Multiple parton interactions and forward double pion production in pp and dA scattering

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

Strikman, M.; Vogelsang, W.

2011-02-01

We estimate the contributions by double-parton interactions to the cross sections for pp{yields}{pi}{sup 0}{pi}{sup 0}X and dA{yields}{pi}{sup 0}{pi}{sup 0}X at the Relativistic Heavy Ion Collider (RHIC). We find that such contributions become important at large forward rapidities of the produced pions. This is, in particular, the case for dA scattering, where they strongly enhance the azimuthal-angular independent pedestal component of the cross section, providing a natural explanation of this feature of the RHIC dA data. We argue that the discussed processes open a window to studies of double quark distributions in nucleons. We also briefly address the roles of shadowingmore » and energy loss in dA scattering, which we show to affect the double-inclusive pion cross section much more strongly than the single-inclusive one. We discuss the implications of our results for the interpretation of pion azimuthal correlations.« less

Transoral robotic surgery for the base of tongue squamous cell carcinoma: a preliminary comparison between da Vinci Xi and Si.

PubMed

Alessandrini, Marco; Pavone, Isabella; Micarelli, Alessandro; Caporale, Claudio

2017-09-13

Considering the emerging advantages related to da Vinci Xi robotic platform, the aim of this study is to compare for the first time the operative outcomes of this tool to the previous da Vinci Si during transoral robotic surgery (TORS), both performed for squamous cell carcinomas (SCC) of the base of tongue (BOT). Intra- and peri-operative outcomes of eight patients with early stage (T1-T2) of the BOT carcinoma and undergoing TORS by means of the da Vinci Xi robotic platform (Xi-TORS) are compared with the da Vinci Si group ones (Si-TORS). With respect to Si-TORS group, Xi-TORS group demonstrated a significantly shorter overall operative time, console time, and intraoperative blood loss, as well as peri-operative pain intensity and length of mean hospital stays and nasogastric tube positioning. Considering recent advantages offered by surgical robotic techniques, the da Vinci Xi Surgical System preliminary outcomes could suggest its possible future routine implementation in BOT squamous cell carcinoma procedures.

Identification of a 27.8 kDa protein from flounder gill cells involved in lymphocystis disease virus binding and infection.

PubMed

Wang, Mu; Sheng, Xiu-Zhen; Xing, Jing; Tang, Xiao-Qian; Zhan, Wen-Bin

2011-03-16

In vitro, lymphocystis disease virus (LCDV) infection of flounder gill (FG) cell cultures causes obvious cytopathic effect (CPE). We describe attempts to isolate and characterize the LCDV-binding molecule(s) on the plasma membrane of FG cells that were responsible for virus entry. The results showed that the co-immunoprecipitation assay detected a 27.8 kDa molecule from FG cells that bound to LCDV. In a blocking ELISA, pre-incubation of FG cell membrane proteins with the specific antiserum developed against the 27.8 kDa protein could block LCDV binding. Similarly, antiserum against 27.8 kDa protein could also inhibit LCDV infection of FG cells in vitro. Mass spectrometric analysis established that the 27.8 kDa protein and beta-actin had a strong association. These results strongly supported the possibility that the 27.8 kDa protein was the putative receptor specific for LCDV infection of FG cells.

[Trattamento della dipendenza da alcol. Alcol e persone senza fissa dimora: punto di vista sociale].

PubMed

Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Cereatti, Federica; Gencarelli, Simona; Messina, Marisa Patrizia; Vitali, Mario; De Rosa, Francesca; Ledda, Roberta; Mancini, Serena; Attilia, Maria Luisa

2018-01-01

RIASSUNTO. Il fenomeno delle persone senza fissa dimora sta assumendo in questi anni una rilevanza sociale devastante, con una prevalenza stimata in USA e in Europa compresa tra il 5,6% e il 13,9%. Queste persone hanno una scarsa qualità di vita, una limitata o assente vita sociale, sono spesso disoccupate o lavorano solo saltuariamente. Sono a rischio di problemi con la legge, sono spesso affette da dipendenza da droghe, da patologie psichiatriche e internistiche. L'alcol spesso non rappresenta la causa della loro condizione sociale, ma solo la conseguenza, contribuendo in questo modo al loro degrado bio-psico-sociale. Nel 2009 lo US Department of Housing and Urban Development's Homelessness Assistance Programs e nel 2010 la European Consensus Conference on Homelessness hanno segnato un grande passo avanti nella riabilitazione sociale di queste persone, utilizzando il concetto del "case management". In particolare lo Standard Case Management si è dimostrato in grado di migliorare la stabilità abitativa, di ridurre l'uso di droghe e di rimuovere le barriere lavorative. L'Assertive Community Treatment si è dimostrato, invece, in grado di migliorare la stabilità abitativa e ha un rapporto costo/beneficio migliore per i pazienti affetti da doppia diagnosi.

Oleosins (24 and 18 kDa) are hydrolyzed not only in extracted soybean oil bodies but also in soybean germination.

PubMed

Chen, Yeming; Zhao, Luping; Cao, Yanyun; Kong, Xiangzhen; Hua, Yufei

2014-01-29

After oil bodies (OBs) were extracted from ungerminated soybean by pH 6.8 extraction, it was found that 24 and 18 kDa oleosins were hydrolyzed in the extracted OBs, which contained many OB extrinsic proteins (i.e., lipoxygenase, β-conglycinin, γ-conglycinin, β-amylase, glycinin, Gly m Bd 30K (Bd 30K), and P34 probable thiol protease (P34)) as well as OB intrinsic proteins. In this study, some properties (specificity, optimal pH and temperature) of the proteases of 24 and 18 kDa oleosins and the oleosin hydrolysis in soybean germination were examined, and the high relationship between Bd 30K/P34 and the proteases was also discussed. The results showed (1) the proteases were OB extrinsic proteins, which had high specificity to hydrolyze 24 and 18 kDa oleosins, and cleaved the specific peptide bonds to form limited hydrolyzed products; (2) 24 and 18 kDa oleosins were not hydrolyzed in the absence of Bd 30K and P34 (or some Tricine-SDS-PAGE undetectable proteins); (3) the protease of 24 kDa oleosin had strong resistance to alkaline pH while that of 18 kDa oleosin had weak resistance to alkaline pH, and Bd 30K and P34, resolved into two spots on two-dimensional electrophoresis gel, also showed the same trend; (4) 16 kDa oleosin as well as 24 and 18 kDa oleosins were hydrolyzed in soybean germination, and Bd 30K and P34 were always contained in the extracted OBs from germinated soybean even when all oleosins were hydrolyzed; (5) the optimal temperature and pH of the proteases were respectively determined as in the ranges of 35-50 °C and pH 6.0-6.5, while 60 °C or pH 11.0 could denature them.

Detecção da fase impulsiva de uma explosão solar gigante até 405 GHz

NASA Astrophysics Data System (ADS)

Raulin, J.-P.; Makhmutov, V.; Kaufmann, P.; Pacini, A. A.; Luethi, T.; Hudson, H. S.; Gary, D. E.; Yoshimori, M.

2003-08-01

A explosão ocorrida no dia 25/08/2001 foi uma das mais intensas do presente ciclo solar em ondas de rádio de altas frequências. Foram medidas em ondas milimétricas e submilimétricas, aproximadamente, 105 e vários milhares de unidades de fluxo solar, respectivamente. Apresentamos um estudo deste evento em múltiplas frequências, desde microondas (1GHz), até ondas submilimétricas (405 GHz) detectadas pelo Telescópio Solar para ondas Submilimétricas (SST). Esta base de dados foi complementada utilizando-se o experimento Yohkoh, incluindo a emissão em raios-X duros e raios-g (até 100 MeV), e imagens em raios-X moles da região ativa envolvida. Enfocamos e discutimos principalmente os seguintes aspectos da fase impulsiva do evento: (i) as implicações deduzidas do espectro eletromagnético, obtido pela primeira vez até 405 GHz; (ii) a dinâmica da região ativa. Os resultados mostram que para explicar o espectro rádio observado, são necessários entre 3.5×1037 e 1.5×1039 elétrons acelerados acima de 20 keV em uma região de campo magnético entre 300 e 800 Gauss. A estimativa do fluxo de fótons que seria produzido por estes elétrons, mostra que grande parte deles não precipitou na baixa atmosfera. A evolução temporal da emissão em raios-X moles revela que a configuração magnética da região ativa foi muito dinâmica durante a fase impulsiva da explosão. Em particular, mostramos que a produção dos elétrons altamente energéticos foi iniciada junto com a aparição, na baixa coroa solar, de um novo sistema compacto de estruturas magnéticas. Este fato sugere que os locais de aceleração estão localizados na baixa atmosfera do Sol, como resultado da interação entre o novo sistema compacto e o campo magnético ambiente da região ativa.

Determinação de regiões de órbitas diretas estáveis ao redor da Lua

NASA Astrophysics Data System (ADS)

de Melo, C. F.; Winter, O. C.; Vieira Neto, E.

2003-08-01

Neste Trabalho estamos investigando regiões do sistema Terra-Lua que contêm órbitas diretas estáveis ao redor da Lua visando a utilização destas órbitas em futuras missões de veículos espaciais como alternativas de trajetórias com baixo custo de manutenção. Adotando-se o problema restrito de três corpos, Terra-Lua-partícula, a localização e a extensão destas regiões de estabilidade foram investigadas numericamente considerando como estável toda órbita que permanece ao redor a Lua por, no mínimo, 1000 dias com energia de dois corpos da partícula em relação à Lua negativa. A estabilidade de tais regiões está associada a duas famílias de órbitas periódicas simples H1 e H2 e a órbitas quase-periódicas associadas a elas. Uma vez identificadas as regiões de estabilidade passamos a analisá-las introduzindo, paulatinamente, outras interações relevantes ao sistema como as perturbações do Sol (via problema restrito de quatro corpos), das marés, da pressão de radiação e do achatamento terrestre. Os resultados encontrados até o momento mostram que a perturbação do Sol é a única que reduz significativamente o tamanho das regiões de estabilidade. Também estamos investigando o comportamento de tais regiões quando características intrínsecas do sistema como as excentricidades das órbitas da Terra e da Lua e a inclinação da órbita Lua são consideradas. Com este estudo estamos reunindo informações que nos permitirão compreender a evolução das regiões de estabilidade no sistema Terra-Lua, bem como estabelecer parâmetros adequados para a utilização das trajetórias estáveis em futuras missões espaciais. Agradecimentos: Este projeto conta com o apoio do CNPq, da Capes e da Fapesp.

On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Zhao, Ziyu; Liu, Jinxing; Soh, Ai Kah

2018-01-01

In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials' amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

Agarose and Polyacrylamide Gel Electrophoresis Methods for Molecular Mass Analysis of 5–500 kDa Hyaluronan

PubMed Central

Bhilocha, Shardul; Amin, Ripal; Pandya, Monika; Yuan, Han; Tank, Mihir; LoBello, Jaclyn; Shytuhina, Anastasia; Wang, Wenlan; Wisniewski, Hans-Georg; de la Motte, Carol; Cowman, Mary K.

2011-01-01

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5–500 kDa have been investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffers systems were determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition, over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample, and calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa, at sample loads of 0.5 µg (for polyacrylamide) to 2.5 µg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150 kDa HA standard. PMID:21684248

Tão perto de casa, tão longe de nós: etnografia das novas margens no centro da urbe

PubMed Central

Fernandes, Por Luís

2011-01-01

Philippe Bourgois é, desde 2007, “Richard Perry University professor” no Departamento de Antropologia e de Medicina Familiar e de Práticas Comunitárias na Universidade da Pensilvânia. Esteve durante largos anos ligado ao Departamento de Antropologia, História e Medicina Social da Universidade da Califórnia, São Francisco. A publicação, em 1995, de In Search of Respect: Selling Crack in El Barrio1 projectaria o seu nome muito para além dos Estados Unidos: uma etnografia no coração porto-riquenho do Harlem, em torno dos actores e dos ambientes da venda de crack. Seguir-se-ia um longo trabalho de terreno em acampamentos de dependentes de heroína em São Francisco, orientando o seu trabalho para as formas mais radicais da pobreza e da marginalidade nos EUA. É deste trabalho de terreno que sai o seu último livro, Righteous Dopefiend2. Em Junho de 2007 esteve em Lisboa para participar na 3.a edição do “Ethnografeast”. Foi então que aproveitámos a oportunidade para ouvir um percurso invulgar contado pelo próprio: uma longa conversa no Hotel Zurique, cujo nome só vem ao caso por evocar o país onde passou uma parte da infância. PMID:22013286

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study.

PubMed

Menéndez-González, Manuel; Tavares, Francisco; Zeidan, Nahla; Salas-Pacheco, José M; Arias-Carrión, Oscar

2014-01-01

The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.

PubMed Central

Radford, N B; Fina, M; Benjamin, I J; Moreadith, R W; Graves, K H; Zhao, P; Gavva, S; Wiethoff, A; Sherry, A D; Malloy, C R; Williams, R S

1996-01-01

Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart. Images Fig. 1 Fig. 3 PMID:8637874

Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

PubMed

Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

2015-07-01

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of DA-6 and EDTA alone or in combination on uptake, subcellular distribution and chemical form of Pb in Lolium perenne.

PubMed

He, Shanying; Wu, Qiuling; He, Zhenli

2013-11-01

The effects of growth-promoting hormone diethyl aminoethyl hexanoate (DA-6) and EDTA, either alone or in combination applied to original soil or lead (Pb) spiked soil on Pb phytoextraction, subcellular distribution and chemical forms in Lolium perenne were studied. EDTA addition alone significantly reduced plant biomass though it increased Pb accumulation (P<0.05). Foliar spray of DA-6 alone increased both plant biomass and Pb accumulation (P<0.05), with 10μM DA-6 being the most effective. DA-6 combined with EDTA compensated the adverse effect of the latter on plant growth, and resulted in a synergistic effect on Pb uptake and translocation, with the maximum accumulation occurring in the EDTA+10μM DA-6 treatment. At the subcellular level, about 35-66% of Pb was distributed in cell wall and 21-42% in soluble fraction, with a minority present in cellular organelles fraction. EDTA addition alone increased the proportion of Pb in soluble and cellular organelles fraction, while DA-6 detoxified Pb in plant by storing additional Pb in cell wall, and 10μM DA-6 was the most effective. Of the total Pb in plant shoot, 27-52% was NaCl extractable, 22-47% HAc extractable, followed by other fractions. Contrary to EDTA, DA-6 significantly decreased Pb migration in plant. These results suggest that Pb fixation by pectates and proteins in cell wall and compartmentalization by vacuole might be responsible for Pb detoxification in plant, and the combined use of EDTA and 10μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Pb contaminated soil. Copyright © 2013 Elsevier Ltd. All rights reserved.

Women and Technical Professions. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs for women in technical professions that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) Artemis and Diana (vocational guidance programs to help direct girls toward technology-related careers); (2) CEEWIT (an Internet-based information and…

Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric cancer cells

PubMed Central

Jin, Rong; Xia, Yiqun; Chen, Qiuxiang; Li, Wulan; Chen, Dahui; Ye, Hui; Zhao, Chengguang; Du, Xiaojing; Shi, Dengjian; Wu, Jianzhang; Liang, Guang

2016-01-01

Background The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation

In vitro activities of DA-7867, a novel oxazolidinone, against recent clinical isolates of aerobic and anaerobic bacteria.

PubMed

Yong, Dongeun; Yum, Jong Hwa; Lee, Kyungwon; Chong, Yunsop; Choi, Sung Hak; Rhee, Jae Keol

2004-01-01

In vitro activities of DA-7867, a novel oxazolidinone, were compared to those of linezolid and commonly used antimicrobials. DA-7867 had the lowest MIC for 90% of the aerobic gram-positive bacterial strains tested,

Synergetic effects of DA-6/GA₃ with EDTA on plant growth, extraction and detoxification of Cd by Lolium perenne.

PubMed

He, Shanying; Wu, Qiuling; He, Zhenli

2014-12-01

Research is needed to improve efficiency of phytoextraction of heavy metals from contaminated soils. A pot experiment was carried out to study the effects of plant growth regulators (PGRs) (diethyl aminoethyl hexanoate (C18H33NO8, DA-6) and gibberellic acid 3 (C19H22O6, GA3)) and/or EDTA on Cd extraction, subcellular distribution and chemical forms in Lolium perenne. The addition of EDTA or PGRs significantly enhanced Cd extraction efficiency (P<0.05), with the decreasing order of: 1 μM DA-6>10 μM DA-6>10 μM GA3>2.5 mmol kg(-1) EDTA>other treatments of PGR alone. PGRs+EDTA resulted in a further increase in Cd extraction efficiency, with EDTA+1 μM DA-6 being the most efficient. At the subcellular level, about 44-57% of Cd was soluble fraction, 18-44% in cell walls, and 12-25% in cellular organelles fraction. Chemical speciation analysis showed that 40-54% of Cd was NaCl extractable, 7-23% HAc extractable, followed by other fractions. EDTA increased the proportions of Cd in soluble and cellular organelles fraction, as well as the metal migration in shoot; therefore, the toxicity to plant increased and plant growth was inhibited. Conversely, PGRs fixed more Cd in cell walls and reduced Cd migration in shoot; thus, metal toxicity was reduced. In addition, PGRs promoted plant biomass growth significantly (P<0.05), with 1 μM DA-6 being the most effective. A combination of DA-6/GA3 with EDTA can alleviate the adverse effect of EDTA on plant growth, and the treatment of EDTA+1 μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Cd contaminated soil. Copyright © 2014 Elsevier Ltd. All rights reserved.

Católicos, fidelidade conjugal e AIDS: entre a cruz da doutrina moral e as espadas do cotidiano sexual dos adeptos1

PubMed Central

Rios, Luis Felipe; de Aquino, Francisca Luciana; Muñoz-Laboy, Miguel; Oliveira, Cinthia; Parker, Richard

2009-01-01

Neste artigo discutimos a visão da Igreja Católica sobre sexualidade na interface com a epidemia do HIV/AIDS. Nossa reflexão está embasada em pesquisa etnográfica que envolveu dois meses de observação participante do cotidiano de católicos de um bairro popular da Região Metropolitana do Recife, além de contar com entrevistas a onze dos leigos engajados nos serviços religiosos da igreja do bairro e a oito sacerdotes que realizam seus trabalhos religiosos em outras localidades. Nelas abordamos diferentes temáticas relacionadas ao enfrentamento da epidemia da AIDS. Nesse contexto, conjugalidade e fidelidade se afiguram como importantes analisadores de como aqueles lidam com a epidemia, em uma variedade de re-descrições práticas e de re-interpretações conceptuais das assertivas do discurso moral religioso – ainda que, muitos impasses permaneçam em aberto em termos das prerrogativas da Igreja e seus possíveis rebatimentos na saúde sexual dos adeptos. PMID:21765650

Evaluation of the immunomodulatory effect of the 14 kDa protein isolated from aged garlic extract on dendritic cells.

PubMed

Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Safari, Elahe; Bozorgmehr, Mahmood; Ghazanfari, Tooba; Moazzeni, Seyed Mohammad

2011-01-01

Garlic is used all over the world for treatment of different diseases. A wide range of biological activities of garlic has been verified in vitro and in vivo. One of major proteins of garlic which has been isolated and purified is the 14 kDa protein. This protein has been shown to have immunomodulatory effects. In this study, the effect of the 14 kDa protein isolated from aged garlic extract (AGE) was investigated on maturation and immunomodulatory activity of dendritic cells (DC). Proteins were purified from AGE by biochemical method; the semi-purified 14 kDa protein was run on gel filtration Sephadex G50 and its purity was checked by SDS-PAGE. DC were isolated from spleen of BALB/c mice by Nycodenz centrifugation and their adhesiveness to plastic dish. 14 kDa protein from AGE was added to overnight culture of DC medium and the expression percentage of CD40, CD86, and MHC-II was evaluated by flowcytometric analysis. Also, proliferation of T-cells was measured by allogenic mixed lymphocyte reaction (MLR) test. The purified 14 kDa protein isolated from AGE increased the expression of CD40 molecule on DC, but it did not influence CD86 and MHCII molecules. Furthermore, no significant differences were noticed in the pulsed-DC with 14 kDa protein and non-pulsed DC on the MLR. Copyright © 2011 Elsevier Inc. All rights reserved.

UniDA: Uniform Device Access Framework for Human Interaction Environments

PubMed Central

Varela, Gervasio; Paz-Lopez, Alejandro; Becerra, Jose Antonio; Vazquez-Rodriguez, Santiago; Duro, Richard José

2011-01-01

Human interaction environments (HIE) must be understood as any place where people carry out their daily life, including their work, family life, leisure and social life, interacting with technology to enhance or facilitate the experience. The integration of technology in these environments has been achieved in a disorderly and incompatible way, with devices operating in isolated islands with artificial edges delimited by the manufacturers. In this paper we are presenting the UniDA framework, an integral solution for the development of systems that require the integration and interoperation of devices and technologies in HIEs. It provides developers and installers with a uniform conceptual framework capable of modelling an HIE, together with a set of libraries, tools and devices to build distributed instrumentation networks with support for transparent integration of other technologies. A series of use case examples and a comparison to many of the existing technologies in the field has been included in order to show the benefits of using UniDA. PMID:22163700

UniDA: uniform device access framework for human interaction environments.

PubMed

Varela, Gervasio; Paz-Lopez, Alejandro; Becerra, Jose Antonio; Vazquez-Rodriguez, Santiago; Duro, Richard José

2011-01-01

Human interaction environments (HIE) must be understood as any place where people carry out their daily life, including their work, family life, leisure and social life, interacting with technology to enhance or facilitate the experience. The integration of technology in these environments has been achieved in a disorderly and incompatible way, with devices operating in isolated islands with artificial edges delimited by the manufacturers. In this paper we are presenting the UniDA framework, an integral solution for the development of systems that require the integration and interoperation of devices and technologies in HIEs. It provides developers and installers with a uniform conceptual framework capable of modelling an HIE, together with a set of libraries, tools and devices to build distributed instrumentation networks with support for transparent integration of other technologies. A series of use case examples and a comparison to many of the existing technologies in the field has been included in order to show the benefits of using UniDA.

OpenDA Open Source Generic Data Assimilation Environment and its Application in Process Models

NASA Astrophysics Data System (ADS)

El Serafy, Ghada; Verlaan, Martin; Hummel, Stef; Weerts, Albrecht; Dhondia, Juzer

2010-05-01

Data Assimilation techniques are essential elements in state-of-the-art development of models and their optimization with data in the field of groundwater, surface water and soil systems. They are essential tools in calibration of complex modelling systems and improvement of model forecasts. The OpenDA is a new and generic open source data assimilation environment for application to a choice of physical process models, applied to case dependent domains. OpenDA was introduced recently when the developers of Costa, an open-source TU Delft project [http://www.costapse.org; Van Velzen and Verlaan; 2007] and those of the DATools from the former WL|Delft Hydraulics [El Serafy et al 2007; Weerts et al. 2009] decided to join forces. OpenDA makes use of a set of interfaces that describe the interaction between models, observations and data assimilation algorithms. It focuses on flexible applications in portable systems for modelling geophysical processes. It provides a generic interfacing protocol that allows combination of the implemented data assimilation techniques with, in principle, any time-stepping model duscribing a process(atmospheric processes, 3D circulation, 2D water level, sea surface temperature, soil systems, groundwater etc.). Presently, OpenDA features filtering techniques and calibration techniques. The presentation will give an overview of the OpenDA and the results of some of its practical applications. Application of data assimilation in portable operational forecasting systems—the DATools assimilation environment, El Serafy G.Y., H. Gerritsen, S. Hummel, A. H. Weerts, A.E. Mynett and M. Tanaka (2007), Journal of Ocean Dynamics, DOI 10.1007/s10236-007-0124-3, pp.485-499. COSTA a problem solving environment for data assimilation applied for hydrodynamical modelling, Van Velzen and Verlaan (2007), Meteorologische Zeitschrift, Volume 16, Number 6, December 2007 , pp. 777-793(17). Application of generic data assimilation tools (DATools) for flood

da Vinci robot-assisted keyhole neurosurgery: a cadaver study on feasibility and safety.

PubMed

Marcus, Hani J; Hughes-Hallett, Archie; Cundy, Thomas P; Yang, Guang-Zhong; Darzi, Ara; Nandi, Dipankar

2015-04-01

The goal of this cadaver study was to evaluate the feasibility and safety of da Vinci robot-assisted keyhole neurosurgery. Several keyhole craniotomies were fashioned including supraorbital subfrontal, retrosigmoid and supracerebellar infratentorial. In each case, a simple durotomy was performed, and the flap was retracted. The da Vinci surgical system was then used to perform arachnoid dissection towards the deep-seated intracranial cisterns. It was not possible to simultaneously pass the 12-mm endoscope and instruments through the keyhole craniotomy in any of the approaches performed, limiting visualization. The articulated instruments provided greater dexterity than existing tools, but the instrument arms could not be placed in parallel through the keyhole craniotomy and, therefore, could not be advanced to the deep cisterns without significant clashing. The da Vinci console offered considerable ergonomic advantages over the existing operating room arrangement, allowing the operating surgeon to remain non-sterile and seated comfortably throughout the procedure. However, the lack of haptic feedback was a notable limitation. In conclusion, while robotic platforms have the potential to greatly enhance the performance of transcranial approaches, there is strong justification for research into next-generation robots, better suited to keyhole neurosurgery.

The use of centrifugation to study early Drosophila embryogenesis

NASA Technical Reports Server (NTRS)

Abbott, M. K.; Spooner, B. S. (Principal Investigator)

1993-01-01

By the end of 10th nuclear cycle, the somatic nuclei of the Drosophila embryo have migrated to the periphery of the egg. Centrifugation of embryos did not result in the displacement of these nuclei, since cytoskeletal elements anchor them to the cortex. But, mild centrifugal forces displace the centrally located, nascent yolk nuclei. If this increased sensitivity to hypergravity occurs before the beginning of nuclear differentiation during cycle 8, when the nascent yolk and somatic nuclei physically separate, then it would mark the earliest functional difference between these two lineages.

[Short-term efficacy of da Vinci robotic surgical system on rectal cancer in 101 patients].

PubMed

Zeng, Dong-Zhu; Shi, Yan; Lei, Xiao; Tang, Bo; Hao, Ying-Xue; Luo, Hua-Xing; Lan, Yuan-Zhi; Yu, Pei-Wu

2013-05-01

To investigate the feasibility and safety of da Vinci robotic surgical system in rectal cancer radical operation, and to summarize its short-term efficacy and clinical experience. Data of 101 cases undergoing da Vinci robotic surgical system for rectal cancer radical operation from March 2010 to September 2012 were retrospectively analyzed. Evaluation was focused on operative procedure, complication, recovery and pathology. All the 101 cases underwent operation successfully and safely without conversion to open procedure. Rectal cancer radical operation with da Vinci robotic surgical system included 73 low anterior resections and 28 abdominoperineal resections. The average operative time was (210.3±47.2) min. The average blood lose was (60.5±28.7) ml without transfusion. Lymphadenectomy harvest was 17.3±5.4. Passage of first flatus was (2.7±0.7) d. Distal margin was (5.3±2.3) cm without residual cancer cells. The complication rate was 6.9%, including anastomotic leakage(n=2), perineum incision infection(n=2), pulmonary infection (n=2), urinary retention (n=1). There was no postoperative death. The mean follow-up time was(12.9±8.0) months. No local recurrence was found except 2 cases with distant metastasis. Application of da Vinci robotic surgical system in rectal cancer radical operation is safe and patients recover quickly The short-term efficacy is satisfactory.

Visual degradation in Leonardo da Vinci's iconic self-portrait: A nanoscale study

NASA Astrophysics Data System (ADS)

Conte, A. Mosca; Pulci, O.; Misiti, M. C.; Lojewska, J.; Teodonio, L.; Violante, C.; Missori, M.

2014-06-01

The discoloration of ancient paper, due to the development of oxidized groups acting as chromophores in its chief component, cellulose, is responsible for severe visual degradation in ancient artifacts. By adopting a non-destructive approach based on the combination of optical reflectance measurements and time-dependent density functional theory ab-initio calculations, we describe and quantify the chromophores affecting Leonardo da Vinci's iconic self-portrait. Their relative concentrations are very similar to those measured in modern and ancient samples aged in humid environments. This analysis quantifies the present level of optical degradation of the Leonardo da Vinci's self-portrait which, compared with future measurements, will assess its degradation rate. This is a fundamental information in order to plan appropriate conservation strategies.

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

PubMed

Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

2016-05-01

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

A 115 kDa calmodulin-binding protein is located in rat liver endosome fractions.

PubMed Central

Enrich, C; Bachs, O; Evans, W H

1988-01-01

The distribution of calmodulin-binding polypeptides in various rat liver subcellular fractions was investigated. Plasma-membrane, endosome, Golgi and lysosome fractions were prepared by established procedures. The calmodulin-binding polypeptides present in the subcellular fractions were identified by using an overlay technique after transfer from gels to nitrocellulose sheets. Distinctive populations of calmodulin-binding polypeptides were present in all the fractions examined except lysosomes. A major 115 kDa calmodulin-binding polypeptide of pI 4.3 was located to the endosome subfractions, and it emerges as a candidate endosome-specific protein. Partitioning of endosome fractions between aqueous and Triton X-114 phases indicated that the calmodulin-binding polypeptide was hydrophobic. Major calmodulin-binding polypeptides of 140 and 240 kDa and minor polypeptides of 40-60 kDa were present in plasma membranes. The distribution of calmodulin in the various endosome and plasma-membrane fractions was also analysed, and the results indicated that the amounts were high compared with those in the cytosol. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3214436

Leonardo da Vinci and Kethem-Kiveris vena.

PubMed

Dolezal, Antonín; Skorepova-Honzlova, Zita; Jelen, Karel

2012-01-01

In the drawing of coitus by Leonardo da Vinci are pictured the contemporary hypotheses regarding this act. The authors analyze the mamillaruteral connection depicted by the artist and grow up to believe that this is a hypothetical kiveris vena, female vein described by Anatomist Master Nicolai Physicus from the Salerno School. The Hebrew roots were found in the name. The connection is described also by Mondino in The Anathomia. The same connection can be found in the picture of the pregnant woman in Fasciculus Medicinæ by Johannes De Ketham.

The genome sequence of Agrotis segetum granulovirus, isolate AgseGV-DA, reveals a new Betabaculovirus species of a slow killing granulovirus.

PubMed

Gueli Alletti, Gianpiero; Eigenbrod, Marina; Carstens, Eric B; Kleespies, Regina G; Jehle, Johannes A

2017-06-01

The European isolate Agrotis segetum granulovirus DA (AgseGV-DA) is a slow killing, type I granulovirus due to low dose-mortality responses within seven days post infection and a tissue tropism of infection restricted solely to the fat body of infected Agrotis segetum host larvae. The genome of AgseGV-DA was completely sequenced and compared to the whole genome sequences of the Chinese isolates AgseGV-XJ and AgseGV-L1. All three isolates share highly conserved genomes. The AgseGV-DA genome is 131,557bp in length and encodes for 149 putative open reading frames, including 37 baculovirus core genes and the per os infectivity factor ac110. Comprehensive investigations of repeat regions identified one putative non-hr like origin of replication in AgseGV-DA. Phylogenetic analysis based on concatenated amino acid alignments of 37 baculovirus core genes as well as pairwise distances based on the nucleotide alignments of partial granulin, lef-8 and lef-9 sequences with deposited betabaculoviruses confirmed AgseGV-DA, AgseGV-XJ and AgseGV-L1 as representative isolates of the same Betabaculovirus species. AgseGV encodes for a distinct putative enhancin, distantly related to enhancins from other granuloviruses. Copyright © 2017. Published by Elsevier Inc.

Anti-diabetic effects of DA-11004, a synthetic IDPc inhibitor in high fat high sucrose diet-fed C57BL/6J mice.

PubMed

Shin, Chang Yell; Jung, Mi Young; Lee, In Ki; Son, Miwon; Kim, Dong Sung; Lim, Joong In; Kim, Soon Hoe; Yoo, Moohi; Huh, Tae Lin; Sohn, Young Taek; Kim, Won Bae

2004-01-01

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

Studying and Working Abroad. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles recent successful examples of students studying and working abroad as part of the European Commission's Leonardo da Vinci program, which is designed to give students across the European Union the opportunity to experience vocational training in a foreign country. The following examples are presented: (1) 3 Finnish students…

Tonic 5nM DA Stabilizes Neuronal Output by Enabling Bidirectional Activity-Dependent Regulation of the Hyperpolarization Activated Current via PKA and Calcineurin

PubMed Central

Krenz, Wulf-Dieter C.; Rodgers, Edmund W.; Baro, Deborah J.

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP’s first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output. PMID

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

PubMed

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Temperature and Gravity Dependence of Trace Element Abundances in Hot DA White Dwarfs (94-EUVE-094)

NASA Technical Reports Server (NTRS)

Finley, David S.

1998-01-01

EUV spectroscopy has shown that DA white dwarfs hotter than about 45,000 K may contain trace heavy elements, while those hotter than about 50,000 K almost always have significant abundances of trace heavy elements. One of our continuing challenges is to identify and determine the abundances of these trace constituents, and then to relate the observed abundance patterns to the present conditions and previous evolutionary histories of the hot DA white dwarfs.

Proof of mechanism study of a novel serotonin transporter blocker, DA-8031, using [11C]DASB positron emission tomography and in vivo microdialysis.

PubMed

Park, Hyun Soo; Jung, In Soon; Lim, Nam Hee; Sung, Ji Hyun; Lee, Sukhyang; Moon, Byung Seok; Lee, Byung Chul; Kang, Kyung Koo; Kim, Sang Eun

2014-07-01

To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation, we measured serotonin transporter (SERT) occupancy by DA-8031, as well as DA-8031-induced changes in extracellular serotonin levels, in the rat brain using positron emission tomography (PET) and 11C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([11C]DASB) and in vivo microdialysis, respectively. [11C]DASB PET scans were performed in rats with graded doses of DA-8031 (vehicle: 10, 30, and 100 mg/kg). SERT occupancy in the midbrain was determined using binding potentials for [11C]DASB calculated by the multilinear reference tissue model. Extracellular serotonin levels were monitored in the dorsal raphe nucleus of rats after the administration of DA-8031 (10-100 mg/kg) using in vivo microdialysis. PET data indicated a reduction of [11C]DASB binding to SERTs in the midbrain as a function of DA-8031 dose. SERT occupancy for each DA-8031 dose (10-100 mg/kg) ranged between 31% and 84%. The drug dose required for 50% occupancy of SERT was 13.5 mg/kg in the midbrain, comparable with previous preclinical behavioral data (∼10-30 mg/kg). In vivo microdialysis showed that DA-8031 produced a dose-dependent increase in extracellular serotonin levels in the dorsal raphe nucleus (33%-81% increase for doses of 10-100 mg/kg). These preclinical data provide a proof of mechanism for DA-8031 as a novel compound of targeting the SERT for the treatment of premature ejaculation, warranting further clinical trials. They also offer insight into the optimal drug dose needed to exert therapeutic effects while minimizing adverse effects in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluating the potential of marine Bacteriovorax sp. DA5 as a biocontrol agent against vibriosis in Litopenaeus vannamei larvae.

PubMed

Wen, Chongqing; Xue, Ming; Liang, Huafang; Zhou, Shining

2014-09-17

The potential application of Bdellovibrio-and-like organisms (BALOs) for the biocontrol of bacterial diseases has been widely recognized. However, no marine BALOs have been reported for Vibrio-related infections in penaeid shrimp. In the present study, the bacteriolytic ability of the marine Bacteriovorax strain DA5 against Vibrio alginolyticus zouA was examined by cocultivation and electron microscopy, and optimal lysis was observed at 30-35°C and 20-30‰ salinity along with a high multiplicity of infection. Then, we showed that experimentally infected Litopenaeus vannamei larvae exhibited significantly higher survival with incremental DA5 levels. Finally, variation in the bacterial counts and the bacterial community in larval rearing water was investigated after prophylactic application of DA5. The elimination effect of DA5 on vibrios was visible at early time points, whereas only a few non-dominant bacteria, rather than the predominant populations, were affected through analysis of denaturing gradient gel electrophoresis of the 16S rDNA V3 region. Accordingly, the prophylactic and therapeutic efficacies of DA5 on vibriosis associated with L. vannamei could markedly enhance larval survivability, and these results will facilitate the application of marine Bacteriovorax to control vibriosis in shrimp larviculture. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of standard laparoscopic distal pancreatectomy with minimally invasive distal pancreatectomy using the da Vinci S system.

PubMed

Ito, Masahiro; Asano, Yukio; Shimizu, Tomohiro; Uyama, Ichiro; Horiguchi, Akihiko

2014-01-01

Minimally invasive procedures for pancreatic pathologies are increasingly being used, including distal pancreatectomy. This study aimed to assess the indications for and outcomes of the da Vinci distal pancreatectomy procedure. We reviewed the medical records of patients who underwent pancreatic head resection from April 2009 to September 2013. Four patients (mean age, 52.7 years) underwent da Vinci distal pancreatectomy and 10 (mean age, 68.0 +/- 12.1 years) underwent laparoscopic distal pancreatectomy. The mean surgical duration was 292 +/- 153 min and 306 +/- 29 min, the mean blood loss was 153 +/- 71 mL and 61.7 +/- 72 mL, and the mean postoperative length of stay was 24 +/- 11 days and 14 +/- 3 days in the da Vinci distal pancreatectomy and laparoscopic distal pancreatectomy groups, respectively. One patient who underwent da Vinci distal pancreatectomy developed a pancreatic fistula, while 2 patients in the laparoscopic distal pancreatectomy group developed splenic ischemia and gastric torsion, respectively. Laparoscopic and robotic pancreatic resection were both safe and feasible in selected patients with distal pancreatic pathologies. Further studies are necessary to clarify the role of robotic surgery in the advanced laparoscopic era.

32 CFR 644.425 - Authority and procedure for disposal of surplus property by DA to eligible public agencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Authority and procedure for disposal of surplus property by DA to eligible public agencies. 644.425 Section 644.425 National Defense Department of Defense... property by DA to eligible public agencies. FPMR 101-47.303-2 provides that the disposal agency shall allow...

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

PubMed

Yuan, Yao Zong; Fang, Jing Yuan; Zou, Duo Wu; Levinson, Nigel; Jenner, Bartosz; Wilkinson, Joanne

2016-11-01

To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway.

PubMed

Soni, Kiran Kumar; Shin, Yu Seob; Choi, Bo Ram; Karna, Keshab Kumar; Kim, Hye Kyung; Lee, Sung Won; Kim, Chul Young; Park, Jong Kwan