Promoter proximal polyadenylation sites reduce transcription activity
DEFF Research Database (Denmark)
Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick
2012-01-01
Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...
Directory of Open Access Journals (Sweden)
Marleny Cabral
2016-11-01
Full Text Available There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs in ribosomal DNA (rDNA and non-rDNA locations (e.g., silent replication origins and tRNA genes. The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p. Conditions of caloric restriction (CR, which extend life span, also cause reduced replication pausing at the 5S rDNA and at tRNA genes. In aged and CR cells, the RPSs are less occupied by their specific non-histone protein complexes (e.g., the preinitiation complex TFIIIC, likely because members of these complexes have primarily cytosolic localization. These conditions may lead to reduced replication pausing and may lower replication stress at these sites during aging.
CDK9-dependent RNA polymerase II pausing controls transcription initiation.
Gressel, Saskia; Schwalb, Björn; Decker, Tim Michael; Qin, Weihua; Leonhardt, Heinrich; Eick, Dirk; Cramer, Patrick
2017-10-10
Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a 'multi-omics' approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells ('pause-initiation limit'). We further engineer a human cell line to allow for specific and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release. CDK9 activity decreases the pause duration but also increases the productive initiation frequency. This shows that CDK9 stimulates release of paused polymerase and activates transcription by increasing the number of transcribing polymerases and thus the amount of mRNA synthesized per time. CDK9 activity is also associated with long-range chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to regulate transcription.
StpA and Hha stimulate pausing by RNA polymerase by promoting DNA-DNA bridging of H-NS filaments.
Boudreau, Beth A; Hron, Daniel R; Qin, Liang; van der Valk, Ramon A; Kotlajich, Matthew V; Dame, Remus T; Landick, Robert
2018-06-20
In enterobacteria, AT-rich horizontally acquired genes, including virulence genes, are silenced through the actions of at least three nucleoid-associated proteins (NAPs): H-NS, StpA and Hha. These proteins form gene-silencing nucleoprotein filaments through direct DNA binding by H-NS and StpA homodimers or heterodimers. Both linear and bridged filaments, in which NAPs bind one or two DNA segments, respectively, have been observed. Hha can interact with H-NS or StpA filaments, but itself lacks a DNA-binding domain. Filaments composed of H-NS alone can inhibit transcription initiation and, in the bridged conformation, slow elongating RNA polymerase (RNAP) by promoting backtracking at pause sites. How the other NAPs modulate these effects of H-NS is unknown, despite evidence that they help regulate subsets of silenced genes in vivo (e.g. in pathogenicity islands). Here we report that Hha and StpA greatly enhance H-NS-stimulated pausing by RNAP at 20°C. StpA:H-NS or StpA-only filaments also stimulate pausing at 37°C, a temperature at which Hha:H-NS or H-NS-only filaments have much less effect. In addition, we report that both Hha and StpA greatly stimulate DNA-DNA bridging by H-NS filaments. Together, these observations indicate that Hha and StpA can affect H-NS-mediated gene regulation by stimulating bridging of H-NS/DNA filaments.
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Gabriele Büchel
2017-12-01
Full Text Available MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II. To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes in neuroblastoma cells. The analysis shows that N-MYC forms complexes with TFIIIC, TOP2A, and RAD21, a subunit of cohesin. N-MYC and TFIIIC bind to overlapping sites in thousands of Pol II promoters and intergenic regions. TFIIIC promotes association of RAD21 with N-MYC target sites and is required for N-MYC-dependent promoter escape and pause release of Pol II. Aurora-A competes with binding of TFIIIC and RAD21 to N-MYC in vitro and antagonizes association of TOP2A, TFIIIC, and RAD21 with N-MYC during S phase, blocking N-MYC-dependent release of Pol II from the promoter. Inhibition of Aurora-A in S phase restores RAD21 and TFIIIC binding to chromatin and partially restores N-MYC-dependent transcriptional elongation. We propose that complex formation with Aurora-A controls N-MYC function during the cell cycle.
Januario, Leticia Bergamin; Madeleine, Pascal; Cid, Marina Machado; Samani, Afshin; Oliveira, Ana Beatriz
2018-01-01
This study investigated the acute effects of changing the work pace and implementing two pause types during an assembly task. Eighteen healthy women performed a simulated task in four different conditions: 1) slow or 2) fast work pace with 3) passive or 4) active pauses every two minutes. The root mean square (RMS) and exposure variation analysis (EVA) from the trapezius and serratus anterior muscles, as well as the rate of perceived exertion (RPE) from the neck-shoulder region, were observed. Decreased RMS and RPE as well as more variable muscle activity (EVA) were observed in the slow work pace compared with the fast one. The pause types had a limited effect, but active pauses resulted in increased RMS of the clavicular trapezius. The findings revealed the importance of work pace in the reduction of perceived exertion and promotion of variation in muscle activation during assembly tasks. However, the pause types had no important effect on the evaluated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.
Plastid ribosome pausing is induced by multiple features and is linked to protein complex assembly
DEFF Research Database (Denmark)
Gawroński, Piotr; Jensen, Poul Erik; Karpinski, Stanislaw
2018-01-01
Many mRNAs contain pause sites that briefly interrupt the progress of translation. Specific features that induce ribosome pausing have been described; however, their individual contributions to pause-site formation, and the overall biological significance of ribosome pausing, remain largely uncle...
Responsible gambling tools: pop-up messages and pauses on video lottery terminals.
Cloutier, Martin; Ladouceur, Robert; Sévigny, Serge
2006-09-01
The authors examined the effect of messages and pauses, presented on video lottery terminal screens, on erroneous beliefs and persistence to play. At posttest, the strength of erroneous beliefs was lower for participants who received messages conveying information about randomness in gambling as compared to those who received pauses. Pauses also diminished the strength of erroneous beliefs, and there was no difference between the effects of pauses and messages on the number of games played. The authors discuss these results in terms of the use of messages and pauses on video lottery terminals as a strategy for promoting responsible gambling.
Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor
International Nuclear Information System (INIS)
Wang, C.-P.; Lee, Y.-F.; Chang, C.; Lee, H.-J.
2006-01-01
The human testicular receptor 4 (TR4) shares structural homology with members of the nuclear receptor superfamily. Some other members of this superfamily were able to regulate the transcriptional activity of the human oxytocin (OXT) promoter by binding to the first DR0 regulatory site. However, little investigation was conducted systematically in the study of the second dDR4 site of OXT proximal promoter, and the relationship between the first and the second sites of OXT promoter. Here, we demonstrated for the first time that TR4 could increase the proximal promoter activity of the human OXT gene via DR0, dDR4, and OXT (both DR0 and dDR4) elements, respectively. TR4 might induce OXT gene expression through the OXT element in a dose-dependent manner. However, there is no synergistic effect between DR0 and dDR4 elements during TR4 transactivation. Taken together, these results suggested that TR4 should be one of important regulators of OXT gene expression
Comparison of pause predictions of two sequence-dependent transcription models
International Nuclear Information System (INIS)
Bai, Lu; Wang, Michelle D
2010-01-01
Two recent theoretical models, Bai et al (2004, 2007) and Tadigotla et al (2006), formulated thermodynamic explanations of sequence-dependent transcription pausing by RNA polymerase (RNAP). The two models differ in some basic assumptions and therefore make different yet overlapping predictions for pause locations, and different predictions on pause kinetics and mechanisms. Here we present a comprehensive comparison of the two models. We show that while they have comparable predictive power of pause locations at low NTP concentrations, the Bai et al model is more accurate than Tadigotla et al at higher NTP concentrations. The pausing kinetics predicted by Bai et al is also consistent with time-course transcription reactions, while Tadigotla et al is unsuited for this type of kinetic prediction. More importantly, the two models in general predict different pausing mechanisms even for the same pausing sites, and the Bai et al model provides an explanation more consistent with recent single molecule observations
Directory of Open Access Journals (Sweden)
Stephanie E Hesselson
2009-09-01
Full Text Available Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC and Solute Carrier (SLC superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.
Promoting proximal formative assessment with relational discourse
Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.
2012-02-01
The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.
The Surgical Teams' Perception of the Effects of a Routine Intraoperative Pause.
Erestam, Sofia; Angenete, Eva; Derwinger, Kristoffer
2016-12-01
A pause routine may reduce stress and errors during surgery. The aim of this study was to explore how the team, divided into the different professional groups, perceived the implementation of a pause routine and its possible impact on safety. A pause routine was introduced at a University hospital operating theatre in Sweden in 2013. Questionnaires were distributed about 1 year later to all members of the operating theatre team. The questions included different perspectives of possible effects of the pause routine. A majority were positive to scheduled pauses. The surgeons often felt refreshed and at times changed their view on both anatomy and their surgical strategy. They were also perceived by other team members as improved regarding communication. All groups felt that patient safety was promoted. There were differences by profession in perception of team communication. The pause routine was well perceived by the surgical team. A majority believed that scheduled and regular pauses contribute to improved patient safety and better team communication. There were also findings of differences in communication and experience of team coherence between personnel categories that could benefit from further acknowledgement and exploration.
Pauses in Written Composition: On the Importance of Where Writers Pause
Medimorec, Srdan; Risko, Evan F.
2017-01-01
Much previous research has conceptualized pauses during writing as indicators of the engagement of higher-level cognitive processes. In the present study 101 university students composed narrative or argumentative essays, while their key logging was recorded. We investigated the relation between pauses within three time intervals (300-999,…
Huang, Wenxi; Liu, Wanting; Jin, Jingjie; Xiao, Qilan; Lu, Ruibin; Chen, Wei; Xiong, Sheng; Zhang, Gong
2018-03-25
Translational pausing coordinates protein synthesis and co-translational folding. It is a common factor that facilitates the correct folding of large, multi-domain proteins. For small proteins, pausing sites rarely occurs in the gene body, and the 3'-end pausing sites are only essential for the folding of a fraction of proteins. The determinant of the necessity of the pausings remains obscure. In this study, we demonstrated that the steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins. Validated by experiments with 5 model proteins, we found that the rigid protein structures do not, while the flexible structures do need 3'-end pausings to fold correctly. Therefore, rational optimization of translational pausing can improve soluble expression of small proteins with flexible structures, but not the rigid ones. The rigidity of the structure can be quantitatively estimated in silico using molecular dynamic simulation. Nevertheless, we also found that the translational pausing optimization increases the fitness of the expression host, and thus benefits the recombinant protein production, independent from the soluble expression. These results shed light on the structural basis of the translational pausing and provided a practical tool for industrial protein fermentation. Copyright © 2017. Published by Elsevier Inc.
Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells
International Nuclear Information System (INIS)
Mellas, J.; Hammerman, M.R.
1986-01-01
We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells
Fuel Loss and Jams due to Pausing Railroad Crossings
Tomoeda, Akiyasu; Nishinari, Katsuhiro; Harada, Yoshiaki
2008-01-01
In Japan, all cars must pause before crossing the railroad for avoiding the accidents. This rule was established by a law in 1960. In fact, however, railroad crossings come to the serious bottlenecks because of this pausing rule and this bottleneck causes heavy jams. In this study, by using cellular automaton model we have investigated the traffic flow at railroad crossings in two cases: with pausing and without pausing. Moreover, the lost time due to pausing at railroad crossings have been a...
Interword and intraword pause threshold in writing.
Chenu, Florence; Pellegrino, François; Jisa, Harriet; Fayol, Michel
2014-01-01
Writing words in real life involves setting objectives, imagining a recipient, translating ideas into linguistic forms, managing grapho-motor gestures, etc. Understanding writing requires observation of the processes as they occur in real time. Analysis of pauses is one of the preferred methods for accessing the dynamics of writing and is based on the idea that pauses are behavioral correlates of cognitive processes. However, there is a need to clarify what we are observing when studying pause phenomena, as we will argue in the first section. This taken into account, the study of pause phenomena can be considered following two approaches. A first approach, driven by temporality, would define a threshold and observe where pauses, e.g., scriptural inactivity occurs. A second approach, linguistically driven, would define structural units and look for scriptural inactivity at the boundaries of these units or within these units. Taking a temporally driven approach, we present two methods which aim at the automatic identification of scriptural inactivity which is most likely not attributable to grapho-motor management in texts written by children and adolescents using digitizing tablets in association with Eye and Pen (©) (Chesnet and Alamargot, 2005). The first method is purely statistical and is based on the idea that the distribution of pauses exhibits different Gaussian components each of them corresponding to a different type of pause. After having reviewed the limits of this statistical method, we present a second method based on writing dynamics which attempts to identify breaking points in the writing dynamics rather than relying only on pause duration. This second method needs to be refined to overcome the fact that calculation is impossible when there is insufficient data which is often the case when working with young scriptors.
A Comparative Analysis of Pausing in Child and Adult Storytelling
Redford, Melissa A.
2012-01-01
The goals of the current study were (1) to assess differences in child and adult pausing, and (2) to determine whether characteristics of child and adult pausing can be explained by the same language variables. Spontaneous speech samples were obtained from ten 5-year-olds and their accompanying parent using a storytelling/retelling task. Analyses of pause frequency, duration, variation in durations, and pause location indicated that pause time decreased with retelling, but not with age group except when child and adult pausing was considered in its speech and language context. The results suggest that differences in child and adult pausing reflect differences in child and adult language, not in the cognitive resources allocated to language production PMID:23772097
Realities of proximity facility siting
International Nuclear Information System (INIS)
DeMott, D.L.
1981-01-01
Numerous commercial nuclear power plant sites have 2 to 3 reactors located together, and a group of Facilities with capabilities for fuel fabrication, a nuclear reactor, a storage area for spent fuel, and a maintenance area for contaminated equipment and radioactive waste storage are being designed and constructed in the US. The proximity of these facilities to each other provides that the ordinary flow of materials remain within a limited area. Interactions between the various facilities include shared resources such as communication, fire protection, security, medical services, transportation, water, electrical, personnel, emergency planning, transport of hazardous material between facilities, and common safety and radiological requirements between facilities. This paper will explore the advantages and disadvantages of multiple facilities at one site. Problem areas are identified, and recommendations for planning and coordination are discussed
Congenital anomalies and proximity to landfill sites.
LENUS (Irish Health Repository)
Boyle, E
2004-01-01
The occurrence of congenital anomalies in proximity to municipal landfill sites in the Eastern Region (counties Dublin, Kildare, Wicklow) was examined by small area (district electoral division), distance and clustering tendancies in relation to 83 landfills, five of which were major sites. The study included 2136 cases of congenital anomaly, 37,487 births and 1423 controls between 1986 and 1990. For the more populous areas of the region 50% of the population lived within 2-3 km of a landfill and within 4-5 km for more rural areas. In the area-level analysis, the standardised prevalence ratios, empirical and full Bayesian modelling, and Kulldorff\\'s spatial scan statistic found no association between the residential area of cases and location of landfills. In the case control analysis, the mean distance of cases and controls from the nearest landfill was similar. The odds ratios of cases compared to controls for increasing distances from all landfills and major landfills showed no significant difference from the baseline value of 1. The kernel and K methods showed no tendency of cases to cluster in relationship to landfills. In conclusion, congenital anomalies were not found to occur more commonly in proximity to municipal landfills.
Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells
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Giorgio Grasselli
2016-03-01
Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.
Global distribution of pauses observed with satellite measurements
Indian Academy of Sciences (India)
Here we study the commonality and differences observed in the variability of all the pauses. We also examined how good other datasets will represent these features among (and in between) different satellite measurements, re-analysis, and model data. Hemispheric differences observed in all the pauses are also reported.
Pauses by Student and Professional Translators in Translation Process
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Rusdi Noor Rosa
2018-01-01
Full Text Available Translation as a process of meaning making activity requires a cognitive process one of which is realized in a pause, a temporary stop or a break indicating doing other than typing activities in a certain period of translation process. Scholars agree that pauses are an indicator of cognitive process without which there will never be any translation practices. Despite such agreement, pauses are debatable as well, either in terms of their length or in terms of the activities managed by a translator while taking pauses. This study, in particular, aims at finding out how student translators and professional translators managed the pauses in a translation process. This was a descriptive research taking two student translators and two professional translators as the participants who were asked to translate a text from English into bahasa Indonesia. The source text (ST was a historical recount text entitled ‘Early History of Yellowstone National Park’ downloaded from http://www.nezperce.com/yelpark9.html composed of 230-word long from English into bahasa Indonesia. The data were collected using Translog protocols, think aloud protocols (TAPs and screen recording. Based on the data analysis, it was found that student translators took the longest pauses in the drafting phase spent to solve the problems related to finding out the right equivalent for the ST words or terms and to solve the difficulties encountered in encoding their ST understanding in the TL; meanwhile, professional translators took the longest pauses in the pos-drafting phase spent to ensure whether their TT had been natural and whether their TT had corresponded to the prevailing grammatical rules of the TL.
AKT increases VEGF expression in tumor cells by transactivating the proximal VEGF promoter
International Nuclear Information System (INIS)
Pore, N.; Bernhard, E.J.; Shu, H.-K.; Li, B.; O'Rourke, D.M.; Maity, A.; Haas-Kogan, D.
2003-01-01
Vascular endothelial growth factor (VEGF) is overexpressed in many cancers including glioblastomas and may contribute to their growth. Epidermal growth factor receptor (EGFR) amplification and loss of PTEN, commonly found in glioblastomas leading to increase phosphatidylinositol-3-kinase (PI3K) activity and VEGF expression. In the current study we show that AKT, which is downstream of PI3K, regulates VEGF expression. U87MG human glioblastoma cells lack wildtype PTEN and express high levels of phosphorylated AKT. Over expression of AKT either by stable expression in immortalized human astrocytes or by transduction with adenovirus containing activated myristoylated AKT in SF188 glioblastoma cells increases VEGF expression. Moreover the elevation of angiogenesis by constitutively expressed AKT is further confirmed by in vivo matrigel plug assay in nude mice. The upregulation of VEGF by AKT is mediated through a region in the proximal promoter located between -88 and -70 (+1 is transcription start site). In transient transfection activity of a luciferase reporter containing the -88/+54 region of the VEGF promoter is increased by cotransfection with myristoylated AKT and downregulated by a dominant negative AKT expression vector. Mutation of the putative Sp1 binding sites located in the -88/-70 region we show that AKT acts through Sp1 to transactivate the VEGF promoter. Cotransfection of the VEGF promoter reporter with both Sp1 and myristoylated AKT expression vectors increases promoter activity to a greater extent than either Sp1 or Akt by itself. In vivo phosphate labeling of proteins reveals that AKT leads to increased Sp1 phosphorylation. Gel shift assays using a radio labeled probe corresponding to nucleotides -88 through -66 in the promoter show increased binding with nuclear extracts from cells transduced with adenovirus expressing myristoylated AKT. In conclusion, our results suggest that loss of PTEN leads to increased VEGF expression by increasing AKT
Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.
Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik
2015-12-01
Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.
Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses
Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik
2015-01-01
Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202
Integration of active pauses and pattern of muscular activity during computer work.
St-Onge, Nancy; Samani, Afshin; Madeleine, Pascal
2017-09-01
Submaximal isometric muscle contractions have been reported to increase variability of muscle activation during computer work; however, other types of active contractions may be more beneficial. Our objective was to determine which type of active pause vs. rest is more efficient in changing muscle activity pattern during a computer task. Asymptomatic regular computer users performed a standardised 20-min computer task four times, integrating a different type of pause: sub-maximal isometric contraction, dynamic contraction, postural exercise and rest. Surface electromyographic (SEMG) activity was recorded bilaterally from five neck/shoulder muscles. Root-mean-square decreased with isometric pauses in the cervical paraspinals, upper trapezius and middle trapezius, whereas it increased with rest. Variability in the pattern of muscular activity was not affected by any type of pause. Overall, no detrimental effects on the level of SEMG during active pauses were found suggesting that they could be implemented without a cost on activation level or variability. Practitioner Summary: We aimed to determine which type of active pause vs. rest is best in changing muscle activity pattern during a computer task. Asymptomatic computer users performed a standardised computer task integrating different types of pauses. Muscle activation decreased with isometric pauses in neck/shoulder muscles, suggesting their implementation during computer work.
Pauses in Striatal Cholinergic Interneurons: What is Revealed by Their Common Themes and Variations?
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Yan-Feng Zhang
2017-10-01
Full Text Available Striatal cholinergic interneurons, the so-called tonically active neurons (TANs, pause their firing in response to sensory cues and rewards during classical conditioning and instrumental tasks. The respective pause responses observed can demonstrate many commonalities, such as constant latency and duration, synchronous occurrence in a population of cells, and coincidence with phasic activities of midbrain dopamine neurons (DANs that signal reward predictions and errors. Pauses can however also show divergent properties. Pause latencies and durations can differ in a given TAN between appetitive vs. aversive outcomes in classical conditioning, initial excitation can be present or absent, and a second pause can variably follow a rebound. Despite more than 20 years of study, the functions of these pause responses are still elusive. Our understanding of pause function is hindered by an incomplete understanding of how pauses are generated. In this mini-review article, we compare pause types, as well as current key hypotheses for inputs underlying pauses that include dopamine-induced inhibition through D2-receptors, a GABA input from ventral tegmental area, and a prolonged afterhyperpolarization induced by excitatory input from the cortex or from the thalamus. We review how each of these mechanisms alone explains some but not all aspects of pause responses. These mechanisms might need to operate in specific but variable sets of sequences to generate a full range of pause responses. Alternatively, these mechanisms might operate in conjunction with an underlying control mechanism within cholinergic interneurons which could potentially provide a framework to generate the common themes and variations seen amongst pause responses.
Pauses in theatrical interpretation: delimitation of prosodic constituents
Directory of Open Access Journals (Sweden)
Lourenço Chacon
2014-07-01
Full Text Available We intend to observe the function of a linguistic resource – the pause – in theatrical interpretation. Connected to the field of speech therapy, we search for theoretical support in the Linguistics field, mainly in prosodic phonology – specifically, we highlight intonational phrase and phonological utterance, prosodic constituents –, proposing a dialogue between these fields, regarding the work with actors. In speech therapy literature, the work with actors focuses, centrally, in organic issues involved in the vocal process, such as “misuse” or “voice abuse”. To a smaller extent, we find, in this literature, researches that emphasize issues regarding interpretation and expressive resources, besides a few emphasizing the importance of linguistic resources in interpretation. Differently, in linguistics literature, the pause is approached, to a larger extent, from the phonetic perspective, related to several language levels. In this research, we analyzed audio recordings of four actors from a same theatrical group, acting the theatrical text Brutas flores, focused on these aims: (1 detect the place where pauses happen in the interpretation of a single text by four actors; (2 survey physical characteristics of length of these pauses; (3 check to what extent the length of a pause is related to the place where it happens, regarding the prosodic limits of intonational phrases (I and phonological utterance (U. We could observe that, although the interpretation is characterized by the subjectivity of the actor, the interpretation is constructed based in the possibilities offered by the prosodic organization of the text itself, being more or less flexible.We were also able to confirm, by considering the length of VVs units containing pauses, the prosodic hierarchy proposed by Nespor & Vogel, once the length of these units in U's limits was significantly higher than the length in I's limits. Thus, our results reinforce the premise that a
Quiet is the new loud: pausing and focus in child and adult Dutch.
Romøren, Anna Sara H; Chen, Aoju
2015-03-01
In a number of languages, prosody is used to highlight new information (or focus). In Dutch, focus is marked by accentuation, whereby focal constituents are accented and post-focal constituents are de-accented. Even if pausing is not traditionally seen as a cue to focus in Dutch, several previous studies have pointed to a possible relationship between pausing and information structure. Considering that Dutch-speaking 4 to 5 year olds are not yet completely proficient in using accentuation for focus and that children generally pause more than adults, we asked whether pausing might be an available parameter for children to manipulate for focus. Sentences with varying focus structure were elicited from 10 Dutch-speaking 4 to 5 year olds and 9 Dutch-speaking adults by means of a picture-matching game. Comparing pause durations before focal and non-focal targets showed pre-target pauses to be significantly longer when the targets were focal than when they were not. Notably, the use of pausing was more robust in the children than in the adults, suggesting that children exploit pausing to mark focus more generally than adults do, at a stage where their mastery of the canonical cues to focus is still developing.
Effects on residential property values of proximity to a site contaminated with radioactive waste
International Nuclear Information System (INIS)
Payne, B.A.; Olshansky, S.J.; Segel, T.E.
1985-01-01
An issue often raised by the public regarding waste sites is whether distance from these sites affects residential property values. Previous research has studied changes in the housing market in communities near Three Mile Island after the 1979 accident and after the 1979 accident and legal precedents of compensation for loss of property value because of proximity to hazardous areas. However, this research has not addressed effects on residential property values of proximity specifically to hazardous chemical or radioactive waste sites. The effects of the proximity of residences to such a site in West Chicago, Illinois - used for many years for disposal of thorium waste from processing ores - were investigated in this study. Sales of single-family residences located within about 0.4 km and 1.6 km from the site. Trends in average annual selling prices were analyzed both before and after publicity appeared about the existence of the radioactive material at the site. Results indicate that older residences (built before 1950) located within about 0.4 km of the disposal site experienced a prolonged depression in selling prices after the publicity in comparison with older residences located farther from the site and with all transactions on newer residences. These results confirm to some extent public perceptions and potentially raise legal issues associated with property values. Suggestions are provided for mitigative measures to alleviate these issues
Influence of pauses in irradiation on radiotherapy effect
International Nuclear Information System (INIS)
Skladowski, K.; Tarnawski, R.; Swierniak, A.
1999-01-01
The main goal of the study was demonstration, that pauses in radiotherapy of head and neck neoplasms dramatically influence on therapy results estimated as tumor control probability (TCP). The reason of this phenomenon is duplication of tumor cell proliferation during pauses in radiotherapy. This hypothesis is demonstrated on the analysis of statistical models, which parameters were estimated from the data of 1350 patients treated with radiotherapy in Center of Oncology in 1980-1989
Mondal, Smarajit; Yakhnin, Alexander V; Babitzke, Paul
2017-07-15
molecule promotes transcription termination in the 5' UTR, with the default being transcription readthrough into the downstream genes. RNA polymerase pausing is thought to participate in several attenuation mechanisms by synchronizing the position of RNA polymerase with RNA folding and/or regulatory factor binding, although this has only been shown in a few instances. We found that NusA- and NusG-stimulated pausing participates in the attenuation mechanism controlling the expression of the Bacillus subtilis trp operon by increasing the TRAP-dependent termination efficiency. The pause signal is organized in a modular fashion containing RNA hairpin, U-tract, and T-tract components. Copyright © 2017 American Society for Microbiology.
Using Habit Reversal to Decrease Filled Pauses in Public Speaking
Mancuso, Carolyn; Miltenberger, Raymond G.
2016-01-01
This study evaluated the effectiveness of simplified habit reversal in reducing filled pauses that occur during public speaking. Filled pauses consist of "uh," "um," or "er"; clicking sounds; and misuse of the word "like." After baseline, participants received habit reversal training that consisted of…
Effects on residential property values of proximity to a site contaminated with radioactive waste
International Nuclear Information System (INIS)
Payne, B.A.; Olshansky, S.J.; Segel, T.E.
1985-01-01
An issue often raised by the public regarding projects that involve hazardous chemical or radioactive waste sites is whether distance from these sites affects residential property values. Previous research has studied changes in the housing market in communities near Three Mile Island after the 1979 accident and legal precedents of compensation for loss of property value because of proximity to hazardous areas. However, this research has not addressed effects on residential property values of proximity specifically to hazardous chemical or radioactive waste sites. The effects of the proximity of residence to such a site in West Chicago, Illinois - used for many years for disposal of thorium waste from processing ores - were investigated in this study. Single-family residence sales located within about 0.4 km of the West Chicago site were compared with residence sales located between 0.4 km and 1.6 km from the site. Trends in average annual selling prices were analyzed both before and after publicity appeared about the existence of the radioactive material at the site. Results indiate that older residences (built before 1950) located within about 0.4 km of the disposal site experienced a prolonged depression in selling prices after the publicity, in comparison with older residences located farther from the site and with all transactions on newer residences. These results confirm to some extent public perceptions and potentially raise legal issues associated with property values. Suggestions are provided for mitigative measures to alleviate these issues. 22 references, 1 figure
Raeder, Aggi
1997-01-01
Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)
Phonetic Pause Unites Phonology and Semantics against Morphology and Syntax
Sakarna, Ahmad Khalaf; Mobaideen, Adnan
2012-01-01
The present study investigates the phonological effect triggered by the different types of phonetic pause used in Quran on morphology, syntax, and semantics. It argues that Quranic pause provides interesting evidence about the close relation between phonology and semantics, from one side, and semantics, morphology, and syntax, from the other…
Effects of a metronome on the filled pauses of fluent speakers.
Christenfeld, N
1996-12-01
Filled pauses (the "ums" and "uhs" that litter spontaneous speech) seem to be a product of the speaker paying deliberate attention to the normally automatic act of talking. This is the same sort of explanation that has been offered for stuttering. In this paper we explore whether a manipulation that has long been known to decrease stuttering, synchronizing speech to the beats of a metronome, will then also decrease filled pauses. Two experiments indicate that a metronome has a dramatic effect on the production of filled pauses. This effect is not due to any simplification or slowing of the speech and supports the view that a metronome causes speakers to attend more to how they are talking and less to what they are saying. It also lends support to the connection between stutters and filled pauses.
Chen, Liang; Chen, Jia-Yu; Zhang, Xuan; Gu, Ying; Xiao, Rui; Shao, Changwei; Tang, Peng; Qian, Hao; Luo, Daji; Li, Hairi; Zhou, Yu; Zhang, Dong-Er; Fu, Xiang-Dong
2017-11-16
R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corroborating with all biochemically established properties of R-loops. Transcription perturbation experiments further indicate that R-loop induction correlates to transcriptional pausing. Interestingly, we note that most mapped R-loops are each linked to a nearby free RNA end; by using a ribozyme to co-transcriptionally cleave nascent RNA, we demonstrate that such a free RNA end coupled with a G/C-skewed sequence is necessary and sufficient to induce R-loop. These findings provide a topological solution for RNA invasion into duplex DNA and suggest an order for R-loop initiation and elongation in an opposite direction to that previously proposed. Copyright © 2017 Elsevier Inc. All rights reserved.
Management of paroxysmal ectopic atrial tachycardia with long sinus pauses in a teenager
Seshadri Balaji
2015-01-01
Sinus pauses in the setting of supraventricular tachycardia is rare in children. We describe an asymptomatic teen with irregular heart rate detected during an incidental exam who was found to have short runs of a slow ectopic atrial tachycardia on electrocardiogram and prolonged sinus pauses on routine ambulatory ECG. Successful catheter ablation of the ectopic atrial tachycardia led to resolution of the sinus pauses.
Visual memory during pauses between successive saccades.
Gersch, Timothy M; Kowler, Eileen; Schnitzer, Brian S; Dosher, Barbara A
2008-12-22
Selective attention is closely linked to eye movements. Prior to a saccade, attention shifts to the saccadic goal at the expense of surrounding locations. Such a constricted attentional field, while useful to ensure accurate saccades, constrains the spatial range of high-quality perceptual analysis. The present study showed that attention could be allocated to locations other than the saccadic goal without disrupting the ongoing pattern of saccades. Saccades were made sequentially along a color-cued path. Attention was assessed by a visual memory task presented during a random pause between successive saccades. Saccadic planning had several effects on memory: (1) fewer letters were remembered during intersaccadic pauses than during maintained fixation; (2) letters appearing on the saccadic path, including locations previously examined, could be remembered; off-path performance was near chance; (3) memory was better at the saccadic target than at all other locations, including the currently fixated location. These results show that the distribution of attention during intersaccadic pauses results from a combination of top-down enhancement at the saccadic target coupled with a more automatic allocation of attention to selected display locations. This suggests that the visual system has mechanisms to control the distribution of attention without interfering with ongoing saccadic programming.
Effect of Sitting Pause Times on Balance After Supine to Standing Transfer in Dim Light.
Johnson, Eric G; Albalwi, Abdulaziz A; Al-Dabbak, Fuad M; Daher, Noha S
2017-06-01
The risk of falling for older adults increases in dimly lit environments. Longer sitting pause times, before getting out of bed and standing during the night, may improve postural stability. The purpose of this study was to measure the effect of sitting pause times on postural sway velocity immediately after a supine to standing transfer in a dimly lit room in older adult women. Eighteen healthy women aged 65 to 75 years who were able to independently perform supine to standing transfers participated in the study. On each of 2 consecutive days, participants assumed the supine position on a mat table and closed their eyes for 45 minutes. Then, participants were instructed to open their eyes and transfer from supine to sitting, with either 2- or 30-second pause in the sitting position followed by standing. The sitting pause time order was randomized. A significant difference was observed in postural sway velocity between the 2- and 30-second sitting pause times. The results revealed that there was less postural sway velocity after 30-second than 2-second sitting pause time (0.61 ± 0.19 vs 1.22 ± 0.68, P Falls related to bathroom usage at night are the most common reported falls among older adults. In the present study, the investigators studied the effect of sitting pause times on postural sway velocity after changing position from supine to standing in a dimly lit environment. The findings showed that the mean postural sway velocity was significantly less after 30-second sitting pause time compared with 2-second sitting pause time. Postural sway velocity decreased when participants performed a sitting pause of 30 seconds before standing in a dimly lit environment. These results suggest that longer sitting pause times may improve adaptability to dimly lit environments, contributing to improved postural stability and reduced risk of fall in older adult women when getting out of bed at night.
Directory of Open Access Journals (Sweden)
David L. Crowe
1999-10-01
Full Text Available Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at —79 by in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.
A rule-based backchannel prediction model using pitch and pause information
Truong, Khiet Phuong; Poppe, Ronald Walter; Heylen, Dirk K.J.
We manually designed rules for a backchannel (BC) prediction model based on pitch and pause information. In short, the model predicts a BC when there is a pause of a certain length that is preceded by a falling or rising pitch. This model was validated against the Dutch IFADV Corpus in a
La pause dans la conversation en arabe marocain
Directory of Open Access Journals (Sweden)
Mounia TOUIAQ
2011-11-01
Full Text Available The work presented here focuses on how the structuring of spontaneous conversation is related to prosody. How the prosodic parameters, including the break, they fit into a logical demarcation, establishment and organization of parts of speech? To what extent are they relevant to the level of dis-course, intersubjective and interactional? Description of these data allowed us to understand different ways of structuring Moroccan spooked Arabic, prosodic point of view, but also in terms of thematic and interactional, without ever losing sight of the conversational speech is the location of enunciation issues to establish meaning. In the situation of a real conversation, the silence is an opportunity for a transfer of initiative or by speaking one or other of these contacts. On the other hand, the speaker who wishes to keep talking should avoid the use of the silent pause and use in preference to the filled pause. We hypothesize that one role of the silent pause is precisely to manage this aspect of the intersubjective and interactional space and to indicate whether a segment aims to allow the speaker to keep talking or given it to the caller.
Profiles and Pauses: Two Practical Activities for the Writing Class
Directory of Open Access Journals (Sweden)
Ernest Hall
1998-01-01
Full Text Available Abstract : This article describes two classroom activities, "Profiling" and "Pause Analysis", that can be successfully used in ESL writing classes. "Profiling" addresses such problems as poor development of ideas, simplistic ideas, and lack of coherence in written texts. "Pause Analysis" focusses on the thinking processes that students engage in while drafting text, processes such as searching for ideas, evaluatÂing ideas, and postponing ideas. Both activities enable the instructor to assume the role of intervener in the students' writing processes, rather than evaluator of the text produced. In drawing The attention of the student write to both product and process, "Profiling" and "Pause Analysis" help them develop an awareness of the relation-ship between ideas in English expository text and the thinking proÂcesses that writers engage in while drafting such text.
ON THE PAUSED WARMING CONTROVERSY BASED ON IPCC AR5 AND BEYOND
Directory of Open Access Journals (Sweden)
MIKA J.
2014-03-01
Full Text Available The paused warming since ca. 2002 (maybe, 1998 is not satisfactorily reflected by the IPCC WGI (2013 Report. The aim of the present study is to collect, present and discuss the key arguments of the issue, selected strictly from this valuable Report. Our study tackles three aspects: (i Symptoms of pausing, including atmospheric changes, near-surface oceans, cryosphere and geographical differences. (ii Possible reasons of the paused warming, including external forcing factors, playing rather minor role, and the enhanced ocean heat uptake. Though missing warming is 0.2 K/decade compared to the model expectations, the whole climate system integrates continuously increasing amount of heat, 95 % of which is locked in the oceans. (iii Consequences of the pausing for the three main branches of the IPCC activity. For climate science, correct simulation of the enhanced heat uptake is a challenge. Since characteristic time scale of most adaptation measures is 1-2 decades, or shorter, near-term projections may not drive adaptation until climate models become able meet this challenge. On the other hand, pausing warming does not question the need for mitigation, since it is physically unlikely, that oceans can uptake endless amount of heat. Vertical temperature gradients of the upper ocean layers already show stagnation.
Neural correlates of the processing of unfilled and filled pauses
Eklund, Robert; Fransson, Peter; Ingvar, Martin
2015-01-01
Spontaneously produced Unfilled Pauses (UPs) andFilled Pauses (FPs) were played to subjects in an fMRI experiment. While both stimuli resulted in increased activity in the Primary Auditory Cortex, FPs, unlike UPs, also elicited modulation in the Supplementary Motor Area, Brodmann Area 6. This observation provides neurocognitive confirmation of the oft-reported difference between FPs and other kinds of speech disfluency and also could provide a partial explanation for the previously reported b...
Larsen, Nicolai B; Sass, Ehud; Suski, Catherine; Mankouri, Hocine W; Hickson, Ian D
2014-04-07
Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.
Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T
2015-10-26
Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.
Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K
2010-11-01
TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.
Single-molecule analysis of inhibitory pausing states of V1-ATPase.
Uner, Naciye Esma; Nishikawa, Yoshihiro; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki
2012-08-17
V(1)-ATPase, the hydrophilic V-ATPase domain, is a rotary motor fueled by ATP hydrolysis. Here, we found that Thermus thermophilus V(1)-ATPase shows two types of inhibitory pauses interrupting continuous rotation: a short pause (SP, 4.2 s) that occurred frequently during rotation, and a long inhibitory pause (LP, >30 min) that terminated all active rotations. Both pauses occurred at the same angle for ATP binding and hydrolysis. Kinetic analysis revealed that the time constants of inactivation into and activation from the SP were too short to represent biochemically predicted ADP inhibition, suggesting that SP is a newly identified inhibitory state of V(1)-ATPase. The time constant of inactivation into LP was 17 min, consistent with one of the two time constants governing the inactivation process observed in bulk ATPase assay. When forcibly rotated in the forward direction, V(1) in LP resumed active rotation. Solution ADP suppressed the probability of mechanical activation, suggesting that mechanical rotation enhanced inhibitory ADP release. These features were highly consistent with mechanical activation of ADP-inhibited F(1), suggesting that LP represents the ADP-inhibited state of V(1)-ATPase. Mechanical activation largely depended on the direction and angular displacement of forced rotation, implying that V(1)-ATPase rotation modulates the off rate of ADP.
International Nuclear Information System (INIS)
Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.
2015-01-01
The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC) n , located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC) 2 alleles were observed; however, in western gorilla, (GGGGC) n alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC) n was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC) n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC) 2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC) n short tandem repeats are inherited, and that the (GGGGC) 2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC) n , where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC) n microsatellite instability • AHR promoter activity of a construct with (GGGGC) 2 was lower than that of (GGGGC) 4 • The frequency of (GGGGC) 2 in lung cancer patients was 8-fold higher than in neonates • The
Pauses in spontaneous written communication: a keystroke logging study
Directory of Open Access Journals (Sweden)
Evgeny Chukharev-Hudilainen
2014-06-01
Full Text Available Spontaneous writing observed in chats, instant messengers, and social media has become established as productive modes of communication and discourse genres. However, they remain understudied from the perspective of writing process research. In this paper, we present an empirical study wherein keystrokes made by chat users in a game were recorded. The distributions of the inter-key intervals were analyzed and fitted with ex-Gaussian distribution equation, and an argument for psycholinguistic interpretation of the distribution parameters is presented. This analysis leads to establishing a threshold of 500 ms for the identification of pauses in spontaneous writing. Furthermore, we demonstrate that pauses longer than 1.2 s may correspond to higher-level linguistic processing beyond a single propositional expression (functional element of the discourse.
Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II
Directory of Open Access Journals (Sweden)
Ryan P. McNamara
2016-03-01
Full Text Available The transition of RNA polymerase II (Pol II from transcription initiation into productive elongation in eukaryotic cells is regulated by the P-TEFb kinase, which phosphorylates the C-terminal domain of paused Pol II at promoter-proximal regions. Our recent study found that P-TEFb (in an inhibited state bound to the 7SK snRNP complex interacts with the KAP1/TRIM28 transcriptional regulator, and that KAP1 and the 7SK snRNP co-occupy most gene promoters containing paused Pol II. Here we provide a detailed experimental description and analysis of the ChIP-seq datasets that have been deposited into Gene Expression Omnibus (GEO: GS72622, so that independent groups can replicate and expand upon these findings. We propose these datasets would provide valuable information for researchers studying mechanisms of transcriptional regulation including Pol II pausing and pause release. Keywords: P-TEFb/7SK snRNP, KAP1, RNA polymerase II, ChIP-seq, Transcription elongation
Walcott, Gregory P; Melnick, Sharon B; Walker, Robert G; Banville, Isabelle; Chapman, Fred W; Killingsworth, Cheryl R; Ideker, Raymond E
2009-04-01
Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Part A: 48 swine were anesthetized, fibrillated for 7min and randomized. Chest compressions were initiated for 90s followed by defibrillation and then resumption of chest compressions. Four groups were studied-G2000: 40s pause beginning 20s before, and ending 20s after defibrillation, A1: a 20s pause just before defibrillation, A2: a 20s pause ending 30s prior to defibrillation, and group A3: a 10s pause ending 30s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4h. The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p<0.05). Survival did not differ significantly among groups A1, A2, A3, and B. These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit.
Walcott, Gregory P.; Melnick, Sharon B.; Walker, Robert G.; Banville, Isabelle; Chapman, Fred W.; Killingsworth, Cheryl R.; Ideker, Raymond E.
2014-01-01
Background Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Methods Part A: 48 swine were anesthetized, fibrillated for 7 min and randomized. Chest compressions were initiated for 90 s followed by defibrillation and then resumption of chest compressions. Four groups were studied—G2000: 40 s pause beginning 20 s before, and ending 20 s after defibrillation, A1: a 20 s pause just before defibrillation, A2: a 20 s pause ending 30 s prior to defibrillation, and group A3: a 10 s pause ending 30 s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4 h. Results The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p < 0.05). Survival did not differ significantly among groups A1, A2, A3, and B. Conclusions These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit. PMID:19185411
O'Connell, Daniel C; Kowal, Sabine
2004-11-01
Erard's (2004) publication in the New York Times of a journalistic history of the filled pause serves as the occasion for this critical review of the past half-century of research on the filled pause. Historically, the various phonetic realizations or instantiations of the filled pause have been presented with an odd recurrent admixture of the interjection ah. In addition, the filled pause has been consistently associated with both hesitation and disfluency. The present authors hold that such a mandatory association of the filled pause with disfluency is the product of The written language bias in linguistics [Linell, 1982] and disregards much cogent evidence to the contrary. The implicit prescriptivism of well formedness--a demand derived from literacy--must be rejected; literate well formedness is not a necessary or even typical property of spontaneous spoken discourse; its structures and functions--including those of the filled pause--are very different from those of written language The recent work of Clark and Fox Tree (2002) holds promise for moving the status of the filled pause not only toward that of a conventional word, but also toward its status as an interjection. This latter development is also being fostered by lexicographers. Nonetheless, in view of ongoing research regarding the disparate privileges of occurrence and functions of filled pauses in comparison with interjections, the present authors are reluctant to categorize the filled pause as an interjection.
Global distribution of pauses observed with satellite measurements
Indian Academy of Sciences (India)
We present global distribution of altitudes and temperatures of these pauses observed with long-term space borne high- ... metries between northern and southern hemispheres continue up to the mesopause. We analyze ..... the mean temperature increases from the equa- .... monsoon circulation causes zonal asymmetry in.
DEFF Research Database (Denmark)
Larsen, Nicolai B; Sass, Ehud; Suski, Catherine
2014-01-01
Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus...... as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications....
Dynamic usage of transcription start sites within core promoters
DEFF Research Database (Denmark)
Kawaji, Hideya; Frith, Martin C; Katayama, Shintaro
2006-01-01
BACKGROUND: Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level......, based on large-scale sequencing of transcript 5' ends. RESULTS: In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites...... is associated with CpG islands, broad and multimodal promoter structures, and imprinting. CONCLUSION: Our results reveal a new level of biologic complexity within promoters--fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic...
Directory of Open Access Journals (Sweden)
Florence eChenu
2014-03-01
Full Text Available Writing words in real life involves setting objectives, imagining a recipient, translating ideas into linguistic forms, managing grapho-motor gestures, etc. Understanding writing requires observation of the processes as they occur in real time. Analysis of pauses is one of the preferred methods for accessing the dynamics of writing and is based on the idea that pauses are behavioral correlates of cognitive processes. However, there is a need to clarify what we are observing when studying pause phenomena, as we will argue in the first section. This taken into account, the study of pause phenomena can be considered following two approaches. A first approach, driven by temporality, would define a threshold and observe where pauses, e.g. scriptural inactivity occurs. A second approach, linguistically driven, would define structural units and look for scriptural inactivity at the boundaries of these units or within these units. Taking a temporally driven approach, we present two methods which aim at the automatic identification of scriptural inactivity which is most likely not attributable to grapho-motor management in texts written by children and adolescents using digitizing tablets in association with Eye and Pen© (Chesnet & Alamargot, 2005. The first method is purely statistical and is based on the idea that the distribution of pauses exhibits different Gaussian components each of them corresponding to a different type of pause. After having reviewed the limits of this statistical method, we present a second method based on writing dynamics which attempts to identify breaking points in the writing dynamics rather than relying only on pause duration. This second method needs to be refined to overcome the fact that calculation is impossible when there is insufficient data which is often the case when working with young scriptors.
DEFF Research Database (Denmark)
Samani, Afshin; Holtermann, Andreas; Søgaard, Karen
2009-01-01
) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40s over 2 days, before, immediately and 24h after eccentric exercise. Surface EMG signals were recorded from four parts of the trapezius during computer work. FINDINGS: EMG amplitude during computer work decreased......BACKGROUND: The aim of this laboratory study was to investigate the effects of eccentric exercises on the trapezius muscle spatial electromyographic (EMG) activity during computer work with active and passive pauses. METHODS: Twelve healthy male subjects performed computer work with passive (relax...... immediately after exercise (Pwork with active pauses compared with passive ones (P
Raptor nest-site use in relation to the proximity of coalbed methane development
Carlile, J.D.; Sanders, Lindsey E.; Chalfoun, Anna D.; Gerow, K.G.
2018-01-01
Raptor nest–site use in relation to the proximity of coalbed–methane development. Energy development such as coalbed–methane (CBM) extraction is a major land use with largely unknown consequences for many animal species. Some raptor species may be especially vulnerable to habitat changes due to energy development given their ecological requirements and population trajectories. Using 12,977 observations of 3,074 nests of 12 raptor species across nine years (2003–2011) in the Powder River Basin, Wyoming, USA, we evaluated relationships between raptor nest–site use and CBM development. Our objectives were to determine temporal trends in nest–use rates, and whether nest–site use was related to the proximity of CBM development. Across the study area, nest–use rates varied across species and years in a non–linear fashion. We developed a novel randomization test to assess differences in use between nests at developed and undeveloped sites, while controlling for annual variation in nest–site use. Red–tailed hawks (Buteo jamaicensis), burrowing owls (Athene cunicularia), and long–eared owls (Asio otus) used nests in undeveloped areas more than nests in developed areas (i.e. nests near CBM development). Differences between development groups were equivocal for the remaining nine species; however, we caution that we likely had lower statistical power to detect differences for rarer species. Our findings suggest potential avoidance of nesting in areas near CBM development by some species and reveal that CBM effects may be fairly consistent across distances between 400–2,415 m from wells. Future work should consider habitat preferences and fitness outcomes, and control for other key factors such as local prey availability, raptor densities, and weather.
Energy Technology Data Exchange (ETDEWEB)
Spink, Barbara C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Bloom, Michael S. [Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Wu, Susan [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Sell, Stewart; Schneider, Erasmus [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Ding, Xinxin [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Spink, David C., E-mail: spink@wadsworth.org [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)
2015-01-01
The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung
DEFF Research Database (Denmark)
Kohtz, Lea Susan; Niebuhr, Oliver
2017-01-01
willingness was found to decrease with increasing pause duration, particularly above a "tolerance threshold" of 600 ms. Refining and qualifying this replicated result, the perception experiment showed additional effects of speaking-rate context and pause quality (silence vs. breathing vs. café noise......) on perceived willingness judgments. The overall results picture is discussed with respect to the origin of the "tolerance threshold", the status of breathing in speech, and the function of pauses in communication....
Profiling Speech and Pausing in Amyotrophic Lateral Sclerosis (ALS and Frontotemporal Dementia (FTD.
Directory of Open Access Journals (Sweden)
Yana Yunusova
Full Text Available This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS and those with frontotemporal dementia (FTD in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls.136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV or progressive nonfluent aphasia (FTD-PNFA. Participants with ALS were further divided into 4 non-overlapping subgroups--mild, respiratory, bulbar (with oral-motor deficit and bulbar-respiratory--based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients.The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures.This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS-FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD.
Theoretical evaluation of transcriptional pausing effect on the attenuation in trp leader sequence
Suzuki, H.; Kunisawa, T.; Otsuka, J.
1986-01-01
The effect of transcriptional pausing on attenuation is investigated theoretically on the basis of the attenuation control mechanism presented by Oxender et al. (Oxender, D. L., G. Zurawski, and C. Yanofsky, 1979, Proc. Natl. Acad. Sci. USA. 76:5524-5528). An extended stochastic model including the RNA polymerase pausing in the leader region is developed to calculate the probability of relative position between the RNA polymerase transcribing the trp leader sequence and the ribosome translati...
Directory of Open Access Journals (Sweden)
Dorcas J Orengo
Full Text Available The insulin/TOR signal transduction pathway plays a critical role in determining such important traits as body and organ size, metabolic homeostasis and life span. Although this pathway is highly conserved across the animal kingdom, the affected traits can exhibit important differences even between closely related species. Evolutionary studies of regulatory regions require the reliable identification of transcription factor binding sites. Here we have focused on the Insulin Receptor (InR expression from its P2 promoter in the Drosophila genus, which in D. melanogaster is up-regulated by hypophosphorylated Drosophila FOXO (dFOXO. We have finely characterized this transcription factor binding sites in vitro along the 1.3 kb region upstream of the InR P2 promoter in five Drosophila species. Moreover, we have tested the effect of mutations in the characterized dFOXO sites of D. melanogaster in transgenic flies. The number of experimentally established binding sites varies across the 1.3 kb region of any particular species, and their distribution also differs among species. In D. melanogaster, InR expression from P2 is differentially affected by dFOXO binding sites at the proximal and distal halves of the species 1.3 kb fragment. The observed uneven distribution of binding sites across this fragment might underlie their differential contribution to regulate InR transcription.
DEFF Research Database (Denmark)
Samani, Afshin; Holtermann, Andreas; Søgaard, Karen
2009-01-01
, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 2 min at two different work paces (low/high). Bipolar SEMG from four parts of the trapezius muscle was recorded. The relative rest time was higher for the lower parts compared with the upper......The aim of this laboratory study was to evaluate effects of active and passive pauses and investigate the distribution of the trapezius surface electromyographic (SEMG) activity during computer mouse work. Twelve healthy male subjects performed four sessions of computer work for 10 min in one day...... of the trapezius (pwork with active pause compared with passive one (p
Yunusova, Yana; Graham, Naida L.; Shellikeri, Sanjana; Phuong, Kent; Kulkarni, Madhura; Rochon, Elizabeth; Tang-Wai, David F.; Chow, Tiffany W.; Black, Sandra E.; Zinman, Lorne H.; Green, Jordan R.
2016-01-01
Objective This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS) and those with frontotemporal dementia (FTD) in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls. Design 136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV) or progressive nonfluent aphasia (FTD-PNFA). Participants with ALS were further divided into 4 non-overlapping subgroups—mild, respiratory, bulbar (with oral-motor deficit) and bulbar-respiratory—based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients. Results The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate) was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures. Conclusions and Relevance This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS—FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD. PMID:26789001
Kim, Yuseob; Lee, Jang H; Babbitt, Gregory A
2010-01-01
Population genetic theory of gene duplication suggests that the preservation of duplicate copies requires functional divergence upon duplication. Genes that can be readily modified to produce new gene expression patterns may thus be duplicated often. In yeast, genes exhibit dichotomous expression patterns based on their promoter architectures. The expression of genes that contain TATA box or occupied proximal nucleosome (OPN) tends to be variable and respond to external signals. On the other hand, genes without TATA box or with depleted proximal nucleosome (DPN) are expressed constitutively. We find that recent duplicates in the yeast genome are heavily biased to be TATA box containing genes and not to be DPN genes. This suggests that variably expressed genes, due to the functional organization in their promoters, have higher duplicability than constitutively expressed genes.
Barack Obama’s pauses and gestures in humorous speeches
DEFF Research Database (Denmark)
Navarretta, Costanza
2017-01-01
The main aim of this paper is to investigate speech pauses and gestures as means to engage the audience and present the humorous message in an effective way. The data consist of two speeches by the USA president Barack Obama at the 2011 and 2016 Annual White House Correspondents’ Association Dinner...... produced significantly more hand gestures in 2016 than in 2011. An analysis of the hand gestures produced by Barack Obama in two political speeches held at the United Nations in 2011 and 2016 confirms that the president produced significantly less communicative co-speech hand gestures during his speeches...... and they emphasise the speech segment which they follow or precede. We also found a highly significant correlation between Obama’s speech pauses and audience response. Obama produces numerous head movements, facial expressions and hand gestures and their functions are related to both discourse content and structure...
Childhood leukemia and residential proximity to industrial and urban sites
International Nuclear Information System (INIS)
García-Pérez, Javier; López-Abente, Gonzalo; Gómez-Barroso, Diana; Morales-Piga, Antonio; Pardo Romaguera, Elena; Tamayo, Ibon; Fernández-Navarro, Pablo
2015-01-01
Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in
Childhood leukemia and residential proximity to industrial and urban sites
Energy Technology Data Exchange (ETDEWEB)
García-Pérez, Javier, E-mail: jgarcia@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); López-Abente, Gonzalo, E-mail: glabente@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); Gómez-Barroso, Diana, E-mail: dgomez@externos.isciii.es [CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); Morales-Piga, Antonio, E-mail: amorales@isciii.es [Rare Disease Research Institute (IIER), Carlos III Institute of Health, Madrid (Spain); Consortium for Biomedical Research in Rare Diseases (CIBERER), Madrid (Spain); Pardo Romaguera, Elena, E-mail: elena.pardo@uv.es [Spanish Registry of Childhood Tumors (RETI-SEHOP), University of Valencia, Valencia (Spain); Tamayo, Ibon, E-mail: ibontama@gmail.com [Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, Donostia (Spain); Fernández-Navarro, Pablo, E-mail: pfernandezn@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); and others
2015-07-15
Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in
DEFF Research Database (Denmark)
Samani, Afshin; Holtermann, Andreas; Søgaard, Karen
2009-01-01
The aim of this laboratory study was to investigate acute effects of experimental muscle pain on spatial electromyographic (EMG) activity of the trapezius muscle during computer work with active and passive pauses. Twelve healthy male subjects performed four sessions of computer work for 2 min...... in one day, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40 s without and with presence of experimental pain. Surface EMG signals were recorded from four parts of the trapezius. The centroid of exposure variation analysis along the time axis...... was lower during computer work with active pauses when compared with passive one in all muscle parts (P
Backtracking dynamics of RNA polymerase: pausing and error correction
International Nuclear Information System (INIS)
Sahoo, Mamata; Klumpp, Stefan
2013-01-01
Transcription by RNA polymerases is frequently interrupted by pauses. One mechanism of such pauses is backtracking, where the RNA polymerase translocates backward with respect to both the DNA template and the RNA transcript, without shortening the transcript. Backtracked RNA polymerases move in a diffusive fashion and can return to active transcription either by diffusive return to the position where backtracking was initiated or by cleaving the transcript. The latter process also provides a mechanism for proofreading. Here we present some exact results for a kinetic model of backtracking and analyse its impact on the speed and the accuracy of transcription. We show that proofreading through backtracking is different from the classical (Hopfield–Ninio) scheme of kinetic proofreading. Our analysis also suggests that, in addition to contributing to the accuracy of transcription, backtracking may have a second effect: it attenuates the slow down of transcription that arises as a side effect of discriminating between correct and incorrect nucleotides based on the stepping rates. (paper)
Backtracking dynamics of RNA polymerase: pausing and error correction
Sahoo, Mamata; Klumpp, Stefan
2013-09-01
Transcription by RNA polymerases is frequently interrupted by pauses. One mechanism of such pauses is backtracking, where the RNA polymerase translocates backward with respect to both the DNA template and the RNA transcript, without shortening the transcript. Backtracked RNA polymerases move in a diffusive fashion and can return to active transcription either by diffusive return to the position where backtracking was initiated or by cleaving the transcript. The latter process also provides a mechanism for proofreading. Here we present some exact results for a kinetic model of backtracking and analyse its impact on the speed and the accuracy of transcription. We show that proofreading through backtracking is different from the classical (Hopfield-Ninio) scheme of kinetic proofreading. Our analysis also suggests that, in addition to contributing to the accuracy of transcription, backtracking may have a second effect: it attenuates the slow down of transcription that arises as a side effect of discriminating between correct and incorrect nucleotides based on the stepping rates.
Directory of Open Access Journals (Sweden)
Cristina Marino Buslje
Full Text Available Identification of catalytic residues (CR is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI, and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls, combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution.
Marino Buslje, Cristina; Teppa, Elin; Di Doménico, Tomas; Delfino, José María; Nielsen, Morten
2010-11-04
Identification of catalytic residues (CR) is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI), and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL) conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI) was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC) was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls), combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution.
Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A
2007-08-01
Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.
Effective Use of Pause Procedure to Enhance Student Engagement and Learning
Bachhel, Rachna; Thaman, Richa Ghay
2014-01-01
Introduction: Active learning strategies have been documented to enhance learning. We created an active learning environment in neuromuscular physiology lectures for first year medical students by using ‘Pause Procedure’.
Directory of Open Access Journals (Sweden)
Ricardo Luiz Cordioli
Full Text Available To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT during moderately-high-frequency positive pressure ventilation (MHFPPV delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS.Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57-63 mmHg for 30 minutes.The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O, but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O, higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg, lower shunt (23 [20, 23] vs 32 [27, 49]%, lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%, and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT.During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space.
Cheon, Jongpil; Chung, Sungwon; Crooks, Steven M.; Song, Jaeki; Kim, Jeakyeong
2014-01-01
Since the complex and transient information in instructional animations requires more cognitive resources, the segmenting principle has been proposed to reduce cognitive overload by providing smaller chunks with pauses between segments. This study examined the effects of different types of activities during pauses in a segmented animation. Four…
On the biased motion of a brownian particle for the pausing time behavior of the CTRW
International Nuclear Information System (INIS)
Kim, K.S.
1982-01-01
The purpose of this paper is to discuss the biased Brownian motion with the absorbing barrier for the pausing time behavior of the CTRW (continuous-time random walk method), regarding a Brownian particle as a walker. For two pausing time density functions, the respective values for the transport averaged velocity and the dispersion are calculated as the time t becomes large. (KAERI)
DEFF Research Database (Denmark)
MacKenzie, Brian; Kiørboe, Thomas
1995-01-01
measure of prey encounter rate in unsatiated larvae) were significantly higher in turbulent than in calm water at low food abundances for two size groups of cod. The difference in cod attack position rate between calm and turbulent water was much less when prey was more abundant. Attack position rates...... of herring larvae were higher in turbulent water than in calm water, but the difference was not significant. Interspecific differences in swimming and pausing behavior were related to differences in prey search strategy used by the two species (cod: pause-travel; herring: cruise). We used a newly developed...... search model for pause-travel predators in calm and turbulent environments to compare encounter rates for predators using cruise and pause-travel search strategies. Encounter rates for cod and herring larvae, estimated with respective search models, were similar in calm and low turbulence water; at high...
Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng
2017-01-01
Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.
Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung
2015-01-01
Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). PMID:26220934
An Exploratory Study of Pauses in Computer-Assisted EFL Writing
Xu, Cuiqin; Ding, Yanren
2014-01-01
The advance of computer input log and screen-recording programs over the last two decades has greatly facilitated research into the writing process in real time. Using Inputlog 4.0 and Camtasia 6.0 to record the writing process of 24 Chinese EFL writers in an argumentative task, this study explored L2 writers' pausing patterns in computer-assisted…
Korak, J Adam; Paquette, Max R; Brooks, Justin; Fuller, Dana K; Coons, John M
2017-09-01
Rest-pause (4-s unloaded rest between repetitions) training effects on one repetition maximum (1 RM), lifting volume, and neural activation via electromyography (EMG) are currently vague in the literature and can benefit strength and conditioning professionals for resistance training programme design. Therefore, this study compared 1 RM, neural activation via (EMG), and volume differences between rest-pause vs. traditional resistance training. Trained males (N = 20) were randomly assigned to either a rest-pause or a traditional training group. Pre- and post-1 RM testing was recorded. Training sessions were completed twice a week for 4 weeks and consisted of four sets of bench press to volitional fatigue at 80% of pre-test 1 RM with a 2-min rest between sets. Total volume completed was recorded on each training day. Neural activation of the pectoralis major was measured on the first and last training days. A two-way repeated-measures ANOVA indicated both groups significantly increased their 1 RMs following the 4-week training protocol (p .05). An independent samples t test indicated that total volume lifted was significantly higher for the rest-pause group (56,778 vs. 38,315 lbs; p < .05) throughout the protocol and independently during weeks 2, 3, and 4. While strength and neural activation changes did not differ between groups, both increased 1 RMs and the rest-pause group achieved greater increases in volume than the traditional group. If volume is the focus of training, the rest-pause method should be utilized.
R A Cowley, the "Golden Hour," the "Momentary Pause," and the "Third Space".
Clark, David E
2017-12-01
R Adams Cowley (1917-1991), the Baltimore thoracic and trauma surgeon, was an outstanding politician and promoter of emergency medical services. His skills included the effective use of language, for example, identifying the critical time immediately after injury as a "golden hour," and describing shock as a "momentary pause in the act of death." Conversely, Cowley avoided the tendency of some contemporaries to justify massive crystalloid infusion by invoking a "third space." Cowley is often assumed to have originated the first two phrases, but, in fact, their histories go back at least to the 19th century and illustrate the development of surgical science. The "third space" is often assumed to have originated with Cowley's contemporary, Tom Shires (1925-2007), but, in fact, neither of them used the phrase to describe Shires' controversial theories about an extracellular fluid deficit after trauma. Reviewing the actual etymology of these terms may help clarify the history of the underlying scientific ideas and enable more effective communication in the future.
Promoter Melting Plays Critical Role in Lymphocyte Activation | Center for Cancer Research
Transcription in eukaryotic cells is a precisely timed ballet that consists of RNA polymerase II (pol II) recruitment to gene promoters, assembly of the multiprotein preinitiation complex, opening of the DNA, escape of pol II from the promoter, pol II pausing downstream, mRNA elongation, and, eventually, termination. The two main points of regulation are thought to be
Model of the pathway of −1 frameshifting: Long pausing
Directory of Open Access Journals (Sweden)
Ping Xie
2016-03-01
Full Text Available It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot. In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD sequence—is also necessary to stimulate the efficient −1 frameshifting. However, the molecular and physical mechanism of the −1 frameshifting is poorly understood. Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA. With the model, the single-molecule fluorescence data (Chen et al. (2014 [29] on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively. Moreover, the model is also consistent with the experimental data (Yan et al. (2015 [30] on translocation excursions and broad branching of frameshifting pathways. In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.
Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka
2017-02-08
Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.
Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung
2015-07-27
Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Calcium Imaging Reveals Coordinated Simple Spike Pauses in Populations of Cerebellar Purkinje Cells
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Jorge E. Ramirez
2016-12-01
Full Text Available The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic gamma-Aminobutyric acid producing (GABAergic network, and blocking ionotropic gamma-Aminobutyric acid receptor (GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (inactivity between neighboring Purkinje cells, and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.
Identification of cis-acting regulatory elements in the human oxytocin gene promoter.
Richard, S; Zingg, H H
1991-12-01
promoter resides in a small region extending only 50 bases upstream of the cap site and that this activity is the result of a cooperative interaction of at least three distinct proximal promoter elements.
Modified pause schemes and working days for more volume flexibility in manufactering
Rhijn, G.; Looze, M. de; Bosch, T.
2005-01-01
The effects of two measures to increase the volume flexibility, namely the introduction of an alternating pause scheme and the elongation of the working day, were evaluated in two manufacturing companies. Both measures led to an increase in volume output of about 16% at relatively low costs. The
International Nuclear Information System (INIS)
Wilson, M.C.; Fraser, N.W.; Darnell, J.E. Jr.
1979-01-01
Cells infected with Ad-2 virus were irradiated so that uv-induced lesions were introduced every 500 to 1000 nucleotides in the genomes, consequently leading to the premature termination of RNA transcription. Such cells when labeled with [ 3 H]uridine accumulate labeled promoter proximal RNA. Hybridization of this RNA after size fractionation to restriction fragments of the Ad-2 genome allowed the identification of DNA sequences containing active RNA initiation sites. Early during the infectious cycle two active RNA initiation sites were found within the left 11% of the Ad-2 genome within the 0 to 3.0 and 4.4 to 8.0 restriction fragments. During late infection (15 hr) an additional uv resistant transcript was detected indicating that a newly activated RNA initiation site, presumably for protein IX, resides within the fragment 8.0 to 11.2
Malyavantham, Kishore S; Bhattacharya, Sambit; Barbeitos, Marcos; Mukherjee, Lopamudra; Xu, Jinhui; Fackelmayer, Frank O; Berezney, Ronald
2009-01-01
Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1γ, nascent transcript sites (TS), active DNA replicating sites in early S phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture. PMID:18618731
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J. Lisý
2014-01-01
Full Text Available Introduction. Balloon dilatation is a method of choice for treatment of laryngeal stenosis in children. The aim of procedure in apneic pause is to avoid new insertion of tracheostomy cannula. Patients and Methods. The authors performed balloon dilatation of subglottic laryngeal strictures (SGS in 5 children (3 girls and 2 boys without tracheotomy. Two of them with traumatic and inflammatory SGS had a tracheal cannula removed in the past. The other 3 children with postintubation SGS had never had a tracheostomy before. The need for tracheostomy due to worsening stridor was imminent for all of them. Results. The total of seven laryngeal dilatations by balloon esophagoplasty catheter in apneic pause was performed in the 5 children. The procedure averted the need for tracheostomy placement in 4 of them (80%. Failure of dilatation in girl with traumatic stenosis and concomitant severe obstructive lung disease led to repeated tracheostomy. Conclusion. Balloon dilatation of laryngeal stricture could be done in the absence of tracheostomy in apneic pause. Dilatation averted threatening tracheostomy in all except one case. Early complication after the procedure seems to be a negative prognostic factor for the outcome of balloon dilatation.
Automated detection of unfilled pauses in speech of healthy and brain-damaged individuals
Ossewaarde, Roelant; Jonkers, Roel; Jalvingh, Fedor; Bastiaanse, Yvonne
Automated detection of un lled pauses in speech of healthy and brain-damaged individuals Roelant Ossewaardea,b, Roel Jonkersa, Fedor Jalvingha,c, Roelien Bastiaansea aCenter for Language and Cognition, University of Groningen; bInstitute for ICT, HU University of Applied Science, Utrecht; cSt.
Maracatus Solar e Reis de Paus: tradição e modernidade no carnaval de rua em Fortaleza
Silva, Roberto Antônio de Sousa da
2013-01-01
Trata-se de um estudo etnográfico e comparativo dos Maracatus Solar (2006) e Reis de Paus (1960), cujo objetivo foi verificar o que existe de antigo e tradicional no novo maracatu praticado pela agremiação Solar e, em contrapartida, o que existe de novo ou moderno no velho maracatu ritualizado pela agremiação Reis de Paus. Cabe ressaltar que por meio deste estudo de caso pretendeu-se também observar etnograficamente e compreender melhor os processos de rupturas e continuidades ...
A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology.
Schmidt, Robert; Berke, Joshua D
2017-04-19
Many studies have implicated the basal ganglia in the suppression of action impulses ('stopping'). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a 'Go' process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary 'Stop' process, there appear to be separate, complementary 'Pause' and 'Cancel' mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time-in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed-accuracy trade-offs.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. © 2017 The Author(s).
Characterization of the human UDP-galactose:ceramide galactosyltransferase gene promoter.
Tencomnao, T; Yu, R K; Kapitonov, D
2001-02-16
UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.45) is a key enzyme in the biosynthesis of galactocerebroside, the most abundant glycosphingolipid in the myelin sheath. An 8 kb fragment upstream from the transcription initiation site of CGT gene was isolated from a human genomic DNA library. Primer extension analysis revealed a single transcription initiation site 329 bp upstream from the ATG start codon. Neither a consensus TATA nor a CCAAT box was identified in the proximity to the transcription start site; however, this region contains a high GC content and multiple putative regulatory elements. To investigate the transcriptional regulation of CGT, a series of 5' deletion constructs of the 5'-flanking region were generated and cloned upstream from the luciferase reporter gene. By comparing promoter activity in the human oligodendroglioma (HOG) and human neuroblastoma (LAN-5) cell lines, we found that the CGT promoter functions in a cell type-specific manner. Three positive cis-acting regulatory regions were identified, including a proximal region at -292/-256 which contains the potential binding sites for known transcription factors (TFs) such as Ets and SP1 (GC box), a distal region at -747/-688 comprising a number of binding sites such as the ERE half-site, NF1-like, TGGCA-BP, and CRE, and a third positive cis-acting region distally localized at -1325/-1083 consisting of binding sites for TFs such as nitrogen regulatory, TCF-1, TGGCA-BP, NF-IL6, CF1, bHLH, NF1-like, GATA, and gamma-IRE. A negative cis-acting domain localized in a far distal region at -1594/-1326 was also identified. Our results suggest the presence of both positive and negative cis-regulatory regions essential for the cell-specific expression in the TATA-less promoter of the human CGT gene.
Developing and promoting an intranet site for a drug information service.
Costerison, Emily C; Graham, Angie S
2008-04-01
The development and promotion of a drug information service (DIS) intranet site are described. Stanford Hospital and Clinics (SHC) is an acute and tertiary care facility with 613 licensed inpatient beds and 48 outpatient clinics. A DIS intranet site was developed to allow better accessibility to pharmacy forms and products (e.g., drug shortage list, reference guides) and to reduce repetitive requests to the DIS. The goal was to continue to provide information to SHC health care providers but allow the drug information specialist to focus on answering clinical questions. The intranet site was completed over a four-month period. The intranet site was divided into seven webpages: DIS overview, pharmacy and therapeutics, frequently asked questions, quick drug reference guide, ask the pharmacist, drug information resources, and referral center. The preparation for and implementation of the promotional phase took approximately two months. Promotional strategies included the creation and dissemination of brochures and stickers. The intranet site went live on January 1, 2007, and the advertising campaign began one month later. The utility of the site was measured for five months by tracking the number of visits to the site, the number of visits to each webpage, and the number of downloaded files. Request volume, caller affiliation, and question types received by the DIS call center were also recorded. Establishing a DIS intranet site required a considerable time investment and a willingness to work with existing infrastructures, such as the marketing and communications department and Web marketing staff.
Innervation of the renal proximal convoluted tubule of the rat
International Nuclear Information System (INIS)
Barajas, L.; Powers, K.
1989-01-01
Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries
Liu, Fu-Jun; Song, Xiulong; Yang, Dongfang; Deng, Ruitang; Yan, Bingfang
2008-01-01
CYP3A4 (cytochrome P450 3A4) is involved in the metabolism of more than 50% of drugs and other xenobiotics. The expression of CYP3A4 is induced by many structurally dissimilar compounds. The PXR (pregnane X receptor) is recognized as a key regulator for the induction, and the PXR-directed transactivation of the CYP3A4 gene is achieved through a co-ordinated mechanism of the distal module with the proximal promoter. Recently, a far module was found to support constitutive expression of CYP3A4. The far module, like the distal module, is structurally clustered by a PXR response element (F-ER6) and elements recognized by HNF-4alpha (hepatocyte nuclear receptor-4alpha). We hypothesized that the far module supports PXR transactivation of the CYP3A4 gene. Consistent with the hypothesis, fusion of the far module to the proximal promoter of CYP3A4 markedly increased rifampicin-induced reporter activity. The increase was synergistically enhanced when both the far and distal modules were fused to the proximal promoter. The increase, however, was significantly reduced when the F-ER6 was disrupted. Chromatin immunoprecipitation detected the presence of PXR in the far module. Interestingly, HNF-4alpha increased the activity of the distal-proximal fused promoter, but decreased the activity of the far-proximal fused promoter. Given the fact that induction of CYP3A4 represents an important detoxification mechanism, the functional redundancy and synergistic interaction in supporting PXR transactivation suggest that the far and distal modules ensure the induction of CYP3A4 during chemical insults. The difference in responding to HNF-4alpha suggests that the magnitude of the induction is under control through various transcriptional networks.
Quiet is the New Loud : Pausing and Focus in Child and Adult Dutch
Romøren, Anna Sara H; Chen, Aoju
2015-01-01
In a number of languages, prosody is used to highlight new information (or focus). In Dutch, focus is marked by accentuation, whereby focal constituents are accented and post-focal constituents are de-accented. Even if pausing is not traditionally seen as a cue to focus in Dutch, several previous
Proximal Tibia Bone Graft: An alternative Donor Source especially for Foot and Ankle Procedures
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Jia TY
2015-03-01
Full Text Available Among the many donor sites for harvesting autologous bone graft, the iliac crest has been the most commonly used. However, for foot and ankle procedures the proximal tibia has gained popularity as an alternative donor site due to its anatomic proximity to the primary surgical site. In this article we evaluated the possible complications associated with harvesting proximal tibia bone graft. Our study showed the low incidence of morbidity in harvesting proximal tibia bone graft, thereby providing a good alternative donor for foot and ankle procedures.
Xie, Ping
2015-10-09
Proteins in the cell are synthesized by a ribosome translating the genetic information encoded on the single-stranded messenger RNA (mRNA). It has been shown that the ribosome can also translate through the duplex region of the mRNA by unwinding the duplex. Here, based on our proposed model of the ribosome translation through the mRNA duplex we study theoretically the distribution of dwell times of the ribosome translation through the mRNA duplex under the effect of a pulling force externally applied to the ends of the mRNA to unzip the duplex. We provide quantitative explanations of the available single molecule experimental data on the distribution of dwell times with both short and long durations, on rescuing of the long paused ribosomes by raising the pulling force to unzip the duplex, on translational arrests induced by the mRNA duplex and Shine-Dalgarno(SD)-like sequence in the mRNA. The functional consequences of the pauses or arrests caused by the mRNA duplex and the SD sequence are discussed and compared with those obtained from other types of pausing, such as those induced by "hungry" codons or interactions of specific sequences in the nascent chain with the ribosomal exit tunnel.
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Isaacs Richard J
2007-05-01
Full Text Available Abstract Background Topoisomerase IIα has been shown to be down-regulated in doxorubicin-resistant cell lines. The specificity proteins Sp1 and Sp3 have been implicated in regulation of topoisomerase IIα transcription, although the mechanism by which they regulate expression is not fully understood. Sp1 has been shown to bind specifically to both proximal and distal GC elements of the human topoisomerase IIα promoter in vitro, while Sp3 binds only to the distal GC element unless additional flanking sequences are included. While Sp1 is thought to be an activator of human topoisomerase IIα, the functional significance of Sp3 binding is not known. Therefore, we sought to determine the functional relationship between Sp1 and Sp3 binding to the topoisomerase IIα promoter in vivo. We investigated endogenous levels of Sp1, Sp3 and topoisomerase IIα as well as binding of both Sp1 and Sp3 to the GC boxes of the topoisomerase IIα promoter in breast cancer cell lines in vivo after short term doxorubicin exposure. Results Functional effects of Sp1 and Sp3 were studied using transient cotransfection assays using a topoisomerase IIα promoter reporter construct. The in vivo interactions of Sp1 and Sp3 with the GC elements of the topoisomerase IIα promoter were studied in doxorubicin-treated breast cancer cell lines using chromatin immunoprecipitation assays. Relative amounts of endogenous proteins were measured using immunoblotting. In vivo DNA looping mediated by proteins bound at the GC1 and GC2 elements was studied using the chromatin conformation capture assay. Both Sp1 and Sp3 bound to the GC1 and GC2 regions. Sp1 and Sp3 were transcriptional activators and repressors respectively, with Sp3 repression being dominant over Sp1-mediated activation. The GC1 and GC2 elements are linked in vivo to form a loop, thus bringing distal regulatory elements and their cognate transcription factors into close proximity with the transcription start site
A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo
DEFF Research Database (Denmark)
Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren
2008-01-01
RNAs, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly....
Variation of wave speed determined by the PU-loop with proximity to a reflection site.
Li, Ye; Borlotti, Alessandra; Parker, Kim H; Khir, Ashraf W
2011-01-01
Wave speed is directly related to arterial distensibility and is widely used by clinicians to assess arterial stiffness. The PU-loop method for determining wave speed is based on the water hammer equation for flow in flexible tubes and artery using the method of characteristics. This technique determines wave speed using simultaneous measurements of pressure and velocity at a single point. The method shows that during the early part of systole, the relationship between pressure and velocity is generally linear, and the initial slope of the PU-loop is proportional to wave speed. In this work, we designed an in-vitro experiment to investigate the effect of proximity to a reflection site on the wave speed determined by the PU-loop through varying the distance between the measurement and reflection sites. Measurements were made in a flexible tube with a reflection site at the distal end formed by joining the tube to another tube with a different diameter and material properties. Six different flexible tubes were used to generate both positive and negative reflection coefficients of different magnitudes. We found that the wave speed determined by the PU-loop did not change when the measurement site was far from the reflection site but did change as the distance to the reflection site decreased. The calculated wave speed increased with positive reflections and decreased with negative reflections. The magnitude of the change in wave speed at a fixed distance from the reflection site increased with increasing the value of the reflection coefficient.
Directory of Open Access Journals (Sweden)
Man-Tat eLau
2012-03-01
Full Text Available As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSHβ but suppresses LHβ expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSHβ in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSHβ transcription, the present study was undertaken to analyze the promoter of goldfish FSHβ gene (fshb with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the LβT2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSHβ promoter-SEAP (secreted alkaline phosphatase were co-transfected with an expression plasmid for Smads (2 or 3 followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements (SRE were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (SBE; AGAC, -1675/-1672 whereas the proximal site (GACCTTGA, -212/-205 was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSHβ expression by gonadotropin-releasing hormone (GnRH and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSHβ that are responsible for activin
Directory of Open Access Journals (Sweden)
Ansaya Thonpho
Full Text Available Pyruvate carboxylase (PC is an enzyme that plays a crucial role in many biosynthetic pathways in various tissues including glucose-stimulated insulin secretion. In the present study, we identify promoter usage of the human PC gene in pancreatic beta cells. The data show that in the human, two alternative promoters, proximal and distal, are responsible for the production of multiple mRNA isoforms as in the rat and mouse. RT-PCR analysis performed with cDNA prepared from human liver and islets showed that the distal promoter, but not the proximal promoter, of the human PC gene is active in pancreatic beta cells. A 1108 bp fragment of the human PC distal promoter was cloned and analyzed. It contains no TATA box but possesses two CCAAT boxes, and other putative transcription factor binding sites, similar to those of the distal promoter of rat PC gene. To localize the positive regulatory region in the human PC distal promoter, 5'-truncated and the 25-bp and 15-bp internal deletion mutants of the human PC distal promoter were generated and used in transient transfections in INS-1 832/13 insulinoma and HEK293T (kidney cell lines. The results indicated that positions -340 to -315 of the human PC distal promoter serve as (an activator element(s for cell-specific transcription factor, while the CCAAT box at -71/-67, a binding site for nuclear factor Y (NF-Y, as well as a GC box at -54/-39 of the human PC distal promoter act as activator sequences for basal transcription.
Mustafa Diab, Mohamed; Wu, Hao-Hua; Eliezer, Edmund; Haonga, Billy; Morshed, Saam; Shearer, David W
2018-02-01
In many low and middle-income countries (LMICs) SIGN nail is commonly used for antegrade femoral intramedullary (IM) nailing, using a start site either at the tip of the greater trochanter or piriformis fossa. While a correct start site is considered an essential technical step; few studies have evaluated the impact of using an erroneous start site. This is particularly relevant in settings with limited access to fluoroscopy to aid in creating a nail entry point. The purpose of this study was to evaluate the impact of antegrade SIGN IM nailing start site on radiographic alignment and health-related quality of life. In this prospective cohort study, adult patients with proximal femur fractures (OTA 32, subtrochanteric zone) treated with antegrade IM SIGN nail at Muhimbili Orthopaedic Institute (MOI), Dar es Salaam, Tanzania were enrolled. Start site was determined on the immediate postoperative X-ray and was graded on a continuous scale based on distance of the IM nail center from the greater trochanteric tip. The primary outcome measurement was coronal alignment on the post-operative x-ray. The secondary outcomes were reoperation rates, RUST scores and EQ5D scores at one year follow-up. Seventy-nine patients were enrolled. 50 of them (63.3%) had complete data at 1year and were included in the final data analysis. Of the fifty patients, nine (18%) had IM nails placed laterally, 26 (52%) medially and 15 (30%) directly over the tip of the greater trochanter. Compared to a start site at the tip or medial to the greater trochanter, a lateral start site was 9 times more likely to result in a varus malalignment (95% CI: 1.42-57.70, p=0.021). Lateral start site was associated with varus malalignment. Although lateral start site was not significantly associated with reoperation, varus deformity was associated with higher reoperation rates. Surgeons should consider avoiding a start site lateral to the tip of the greater trochanter or allow the nail to rotate to avoid
Expert system for modelling stopover site selection by barnacle geese
Shariati Najafabadi, Mitra; Skidmore, Andrew K.; Darvishzadeh, Roshanak; Exo, Klaus-Michael; Kölzsch, Andrea; Griffin, Larry; Stahl, Julia; Cabot, David; Toxopeus, Albertus G.
2017-01-01
The study of stopover sites has received a lot of attention in avian ecology, being especially important for many long-distance migrants, some of which have to pause several times during migration. The survival of many migratory birds depends primarily on food availability at these stopovers.
Eklund, Robert; Ingvar, Martin
2016-01-01
Spontaneously produced Unfilled Pauses (UPs) and Filled Pauses (FPs) were played to subjects in an fMRI experiment. For both stimuli increased activity was observed in the Primary Auditory Cortex (PAC). However, FPs, but not UPs, elicited modulation in the Supplementary Motor Area (SMA), Brodmann Area 6. Our results provide neurocognitive confirmation of the alleged difference between FPs and other kinds of speech disfluency and could also provide a partial explanation for the previously repo...
McMorrow, Martin J.; And Others
1987-01-01
A cues-pause-point procedure was used to train two severely retarded females to remain quiet before, during, and briefly after the presentation of questions and then to verbalize on the basis of environmental cues whose labels represented the correct responses. Echolalia was rapidly replaced by correct responding on the trained stimuli. (Author/JW)
Robinson, Michael D; Wilkowski, Benjamin M; Meier, Brian P; Moeller, Sara K; Fetterman, Adam K
2012-01-01
Low-anger individuals are less reactive, both emotionally and behaviourally, to a large variety of situational primes to anger and aggression. Why this is so, from an affective processing perspective, has been largely conjectural. Four studies (total N=270) sought to link individual differences in anger to tendencies exhibited in basic affective processing tasks. On the basis of motivational factors and considerations, it was hypothesised that negative evaluations would differentially activate a psychological alarm system at low levels of anger, resulting in a pause that should be evident in the speed of making subsequent evaluations. Just such a pattern was evident in all studies. By contrast, high-anger individuals did not pause following their negative evaluations. In relation to this affective processing tendency, at least, dramatically different effects were observed among low- versus high-anger individuals. Implications for the personality-processing literature, theories of trait anger, and fast-acting regulatory processes are discussed.
A strategy for health promotion at multiple corporate sites.
Alexy, B; Eynon, D
1991-02-01
1. The logistical problems associated with delivery of health promotion programs at multiple corporate sites can be addressed through the use of health education packets. 2. The role of the nurse or health coordinator is critical in assisting and guiding the employee as the health plan is executed. 3. Problematic areas related to implementation of programs at remote sites can be alleviated through careful planning and extensive communication. 4. Advertising, input from employees and staff, and follow up are important in the success of a program.
Jouen, A.-L.; Verwey, Willem B.; van der Helden, J.; Scheiber, C.; Neveu, R.; Dominey, P.F.; Ventre-Dominey, J.
2013-01-01
Our sensorimotor experience unfolds in sequences over time. We hypothesize that the processing of movement sequences with and without a temporal pause will recruit distinct but cooperating neural processes, including cortico-striatal and cortico-cerebellar networks. We thus, compare neural activity
Single-site catalyst promoters accelerate metal-catalyzed nitroarene hydrogenation
Wang, Liang
2018-04-04
Atomically dispersed supported metal catalysts are drawing wide attention because of the opportunities they offer for new catalytic properties combined with efficient use of the metals. We extend this class of materials to catalysts that incorporate atomically dispersed metal atoms as promoters. The catalysts are used for the challenging nitroarene hydrogenation and found to have both high activity and selectivity. The promoters are single-site Sn on TiO2 supports that incorporate metal nanoparticle catalysts. Represented as M/Sn-TiO2 (M = Au, Ru, Pt, Ni), these catalysts decidedly outperform the unpromoted supported metals, even for hydrogenation of nitroarenes substituted with various reducible groups. The high activity and selectivity of these catalysts result from the creation of oxygen vacancies on the TiO2 surface by single-site Sn, which leads to efficient, selective activation of the nitro group coupled with a reaction involving hydrogen atoms activated on metal nanoparticles.
Single-site catalyst promoters accelerate metal-catalyzed nitroarene hydrogenation
Wang, Liang; Guan, Erjia; Zhang, Jian; Yang, Junhao; Zhu, Yihan; Han, Yu; Yang, Ming; Cen, Cheng; Fu, Gang; Gates, Bruce C.; Xiao, Feng-Shou
2018-01-01
Atomically dispersed supported metal catalysts are drawing wide attention because of the opportunities they offer for new catalytic properties combined with efficient use of the metals. We extend this class of materials to catalysts that incorporate atomically dispersed metal atoms as promoters. The catalysts are used for the challenging nitroarene hydrogenation and found to have both high activity and selectivity. The promoters are single-site Sn on TiO2 supports that incorporate metal nanoparticle catalysts. Represented as M/Sn-TiO2 (M = Au, Ru, Pt, Ni), these catalysts decidedly outperform the unpromoted supported metals, even for hydrogenation of nitroarenes substituted with various reducible groups. The high activity and selectivity of these catalysts result from the creation of oxygen vacancies on the TiO2 surface by single-site Sn, which leads to efficient, selective activation of the nitro group coupled with a reaction involving hydrogen atoms activated on metal nanoparticles.
Study of the dark pause phenomenon in a low cost exploding wire experiment
International Nuclear Information System (INIS)
Bressa, R.; Chatelain, G.; Lester, M.; Pouzo, J.
1988-01-01
A low cost exploding wire experiment is described and several aspects of the phenomenology in this type of plasmas are researched. Plasma photographies with high time resolution are obtained with a non-expensive Kerr cell switching system. The research is centered in the study of the dark pause phenomenon and the experimental results are interpreted using a very simple model. (author). 3 refs, 12 figs
Linking Core Promoter Classes to Circadian Transcription.
Directory of Open Access Journals (Sweden)
Pål O Westermark
2016-08-01
Full Text Available Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs, is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription.
Rogge, George A; Shen, Li-Ling; Kuhar, Michael J
2010-07-16
Both over expression of cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc), and intra-accumbal injection of cocaine- and amphetamine-regulated transcript (CART) peptides, have been shown to decrease cocaine reward. Also, over expression of CREB in the rat NAc increased CART mRNA and peptide levels, but it is not known if this was due to a direct action of P-CREB on the CART gene promoter. The goal of this study was to test if CREB and P-CREB bound directly to the CRE site in the CART promoter, using chromatin immunoprecipitation (ChIP) assays. ChIP assay with anti-CREB antibodies showed an enrichment of the CART promoter fragment containing the CRE region over IgG precipitated material, a non-specific control. Forskolin, which was known to increase CART mRNA levels in GH3 cells, was utilized to show that the drug increased levels of P-CREB protein and P-CREB binding to the CART promoter CRE-containing region. A region of the c-Fos promoter containing a CRE cis-regulatory element was previously shown to bind P-CREB, and it was used here as a positive control. These data suggest that the effects of CREB over expression on blunting cocaine reward could be, at least in part, attributed to the increased expression of the CART gene by direct interaction of P-CREB with the CART promoter CRE site, rather than by some indirect action. Copyright (c) 2010 Elsevier B.V. All rights reserved.
PROXIMAL: a method for Prediction of Xenobiotic Metabolism.
Yousofshahi, Mona; Manteiga, Sara; Wu, Charmian; Lee, Kyongbum; Hassoun, Soha
2015-12-22
Contamination of the environment with bioactive chemicals has emerged as a potential public health risk. These substances that may cause distress or disease in humans can be found in air, water and food supplies. An open question is whether these chemicals transform into potentially more active or toxic derivatives via xenobiotic metabolizing enzymes expressed in the body. We present a new prediction tool, which we call PROXIMAL (Prediction of Xenobiotic Metabolism) for identifying possible transformation products of xenobiotic chemicals in the liver. Using reaction data from DrugBank and KEGG, PROXIMAL builds look-up tables that catalog the sites and types of structural modifications performed by Phase I and Phase II enzymes. Given a compound of interest, PROXIMAL searches for substructures that match the sites cataloged in the look-up tables, applies the corresponding modifications to generate a panel of possible transformation products, and ranks the products based on the activity and abundance of the enzymes involved. PROXIMAL generates transformations that are specific for the chemical of interest by analyzing the chemical's substructures. We evaluate the accuracy of PROXIMAL's predictions through case studies on two environmental chemicals with suspected endocrine disrupting activity, bisphenol A (BPA) and 4-chlorobiphenyl (PCB3). Comparisons with published reports confirm 5 out of 7 and 17 out of 26 of the predicted derivatives for BPA and PCB3, respectively. We also compare biotransformation predictions generated by PROXIMAL with those generated by METEOR and Metaprint2D-react, two other prediction tools. PROXIMAL can predict transformations of chemicals that contain substructures recognizable by human liver enzymes. It also has the ability to rank the predicted metabolites based on the activity and abundance of enzymes involved in xenobiotic transformation.
The fitness landscapes of cis-acting binding sites in different promoter and environmental contexts.
Directory of Open Access Journals (Sweden)
Ryan K Shultzaberger
2010-07-01
Full Text Available The biophysical nature of the interaction between a transcription factor and its target sequences in vitro is sufficiently well understood to allow for the effects of DNA sequence alterations on affinity to be predicted. But even in relatively simple in vivo systems, the complexities of promoter organization and activity have made it difficult to predict how altering specific interactions between a transcription factor and DNA will affect promoter output. To better understand this, we measured the relative fitness of nearly all Escherichia coli sigma(70 -35 binding sites in different promoter and environmental contexts by competing four randomized -35 promoter libraries controlling the expression of the tetracycline resistance gene (tetagainst each other in increasing concentrations of drug. We sequenced populations after competition to determine the relative enrichment of each -35 sequence. We observed a consistent relationship between the frequency of recovery of each -35 binding site and its predicted affinity for sigma(70 that varied depending on the sequence context of the promoter and drug concentration. Overall the relative fitness of each promoter could be predicted by a simple thermodynamic model of transcriptional regulation, in which the rate of transcriptional initiation (and hence fitness is dependent upon the overall stability of the initiation complex, which in turn is dependent upon the energetic contributions of all sites within the complex. As implied by this model, a decrease in the free energy of association at one site could be compensated for by an increase in the binding energy at another to produce a similar output. Furthermore, these data show that a large and continuous range of transcriptional outputs can be accessed by merely changing the -35, suggesting that evolved or engineered mutations at this site could allow for subtle and precise control over gene expression.
Grade, Carla Vermeulen Carvalho; Mantovani, Carolina Stefano; Fontoura, Marina Alves; Yusuf, Faisal; Brand-Saberi, Beate; Alvares, Lúcia Elvira
2017-10-01
Myostatin (MSTN) is a strong inhibitor of skeletal muscle growth in human and other vertebrates. Its transcription is controlled by a proximal promoter/enhancer (Mstn P/E) containing a TATA box besides CREB, NF-Y, MEIS1 and FXR transcription factor binding sites (TFBSs), which are conserved throughout evolution. The aim of this work was to investigate the role of these TFBSs on Mstn P/E activity and evaluate the potential of their putative ligands as Mstn trans regulators. Mstn P/E mutant constructs were used to establish the role of conserved TFBSs using dual-luciferase assays. Expression analyses were performed by RT-PCR and in situ hybridization in C2C12 myoblasts and E10.5 mouse embryos, respectively. Our results revealed that CREB, NF-Y and MEIS1 sites are required to balance Mstn P/E activity, keeping Mstn transcription within basal levels during myoblast proliferation. Furthermore, our data showed that NF-Y site is essential, although not sufficient, to mediate Mstn P/E transcriptional activity. In turn, CREB and MEIS1 binding sites seem to depend on the presence of NF-Y site to induce Mstn P/E. FXR appears not to confer any effect on Mstn P/E activity, except in the absence of all other conserved TFBS. Accordingly, expression studies pointed to CREB, NF-Y and MEIS1 but not to FXR factors as possible regulators of Mstn transcription in the myogenic context. Altogether, our findings indicated that CREB, NF-Y and MEIS1 conserved sites are essential to control basal Mstn transcription during early myogenesis, possibly by interacting with these or other related factors.
International Nuclear Information System (INIS)
Weaver, J.C.B.; Stover, S.M.; O'Brien, T.R.
1992-01-01
The sites of bony attachment of the tendons, ligaments, and fibrous portion of the joint capsules of the equine metacarpophalangeal (fetlock) joint region were determined by gross dissection. These sites were transposed to standard radiographic views of the fetlock joint to yield illustrations that can be used as an aid in the diagnosis of soft tissue pathology from radiographs. Evidence of direct attachment of the common digital extensor tendon to the proximal phalanx was not found. Branches of the superficial digital flexor tendon were found to insert only on the middle phalanx. The recently described sites of insertion of the branches of the superficial digital flexor tendon to the proximal phalanx were found to be sites for attachment of the deep axial palmar ligaments of the proximal interphalangeal joint
DEFF Research Database (Denmark)
Pedersen, Margit; Hammer, Karin
2008-01-01
. The cloned DNA fragment contained the two divergently oriented promoters, P-R and P-L, transcribing the lysogenic and lytic gene clusters; the two promoter-. proximal genes, cl and mor; and the three CI operator sites, O-R, O-L and O-D. We show that mor encodes a protein and that this protein in concert......-D) is enough to maintain a bistable system. The distantly located operator site, 01:), functions as a helper site by increasing binding of CI at O-R and O-L. In the immune state, O-D increases repression of the lytic promoter, P-L. Our results strongly support the model that a hexameric form of Cl binds...... cooperatively to the three operator sites in the immune state forming a CI-DNA loop structure. Finally, we show that in the anti-immune state, repression of the lysogenic promoter is independent of the known CI operator sites but requires the presence of both CI and MOR....
Huber, Jessica E.; Darling, Meghan; Francis, Elaine J.; Zhang, Dabao
2012-01-01
Purpose: The present study examines the impact of typical aging and Parkinson's disease (PD) on the relationship among breath pausing, syntax, and punctuation. Method: Thirty young adults, 25 typically aging older adults, and 15 individuals with PD participated. Fifteen participants were age- and sex-matched to the individuals with PD.…
Depressionary Effect of Proximity of Residential Properties to Waste ...
African Journals Online (AJOL)
Past studies have researched these impacts using a variety of hedonic models and Marginal Implicit Pricing, however, this study takes a special focus on the resident's perspective based on the linear proximity to waste disposal sites. 260 questionnaires were distributed to residents within 1km to the site and Estate ...
The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei
Zomerdijk, J. C.; Ouellette, M.; ten Asbroek, A. L.; Kieft, R.; Bommer, A. M.; Clayton, C. E.; Borst, P.
1990-01-01
The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site
Directory of Open Access Journals (Sweden)
Christopher A Lavender
2016-08-01
Full Text Available Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.
Symmetry-based reciprocity: evolutionary constraints on a proximate mechanism.
Campennì, Marco; Schino, Gabriele
2016-01-01
Background. While the evolution of reciprocal cooperation has attracted an enormous attention, the proximate mechanisms underlying the ability of animals to cooperate reciprocally are comparatively neglected. Symmetry-based reciprocity is a hypothetical proximate mechanism that has been suggested to be widespread among cognitively unsophisticated animals. Methods. We developed two agent-based models of symmetry-based reciprocity (one relying on an arbitrary tag and the other on interindividual proximity) and tested their ability both to reproduce significant emergent features of cooperation in group living animals and to promote the evolution of cooperation. Results. Populations formed by agents adopting symmetry-based reciprocity showed differentiated "social relationships" and a positive correlation between cooperation given and received: two common aspects of animal cooperation. However, when reproduction and selection across multiple generations were added to the models, agents adopting symmetry-based reciprocity were outcompeted by selfish agents that never cooperated. Discussion. In order to evolve, hypothetical proximate mechanisms must be able to stand competition from alternative strategies. While the results of our simulations require confirmation using analytical methods, we provisionally suggest symmetry-based reciprocity is to be abandoned as a possible proximate mechanism underlying the ability of animals to reciprocate cooperative interactions.
Online social networking sites-a novel setting for health promotion?
Loss, Julika; Lindacher, Verena; Curbach, Janina
2014-03-01
Among adolescents, online social networking sites (SNS) such as Facebook are popular platforms for social interaction and may therefore be considered as 'novel settings' that could be exploited for health promotion. In this article, we examine the relevant definitions in health promotion and literature in order to analyze whether key characteristics of 'settings for health promotion' and the socio-ecological settings approach can be transferred to SNS. As many of our daily activities have shifted to cyberspace, we argue that online social interaction may gain more importance than geographic closeness for defining a 'setting'. While exposition to positive references to risk behavior by peers may render the SNS environment detrimental to health, SNS may allow people to create their own content and therefore foster participation. However, those health promotion projects delivered on SNS up until today solely relied on health education directed at end users. It remains unclear how health promotion on SNS can meet other requirements of the settings approach (e.g. building partnerships, changing the environment). As yet, one should be cautious in terming SNS a 'setting'. Copyright © 2013 Elsevier Ltd. All rights reserved.
Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R
1997-09-05
To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient
Kuhnel, Leslie
2018-01-01
The broad use of social networking and user-generated content has increased the online footprint of many individuals. A generation of healthcare professionals have grown up with online search activities as part of their everyday lives. Sites like Facebook, Twitter, and Instagram have given the public new ways to share intimate details about their public and private lives and the lives of their friends and families. As a result, careproviders have the ability to find out more about their patients with just the tap of a key or the click of a mouse. This type of online searching for patient information is known as patient-targeted googling or PTG. This article provides an overview of the emergence of PTG, identifies the potential benefits and possible pitfalls of engaging in PTG, and explores current ethical frameworks that guide decisions about PTG. The article describes the development of a critical thinking tool developed by the Behavioral Health Ethics Committee at CHI Health, that can serve as a best-practice model for other hospitals and health systems. Called TTaPP (Together Take a Pause and Ponder), this tool is designed to help healthcare professionals across settings practice collaborative critical thinking skills as they consider the ethical questions of whether or not to engage in PTG. Finally, this article suggests areas for further study, including ways to prompt collaboration and appropriate documentation by maximizing electronic medical records systems, exploring the effectiveness of the TTaPP tool as a way to promote a culture of collaborative critical thinking practices, and the attitudes of patients and the public regarding PTG. Copyright 2018 The Journal of Clinical Ethics. All rights reserved.
Web site development: applying aesthetics to promote breast health education and awareness.
Thomas, Barbara; Goldsmith, Susan B; Forrest, Anne; Marshall, Renée
2002-01-01
This article describes the process of establishing a Web site as part of a collaborative project using visual art to promote breast health education. The need for a more "user-friendly" comprehensive breast health Web site that is aesthetically rewarding was identified after an analysis of current Web sites available through the World Wide Web. Two predetermined sets of criteria, accountability and aesthetics, were used to analyze these sites and to generate ideas for creating a breast health education Web site using visual art. Results of the analyses conducted are included as well as the factors to consider for incorporating into a Web site. The process specified is thorough and can be applied to establish a Web site that is aesthetically rewarding and informative for a variety of educational purposes.
Schausi, Diane; Tiffoche, Christophe; Thieulant, Marie-Lise
2003-07-01
We have characterized the intronic promoter of the rat estrogen receptor (ER) alpha gene, responsible for the lactotrope-specific truncated ER product (TERP)-1 isoform expression. Transcriptional regulation was investigated by transient transfections using 5'-deletion constructs. TERP promoter constructs were highly active in MMQ cells, a pure lactotrope cell line, whereas a low basal activity was detected in alphaT3-1 gonadotrope cells or in COS-7 monkey kidney cells. Serial deletion analysis revealed that 1) a minimal -693-bp region encompassing the TATA box is sufficient to allow lactotrope-specific expression; 2) the promoter contains strong positive cis-acting elements both in the distal and proximal regions, and 3) the region spanning the -1698/-1194 region includes repressor elements. Transient transfection studies, EMSAs, and gel shifts demonstrated that estrogen activates the TERP promoter via an estrogen-responsive element (ERE1) located within the proximal region. Mutation of ERE1 site completely abolishes the estradiol-dependent transcription, indicating that ERE1 site is sufficient to confer estrogen responsiveness to TERP promoter. In addition, ERalpha action was synergized by transfection of the pituitary-specific factor Pit-1. EMSAs showed that a single Pit-1 DNA binding element in the vicinity of the TATA box is sufficient to confer response by the TERP promoter. In conclusion, we demonstrated, for the first time, that TERP promoter regulation involves ERE and Pit-1 cis-elements and corresponding trans-acting factors, which could play a role in the physiological changes that occur in TERP-1 transcription in lactotrope cells.
Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria
Energy Technology Data Exchange (ETDEWEB)
Froula, Jeffrey L.; Francino, M. Pilar
2007-05-01
Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.
Do the terms 'proximal' and 'distal' cause confusion amongst radiologists and other clinicians?
International Nuclear Information System (INIS)
Skillicorn, C.J.
2009-01-01
Aim: To investigate the use of the terms 'proximal' and 'distal', and what respondents think the terms mean, when applied to certain structures within the trunk, notably the veins and the biliary tract. Materials and Methods: Fifty-three respondents were interviewed using simplified anatomical diagrams. Respondents were asked what terms they would use to describe sites at opposite ends of the superior vena cava (SVC), internal jugular vein (IJV), common bile duct (CBD), and pancreatic duct. They were also asked which end of each of these structures they would think was being referred to if they read a radiological report that used these terms. Results: The terms 'proximal' and 'distal' were used by at least 50% of all respondents, and, specifically, at least 60% of radiologists at all four anatomical sites. Eighty-five percent (n = 45) of all respondents and 100% (n = 24) of radiologists agreed that the term 'proximal' CBD referred to its superior end. However, at the other sites there was marked disagreement, 67% (n = 16) of radiologists thought the superior SVC and superior IJV were 'proximal', 33% (n = 8) thought they were 'distal'. There was a 54% (n = 13) to 46% (n = 11) split amongst radiologists as to which end of the pancreatic duct was 'proximal'. Conclusion: The terms 'proximal' and 'distal' are the most frequently used terms to describe positions in veins and the biliary system, but there is widespread confusion about their meaning, which could lead to medical error and ultimately patient harm. The use of alternative terms is advised
Do the terms "proximal" and "distal" cause confusion amongst radiologists and other clinicians?
Skillicorn, C J
2009-04-01
To investigate the use of the terms "proximal" and "distal", and what respondents think the terms mean, when applied to certain structures within the trunk, notably the veins and the biliary tract. Fifty-three respondents were interviewed using simplified anatomical diagrams. Respondents were asked what terms they would use to describe sites at opposite ends of the superior vena cava (SVC), internal jugular vein (IJV), common bile duct (CBD), and pancreatic duct. They were also asked which end of each of these structures they would think was being referred to if they read a radiological report that used these terms. The terms "proximal" and "distal" were used by at least 50% of all respondents, and, specifically, at least 60% of radiologists at all four anatomical sites. Eighty-five percent (n=45) of all respondents and 100% (n=24) of radiologists agreed that the term "proximal" CBD referred to its superior end. However, at the other sites there was marked disagreement, 67% (n=16) of radiologists thought the superior SVC and superior IJV were "proximal", 33% (n=8) thought they were "distal". There was a 54% (n=13) to 46% (n=11) split amongst radiologists as to which end of the pancreatic duct was "proximal". The terms "proximal" and "distal" are the most frequently used terms to describe positions in veins and the biliary system, but there is widespread confusion about their meaning, which could lead to medical error and ultimately patient harm. The use of alternative terms is advised.
International Nuclear Information System (INIS)
Cui Wei; Yin Lingling; Dong Lingyue
2012-01-01
Objective: To clarify the mechanism of immediate early response gene 5 (Ier5) transcription induced by radiation. Methods: Deletant construction, site-specific mutagenesis,electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) were used to forecast the promoter region, binding sites and transcription factors of Ier5 gene in HeLa cells. Results: The promoter region of Ier5 gene might be in the region of Ier5 -8 deletant (-408 - -238 bp). The Ier5 gene had two transcription factors of GCF and NFI, and GCF had two binding sites located in the region of -388 - -382 bp and -274 - -270 bp of Ier5 promoter. The binding site of NFI was located in -362 - -357 bp of Ier5 promoter. GCF could inhibit the expression of Ier5 gene and this inhibition was diminished when the radiation dose increased. In contrast, NFI increased the expression of Ier5. Conclusions: The most possible region of Ier5 promoter is from -408 to -238 bp which has two binding sites for the radiosensitivity transcription factors of GCF and NFI that could negatively and positively regulate the expression of Ier5 respectively. (authors)
Better access to microcredits: does geographical proximity matter?
Czech Academy of Sciences Publication Activity Database
Alimukhamedova, Nargiza
-, 2013/2014 Winter (2014), s. 24-25 Institutional support: PRVOUK-P23 Keywords : microcredits * geographical proximity Subject RIV: AH - Economics http://www.e-mfp.eu/sites/ default /files/resources/2014/02/e-MFP_Winter2013-2014_Newsletter%20.pdf
Swami, Srilatha; Krishnan, Aruna V; Peng, Lihong; Lundqvist, Johan; Feldman, David
2013-08-01
Calcitriol (1,25-dihydroxyvitamin D3), the hormonally active metabolite of vitamin D, exerts its anti-proliferative activity in breast cancer (BCa) cells by multiple mechanisms including the downregulation of the expression of estrogen receptor α (ER). We analyzed an ∼3.5 kb ER promoter sequence and demonstrated the presence of two potential negative vitamin D response elements (nVDREs), a newly identified putative nVDRE upstream at -2488 to -2473 bp (distal nVDRE) and a previously published sequence (proximal nVDRE) at -94 to -70 bp proximal to the P1 start site. Transactivation analysis using ER promoter deletion constructs and heterologous promoter-reporter constructs revealed that both nVDREs functioned to mediate calcitriol transrepression. In the electrophoretic mobility shift assay, the vitamin D receptor (VDR) showed strong binding to both nVDREs in the presence of calcitriol, and the chromatin immunoprecipitation assay demonstrated the recruitment of the VDR to the distal nVDRE site. Mutations in the 5' hexameric DNA sequence of the distal nVDRE resulted in the loss of calcitriol-mediated transrepression and the inhibition of protein-DNA complex formation, demonstrating the importance of these nucleotides in VDR DNA binding and transrepression. A putative nuclear factor-Y (NFY) binding site, identified within the distal nVDRE, led to the findings that NFY bound to the distal nVDRE site interfered with the binding of the VDR at the site and reduced calcitriol-mediated transrepression. In conclusion, the ER promoter region contains two negative VDREs that act in concert to bind to the VDR and both nVDREs are required for the maximal inhibition of ER expression by calcitriol. The suppression of ER expression and estrogen-mediated signaling by calcitriol in BCa cells suggests that vitamin D may be useful in the treatment of ER+ BCa.
A systematic examination of the use of Online social networking sites for sexual health promotion
Directory of Open Access Journals (Sweden)
Hellard Margaret E
2011-07-01
Full Text Available Abstract Background In recent years social networking sites (SNSs have grown rapidly in popularity. The popularity of these sites, along with their interactive functions, offer a novel environment in which to deliver health promotion messages. The aim of this paper is to examine the extent to which SNSs are currently being used for sexual health promotion and describe the breadth of these activities. Methods We conducted a systematic search of published scientific literature, electronic sources (general and scientific search engines, blogs and SNSs (Facebook, MySpace to identify existing sexual health promotion activities using SNSs. Health promotion activities were eligible for inclusion if they related to sexual health or behaviour, utilised one or more SNSs, and involved some element of health promotion. Information regarding the source and type of health promotion activity, target population and site activity were extracted. Results 178 sexual health promotion activities met the inclusion criteria and were included in the review; only one activity was identified through a traditional systematic search of the published scientific literature. Activities most commonly used one SNS, were conducted by not-for-profit organisations, targeted young people and involved information delivery. Facebook was the most commonly used SNS (used by 71% of all health promotion activities identified, followed by MySpace and Twitter. Seventy nine percent of activities on MySpace were considered inactive as there had been no online posts within the past month, compared to 22% of activities using Facebook and 14% of activities using Twitter. The number of end-users and posts in the last seven days varied greatly between health promotion activities. Conclusions SNSs are being used for sexual health promotion, although the extent to which they are utilised varies greatly, and the vast majority of activities are unreported in the scientific literature. Future studies
A systematic examination of the use of Online social networking sites for sexual health promotion
2011-01-01
Background In recent years social networking sites (SNSs) have grown rapidly in popularity. The popularity of these sites, along with their interactive functions, offer a novel environment in which to deliver health promotion messages. The aim of this paper is to examine the extent to which SNSs are currently being used for sexual health promotion and describe the breadth of these activities. Methods We conducted a systematic search of published scientific literature, electronic sources (general and scientific search engines, blogs) and SNSs (Facebook, MySpace) to identify existing sexual health promotion activities using SNSs. Health promotion activities were eligible for inclusion if they related to sexual health or behaviour, utilised one or more SNSs, and involved some element of health promotion. Information regarding the source and type of health promotion activity, target population and site activity were extracted. Results 178 sexual health promotion activities met the inclusion criteria and were included in the review; only one activity was identified through a traditional systematic search of the published scientific literature. Activities most commonly used one SNS, were conducted by not-for-profit organisations, targeted young people and involved information delivery. Facebook was the most commonly used SNS (used by 71% of all health promotion activities identified), followed by MySpace and Twitter. Seventy nine percent of activities on MySpace were considered inactive as there had been no online posts within the past month, compared to 22% of activities using Facebook and 14% of activities using Twitter. The number of end-users and posts in the last seven days varied greatly between health promotion activities. Conclusions SNSs are being used for sexual health promotion, although the extent to which they are utilised varies greatly, and the vast majority of activities are unreported in the scientific literature. Future studies should examine the key
A systematic examination of the use of online social networking sites for sexual health promotion.
Gold, Judy; Pedrana, Alisa E; Sacks-Davis, Rachel; Hellard, Margaret E; Chang, Shanton; Howard, Steve; Keogh, Louise; Hocking, Jane S; Stoove, Mark A
2011-07-21
In recent years social networking sites (SNSs) have grown rapidly in popularity. The popularity of these sites, along with their interactive functions, offer a novel environment in which to deliver health promotion messages. The aim of this paper is to examine the extent to which SNSs are currently being used for sexual health promotion and describe the breadth of these activities. We conducted a systematic search of published scientific literature, electronic sources (general and scientific search engines, blogs) and SNSs (Facebook, MySpace) to identify existing sexual health promotion activities using SNSs. Health promotion activities were eligible for inclusion if they related to sexual health or behaviour, utilised one or more SNSs, and involved some element of health promotion. Information regarding the source and type of health promotion activity, target population and site activity were extracted. 178 sexual health promotion activities met the inclusion criteria and were included in the review; only one activity was identified through a traditional systematic search of the published scientific literature. Activities most commonly used one SNS, were conducted by not-for-profit organisations, targeted young people and involved information delivery. Facebook was the most commonly used SNS (used by 71% of all health promotion activities identified), followed by MySpace and Twitter. Seventy nine percent of activities on MySpace were considered inactive as there had been no online posts within the past month, compared to 22% of activities using Facebook and 14% of activities using Twitter. The number of end-users and posts in the last seven days varied greatly between health promotion activities. SNSs are being used for sexual health promotion, although the extent to which they are utilised varies greatly, and the vast majority of activities are unreported in the scientific literature. Future studies should examine the key factors for success among those
The sooner, the better: exercise outcome proximity and intrinsic motivation.
Evans, M Blair; Cooke, Lisa M; Murray, Robyn A; Wilson, Anne E
2014-11-01
Despite evidence that outcomes are highly valued when they are expected sooner rather than further into the future (Ainslie, 1975), limited research effort has been devoted to understanding the role of exercise outcome proximity. The purpose of this study was to examine how temporal proximity to positive outcomes influences exercisers' intrinsic motivation. We expected that focusing people on temporally proximal exercise outcomes would increase intrinsic motivation, especially among low-frequency exercisers. This online experimental study was completed by 135 community exercisers (Mage = 31.11, SD = 10.29; 62% female) who reported an average of 4.86 exercise bouts per week (SD = 2.12). Participants were randomly assigned to a condition that primed temporally proximal positive exercise outcomes (i.e. experienced during or directly following an exercise bout) or temporally distal outcomes (i.e. experienced after days, months, or years of regular exercise). Participants then reported perceptions of behavioral regulation in exercise. As expected, the proximal exercise outcome condition elicited increased intrinsic regulation among those participants who exercised less frequently (i.e. 1 SD below the mean). This study reveals the importance of considering proximity as an important dimension of exercise outcomes-particularly when promoting intrinsic motivation among relatively infrequent exercisers. © 2014 The International Association of Applied Psychology.
Sexual health promotion on social networking sites: a process evaluation of The FaceSpace Project.
Nguyen, Phuong; Gold, Judy; Pedrana, Alisa; Chang, Shanton; Howard, Steve; Ilic, Olivia; Hellard, Margaret; Stoove, Mark
2013-07-01
This article reports findings from an evaluation of reach and engagement of The FaceSpace Project, a novel sexual health promotion project delivered through social networking sites that targeted young people aged 16-29 years. Multiple methods were used to evaluate project reach and engagement. The evaluation focussed on quantitative data (online usage statistics, online surveys), complemented by available qualitative data (project team meeting notes). The project reached 900 fans who were mostly between 18 and 34 years of age. The most successful ways of increasing audience reach were via Facebook advertisements and tagging photos of young people attending a music festival on the project Facebook page. Peaks in Facebook page interactions (comments and "likes") coincided with recruitment peaks and when videos were posted. However, video views varied greatly between postings. Feedback from the project team for increasing engagement in future social networking site interventions included having one centralized Facebook page and using episodic videos. This evaluation is among the first to assess the use of social networking sites for sexual health promotion and provides information to inform the implementation and evaluation of future projects using new media. Social networking sites offer great potential to reach and engage young people for sexual health promotion. However, further work is required to improve implementation and promote audience reach and engagement as well as to determine effectiveness of social networking sites in changing knowledge, attitudes, and behaviors. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Effect of age on proximal esophageal response to swallowing
Directory of Open Access Journals (Sweden)
Roberto Oliveira Dantas
2010-12-01
Full Text Available CONTEXT: It has been demonstrated that the ageing process affects esophageal motility. OBJECTIVES: To evaluate the effect of the age on the proximal esophageal response to wet swallows. METHOD: We measured the proximal esophageal response to swallows of a 5 mL bolus of water in 69 healthy volunteers, 20 of them aged 18-30 years (group I, 27 aged 31-50 years (group II, and 22 aged 51-74 years (group III. We used the manometric method with continuous perfusion. The proximal esophageal contractions were recorded 5 cm from a pharyngeal recording site located 1 cm above the upper esophageal sphincter. The time between the onset of the pharyngeal and of the proximal esophageal recording (pharyngeal-esophageal time and the amplitude, duration and area under the curve of the proximal esophageal contraction were measured. RESULTS: The pharyngeal-esophageal time was shorter in group I subjects than in group II and III subjects (P<0.05. The duration of proximal esophageal contractions was longer in group I than in groups II and III (P<0.001. There was no differences between groups in the amplitude or area under the curve of contractions. There were no differences between groups II and III for any of the measurements. CONCLUSION: We conclude that the age may affects the response of the proximal esophagus to wet swallows.
Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.
2017-01-01
Purpose: Three previous articles provided rationale, methods, and several forms of validity support for a diagnostic marker of childhood apraxia of speech (CAS), termed the pause marker (PM). Goals of the present article were to assess the validity and stability of the PM Index (PMI) to scale CAS severity. Method: PM scores and speech, prosody,…
DEFF Research Database (Denmark)
Navarretta, Costanza
2017-01-01
president mocks himself, his collaborators, political adversary and the press corps making the audience react with cheers, laughter and/or applause. The results of the prediction experiment demonstrate that information about spoken sequences, pauses and co-speech gestures by Obama can be used to predict...
Effect of angiotensin II receptor blockade on proximal tubular fluid reabsorption
DEFF Research Database (Denmark)
Leyssac, P P; Karlsen, F M; Holstein-Rathlou, N H
1997-01-01
flow rate decreased by 2.0 +/- 0.8 nl/min, and early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean +/- SE). No changes were observed after microperfusion with saline. Because the tubuloglomerular feedback mechanism was operating in the closed-loop mode, the decreased NaCl load...... to the macula densa will be compensated by an increase in the single-nephron glomerular filtration rate. In agreement with this, the early proximal flow rate, measured proximal to the site of losartan administration, increased by 5.7 +/- 1.3 nl/min. The increase in the rate of proximal reabsorption between...
Directory of Open Access Journals (Sweden)
Xiao P Peng
2018-01-01
Full Text Available Smc5/6, a member of the conserved SMC family of complexes, is essential for growth in most organisms. Its exact functions in a mitotic cell cycle are controversial, as chronic Smc5/6 loss-of-function alleles produce varying phenotypes. To circumvent this issue, we acutely depleted Smc5/6 in budding yeast and determined the first cell cycle consequences of Smc5/6 removal. We found a striking primary defect in replication of the ribosomal DNA (rDNA array. Each rDNA repeat contains a programmed replication fork barrier (RFB established by the Fob1 protein. Fob1 removal improves rDNA replication in Smc5/6 depleted cells, implicating Smc5/6 in the management of programmed fork pausing. A similar improvement is achieved by removing the DNA helicase Mph1 whose recombinogenic activity can be inhibited by Smc5/6 under DNA damage conditions. DNA 2D gel analyses further show that Smc5/6 loss increases recombination structures at RFB regions; moreover, mph1∆ and fob1∆ similarly reduce this accumulation. These findings point to an important mitotic role for Smc5/6 in restraining recombination events when protein barriers in rDNA stall replication forks. As rDNA maintenance influences multiple essential cellular processes, Smc5/6 likely links rDNA stability to overall mitotic growth.
Zhang, Weimin; Lu, Huijie; Jiang, Haiyan; Li, Mu; Zhang, Shen; Liu, Qiongyou; Zhang, Lihong
2012-02-01
Aromatase (CYP19A1) catalyzes the conversion of androgens to estrogens. In teleosts, duplicated copies of cyp19a1 genes, namely cyp19a1a and cyp19a1b, were identified, however, the transcriptional regulation of these two genes remains poorly understood. In the present study, the 5'-flanking regions of the orange-spotted grouper cyp19a1a (gcyp19a1a) and cyp19a1b (gcyp19a1b) genes were isolated and characterized. The proximal promoter regions of both genes were relatively conserved when compared to those of the other teleosts. Notably, a conserved FOXO transcriptional factor binding site was firstly reported in the proximal promoter of gcyp19a1a, and deletion of the region (-112 to -60) containing this site significantly decreased the promoter activities. The deletion of the region (-246 to -112) containing the two conserved FTZ-F1 sites also dramatically decreased the transcriptional activities of gcyp19a1a promoter, and both two FTZ-F1 sites were shown to be stimulatory cis-acting elements. A FTZ-F1 homologue isolated from ricefield eel (eFTZ-F1) up-regulated gcyp19a1a promoter activities possibly via the FTZ-F1 sites, however, a previously identified orange-spotted grouper FTZ-F1 homologue (gFTZ-F1) did not activate the transcription of gcyp19a1a promoter unexpectedly. As to gcyp19a1b promoter, all the deletion constructs did not show good promoter activities in either TM4 or U251-MG cells. Estradiol (100nM) up-regulated gcyp19a1b promoter activities by about 13- and 36-fold in TM4 and U251-MG cells, respectively, via the conserved ERE motif, but did not stimulate gcyp19a1a promoter activities. These results are helpful to further elucidate the regulatory mechanisms of cyp19a1a and cyp19a1b expression in the orange-spotted grouper as well as other teleosts. Copyright © 2011 Elsevier Inc. All rights reserved.
Kavon, Nicole M.; McLaughlin, T. F.
1995-01-01
This paper examines behavior interventions for echolalic behavior in children with autism, including verbal prompting (focusing on the echolalic behavior itself) and the cues-pause-point procedure (which employs the child's prerequisite skills to teach correct verbal responses). A review of the literature indicated that both techniques were…
E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.
Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V
2016-01-01
Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.
E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.
Directory of Open Access Journals (Sweden)
Ha-Na Na
Full Text Available Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR, and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1. In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.
Correlation analysis of alveolar bone loss in buccal/palatal and proximal surfaces in rats
Directory of Open Access Journals (Sweden)
Carolina Barrera de Azambuja
2012-12-01
Full Text Available The aim was to correlate alveolar bone loss in the buccal/palatal and the mesial/distal surfaces of upper molars in rats. Thirty-three, 60-day-old, male Wistar rats were divided in two groups, one treated with alcohol and the other not treated with alcohol. All rats received silk ligatures on the right upper second molars for 4 weeks. The rats were then euthanized and their maxillae were split and defleshed with sodium hypochlorite (9%. The cemento-enamel junction (CEJ was stained with 1% methylene blue and the alveolar bone loss in the buccal/palatal surfaces was measured linearly in 5 points on standardized digital photographs. Measurement of the proximal sites was performed by sectioning the hemimaxillae, restaining the CEJ and measuring the alveolar bone loss linearly in 3 points. A calibrated and blinded examiner performed all the measurements. Intraclass Correlation Coefficient revealed values of 0.96 and 0.89 for buccal/lingual and proximal surfaces, respectively. The Pearson Correlation Coefficient (r between measurements in buccal/palatal and proximal surfaces was 0.35 and 0.05 for the group treated with alcohol, with and without ligatures, respectively. The best correlations between buccal/palatal and proximal surfaces were observed in animals not treated with alcohol, in sites both with and without ligatures (r = 0.59 and 0.65, respectively. A positive correlation was found between alveolar bone loss in buccal/palatal and proximal surfaces. The correlation is stronger in animals that were not treated with alcohol, in sites without ligatures. Areas with and without ligature-induced periodontal destruction allow detection of alveolar bone loss in buccal/palatal and proximal surfaces.
Dental flossing as a diagnostic method for proximal gingivitis: a validation study.
Grellmann, Alessandra Pascotini; Kantorski, Karla Zanini; Ardenghi, Thiago Machado; Moreira, Carlos Heitor Cunha; Danesi, Cristiane Cademartori; Zanatta, Fabricio Batistin
2016-05-20
This study evaluated the clinical diagnosis of proximal gingivitis by comparing two methods: dental flossing and the gingival bleeding index (GBI). One hundred subjects (aged at least 18 years, with 15% of positive proximal sites for GBI, without proximal attachment loss) were randomized into five evaluation protocols. Each protocol consisted of two assessments with a 10-minute interval between them: first GBI/second floss, first floss/second GBI, first GBI/second GBI, first tooth floss/second floss, and first gum floss-second floss. The dental floss was slid against the tooth surface (TF) and the gingival tissue (GF). The evaluated proximal sites should present teeth with established point of contact and probing depth ≤ 3mm. One trained and calibrated examiner performed all the assessments. The mean percentages of agreement and disagreement were calculated for the sites with gingival bleeding in both evaluation methods (GBI and flossing). The primary outcome was the percentage of disagreement between the assessments in the different protocols. The data were analyzed by one-way ANOVA, McNemar, chi-square and Tukey's post hoc tests, with a 5% significance level. When gingivitis was absent in the first assessment (negative GBI), bleeding was detected in the second assessment by TF and GF in 41.7% (p gingivitis in the second assessment (negative GBI), TF and GF detected bleeding in the first assessment in 38.9% (p = 0.004) and 58.3% (p gingivitis than GBI.
Health promotion site selection blues: barriers to participation and implementation.
Cherniack, Martin; Morse, Tim; Henning, Robert; Seidner, Adam; Punnett, Laura
2010-06-01
To shed light on research-to-practice challenges in workplace health promotion research. More than 1200 companies serviced by a national insurer were assessed by measures, including management surveys, and insurance premium costs and risk profile. A 21-item Workplace Readiness Checklist was the core assessment tool. Quantitative and qualitative measures were used to identify 12 to 14 companies deemed most "ready for change." The four priority candidate companies decided against participation. A post hoc survey to evaluate reasons for non-participation identified factors such as time allocations, the deteriorating economic environment, and the participatory nature of the interventions proposed for half of the study sites. Differing priorities within management also seemed to interfere with participation. A highly structured process for determining corporate readiness for participatory health promotion produced contradictory results.
[Partial replantation following proximal limb injury].
Dubert, T; Malikov, S A; Dinh, A; Kupatadze, D D; Oberlin, C; Alnot, J Y; Nabokov, B B
2000-11-01
Proximal replantation is a technically feasible but life-threatening procedure. Indications must be restricted to patients in good condition with a good functional prognosis. The goal of replantation must be focused not only on reimplanting the amputated limb but also on achieving a good functional outcome. For the lower limb, simple terminalization remains the best choice in many cases. When a proximal amputation is not suitable for replantation, the main aim of the surgical procedure must be to reconstruct a stump long enough to permit fitting a prosthesis preserving the function of the adjacent joint. If the proximal stump beyond the last joint is very short, it may be possible to restore some length by partial replantation of spared tissues from the amputated part. We present here the results we obtained following this policy. This series included 16 cases of partial replantations, 14 involving the lower limb and 2 the upper limb. All were osteocutaneous microsurgical transfers. For the lower limb, all transfers recovered protective sensitivity following tibial nerve repair. The functional calcaeoplantar unit was used in 13 cases. The transfer of this specialized weight bearing tissue provided a stable distal surface making higher support unnecessary. In one case, we raised a 13-cm vascularized tibial segment covered with foot skin for additional length. For the upper limb, the osteocutaneous transfer, based on the radial artery, was not reinnervated, but this lack of sensitivity did not impair prosthesis fitting. One vascular failure was finally amputated. This was the only unsuccessful result. For all other patients, the surgical procedure facilitated prosthesis fitting and preserved the proximal joint function despite an initially very proximal amputation. The advantages of partial replantation are obvious compared with simple terminalization or secondary reconstruction. There is no secondary donor site and, because there is no major muscle mass in the
Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; Bae, Taeok
2012-06-01
In Staphylococcus aureus, the SaeRS two-component system controls the expression of multiple virulence factors. Of the two promoters in the sae operon, P1 is autoinduced and has two binding sites for the response regulator SaeR. In this study, we examined the organizational requirements of the SaeR binding sites in P1 for transcription activation. Mutational studies showed that both binding sites are essential for binding to phosphorylated SaeR (P-SaeR) and transcription activation. When the 21-bp distance between the centers of the two SaeR binding sites was altered to 26 bp, 31 bp, 36 bp, or 41 bp, only the 31-bp mutant retained approximately 40% of the original promoter activity. When the -1-bp spacing (i.e.,1-bp overlap) between the primary SaeR binding site and the -35 promoter region was altered, all mutant P1 promoters failed to initiate transcription; however, when the first nucleotide of the -35 region was changed from A to T, the mutants with 0-bp or 22-bp spacing showed detectable promoter activity. Although P-SaeR was essential for the binding of RNA polymerase to P1, it was not essential for the binding of the enzyme to the alpha-hemolysin promoter. When the nonoptimal spacing between promoter elements in P1 or the coagulase promoter was altered to the optimal spacing of 17 bp, both promoters failed to initiate transcription. These results suggest that SaeR binding sites are under rather strict organizational restrictions and provide clues for understanding the molecular mechanism of sae-mediated transcription activation.
Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.
2017-01-01
Purpose: The purpose of this 2nd article in this supplement is to report validity support findings for the Pause Marker (PM), a proposed single-sign diagnostic marker of childhood apraxia of speech (CAS). Method: PM scores and additional perceptual and acoustic measures were obtained from 296 participants in cohorts with idiopathic and…
The Differential Effects of Social Media Sites for Promoting Cancer Risk Reduction.
Lauckner, Carolyn; Whitten, Pamela
2016-09-01
Social media are potentially valuable tools for disseminating cancer education messages, but the differential effects of various sites on persuasive outcomes are unknown. In an effort to inform future health promotion, this research tested the effects of Facebook, YouTube, Twitter, and blogs for delivering a cancer risk reduction message. Using an experimental design, participants were randomly placed in several conditions that delivered the same message but with different forms of social media. Effects on comprehension and attitudes were examined, as they are important variables in the behavior change process. YouTube led to higher comprehension and stronger attitudes toward cancer risk reduction than Twitter, but there were no differences between other sites. Additionally, YouTube led to stronger attitudes toward cancer risk reduction as compared to Facebook, but not any other sites. These results demonstrate that, even if the message is kept constant, the form of social media used to deliver content can have an effect on persuasive outcomes. More research is needed to determine the mechanisms behind the differences found, however. Altogether, this line of research is valuable for any individuals seeking to use social media for health promotion purposes and could have direct implications for the development of cancer risk reduction campaigns.
Energy Technology Data Exchange (ETDEWEB)
Ti, Shih-Chieh; Pamula, Melissa C.; Howes, Stuart C.; Duellberg, Christian; Cade, Nicholas I.; Kleiner, Ralph E.; Forth, Scott; Surrey, Thomas; Nogales, Eva; Kapoor, Tarun M.
2016-04-01
The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. In this research, we have purified and characterized tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.
von Thiele Schwarz, Ulrica; Augustsson, Hanna; Hasson, Henna; Stenfors-Hayes, Terese
2015-02-01
To test the effects of integrating health protection and health promotion with a continuous improvement system (Kaizen) on proximal employee outcomes (health promotion, integration, and Kaizen) and distal outcomes (workability, productivity, self-rated health and self-rated sickness absence). Twelve units in a county hospital in Sweden were randomized to control or intervention groups using a quasiexperimental study design. All staff (approximately 500) provided self-ratings in questionnaires at baseline, and a 12- and 24-month follow-up (response rate, 79% to 87.5%). There was a significant increase in the proximal outcomes over time in the intervention group compared with the control group, and a trend toward improvement in the distal outcomes workability and productivity. Integration seems to promote staff engagement in health protection and promotion, as well as to improve their understanding of the link between work and health.
Dahan, M; Anract, P; Babinet, A; Larousserie, F; Biau, D
2017-11-01
The proximal femuris is an uncommon site of osteosarcoma. The unusual manifestations at this site may lead to diagnostic and therapeutic mistakes. We therefore performed a retrospective study to estimate the proportions of patients with imaging study findings and/or clinical manifestations typical for osteosarcoma and/or inappropriate treatment decisions. Proximal femoral osteosarcoma often produces atypical clinical and radiological presentations. Consecutive patients who underwent surgery at our center to treat proximal femoral osteosarcoma were included. For each patient, we collected the epidemiological characteristics, clinical symptoms, imaging study findings, treatment, and tumor outcome. Proportions were computed with their confidence intervals. Twelve patients had surgery for proximal femoral osteosarcoma between 1986 and 2015. Imaging findings were typical in 1 (8%) patient; they consisted of ill-defined osteolysis in 11/12 (92%) patients, a periosteal reaction in 1/12 (8%) patient, soft tissue involvement in 7/12 (58%) patients, and immature osteoid matrix in 11/12 (92%) patients. No patient had the typical combination of pain with a soft tissue swelling. Management was inappropriate in 2/12 (17%) patients, who did not undergo all the recommended imaging studies before surgery and were treated in another center before the correct diagnosis was established. At last follow-up, 4 patients had died (after a mean of 7 years) and 8 were alive (after a mean of 4 years). Proximal femoral osteosarcoma is uncommon and rarely produces the typical clinical and imaging study findings. The atypical presentation often results in diagnostic errors and inappropriate treatments. Ill-defined osteolysis on standard radiographs should prompt computed tomography or magnetic resonance imaging of the proximal femur. Treatment in a specialized center is imperative. IV, retrospective study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Seal, S N; Davis, D L; Burch, J B
1991-05-01
The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.
A-type nuclear lamins act as transcriptional repressors when targeted to promoters
International Nuclear Information System (INIS)
Lee, Damian C.; Welton, K. Linnea; Smith, Erica D.; Kennedy, Brian K.
2009-01-01
Regions of heterochromatin are often found at the periphery of the mammalian nucleus, juxtaposed to the nuclear lamina. Genes in these regions are likely maintained in a transcriptionally silent state, although other locations at the nuclear periphery associated with nuclear pores are sites of active transcription. As primary components of the nuclear lamina, A- and B-type nuclear lamins are intermediate filament proteins that interact with DNA, histones and known transcriptional repressors, leading to speculation that they may promote establishment of repressive domains. However, no direct evidence of a role for nuclear lamins in transcriptional repression has been reported. Here we find that human lamin A, when expressed in yeast and cultured human cells as a fusion protein to the Gal4 DNA-binding domain (DBD), can mediate robust transcriptional repression of promoters with Gal4 binding sites. Full repression by lamin A requires both the coiled-coil rod domain and the C-terminal tail domain. In human cells, other intermediate filament proteins such as lamin B and vimentin are unable to confer robust repression as Gal4-DBD fusions, indicating that this property is specific to A-type nuclear lamins. These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter
Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding site.
Ulaganathan, Vijay K; Sperl, Bianca; Rapp, Ulf R; Ullrich, Axel
2015-12-24
Variant rs351855-G/A is a commonly occurring single-nucleotide polymorphism of coding regions in exon 9 of the fibroblast growth factor receptor FGFR4 (CD334) gene (c.1162G>A). It results in an amino-acid change at codon 388 from glycine to arginine (p.Gly388Arg) in the transmembrane domain of the receptor. Despite compelling genetic evidence for the association of this common variant with cancers of the bone, breast, colon, prostate, skin, lung, head and neck, as well as soft-tissue sarcomas and non-Hodgkin lymphoma, the underlying biological mechanism has remained elusive. Here we show that substitution of the conserved glycine 388 residue to a charged arginine residue alters the transmembrane spanning segment and exposes a membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3) binding site Y(390)-(P)XXQ(393). We demonstrate that such membrane-proximal STAT3 binding motifs in the germline of type I membrane receptors enhance STAT3 tyrosine phosphorylation by recruiting STAT3 proteins to the inner cell membrane. Remarkably, such germline variants frequently co-localize with somatic mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo. Thus, our findings elucidate the molecular mechanism behind the genetic association of rs351855 with accelerated cancer progression and suggest that germline variants of cell-surface molecules that recruit STAT3 to the inner cell membrane are a significant risk for cancer prognosis and disease progression.
Zulkifli, Putri Afzan Maria Binti
2013-01-01
Pause analysis is a method that investigates processes of writing by measuring the amount of time between pen strokes. It provides the field of second language studies with a means to explore the cognitive processes underpinning the nature of writing. This study examined the potential of using free handwritten copying of sentences as a means of investigating components of the cognitive processes of adults who have English as their Second Language (ESL).\\ud \\ud A series of one pilot and three ...
Diercks, Ron L.; Bain, Gregory; Itoi, Eiji; Di Giacomo, Giovanni; Sugaya, Hiroyuki
2015-01-01
This chapter describes the bony structures of the proximal humerus. The proximal humerus is often regarded as consisting of four parts, which assists in understanding function and, more specially, describes the essential parts in reconstruction after fracture or in joint replacement. These are the
Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.
2017-01-01
Purpose: The goal of this article (PM I) is to describe the rationale for and development of the Pause Marker (PM), a single-sign diagnostic marker proposed to discriminate early or persistent childhood apraxia of speech from speech delay. Method: The authors describe and prioritize 7 criteria with which to evaluate the research and clinical…
Derman, Serdar; Bardakçi, Mehmet; Öztürk, Mustafa Serkan
2017-01-01
Suprasegmental features are essential in conveying meaning; however, they are one of the neglected topics in teaching Turkish as a foreign/second language. This paper aims to examine read speech by Arabic students learning Turkish as a second language and describe their read speech in terms of stress and pause. Within this framework, 34 Syrian…
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Botella Luisa M
2010-06-01
Full Text Available Abstract Background Activin receptor-like kinase 1 (ALK1 is a Transforming Growth Factor-β (TGF-β receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1 give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. Results We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210 was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. Conclusions Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into
Belke, Terry W.
2011-01-01
The current study examined the variables that influence postreinforcement pause (PRP) duration in rats when wheel running serves as the reinforcing consequence. The relationship between revolutions and PRP duration when revolutions were manipulated within a session and the effect of changing the response requirement from fixed to variable on PRP…
Proximity detection system underground
Energy Technology Data Exchange (ETDEWEB)
Denis Kent [Mine Site Technologies (Australia)
2008-04-15
Mine Site Technologies (MST) with the support ACARP and Xstrata Coal NSW, as well as assistance from Centennial Coal, has developed a Proximity Detection System to proof of concept stage as per plan. The basic aim of the project was to develop a system to reduce the risk of the people coming into contact with vehicles in an uncontrolled manner (i.e. being 'run over'). The potential to extend the developed technology into other areas, such as controls for vehicle-vehicle collisions and restricting access of vehicle or people into certain zones (e.g. non FLP vehicles into Hazardous Zones/ERZ) was also assessed. The project leveraged off MST's existing Intellectual Property and experience gained with our ImPact TRACKER tagging technology, allowing the development to be fast tracked. The basic concept developed uses active RFID Tags worn by miners underground to be detected by vehicle mounted Readers. These Readers in turn provide outputs that can be used to alert a driver (e.g. by light and/or audible alarm) that a person (Tag) approaching within their vicinity. The prototype/test kit developed proved the concept and technology, the four main components being: Active RFID Tags to send out signals for detection by vehicle mounted receivers; Receiver electronics to detect RFID Tags approaching within the vicinity of the unit to create a long range detection system (60 m to 120 m); A transmitting/exciter device to enable inner detection zone (within 5 m to 20 m); and A software/hardware device to process & log incoming Tags reads and create certain outputs. Tests undertaken in the laboratory and at a number of mine sites, confirmed the technology path taken could form the basis of a reliable Proximity Detection/Alert System.
Novel Biosensor of Membrane Protein Proximity Based on Fluorogen Activated Proteins.
Vasilev, Kalin V; Gallo, Eugenio; Shank, Nathaniel; Jarvik, Jonathan W
2016-01-01
We describe a novel biosensor system for reporting proximity between cell surface proteins in live cultured cells. The biosensor takes advantage of recently developed fluorogen-activating proteins (FAPs) that display fluorescence only when bound to otherwise-nonfluorescent fluorogen molecules. To demonstrate feasibility for the approach, two recombinant rapamycin-binding proteins were expressed as single-pass plasma membrane proteins in HeLa cells; one of the proteins (scAvd- FRB) carried an extracellular avidin tag; the other (HL1-TO1-FKBP) carried an extracellular FAP. Cells were incubated with a membrane-impermeable bivalent ligand (biotin-PEG2000-DIR) consisting of biotin joined to a dimethyl-indole red (DIR) fluorogen by a polyethylene glycol linker, thus tethering the fluorogen to the scAvd-FRB fusion protein. Addition of rapamycin, which promotes FKBP-FRB dimerization and thereby brings the FAP in close proximity to the tethered fluorogen, led to a significant increase in DIR fluorescence. We call the new proximity assay TEFLA, for tethered fluorogen assay.
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Gary Jacobs
2014-03-01
Full Text Available This focused review article underscores how metal reduction promoters can impact deactivation phenomena associated with cobalt Fischer-Tropsch synthesis catalysts. Promoters can exacerbate sintering if the additional cobalt metal clusters, formed as a result of the promoting effect, are in close proximity at the nanoscale to other cobalt particles on the surface. Recent efforts have shown that when promoters are used to facilitate the reduction of small crystallites with the aim of increasing surface Co0 site densities (e.g., in research catalysts, ultra-small crystallites (e.g., <2–4.4 nm formed are more susceptible to oxidation at high conversion relative to larger ones. The choice of promoter is important, as certain metals (e.g., Au that promote cobalt oxide reduction can separate from cobalt during oxidation-reduction (regeneration cycles. Finally, some elements have been identified to promote reduction but either poison the surface of Co0 (e.g., Cu, or produce excessive light gas selectivity (e.g., Cu and Pd, or Au at high loading. Computational studies indicate that certain promoters may inhibit polymeric C formation by hindering C-C coupling.
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Seim Inge
2009-05-01
Full Text Available Abstract Background The murine ghrelin gene (Ghrl, originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0. We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. Findings 5' RACE revealed two transcription start sites (TSSs in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR, we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. Conclusion We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1 raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.
Heaney, Christopher D; Myers, Kevin; Wing, Steve; Hall, Devon; Baron, Dothula; Stewart, Jill R
2015-04-01
Swine farming has gone through many changes in the last few decades, resulting in operations with a high animal density known as confined animal feeding operations (CAFOs). These operations produce a large quantity of fecal waste whose environmental impacts are not well understood. The purpose of this study was to investigate microbial water quality in surface waters proximal to swine CAFOs including microbial source tracking of fecal microbes specific to swine. For one year, surface water samples at up- and downstream sites proximal to swine CAFO lagoon waste land application sites were tested for fecal indicator bacteria (fecal coliforms, Escherichia coli and Enterococcus) and candidate swine-specific microbial source-tracking (MST) markers (Bacteroidales Pig-1-Bac, Pig-2-Bac, and Pig-Bac-2, and methanogen P23-2). Testing of 187 samples showed high fecal indicator bacteria concentrations at both up- and downstream sites. Overall, 40%, 23%, and 61% of samples exceeded state and federal recreational water quality guidelines for fecal coliforms, E. coli, and Enterococcus, respectively. Pig-1-Bac and Pig-2-Bac showed the highest specificity to swine fecal wastes and were 2.47 (95% confidence interval [CI]=1.03, 5.94) and 2.30 times (95% CI=0.90, 5.88) as prevalent proximal down- than proximal upstream of swine CAFOs, respectively. Pig-1-Bac and Pig-2-Bac were also 2.87 (95% CI=1.21, 6.80) and 3.36 (95% CI=1.34, 8.41) times as prevalent when 48 hour antecedent rainfall was greater than versus less than the mean, respectively. Results suggest diffuse and overall poor sanitary quality of surface waters where swine CAFO density is high. Pig-1-Bac and Pig-2-Bac are useful for tracking off-site conveyance of swine fecal wastes into surface waters proximal to and downstream of swine CAFOs and during rain events. Copyright © 2014 Elsevier B.V. All rights reserved.
GATA-1 directly regulates Nanog in mouse embryonic stem cells
Energy Technology Data Exchange (ETDEWEB)
Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)
2015-09-25
Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.
Gordon, Tessa; Eva, Placheta; Borschel, Gregory H
2015-10-01
Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to 'protect' chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.
Fagan, Ernest Blake; Gibbons, Claire; Finnegan, Sean C; Petterson, Stephen; Peterson, Lars E; Phillips, Robert L; Bazemore, Andrew W
2015-02-01
The US Graduate Medical Education (GME) system is failing to produce primary care physicians in sufficient quantity or in locations where they are most needed. Decentralization of GME training has been suggested by several federal advisory boards as a means of reversing primary care maldistribution, but supporting evidence is in need of updating. We assessed the geographic relationship between family medicine GME training sites and graduate practice location. Using the 2012 American Medical Association Masterfile and American Academy of Family Physicians membership file, we obtained the percentage of family physicians in direct patient care located within 5, 25, 75, and 100 miles and within the state of their family medicine residency program (FMRP). We also analyzed the effect of time on family physician distance from training site. More than half of family physicians practice within 100 miles of their FMRP (55%) and within the same state (57%). State retention varies from 15% to 75%; the District of Columbia only retains 15% of family physician graduates, while Texas and California retain 75%. A higher percentage of recent graduates stay within 100 miles of their FMRP (63%), but this relationship degrades over time to about 51%. The majority of practicing family physicians remained proximal to their GME training site and within state. This suggests that decentralized training may be a part of the solution to uneven distribution among primary care physicians. State and federal policy-makers should prioritize funding training in or near areas with poor access to primary care services.
Functional analysis of human and chimpanzee promoters.
Heissig, Florian; Krause, Johannes; Bryk, Jaroslaw; Khaitovich, Philipp; Enard, Wolfgang; Pääbo, Svante
2005-01-01
It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.
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Minghua Xu
2014-01-01
Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.
Bahadur, Urvashi; Ganjam, Goutham K; Vasudevan, Nandini; Kondaiah, Paturu
2005-02-28
Estrogen is an important steroid hormone that mediates most of its effects on regulation of gene expression by binding to intracellular receptors. The consensus estrogen response element (ERE) is a 13bp palindromic inverted repeat with a three nucleotide spacer. However, several reports suggest that many estrogen target genes are regulated by diverse elements, such as imperfect EREs and ERE half sites (ERE 1/2), which are either the proximal or the distal half of the palindrome. To gain more insight into ERE half site-mediated gene regulation, we used a region from the estrogen-regulated chicken riboflavin carrier protein (RCP) gene promoter that contains ERE half sites. Using moxestrol, an analogue of estrogen and transient transfection of deletion and mutation containing RCP promoter/reporter constructs in chicken hepatoma (LMH2A) cells, we identified an estrogen response unit (ERU) composed of two consensus ERE 1/2 sites and one non-consensus ERE 1/2 site. Mutation of any of these sites within this ERU abolishes moxestrol response. Further, the ERU is able to confer moxestrol responsiveness to a heterologous promoter. Interestingly, RCP promoter is regulated by moxestrol in estrogen responsive human MCF-7 cells, but not in other cell lines such as NIH3T3 and HepG2 despite estrogen receptor-alpha (ER-alpha) co transfection. Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ERalpha antibody. Surprisingly, estrogen receptor cannot bind to these promoter elements in isolation. Thus, there appears to be a definite requirement for some other factor(s) in addition to estrogen receptor, for the generation of a suitable response of this promoter to estrogen. Our studies therefore suggest a novel mechanism of gene regulation by estrogen, involving ERE half sites without direct binding of ER to the
DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter
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Cominelli Eleonora
2011-11-01
Full Text Available Abstract Background We previously demonstrated that the Arabidopsis thaliana AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. AtMYB60 is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA. Results To investigate the molecular mechanisms governing AtMYB60 expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of AtMYB60 promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the AtMYB60 promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of AtMYB60 expression. Conclusions These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications.
Asthma, respiratory symptoms and lung function in children living near a petrochemical site.
Rovira, E.; Cuadras, A.; Aguilar, X.; Esteban, L.; Borràs-Santos, A.; Zock, J.P.; Sunyer, J.
2014-01-01
Residential proximity to environmental hazards has been related to adverse health outcomes. Respiratory health and allergies in children living near petrochemical sites have not been extensively studied. We evaluated the association between residential proximity to the petrochemical site of
Directory of Open Access Journals (Sweden)
Tessa Gordon
2015-01-01
Full Text Available Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ′protect′ chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.
Cabaroglu, Nese; Basaran, Suleyman; Roberts, Jon
2010-01-01
This study compares pauses, repetitions and recasts in matched task interactions under face-to-face and computer-mediated conditions. Six first-year English undergraduates at a Turkish University took part in Skype-based voice chat with a native speaker and face-to-face with their instructor. Preliminary quantitative analysis of transcripts showed…
Proximity credentials: A survey
International Nuclear Information System (INIS)
Wright, L.J.
1987-04-01
Credentials as a means of identifying individuals have traditionally been a photo badge and more recently, the coded credential. Another type of badge, the proximity credential, is making inroads in the personnel identification field. This badge can be read from a distance instead of being veiewed by a guard or inserted into a reading device. This report reviews proximity credentials, identifies the companies marketing or developing proximity credentials, and describes their respective credentials. 3 tabs
Francomano, Jesse A; Harpin, Scott B
2015-01-01
Social networking site use has exploded among youth in the last few years and is being adapted as an important tool for healthcare interventions and serving as a platform for adolescents to gain access to health information. The aim of this study was to examine the strengths, weaknesses, and best practices of utilizing Facebook in adolescent health promotion and research via pragmatic literature review. We also examine how sites can facilitate ethically sound healthcare for adolescents, particularly at-risk youth. We conducted a literature review of health and social sciences literature from the past 5 years related to adolescent health and social network site use. Publications were grouped by shared content then categorized by themes. Five themes emerged: access to healthcare information, peer support and networking, risk and benefits of social network site use in care delivery, overcoming technological barriers, and social network site interventions. More research is needed to better understand how such Web sites can be better utilized to provide access to adolescents seeking healthcare. Given the broad reach of social network sites, all health information must be closely monitored for accurate, safe distribution. Finally, consent and privacy issues are omnipresent in social network sites, which calls for standards of ethical use.
International Nuclear Information System (INIS)
Kiehl, Anita; Huang, Lili; Franchi, David; Anders, David G.
2003-01-01
The human cytomegalovirus (HCMV) UL57 gene lies adjacent to HCMV oriLyt, from which it is separated by an organizationally conserved, mostly noncoding region that is thought to both regulate UL57 expression and activate oriLyt function. However, the UL57 promoter has not been studied. We determined the 5' ends of UL57 transcripts toward an understanding of the potential relationship between UL57 expression and oriLyt activation. The results presented here identified three distinct 5' ends spread over 800 bp, at nt 90302, 90530, and 91138; use of these sites exhibited differential sensitivity to phosphonoformic acid treatment. Interestingly, a 10-kb UL57 transcript accumulated in cycloheximide-treated infected cells, even though other early transcripts were not detectable. However, the 10-kb transcript did not accumulate in cells treated with the more stringent translation inhibitor anisomycin. Consistent with the notion that the identified 5' ends arise from distinct transcription start sites, the sequences upstream of sites I and II functioned as promoters responsive to HCMV infection in transient assays. However, the origin-proximal promoter region III required downstream sequences for transcriptional activity. Mutation of candidate core promoter elements suggested that promoter III is regulated by an initiator region (Inr) and a downstream promoter element. Finally, a 42-bp sequence containing the candidate Inr activated a minimal oriLyt core construct in transient replication assays. Thus, these studies showed that a large, complex promoter region with novel features controls UL57 expression, and identified a sequence that regulates both UL57 transcription and oriLyt activation
Directory of Open Access Journals (Sweden)
Lu Ying
2004-04-01
Full Text Available Abstract Background TGM1(transglutaminase 1 is an enzyme that crosslinks the cornified envelope of mature keratinocytes. Appropriate expression of the TGM1 gene is crucial for proper keratinocyte function as inactivating mutations lead to the debilitating skin disease, lamellar ichthyosis. TGM1 is also expressed in squamous metaplasia, a consequence in some epithelia of vitamin A deficiency or toxic insult that can lead to neoplasia. An understanding of the regulation of this gene in normal and abnormal differentiation states may contribute to better disease diagnosis and treatment. Methods In vivo requirements for expression of the TGM1 gene were studied by fusing various lengths of promoter DNA to a reporter and injecting the DNA into mouse embryos to generate transgenic animals. Expression of the reporter was ascertained by Western blotting and immunohistochemistry. Further delineation of a transcriptionally important distal region was determined by transfections of progressively shortened or mutated promoter DNA into cultured keratinocytes. Results In vivo analysis of a reporter transgene driven by the TGM1 promoter revealed that 1.6 kilobases, but not 1.1 kilobases, of DNA was sufficient to confer tissue-specific and cell layer-specific expression. This same region was responsible for reporter expression in tissues undergoing squamous metaplasia as a response to vitamin A deprivation. Mutation of a distal promoter AP1 site or proximal promoter CRE site, both identified as important transcriptional elements in transfection assays, did not prevent appropriate expression. Further searching for transcriptional elements using electrophoretic mobility shift (EMSA and transfection assays in cultured keratinocytes identified two Sp1 elements in a transcriptionally active region between -1.6 and -1.4 kilobases. While mutation of either Sp1 site or the AP1 site singly had only a small effect, mutation of all three sites eliminated nearly all the
Politics, proximity and the pipeline: Mapping public attitudes toward Keystone XL
International Nuclear Information System (INIS)
Gravelle, Timothy B.; Lachapelle, Erick
2015-01-01
The politics of oil pipelines have become increasingly salient in American politics in recent years. In particular, debates about economic benefits, energy security and environmental impact have been provoked by the proposed Keystone XL pipeline expansion intended to take bitumen from northern Alberta in Canada to refineries on the Gulf Coast in Texas. Drawing on data from recent surveys conducted by the Pew Research Center, this article asks a series of questions. What levels of support for (and opposition to) the pipeline exist among the American public? What are the roles of political factors (such as party identification and ideology), economic attitudes, environmental attitudes and proximity to the proposed pipeline route in shaping attitudes toward the pipeline? And how do political factors and proximity to the pipeline interact? We find that partisanship and ideology drive attitudes toward the Keystone XL pipeline, and that the effect of ideology is attenuated by proximity to the proposed route. The policy implications of these findings for energy infrastructure siting controversies are discussed. -- Highlights: •Americans are divided on the Keystone XL energy pipeline. •Attitudes toward Keystone XL are driven by political party identification and ideology. •Attitudes toward the pipeline are also shaped by attitudes toward the economy and global warming. •The effect of proximity on attitudes toward Keystone XL is non-linear. •Spatial proximity to the pipeline attenuates the effect of ideology
A proximal point algorithm with generalized proximal distances to BEPs
Bento, G. C.; Neto, J. X. Cruz; Lopes, J. O.; Soares Jr, P. A.; Soubeyran, A.
2014-01-01
We consider a bilevel problem involving two monotone equilibrium bifunctions and we show that this problem can be solved by a proximal point method with generalized proximal distances. We propose a framework for the convergence analysis of the sequences generated by the algorithm. This class of problems is very interesting because it covers mathematical programs and optimization problems under equilibrium constraints. As an application, we consider the problem of the stability and change dyna...
Proximal hamstring morphology and morphometry in men: an anatomic and MRI investigation.
Storey, R N; Meikle, G R; Stringer, M D; Woodley, S J
2016-12-01
The proximal musculo-tendinous junction (MTJ) is a common site of hamstring strain injury but the anatomy of this region is not well defined. A morphometric analysis of the proximal MTJs of biceps femoris long head (BFlh), semitendinosus (ST), and semimembranosus (SM) was undertaken from dissection of 10 thighs from five male cadavers and magnetic resonance imaging of 20 thighs of 10 active young men. The length, volume, and cross-sectional area of the proximal tendon, MTJ and muscle belly, and muscle-tendon interface area were calculated. In both groups, MTJs were reconstructed three-dimensionally. The proximal tendons and MTJs were expansive, particularly within SM and BFlh. Morphology varied between muscles although length measurements within individual muscles were similar in cadavers and young men. Semimembranosus had the longest proximal tendon (cadavers: mean 33.6 ± 2.0 cm; young men: mean 31.7 ± 1.6 cm) and MTJ (>20 cm in both groups) and the greatest muscle-tendon interface area, followed by BFlh and ST. Mean muscle belly volumes were more than three times greater in young men than elderly male cadavers (P hamstring anatomy, an important factor in the pathogenesis of hamstring strain injury. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Synostosis of proximal phalangeal bases for loss of distal metacarpal
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Pankaj Jindal
2016-01-01
Full Text Available A finger rendered unstable due to loss of metacarpal head can be stabilized by creating a synostosis at the base of the proximal phalanx of the affected finger with the adjacent normal finger. A cortico cancellous graft bridges the two adjacent proximal phalanges at their bases which are temporarily stabilized with an external fixator. The procedure can be done for, recurrence of giant cell tumor of metacarpal and for traumatic metacarpal loss. The procedure and long term follow up of one patient is presented who had giant cell tumor. This option should be considered before offering ray amputation. There is no micro vascular surgery involved, nor is there any donor site morbidity. The graft heals well without any absorption. The affected finger shows excellent function in the long term followup.
Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld
Ferholt, Beth; Lecusay, Robert
2010-01-01
This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…
Albert, Béatrice; Matamoro-Vidal, Alexis; Raquin, Christian; Nadot, Sophie
2010-02-01
Pollen grains are generally surrounded by an extremely resistant wall interrupted in places by apertures that play a key role in reproduction; pollen tube growth is initiated at these sites. The shift from a proximal to distal aperture location is a striking innovation in seed plant reproduction. Reversals to proximal aperture position have only very rarely been described in angiosperms. The genus Tillandsia belongs to the Bromeliaceae family, and its aperture pattern has been described as distal monosulcate, the most widespread aperture patterns recorded in monocots and basal angiosperms. Here we report developmental and functional elements to demonstrate that the sulcate aperture in Tillandsia leiboldiana is not distal as previously described but proximal. Postmeitotic tetrad observation indicates unambiguously the proximal position of the sulcus, and in vitro germination of pollen grains confirms that the aperture is functional. This is the first report of a sulcate proximal aperture with proximal germination. The observation of microsporogenesis reveals specific features in the patterns of callose thickenings in postmeiotic tetrads.
Field, Ella; Bellum, John; Kletecka, Damon
2015-07-01
Reducing contamination is essential for producing optical coatings with high resistance to laser damage. One aspect of this principle is to make every effort to limit long interruptions during the coating's deposition. Otherwise, contamination may accumulate during the pause and become embedded in the coating after the deposition is restarted, leading to a lower laser-induced damage threshold (LIDT). However, pausing a deposition is sometimes unavoidable, despite our best efforts. For example, a sudden hardware or software glitch may require hours or even overnight to solve. In order to broaden our understanding of the role of embedded contamination on LIDT, and determine whether a coating deposited under such non-ideal circumstances could still be acceptable, this study explores how halting a deposition overnight impacts the LIDT, and whether ion cleaning can be used to mitigate any negative effects on the LIDT. The coatings investigated are a beam splitter design for high reflection at 1054 nm and high transmission at 527 nm, at 22.5° angle of incidence in S-polarization. LIDT tests were conducted in the nanosecond regime.
Proximal alveolar bone loss in a longitudinal radiographic investigation
International Nuclear Information System (INIS)
Lavstvedt, S.; Bolin, A.; Henrikson, C.O.; Carstensen, J.
1986-01-01
A longitudinal radiographic investigation was made of the progression of the proximal alveolar bone loss over a 10-year period (1970-1980). The material was unselected and consisted of 669 individuals in the county of Stockholm. 61 individuals were randomly selected for evaluation of a recording system using alternative methods of measurement, and 90% of the measurement sites could then be assessed. The correlations between some of the methods were high, such as between measurement of alveolar bone height and root length and between aleveolar bone height and tooth length. To reduce the number of measurements, a partial recording was made, giving a high correlation coefficient between the partial recording and total recording. When five measurement sites were used, the correlation coefficient was 0.96, and a slight increase of the coefficient was obtained when using additional sites
Hockett, Karen S; Marion, Jeffrey L; Leung, Yu-Fai
2017-12-01
Park and protected area managers are tasked with protecting natural environments, a particularly daunting challenge in heavily visited urban-proximate areas where flora and fauna are already stressed by external threats. In this study, an adaptive management approach was taken to reduce extensive off-trail hiking along a popular trail through an ecologically diverse and significant area in the Chesapeake and Ohio National Historical Park near Washington DC. Substantial amounts of off-trail hiking there had created an extensive 16.1 km network of informal (visitor-created) trails on a 39 ha island in the Potomac Gorge. A research design with additive treatments integrating educational and site management actions was applied and evaluated using self-reported behavior from an on-site visitor survey and unobtrusive observations of off-trail hiking behavior at two locations along the trail. Study treatments included: 1) trailhead educational signs developed using attribution theory and injunctive-proscriptive wording, 2) symbolic "no hiking" prompter signs attached to logs placed across all informal trails, 3) placement of concealing leaf litter and small branches along initial sections of informal trails, 4) restoration work on selected trails with low fencing, and 5) contact with a trail steward to personally communicate the trailhead sign information. The final, most comprehensive treatment reduced visitor-reported intentional off-trail hiking from 70.3% to 43.0%. Direct observations documented reduction in off-trail hiking from 25.9% to 2.0%. The educational message and site management actions both contributed to the decline in off-trail travel and the two evaluation methods enhanced our ability to describe the efficacy of the different treatments in reducing off-trail travel. Published by Elsevier Ltd.
Hockett, Karen; Marion, Jeff; Leung, Yu-Fai
2017-01-01
Park and protected area managers are tasked with protecting natural environments, a particularly daunting challenge in heavily visited urban-proximate areas where flora and fauna are already stressed by external threats. In this study, an adaptive management approach was taken to reduce extensive off-trail hiking along a popular trail through an ecologically diverse and significant area in the Chesapeake and Ohio National Historical Park near Washington DC. Substantial amounts of off-trail hiking there had created an extensive 16.1 km network of informal (visitor-created) trails on a 39 ha island in the Potomac Gorge. A research design with additive treatments integrating educational and site management actions was applied and evaluated using self-reported behavior from an on-site visitor survey and unobtrusive observations of off-trail hiking behavior at two locations along the trail. Study treatments included: 1) trailhead educational signs developed using attribution theory and injunctive-proscriptive wording, 2) symbolic “no hiking” prompter signs attached to logs placed across all informal trails, 3) placement of concealing leaf litter and small branches along initial sections of informal trails, 4) restoration work on selected trails with low fencing, and 5) contact with a trail steward to personally communicate the trailhead sign information. The final, most comprehensive treatment reduced visitor-reported intentional off-trail hiking from 70.3% to 43.0%. Direct observations documented reduction in off-trail hiking from 25.9% to 2.0%. The educational message and site management actions both contributed to the decline in off-trail travel and the two evaluation methods enhanced our ability to describe the efficacy of the different treatments in reducing off-trail travel.
Directory of Open Access Journals (Sweden)
Huynen Martijn A
2011-06-01
Full Text Available Abstract Background MicroRNAs (miRNAs play a fundamental role in the regulation of gene expression by translational repression or target mRNA degradation. Regulatory elements in miRNA promoters are less well studied, but may reveal a link between their expression and a specific cell type. Results To explore this link in myeloid cells, miRNA expression profiles were generated from monocytes and dendritic cells (DCs. Differences in miRNA expression among monocytes, DCs and their stimulated progeny were observed. Furthermore, putative promoter regions of miRNAs that are significantly up-regulated in DCs were screened for Transcription Factor Binding Sites (TFBSs based on TFBS motif matching score, the degree to which those TFBSs are over-represented in the promoters of the up-regulated miRNAs, and the extent of conservation of the TFBSs in mammals. Conclusions Analysis of evolutionarily conserved TFBSs in DC promoters revealed preferential clustering of sites within 500 bp upstream of the precursor miRNAs and that many mRNAs of cognate TFs of the conserved TFBSs were indeed expressed in the DCs. Taken together, our data provide evidence that selected miRNAs expressed in DCs have evolutionarily conserved TFBSs relevant to DC biology in their promoters.
Directory of Open Access Journals (Sweden)
Hastie C James
2006-01-01
Full Text Available Abstract Background Pim-1, 2 and 3 are a group of enzymes related to the calcium calmodulin family of protein kinases. Over-expression of Pim-1 and Pim-2 in mice promotes the development of lymphomas, and up-regulation of Pim expression has been observed in several human cancers. Results Here we show that the pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. In vitro mapping showed that Pim-2 predominantly phosphorylated Ser112, while Pim-1 phosphorylated Ser112, but also Ser136 and Ser155 at a reduced rate compared to Ser112. Pim-3 was found to be the least specific for Ser112, and the most effective at phosphorylating Ser136 and Ser155. Pim-3 was also able to phosphorylate other sites in Bad in vitro, including Ser170, another potential in vivo site. Mutation of Ser136 to alanine prevented the phosphorylation of Ser112 and Ser155 by Pim kinases in HEK-293 cells, suggesting that this site must be phosphorylated first in order to make the other sites accessible. Pim phosphorylation of Bad was also found to promote the 14-3-3 binding of Bad and block its association with Bcl-XL. Conclusion All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death.
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Mason Philip J
2004-06-01
Full Text Available Abstract Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC and aplastic anemia. Paroxysmal nocturnal hemoglobinuria (PNH is a clonal blood disorder associated with aplastic anemia and characterized by the presence of one or more clones of blood cells lacking glycosylphosphatidylinositol (GPI anchored proteins due to a somatic mutation in the PIGA gene. Methods We searched for mutations in DNA extracted from PNH patients by amplification of the hTERC gene and denaturing high performance liquid chromatography (dHPLC. After a mutation was found in a potential transcription factor binding site in one patient electrophoretic mobility shift assays were used to detect binding of transcription factors to that site. The effect of the mutation on the function of the promoter was tested by transient transfection constructs in which the promoter is used to drive a reporter gene. Results Here we report the finding of a novel promoter mutation (-99C->G in the hTERC gene in a patient with PNH. The mutation disrupts an Sp1 binding site and destroys its ability to bind Sp1. Transient transfection assays show that mutations in this hTERC site including C-99G cause either up- or down-regulation of promoter activity and suggest that the site regulates core promoter activity in a context dependent manner in cancer cells. Conclusions These data are the first report of an hTERC promoter mutation from a patient sample which can modulate core promoter activity in vitro, raising the possibility that the mutation may affect the transcription of the gene in hematopoietic stem cells in vivo, and that dysregulation of telomerase may play a role in the development of bone marrow failure and the evolution of PNH clones.
Modular endoprosthetic replacement for metastatic tumours of the proximal femur
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Carter Simon R
2008-11-01
Full Text Available Abstract Background and aims Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. Methods 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. Results and conclusion There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0–77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads. 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis was 83.1% with revision as end point. The mean TESS score was 64% (54%–82%. We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related
International Nuclear Information System (INIS)
Koenig, R.J.; Brent, G.A.; Warne, R.L.; Larsen, P.R.; Moore, D.D.
1987-01-01
Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. The authors have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. They show here that T3 receptor binds specifically to a site just upstream of the basal rGH promoter. This binding site includes two copies of a 7-base-pair direct repeat, the centers of which are separated by 10 base pairs. Deletions that specifically remove the T3 receptor binding site drastically reduce response to T3 in transient transfection experiments. These results demonstrate that T3 receptor can recognize specific DNA sequences and suggest that it can act directly as a positive transcriptional regulatory factor
What you find depends on where you look: responses to proximate habitat vary with landscape context
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Mary Ann Cunningham
2016-12-01
Full Text Available There is persistent interest in understanding responses of passerine birds to habitat fragmentation, but research findings have been inconsistent and sometimes contradictory in conclusions about how birds respond to characteristics of sites they occupy, such as habitat patch size or edge density. We examined whether these inconsistencies could result from differences in the amount of habitat in the surrounding landscape, e.g., for woodland birds, the amount of tree cover in the surrounding landscape. We compared responses of 22 woodland bird species to proximate-scale tree cover in open landscapes versus wooded landscapes. Our main expectation was that woodland birds would tolerate less suitable sites (less tree cover at the site scale in open environments where they had little choice-where little tree cover was available in the surrounding area. We compared responses using logistic regression coefficients and loess plots in open and wooded landscapes in eastern North Dakota, USA. Responses to proximate-scale tree cover were stronger, not weaker, as expected, in open landscapes. In some cases the sign of the response changed from positive to negative in contrasting landscapes. We draw two conclusions: First, observed responses to proximate habitat measures such as habitat extent or edge density cannot be interpreted reliably unless landscape context is specified. Second, birds appear more selective, not less so, where habitat is sparse. Habitat loss and fragmentation at the landscape scale are likely to reduce the usefulness of local habitat conservation, and regional drivers in land-use change can have important effects for site-scale habitat use.
The mechanical benefit of medial support screws in locking plating of proximal humerus fractures.
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Wen Zhang
Full Text Available BACKGROUND: The purpose of this study was to evaluate the biomechanical advantages of medial support screws (MSSs in the locking proximal humeral plate for treating proximal humerus fractures. METHODS: Thirty synthetic left humeri were randomly divided into 3 subgroups to establish two-part surgical neck fracture models of proximal humerus. All fractures were fixed with a locking proximal humerus plate. Group A was fixed with medial cortical support and no MSSs; Group B was fixed with 3 MSSs but without medial cortical support; Group C was fixed with neither medial cortical support nor MSSs. Axial compression, torsional stiffness, shear stiffness, and failure tests were performed. RESULTS: Constructs with medial support from cortical bone showed statistically higher axial and shear stiffness than other subgroups examined (P<0.0001. When the proximal humerus was not supported by medial cortical bone, locking plating with medial support screws exhibited higher axial and torsional stiffness than locking plating without medial support screws (P ≤ 0.0207. Specimens with medial cortical bone failed primarily by fracture of the humeral shaft or humeral head. Specimens without medial cortical bone support failed primarily by significant plate bending at the fracture site followed by humeral head collapse or humeral head fracture. CONCLUSIONS: Anatomic reduction with medial cortical support was the stiffest construct after a simulated two-part fracture. Significant biomechanical benefits of MSSs in locking plating of proximal humerus fractures were identified. The reconstruction of the medial column support for proximal humerus fractures helps to enhance mechanical stability of the humeral head and prevent implant failure.
Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and Zta
International Nuclear Information System (INIS)
Liu Pingfan; Speck, Samuel H.
2003-01-01
Expression of two Epstein-Barr virus (EBV) immediate-early gene products, Zta (encoded by the BZLF1 gene) and Rta (encoded by the BRLF1 gene), are required for the switch from latent infection to virus replication. We have analyzed the regions of the BRLF1 gene promoter (Rp) that are required for Rta and Zta transactivation of Rp. Notably, significant synergy between the actions of Rta and Zta on Rp was observed in both a B cell line (DG75) and an epithelial cell line (293), suggesting that during induction of the viral lytic cycle low levels of these viral transactivators are likely sufficient to initiate the entire lytic cascade. However, while two Zta binding sites (ZREs) have been identified in Rp, the proximal ZRE was the dominant site for mediating Zta transactivation. Rta activation of Rp was diminished by mutation of the proximal Sp1 binding site, as previously reported (J. Virol. 75 (2001), 5240), but mutation of this site only had a modest impact on transactivation of Rp by Rta in the presence of Zta. Further deletion analyses of Rp failed to identify a critical site for Rta transactivation of Rp in the presence of Zta, with the exception of deleting the TATAA box of Rp, suggesting that a non-DNA binding mechanism may be involved in the observed activation of Rp by Rta. We also observed promiscuous activation of several reporter constructs by Rta, suggesting that Rta activation of gene expression may involve a general non-DNA binding mechanism. Decreasing the amount of transfected Rta expression vector reduced background Rta activation, while retaining specific activation of Rp
DEFF Research Database (Denmark)
Büchel, Gabriele; Carstensen, Anne; Mak, Ka-Yan
2017-01-01
MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes in neuroblastoma cells. The analysis shows that N-MYC forms complexes...
Jurka, Jerzy W.
1997-01-01
Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.
International Nuclear Information System (INIS)
Kumar, K.P.; Chatterji, D.
1990-01-01
Terbium(III) upon complexation with guanosine 5'-triphosphate showed remarkable enhancement of fluorescence emission at 488 and 545 nm when excited at 295 nm. Analysis of the binding data yielded a value for the mean K d between Tb(III) and GTP of 0.2 μM, with three binding sites for TB(III) on GTP. 31 P and 1 H NMR measurements revealed that Tb(III) mainly binds the phosphate moiety of GTP. Fluorescence titration of the emission signals of the TbGTP complex with varying concentrations of Escherichia coli RNA polymerase resulted in a K d values of 4 μM between the TbGTP and the enzyme. It was observed that TbGTP can be incorporated in the place of GTP during E. coli RNA polymerase catalyzed abortive synthesis of dinucleotide tetraphosphate at T7A2 promoter. Both the substrate TbGTP and the inhibitor of the initiation of transcription rifampicin bind to the β-subunit of E. coli RNA polymerase. This allows the measurement of the fluorescence excited-state energy transfer from the donor TbGTP-RNA polymerase to the acceptor rifampicin. Both emission bands of Tb(III) overlap with the rifampicin absorption, and the distances at 50% efficiency of energy transfer were calculated to be 28 and 24 angstrom for the 488- and 545-nm emission bands, respectively. The distance between the substrate binding site and the rifampicin binding site on the β-subunit of E. coli RNA polymerase was measured to be around 30 angstrom. This suggest that the nature of inhibition of transcription by rifampicin is essentially noncompetitive with the substrate
Social Networking Sites and Self-Promotional Culture. Notes for a Theory of the Mosaic Identity
Directory of Open Access Journals (Sweden)
Lucía Caro Castaño
2017-05-01
Full Text Available This exploratory work theorizes about how social networking sites favor, as identity technologies, a way of conceiving and presenting individual identity in self-promotional terms. As a result of the normalization of this logic –which is coherent with the late capitalism’ promotional culture–, it is growing the incorporation of self-branding practices in the users's daily communication. Besides, it is increasing the perception of the social profiles as micro-media and the interpretation of the own network as a personal audience. In brief, four main trends in the presentation of identity which are promoted by these web services are identified: a distributed and fragmented conception of the self, where the tiles from mass media become key content to express subjectivity; a tendency to quantify relationships and affections; the perception of being in an unavoidable competition with others; and standardization of the audiovisual presentation of self as a communicative material capable of attracting attention and communicate authenticity.
Directory of Open Access Journals (Sweden)
Rachel M. Woodfint
2017-01-01
Full Text Available Identification of tissue- and stage-specific gene promoters is valuable for delineating the functional roles of specific genes in genetically engineered animals. Here, through the comparison of gene expression in different tissues by analysis of a microarray database, the intestinal specificity of mucin 2 (MUC2 expression was identified in mice and humans, and further confirmed in chickens by RT-PCR (reverse transcription-PCR analysis. An analysis of cis-acting elements in avian MUC2 gene promoters revealed conservation of binding sites, within a 2.9 kb proximal promoter region, for transcription factors such as caudal type homeobox 2 (CDX2, GATA binding protein 4 (GATA4, hepatocyte nuclear factor 4 α (HNF4A, and transcription factor 4 (TCF4 that are important for maintaining intestinal homeostasis and functional integrity. By generating transgenic quail, we demonstrated that the 2.9 kb chicken MUC2 promoter could drive green fluorescent protein (GFP reporter expression exclusively in the small intestine, large intestine, and ceca. Fluorescence image analysis further revealed GFP expression in intestine epithelial cells. The GFP expression was barely detectable in the embryonic intestine, but increased during post-hatch development. The spatiotemporal expression pattern of the reporter gene confirmed that the 2.9 kb MUC2 promoter could retain the regulatory element to drive expression of target genes in intestinal tissues after hatching. This new transgene expression system, using the MUC2 promoter, will provide a new method of overexpressing target genes to study gene function in the avian intestine.
PROXIMITY MANAGEMENT IN CRISIS CONDITIONS
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Ion Dorin BUMBENECI
2010-01-01
Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.
Dorman, Robert M; Vali, Kaveh; Harmon, Carroll M; Zaritzky, Mario; Bass, Kathryn D
2016-05-01
We describe the treatment of a patient with long-gap esophageal atresia with an upper pouch fistula, mircogastria and minimal distal esophageal remnant. After 4.5 months of feeding via gastrostomy, a proximal fistula was identified by bronchoscopy and a thoracoscopic modified Foker procedure was performed reducing the gap from approximately 7-5 cm over 2 weeks of traction. A second stage to ligate the fistula and suture approximate the proximal and distal esophagus resulted in a gap of 1.5 cm. IRB and FDA approval was then obtained for endoscopic placement of 10-French catheter mounted magnets in the proximal and distal pouches promoting a magnetic compression anastomosis (magnamosis). Magnetic coupling occurred at 4 days and after magnet removal at 13 days an esophagram demonstrated a 10 French channel without leak. Serial endoscopic balloon dilation has allowed drainage of swallowed secretions as the baby learns bottling behavior at home.
Surgical management of proximal splint bone fractures in the horse
International Nuclear Information System (INIS)
Peterson, P.R.; Pascoe, J.R.; Wheat, J.D.
1987-01-01
Fractures of Metacarpal and Metatarsal II and IV (the splint bones) were treated in 283 horses over an 11 year period. In 21 cases the proximal portion of the fractured bone was stabilized with metallic implants. One or more cortical bone screws were used in 11 horses, and bone plates were applied in 11 horses. One horse received both treatments. Complications of screw fixation included bone failure, implant failure, radiographic lucency around the screws, and proliferative new bone at the ostectomy site. Only two of the horses treated with screw fixation returned to their intended use. Complications of plate fixation included partial fixation failure (backing out of screws), wound drainage, and proliferative bony response around the plate. Six of the 11 horses treated by plate fixation returned to their intended use. The authors recommend consideration of plate fixation techniques for repair of fractures in the proximal third of the splint bone
Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.
McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G
2012-05-01
Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.
Directory of Open Access Journals (Sweden)
Lu Zheng
2009-09-01
Full Text Available Lu Zheng1, Guanghua Luo1, Xiaoying Zhang1, Jun Zhang1, Jiang Zhu1, Jiang Wei1, Qinfeng Mu1, Lujun Chen1, Peter Nilsson-Ehle2, Ning Xu21Comprehensive Laboratory, The Third Affiliated Hospital, Suzhou University, Changzhou China; 2Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, SwedenObjective: It has been reported that single-nucleotide polymorphism (SNP in the proximal promoter region of apolipoprotein M (apoM gene may confer the risk in the development of type 2 diabetes (T2D and coronary artery disease (CAD in the Han Chinese. However, in a recent study demonstrated that plasma apoM level did not correlated to the coronary heart disease. In the present studies, we investigated the SNP T-778C of apoM gene in CAD patients and controls in the Han Chinese population. Moreover we examined whether serum apoM levels could be influenced by this promoter mutation.Material and methods: One hundred twenty-six CAD patients and 118 non-CAD patients were subjected in the present study. All patients were confirmed by the angiography. The genotyping of polymorphisms T-778C in apoM promoter was determined by real-time polymerase chain reaction. Serum apoM levels were semi-quantitatively determined by the dot-blotting analysis. Results: Distribution of apoM T-778C genotype in non-CAD patients was as following: 84.7% were T/T, 15.3% were T/C and 0.0% was C/C. T allele frequencies were 92.4% and C allele, 7.6%. In the CAD patients, 99 patients (78.6% had the T/T genotype, 25 patients (19.8% with T/C genotype and 2 patients (1.6% with C/C genotype. The allele frequency was 88.5% for the T allele and 11.5% for the C allele. There was no statistical significant difference of serum apoM levels found in these three genotypes.Conclusions: There was no significant difference in allele or genotype frequencies between CAD patients and non-CAD patients. Binary logistic regression analysis with adjustments for age
Kim, Joon-Woo; Oh, Chang-Wug; Oh, Jong-Keon; Kyung, Hee-Soo; Park, Kyeong-Hyeon; Kim, Hee-June; Jung, Jae-Wook; Jung, Young-Soo
2017-06-01
High-energy proximal tibial fractures often accompany compartment syndrome and are usually treated by fasciotomy with external fixation followed by secondary plating. However, the initial soft tissue injury may affect bony union, the fasciotomy incision or external fixator pin sites may lead to postoperative wound infections, and the staged procedure itself may adversely affect lower limb function. We assess the results of staged minimally invasive plate osteosynthesis (MIPO) for proximal tibial fractures with acute compartment syndrome. Twenty-eight patients with proximal tibial fractures accompanied by acute compartment syndrome who underwent staged MIPO and had a minimum of 12 months follow-up were enrolled. According to the AO/OTA classification, 6 were 41-A, 15 were 41-C, 2 were 42-A and 5 were 42-C fractures; this included 6 cases of open fractures. Immediate fasciotomy was performed once compartment syndrome was diagnosed and stabilization of the fracture followed using external fixation. After the soft tissue condition normalized, internal conversion with MIPO was done on an average of 37 days (range, 9-158) after index trauma. At the time of internal conversion, the external fixator pin site grades were 0 in 3 cases, 1 in 12 cases, 2 in 10 cases and 3 in 3 cases, as described by Dahl. Radiographic assessment of bony union and alignment and a functional assessment using the Knee Society Score and American Orthopedic Foot and Ankle Society (AOFAS) score were carried out. Twenty-six cases achieved primary bony union at an average of 18.5 weeks. Two cases of nonunion healed after autogenous bone grafting. The mean Knee Society Score and the AOFAS score were 95 and 95.3 respectively, at last follow-up. Complications included 1 case of osteomyelitis in a patient with a grade IIIC open fracture and 1 case of malunion caused by delayed MIPO due to poor wound conditions. Duration of external fixation and the external fixator pin site grade were not related to the
Uncemented allograft-prosthetic composite reconstruction of the proximal femur
Directory of Open Access Journals (Sweden)
Li Min
2014-01-01
Full Text Available Background: Allograft-prosthetic composite can be divided into three groups names cemented, uncemented, and partially cemented. Previous studies have mainly reported outcomes in cemented and partially cemented allograft-prosthetic composites, but have rarely focused on the uncemented allograft-prosthetic composites. The objectives of our study were to describe a surgical technique for using proximal femoral uncemented allograft-prosthetic composite and to present the radiographic and clinical results. Materials and Methods: Twelve patients who underwent uncemented allograft-prosthetic composite reconstruction of the proximal femur after bone tumor resection were retrospectively evaluated at an average followup of 24.0 months. Clinical records and radiographs were evaluated. Results: In our series, union occurred in all the patients (100%; range 5-9 months. Until the most recent followup, there were no cases with infection, nonunion of the greater trochanter, junctional bone resorption, dislocation, allergic reaction, wear of acetabulum socket, recurrence, and metastasis. But there were three periprosthetic fractures which were fixed using cerclage wire during surgery. Five cases had bone resorption in and around the greater trochanter. The average Musculoskeletal Tumor Society (MSTS score and Harris hip score (HHS were 26.2 points (range 24-29 points and 80.6 points (range 66.2-92.7 points, respectively. Conclusions: These results showed that uncemented allograft-prosthetic composite could promote bone union through compression at the host-allograft junction and is a good choice for proximal femoral resection. Although this technology has its own merits, long term outcomes are yet not validated.
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Ana Tobar
Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity
DEVELOPMENT OF A WEB-BASED PROXIMITY BASED MEDIA SHARING APPLICATION
Erol Ozan
2016-01-01
This article reports the development of Vissou, which is a location based web application that enables media recording and sharing among users who are in close proximity to each other. The application facilitates the automated hand-over of the recorded media files from one user to another. There are many social networking applications and web sites that provide digital media sharing and editing functionalities. What differentiates Vissou from other similar applications is the functions and us...
Fractures of the proximal humerus
DEFF Research Database (Denmark)
Brorson, Stig
2013-01-01
Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis...
Transcriptional regulation of HIV-1 host factor COMMD1 by the Sp family.
Kudo, Eriko; Taura, Manabu; Suico, Mary Ann; Goto, Hiroki; Kai, Hirofumi; Okada, Seiji
2018-04-01
Copper metabolism Murr1 domain containing 1 (COMMD1) has multiple functions in the regulation of protein stability at the plasma membrane and in the cytoplasm. However, the regulation of COMMD1 transcriptional has remained to be elucidated. In the present study, the 5'‑flanking region (‑1,192/+83 bp) of the human COMMD1 gene was cloned. It was observed that the COMMD1 promoter region contains GC‑rich region that has 7 putative Sp1‑binding sites via in silico analysis. The proximal promoter region at ‑289/+83 bp was required for COMMD1 basal promoter activity by deletion constructs of COMMD1 promoter. Moreover, Sp1 inhibitor, mithramycin A, suppressed basal COMMD1 promoter activity. The Sp1‑binding site (‑11/‑1 bp) in the proximal promoter region was a critical site for COMMD1 gene regulation by Sp1 and Sp3. Sp1 upregulated COMMD1 promoter activity, whereas Sp3 suppressed it. Endogenous Sp1 and Sp3 bound to the proximal promoter region of COMMD1. Taken together, Sp1 constitutively regulates the basal expression of the COMMD1 gene in human epithelial cell lines.
Hazardous waste sites and housing appreciation rates
McCluskey, Jill Jennifer; Rausser, Gordon C
2000-01-01
The dynamic effect of a hazardous waste site is analyzed by investigating the causal relationship between housing appreciation rates and house location in relation to a hazardous waste site using resale data from individual sales transactions in Dallas County, Texas. The results indicate that in the period in which the hazardous waste site was identified and cleanup occurred, residential property owners in close proximity to the hazardous waste site experienced lower housing appreciation rate...
Comparative analyses of bidirectional promoters in vertebrates
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Taylor James
2008-05-01
Full Text Available Abstract Background Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.
International Nuclear Information System (INIS)
Zhang Zhiming; Zhu Xuesong; Bao Zhaohua; Yang Huilin
2012-01-01
Objective: to explore the initial outcome and efficacy of S 3 proximal humerus locking plate in the treatment of proximal humerus fractures. Methods: Twenty-two patients with proximal humerus fracture were treated with the S 3 proximal humerus locking plate. Most of the fractures were complex, two-part (n=4), three-part (n=11) and four-part (n=7) fractures according to the Neer classification of the proximal humerus fractures. Results: All patients were followed up for 3∼15 months. There were no complications related to the implant including loosening or breakage of the plate. Good and excellent results were documented in 17 patients fair results in 4 patients according the Neer scores of shoulder. Conclusion: New design concepts of S 3 proximal humerus plate provide the subchondral support and the internal fixation support. With the addition of the proper exercise of the shoulder joint, the outcomes would be satisfied. (authors)
The Clinch Bend Regional Industrial Site and economic development opportunities
Energy Technology Data Exchange (ETDEWEB)
NONE
1995-12-31
This effort focuses initially on the Clinch Bend site. Other sites and developable tracts of land are identified with the assistance of communities in proximity to Oak Ridge, the State of Tennessee, and others, and compared with the projected site requirements for large industrial facilities.
International Nuclear Information System (INIS)
Stein, G.; Lian, J.; Stein, J.; Shalhoub, V.; Wright, K.; Pauli, U.; Van Wijnen, A.; Briggs, R.
1989-01-01
Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report the authors demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. The results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level
Seidenstricker, Chad L; Blahous, Edward G; Bouché, Richard T; Saxena, Amol
Metaphyseal and proximal diaphyseal fractures of the lateral column metatarsals can have problems with healing. In particular, those involving the fifth metatarsal have been associated with a high nonunion rate with nonoperative treatment. Although intramedullary screw fixation results in a high union rate, delayed healing and complications can occur. We describe an innovative technique to treat both acute and chronic injuries involving the metatarsal base from the metaphysis to the proximal diaphyseal bone of the fourth and fifth metatarsals. The surgical technique involves evacuation of sclerotic bone at the fracture site, packing the fracture site with compact cancellous bone, and plate fixation. In our preliminary results, 4 patients displayed 100% radiographic union at a mean of 4.75 (range 4 to 6) weeks with no incidence of refracture, at a mean follow-up point of 3.5 (range 1 to 5) years. The early results with our small series suggest that this technique is a useful treatment choice for metaphyseal and proximal diaphyseal fractures of the fourth and fifth metatarsals. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
Preliminary study on leadership proximity
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Ghinea Valentina Mihaela
2017-07-01
Full Text Available In general, it is agreed that effective leadership requires a certain degree of proximity, either physical or mental, which enables leaders to maintain control over their followers and communicate their vision. Although we agree with the leadership proximity principles which states that leaders are able to efficiently serve only those people with whom they interact frequently, in this article we focus instead on the disadvantages of being too close and the way in which close proximity can actually hurt the effectiveness of leadership. The main effects that we discuss regard the way in which proximity and familiarity allow followers to see the weaknesses and faults of the leader much more easily and thus diminish the leader’s heroic aura, and the emotional bias that results from a leader being too familiar with his followers which will impede the process of rational decision making. As a result, we argue that there exists a functional proximity which allows the leader the necessary space in which to perform effective identity work and to hide the backstage aspects of leadership, while also allowing him an emotional buffer zone which will enable him to maintain the ability to see clearly and make rational decisions.
Identification of evolutionarily invariant sequences in the protein C gene promoter
Spek, C. A.; Bertina, R. M.; Reitsma, P. H.
1998-01-01
Recent studies on human protein C gene expression have revealed the presence of three transcription factor binding sites in close proximity to the transcription start site. Binding sites for the liver-enriched hepatocyte nuclear factors 1 and 3 (HNF-1 and HNF-3, respectively) are located immediately
ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.
Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique
2016-07-15
The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.
Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral
2012-04-01
The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.
ProxImaL: efficient image optimization using proximal algorithms
Heide, Felix; Diamond, Steven; Nieß ner, Matthias; Ragan-Kelley, Jonathan; Heidrich, Wolfgang; Wetzstein, Gordon
2016-01-01
domain-specific language and compiler for image optimization problems that makes it easy to experiment with different problem formulations and algorithm choices. The language uses proximal operators as the fundamental building blocks of a variety
Masuda, Sawako; Namba, Kazunori; Mutai, Hideki; Usui, Satoko; Miyanaga, Yuko; Kaneko, Hiroki; Matsunaga, Tatsuo
2014-05-09
The access of bone morphogenetic protein (BMP) to the BMP receptors on the cell surface is regulated by its antagonist noggin, which binds to heparan-sulfate proteoglycans on the cell surface. Noggin is encoded by NOG and mutations in the gene are associated with aberrant skeletal formation, such as in the autosomal dominant disorders proximal symphalangism (SYM1), multiple synostoses syndrome, Teunissen-Cremers syndrome, and tarsal-carpal coalition syndrome. NOG mutations affecting a specific function may produce a distinct phenotype. In this study, we investigated a Japanese pedigree with SYM1 and conductive hearing loss and found that it carried a novel heterozygous missense mutation of NOG (c.406C>T; p.R136C) affecting the heparin-binding site of noggin. As no mutations of the heparin-binding site of noggin have previously been reported, we investigated the crystal structure of wild-type noggin to investigate molecular mechanism of the p.R136C mutation. We found that the positively charged arginine at position 136 was predicted to be important for binding to the negatively charged heparan-sulfate proteoglycan (HSPG). An in silico docking analysis showed that one of the salt bridges between noggin and heparin disappeared following the replacement of the arginine with a non-charged cysteine. We propose that the decreased binding affinity of NOG with the p.R136C mutation to HSPG leads to an excess of BMP signaling and underlies the SYM1 and conductive hearing loss phenotype of carriers. Copyright © 2014 Elsevier Inc. All rights reserved.
Moreau, Morgane J J; Schaeffer, Patrick M
2012-10-01
In E. coli, DNA replication termination occurs at Ter sites and is mediated by Tus. Two clusters of five Ter sites are located on each side of the terminus region and constrain replication forks in a polar manner. The polarity is due to the formation of the Tus-Ter-lock intermediate. Recently, it has been shown that DnaB helicase which unwinds DNA at the replication fork is preferentially stopped at the non-permissive face of a Tus-Ter complex without formation of the Tus-Ter-lock and that fork pausing efficiency is sequence dependent, raising two essential questions: Does the affinity of Tus for the different Ter sites correlate with fork pausing efficiency? Is formation of the Tus-Ter-lock the key factor in fork pausing? The combined use of surface plasmon resonance and GFP-Basta showed that Tus binds strongly to TerA-E and G, moderately to TerH-J and weakly to TerF. Out of these ten Ter sites only two, TerF and H, were not able to form significant Tus-Ter-locks. Finally, Tus's resistance to dissociation from Ter sites and the strength of the Tus-Ter-locks correlate with the differences in fork pausing efficiency observed for the different Ter sites by Duggin and Bell (2009).
Outreach for Outreach: Targeting social media audiences to promote a NASA kids’ web site
Pham, C. C.
2009-12-01
The Space Place is a successful NASA web site that benefits upper elementary school students and educators by providing games, activities, and resources to stimulate interest in science, technology, engineering, and mathematics, as well as to inform the audience of NASA’s contributions. As online social networking grows to be a central component of modern communication, The Space Place has explored the benefits of integrating social networks with the web site to increase awareness of materials the web site offers. This study analyzes the capabilities of social networks, and specifically the demographics of Twitter and Facebook. It then compares these results with the content, audience, and perceived demographics of The Space Place web site. Based upon the demographic results, we identified a target constituency that would benefit from the integration of social networks into The Space Place web site. As a result of this study, a Twitter feed has been established that releases a daily tweet from The Space Place. In addition, a Facebook page has been created to showcase new content and prompt interaction among fans of The Space Place. Currently, plans are under way to populate the Space Place Facebook page. Each social network has been utilized in an effort to spark excitement about the content on The Space Place, as well as to attract followers to the main NASA Space Place web site. To pursue this idea further, a plan has been developed to promote NASA Space Place’s social media tools among the target audience.
PROXIMAL DISABILITY AND SPINAL DEFORMITY INDEX IN PATIENTS WITH PROXIMAL FEMUR FRACTURES
Directory of Open Access Journals (Sweden)
Sylvio Mistro Neto
2015-12-01
Full Text Available Objective : To evaluate the quality of life related to the spine in patients with proximal femoral fractures. Methods : Study conducted in a tertiary public hospital in patients with proximal femoral fractures caused by low-energy trauma, through the Oswestry Disability Index questionnaire to asses complaints related to the spine at the time of life prior to the femoral fracture. The thoracic and lumbar spine of patients were also evaluated applying the radiographic index described by Gennant (Spinal Deformity Index, which assesses the number and severity of fractures. Results : Seventeen subjects completed the study. All had some degree of vertebral fracture. Patients were classified in the categories of severe and very severe disability in the questionnaire about quality of life. It was found that the higher SDI, the better the quality of life. Conclusion : There is a strong association of disability related to the spine in patients with proximal femoral fracture, and this complaint must be systematically evaluated in patients with appendicular fracture.
Filled pause refinement based on the pronunciation probability for lecture speech.
Directory of Open Access Journals (Sweden)
Yan-Hua Long
Full Text Available Nowadays, although automatic speech recognition has become quite proficient in recognizing or transcribing well-prepared fluent speech, the transcription of speech that contains many disfluencies remains problematic, such as spontaneous conversational and lecture speech. Filled pauses (FPs are the most frequently occurring disfluencies in this type of speech. Most recent studies have shown that FPs are widely believed to increase the error rates for state-of-the-art speech transcription, primarily because most FPs are not well annotated or provided in training data transcriptions and because of the similarities in acoustic characteristics between FPs and some common non-content words. To enhance the speech transcription system, we propose a new automatic refinement approach to detect FPs in British English lecture speech transcription. This approach combines the pronunciation probabilities for each word in the dictionary and acoustic language model scores for FP refinement through a modified speech recognition forced-alignment framework. We evaluate the proposed approach on the Reith Lectures speech transcription task, in which only imperfect training transcriptions are available. Successful results are achieved for both the development and evaluation datasets. Acoustic models trained on different styles of speech genres have been investigated with respect to FP refinement. To further validate the effectiveness of the proposed approach, speech transcription performance has also been examined using systems built on training data transcriptions with and without FP refinement.
Costs of promoting exclusive breastfeeding at community level in three sites in South Africa.
Directory of Open Access Journals (Sweden)
Lungiswa Leonora Nkonki
Full Text Available Community-based peer support has been shown to be effective in improving exclusive breastfeeding rates in a variety of settings.We conducted a cost analysis of a community cluster randomised-controlled trial (Promise-EBF, aimed at promoting exclusive infant feeding in three sites in South Africa. The costs were considered from the perspective of health service providers. Peer supporters in this trial visited women to support exclusive infant feeding, once antenatally and four times postpartum.The total economic cost of the Promise-EBF intervention was US$393 656, with average costs per woman and per visit of US$228 and US$52, respectively. The average costs per woman and visit in an operational 'non research' scenario were US$137 and US$32 per woman and visit, respectively. Investing in the promotion of exclusive infant feeding requires substantial financial commitment from policy makers. Extending the tasks of multi-skilled community health workers (CHWs to include promoting exclusive infant feeding is a potential option for reducing these costs. In order to avoid efficiency losses, we recommend that the time requirements for delivering the promotion of exclusive infant feeding are considered when integrating it within the existing activities of CHWs.This paper focuses on interventions for exclusive infant feeding, but its findings more generally illustrate the importance of documenting and quantifying factors that affect the feasibility and sustainability of community-based interventions, which are receiving increased focus in low income settings.
hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.
Directory of Open Access Journals (Sweden)
Shunsuke Ohnishi
Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.
ProxImaL: efficient image optimization using proximal algorithms
Heide, Felix
2016-07-11
Computational photography systems are becoming increasingly diverse, while computational resources-for example on mobile platforms-are rapidly increasing. As diverse as these camera systems may be, slightly different variants of the underlying image processing tasks, such as demosaicking, deconvolution, denoising, inpainting, image fusion, and alignment, are shared between all of these systems. Formal optimization methods have recently been demonstrated to achieve state-of-the-art quality for many of these applications. Unfortunately, different combinations of natural image priors and optimization algorithms may be optimal for different problems, and implementing and testing each combination is currently a time-consuming and error-prone process. ProxImaL is a domain-specific language and compiler for image optimization problems that makes it easy to experiment with different problem formulations and algorithm choices. The language uses proximal operators as the fundamental building blocks of a variety of linear and nonlinear image formation models and cost functions, advanced image priors, and noise models. The compiler intelligently chooses the best way to translate a problem formulation and choice of optimization algorithm into an efficient solver implementation. In applications to the image processing pipeline, deconvolution in the presence of Poisson-distributed shot noise, and burst denoising, we show that a few lines of ProxImaL code can generate highly efficient solvers that achieve state-of-the-art results. We also show applications to the nonlinear and nonconvex problem of phase retrieval.
Directory of Open Access Journals (Sweden)
Shimrat Mamrut
Full Text Available Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.
Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.
2017-01-01
Purpose: Previous articles in this supplement described rationale for and development of the pause marker (PM), a diagnostic marker of childhood apraxia of speech (CAS), and studies supporting its validity and reliability. The present article assesses the theoretical coherence of the PM with speech processing deficits in CAS. Method: PM and other…
Quality of life and community satisfaction in proximity to hazardous waste
International Nuclear Information System (INIS)
Williams, R.G.; Olshansky, S.J.
1986-01-01
The NIMBY Syndrome (Not In My Back Yard) characterizes the social and political problems associated with siting hazardous waste facilities. given a rational choice, everyone would prefer than hazardous wastes be located somewhere other than in their own backyard. While there has not been enough research that addresses the social and political effects of having a hazardous waste site located near communities, there have been qualitative case studies, anecdotal evidence, and environmental disasters such as Times Beach and Love Canal that would lead one to believe that hazardous waste sites are disruptive to communities. Media coverage of hazardous waste sites would lead one to believe that the majority of people in proximity to such sites are distraught, economic development in the area is negatively effected, property values decline, and in general, satisfaction with one's community suffers and quality of life decreases. Yet, social science research on this topic is essentially nonexistent. In fact, to date there is no published research that puts hazardous waste in to the larger theoretical context of community satisfaction and quality of life
Dual-energy radiographic absorptiometry of the lumbar spine and proximal femur
International Nuclear Information System (INIS)
Moscona, A.; Gundry, C.; Sartoris, D.J.; Barrett-Connor, E.; Stein, J.A.; Resnick, D.
1988-01-01
Dual-energy radiographic absorptiometry (DRA), dual-photon absorptiometry (DPA), and single-photon absorptiometry (SPA) were used for comprehensive densitometry of 500 men and women aged 65-100 years, within an epidemiologic study of osteoporosis risk factors. DRA and DPA of the lumbar spine (L1-L4) and proximal femur were performed with a Hologic QDR-100 system and a Lunar DP3 system, respectively, and SPA of the 33% shaft and ultradistal forearm sites was performed with a Lunar SP2 system. DRA and DPA results showed high correlation at both sites (tau=.9,P<.001); data conversion factors were derived. SPA results for the ultradistal site correlated better with vertebral and femoral density (tau=.6,P<.1) than did those for the shaft site (tau=.4,P<.5) but neither forearm measurement was reliable predictive of axial mineral status. The various measurements displayed an age-dependent interrelationship. The DRA method offers the advantage of short examination times (about 5 minutes per site) and high precision (about 1%)
Diagnosis of false proximal anastomosis aneurysms after aortofemoral reconstructive operations
International Nuclear Information System (INIS)
Pokrovskij, A.V.; Dan, V.N.; Karazeev, G.L.
1993-01-01
The paper deals with the diagnostic aspects of false aneurysms of proximal anastomosis of prostheses with the aorta on the basis of examination of 9 patients aged 3-65 years after aortofemoral reconstructive operations. The periods of the occurrence of false aneurysms were 2 weeks to 6 years. The causes of anastomosis aneurysms: infection, endartectomy fro the aorta at the site of applied anastomosis, progressive underlying disease. The authors provide strong evidence for a high informative value of various examinations, including ultrasound echoscanning, computer tomography, radioopaque aortography
Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z
2016-10-01
The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.
Alam, Tanvir
2014-10-02
Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.
International Nuclear Information System (INIS)
Yang, Min; Li, Wei; Liu, Yi-Ying; Fu, Shuang; Qiu, Guang-Bin; Sun, Kai-Lai; Fu, Wei-Neng
2012-01-01
MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (−695 to −692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (−852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (−852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (−852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (−695 to −692) site prevented c-Myc from binding of the site and demethylation treatment of the 5′ flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). In summary, this study concluded that hypermethylation contributed to the transcriptional down
Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...
Low-grade central osteosarcoma in proximal humerus: a rare entity
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Tang F
2017-10-01
Full Text Available Fan Tang,1,2 Li Min,1,2 Yong Zhou,1 Yi Luo,1 Chongqi Tu1 1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA Abstract: Low-grade central osteosarcoma is a rare subtype of tumor with low-grade malignancy. Currently, wide resection with negative resection margin is the standard treatment for this disease. The role of neoadjuvant chemotherapy in low-grade central osteosarcoma was controversial and was mostly considered for tumors containing high-grade focal areas. Local tumor recurrences often exhibited a tumor with higher histologic grade or differentiation with the potential for metastases. In low-grade central osteosarcoma, timely wide resection after definite diagnosis can result in 5-year survival for almost 90%. However, the relatively nonspecific radiological and pathological findings make diagnosis very difficult. MDM2 and CDK4 are specific and provide sensitive markers for the diagnosis of low-grade central osteosarcoma, helping to differentiate low-grade central osteosarcoma from some benign lesions, including fibrous dysplasia, bone giant cell tumor, and chondrosarcoma. Here, we report the case of a 19-year-old woman with low-grade central osteosarcoma located at the proximal humerus. The affected site was rare, but the sensitive biomarkers CDK4 and MDM2 were positive. The patient recovered well after wide tumor resection following a proximal humerus endoprosthesis replacement. Our case highlighted the management strategies in low-grade central osteosarcoma. Being familiar with radiographic features, understanding the biological characteristics, and mastering diagnostic biomarkers can help oncologists avoid embarrassing situations in treatment when this rare tumor is highly suspected, even when located at an uncommon site. The discussion in this report
On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.
Long, Marcus J C; Poganik, Jesse R; Aye, Yimon
2016-03-23
Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.
Neighborhoods and manageable proximity
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Stavros Stavrides
2011-08-01
Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.
Digital contrast subtraction radiography for proximal caries diagnosis
International Nuclear Information System (INIS)
Kang, Byung Cheol; Yoon, Suk Ja
2002-01-01
To determine whether subtraction images utilizing contrast media can improve the diagnostic performance of proximal caries diagnosis compared to conventional periapical radiographic images. Thirty-six teeth with 57 proximal surfaces were radiographied using a size no.2 RVG-ui sensor (Trophy Radiology, Marne-la-Vallee, France). The teeth immersed in water-soluble contrast media and subtraction images were taken. Each tooth was then sectioned for histologic examination. The digital radiographic images and subtraction images were examined and interpreted by three dentists for proximal caries. The results of the proximal caries diagnosis were then verified with the results of the histologic examination. The proximal caries sensitivity using digital subtraction radiography was significantly higher than simply examining a single digital radiograph. The sensitivity of the proximal dentinal carious lesion when analyzed with the subtraction radiograph and the radiograph together was higher than with the subtraction radiograph or the radiograph alone. The use of subtraction radiography with contrast media may be useful for detecting proximal dentinal carious lesions.
Characterization of a Suppressive Cis-acting Element in the Epstein–Barr Virus LMP1 Promoter
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Masahiro Yoshida
2017-11-01
Full Text Available Latent membrane protein 1 (LMP1 is a major oncogene encoded by Epstein–Barr virus (EBV and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited increased LMP1 expression and EBV-mediated immortalization of B cells. However, single mutations of either the E-box or Ikaros sites had limited effects on LMP1 expression and transformation. Our results suggest that this region contains a suppressive cis-regulatory element, but other transcriptional repressors (apart from the E-box and Ikaros transcription factors may remain to be discovered.
Chondrosarcoma of the Proximal Phalanx of the Fourth Digit: A Rare Location
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Thivi Vasilakaki
2012-10-01
Full Text Available Introduction: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. The small bones of the hands and feet are rarely involved by primary chondrosarcoma. Proximal phalanges are the most common sites in the hands, but the fourth digit is the least common site. Case Presentation: We report a case of a 76-year-old Greek female who presented to our hospital with a painful swollen mass measuring 4.5 × 2.6 cm on the fourth digit of the left hand. The radiograph showed a destructive, permeative lytic tumor of the proximal phalanx with extension into soft tissue. The patient underwent curettage, and the microscopic examination of the specimen revealed grade 2 chondrosarcoma. Conclusion: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. Primary chondrosarcoma is the third most common malignancy of bone after myeloma and osteosarcoma, but the small bones of the hands and feet are very rarely involved by chondrosarcoma (1% of all chondrosarcoma. However, in these cases differentiation between a benign lesion and chondrosarcoma may be difficult. Occasionally chondrosarcoma of the hands and feet is associated with multiple recurrences or distal metastasis.
Calculus Rules for V-Proximal Subdifferentials in Smooth Banach Spaces
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Messaoud Bounkhel
2016-01-01
Full Text Available In 2010, Bounkhel et al. introduced new proximal concepts (analytic proximal subdifferential, geometric proximal subdifferential, and proximal normal cone in reflexive smooth Banach spaces. They proved, in p-uniformly convex and q-uniformly smooth Banach spaces, the density theorem for the new concepts of proximal subdifferential and various important properties for both proximal subdifferential concepts and the proximal normal cone concept. In this paper, we establish calculus rules (fuzzy sum rule and chain rule for both proximal subdifferentials and we prove the Bishop-Phelps theorem for the proximal normal cone. The limiting concept for both proximal subdifferentials and for the proximal normal cone is defined and studied. We prove that both limiting constructions coincide with the Mordukhovich constructions under some assumptions on the space. Applications to nonconvex minimisation problems and nonconvex variational inequalities are established.
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Karen S Hathcock
Full Text Available T cell development occurs in the thymus and is critically dependent on productive TCRβ rearrangement and pre-TCR expression in DN3 cells. The requirement for pre-TCR expression results in the arrest of thymocytes at the DN3 stage (β checkpoint, which is uniquely permissive for V-DJβ recombination; only cells expressing pre-TCR survive and develop beyond the DN3 stage. In addition, the requirement for TCRβ rearrangement and pre-TCR expression enforces suppression of TCRβ rearrangement on a second allele, allelic exclusion, thus ensuring that each T cell expresses only a single TCRβ product. However, it is not known whether pre-TCR expression is essential for allelic exclusion or alternatively if allelic exclusion is enforced by developmental changes that can occur in the absence of pre-TCR. We asked if thymocytes that were differentiated without pre-TCR expression, and therefore without pause at the β checkpoint, would suppress all V-DJβ rearrangement. We previously reported that premature CD28 signaling in murine CD4(-CD8(- (DN thymocytes supports differentiation of CD4(+CD8(+ (DP cells in the absence of pre-TCR expression. The present study uses this model to define requirements for TCRβ rearrangement and allelic exclusion. We demonstrate that if cells exit the DN3 developmental stage before TCRβ rearrangement occurs, V-DJβ rearrangement never occurs, even in DP cells that are permissive for D-Jβ and TCRα rearrangement. These results demonstrate that pre-TCR expression is not essential for thymic differentiation to DP cells or for V-DJβ suppression. However, the requirement for pre-TCR signals and the exclusion of alternative stimuli such as CD28 enforce a developmental "pause" in early DN3 cells that is essential for productive TCRβ rearrangement to occur.
A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.
Lemieux, Bruno; Blanchette, Marco; Monette, Anne; Mouland, Andrew J; Wellinger, Raymund J; Chabot, Benoit
2015-01-01
The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.
A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.
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Bruno Lemieux
Full Text Available The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.
Gary Jacobs; Wenping Ma; Burtron H. Davis
2014-01-01
This focused review article underscores how metal reduction promoters can impact deactivation phenomena associated with cobalt Fischer-Tropsch synthesis catalysts. Promoters can exacerbate sintering if the additional cobalt metal clusters, formed as a result of the promoting effect, are in close proximity at the nanoscale to other cobalt particles on the surface. Recent efforts have shown that when promoters are used to facilitate the reduction of small crystallites with the aim of increasing...
Promoter2.0: for the recognition of PolII promoter sequences
DEFF Research Database (Denmark)
Knudsen, Steen; Knudsen, Steen
1999-01-01
transcription start sites. On standardized test setsconsisting of human genomic DNA, the performance of Promoter2.0 compares well with other softwaredeveloped for the same purpose. Availability : Promoter2.0 is available as a Web server at http://www.cbs.dtu.dk/services/promoter/ Contact : steen@cbs.dtu.dk...
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Agarwal RaviP
2009-01-01
Full Text Available We glance at recent advances to the general theory of maximal (set-valued monotone mappings and their role demonstrated to examine the convex programming and closely related field of nonlinear variational inequalities. We focus mostly on applications of the super-relaxed ( -proximal point algorithm to the context of solving a class of nonlinear variational inclusion problems, based on the notion of maximal ( -monotonicity. Investigations highlighted in this communication are greatly influenced by the celebrated work of Rockafellar (1976, while others have played a significant part as well in generalizing the proximal point algorithm considered by Rockafellar (1976 to the case of the relaxed proximal point algorithm by Eckstein and Bertsekas (1992. Even for the linear convergence analysis for the overrelaxed (or super-relaxed ( -proximal point algorithm, the fundamental model for Rockafellar's case does the job. Furthermore, we attempt to explore possibilities of generalizing the Yosida regularization/approximation in light of maximal ( -monotonicity, and then applying to first-order evolution equations/inclusions.
MUS81 promotes common fragile site expression
DEFF Research Database (Denmark)
Ying, Songmin; Minocherhomji, Sheroy; Chan, Kok Lung
2013-01-01
Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the fait......Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair...... the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early...
International Nuclear Information System (INIS)
Aleksandrov, N.L.; Bazelyan, E.M.; Shneider, M. N.
2000-01-01
A one-dimensional model is used to study the dynamics of the hydrodynamic parameters of the lightning channel in the return stroke and after the pulse current is damped. The effect of the continuous residual electric current during pauses between the successive strokes on the plasma cooling in the channel is analyzed. It is shown that a continuous electric current, which is several orders of magnitude lower than the peak current in the return stroke, is capable of maintaining the channel conductivity. This effect cannot be explained merely by Joule heating but is largely governed by the fact that the turbulent heat transport is substantially suppressed. In this case, even a continuous current as low as 50-100 A is capable of maintaining the conductivity of the lightning channel at a level at which only M-components can develop in the channel rather than the dart leader of the subsequent stroke
GSK3β is involved in the relief of mitochondria pausing in a Tau-dependent manner.
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María Llorens-Martín
Full Text Available Mitochondrial trafficking deficits have been implicated in the pathogenesis of several neurological diseases, including Alzheimer's disease (AD. The Ser/Thre kinase GSK3β is believed to play a fundamental role in AD pathogenesis. Given that GSK3β substrates include Tau protein, here we studied the impact of GSK3β on mitochondrial trafficking and its dependence on Tau protein. Overexpression of GSK3β in neurons resulted in an increase in motile mitochondria, whereas a decrease in the activity of this kinase produced an increase in mitochondria pausing. These effects were dependent on Tau proteins, as Tau (-/- neurons did not respond to distinct GSK3β levels. Furthermore, differences in GSK3β expression did not affect other parameters like mitochondria velocity or mitochondria run length. We conclude that GSK3B activity regulates mitochondrial axonal trafficking largely in a Tau-dependent manner.
Distraction lengthening of the proximal phalanx in distal thumb amputations.
Cansü, Eren; Ünal, Mehmet Bekir; Parmaksızoğlu, Fatih; Gürcan, Serkan
2015-01-01
Thumb amputation is a major cause of hand dysfunction, and the treatment for distal thumb amputations remains controversial. Although finger reconstruction methods using distraction lengthening are known to restore finger length and function, we found no reports in the literature regarding phalangeal lengthening in thumb amputations. We aimed to evaluate proximal phalangeal lengthening in thumb amputations at or near the interphalangeal (IP) joint. We retrospectively evaluated patients who had undergone distraction lengthening of the proximal phalanx of the thumb. All patients underwent osteotomy, either during the initial procedure or as a second-stage procedure. Distraction began 10 days after osteotomy with the use of an external fixator that remained in place until ossification of the gap occurred without bone grafting. Patients were evaluated using the QuickDASH score. Fourteen patients with a mean age of 27 years and a mean follow-up period of 7 years were enrolled. The mean phalangeal lengthening achieved was 20 mm. Ossification occurred at all distraction sites, and the fixators were maintained for a mean of 85 days. The mean healing index was 42.5 days/cm. All 14 patients achieved the desired amount of phalangeal lengthening without major complications such as nonunion, premature union, or gross infection. For reconstruction in cases of distal thumb amputations, distraction lengthening of the proximal phalanx can be used to improve absolute length, web space, and grip distance. The technique is safe and effective, improves functionality/cosmesis, and offers a low complication risk.
Euler, Simon A; Petri, Maximilian; Venderley, Melanie B; Dornan, Grant J; Schmoelz, Werner; Turnbull, Travis Lee; Plecko, Michael; Kralinger, Franz S; Millett, Peter J
2017-09-01
Varus failure is one of the most common failure modes following surgical treatment of proximal humeral fractures. Straight antegrade nails (SAN) theoretically provide increased stability by anchoring to the densest zone of the proximal humerus (subchondral zone) with the end of the nail. The aim of this study was to biomechanically investigate the characteristics of this "proximal anchoring point" (PAP). We hypothesized that the PAP would improve stability compared to the same construct without the PAP. Straight antegrade humeral nailing was performed in 20 matched pairs of human cadaveric humeri for a simulated unstable two-part fracture. Biomechanical testing, with stepwise increasing cyclic axial loading (50-N increments each 100 cycles) at an angle of 20° abduction revealed significantly higher median loads to failure for SAN constructs with the PAP (median, 450 N; range, 200-1.000 N) compared to those without the PAP (median, 325 N; range, 100-500 N; p = 0.009). SAN constructs with press-fit proximal extensions (endcaps) showed similar median loads to failure (median, 400 N; range, 200-650 N), when compared to the undersized, commercially available SAN endcaps (median, 450 N; range, 200-600 N; p = 0.240). The PAP provided significantly increased stability in SAN constructs compared to the same setup without this additional proximal anchoring point. Varus-displacing forces to the humeral head were superiorly reduced in this setting. This study provides biomechanical evidence for the "proximal anchoring point's" rationale. Straight antegrade humeral nailing may be beneficial for patients undergoing surgical treatment for unstable proximal humeral fractures to decrease secondary varus displacement and thus potentially reduce revision rates.
Jovanovich, Elizabeth Nora; Howard, James F
2017-12-01
Posttraumatic brachial plexopathies can occur following displaced proximal humeral fractures, causing profound functional deficits. Described here is an unusual case of a displaced proximal humeral metaphyseal fracture in a young child. The patient underwent closed reduction and serial casting, but hand weakness and forearm sensory loss persisted. Needle electromyography localized the injury to the mid/proximal arm near the fracture site, resulting in damage to the posterior and medial cords of the brachial plexus with profound involvement of the radial, ulnar, and median nerves and sparing of the axillary nerve. After months of occupational therapy, hand strength improved, with a nearly full return of function. V. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Hoogsteen base pairs proximal and distal to echinomycin binding sites on DNA
International Nuclear Information System (INIS)
Mendel, D.; Dervan, P.B.
1987-01-01
Forms of the DNA double helix containing non-Watson-Crick base-pairing have been discovered recently based on x-ray diffraction analysis of quionoxaline antibiotic-oligonucleotide complexes. In an effort to find evidence for Hoogsteen base-pairing at quinoxaline-binding sites in solution, chemical footprinting (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined. The authors report that purines (A>G) in the first and/or fourth base-pair positions of occupied echinomycin-binding sites are hyperreactive to diethyl pyrocarbonate. The correspondence of the solid-state data and the sites of diethyl pyrocarbonate hyperreactivity suggests that diethyl pyrocarbonate may be a sensitive reagent for the detection of Hoogsteen base-pairing in solution. Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. This hyperreactive segment may be an altered form of right-handed DNA that is entirely Hoogsteen base-paired
International Nuclear Information System (INIS)
Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn
2013-01-01
Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i
Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
Directory of Open Access Journals (Sweden)
Brian G. Murphy
2012-05-01
Full Text Available Feline immunodeficiency virus (FIV, the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.
Preoperative assessment of the cancellous bone mineral density of the proximal humerus using CT data
International Nuclear Information System (INIS)
Krappinger, Dietmar; Roth, Tobias; Gschwentner, Martin; Suckert, Armin; Blauth, Michael; Hengg, Clemens; Kralinger, Franz
2012-01-01
Osteoporotic fractures of the proximal humerus show an increasing incidence. Osteoporosis not only influences the fracture risk after low-energy trauma, but also affects the mechanical stability of internal fixation. Preoperative assessment of the local bone quality may be useful in the surgical treatment of patients sustaining these injuries. The aim of the present study was to present a method for the preoperative assessment of the local cancellous bone mineral density (BMD) of the proximal humerus using CT data. In the first part of the study, CT scans of 30 patients with unilateral fractures of the proximal humerus after low-energy trauma were used. The local BMD was assessed on the contralateral uninjured side. All 30 patients additionally underwent dual-emission X-ray absorptiometry (DXA) of the lumbar spine, proximal femur, and forearm of the side of the uninjured proximal humerus within 6 weeks after trauma. Three independent trauma surgeons performed measurements on the uninjured proximal humerus twice with a time interval of 4 weeks in order to assess the inter- and intraobserver reliability of the method. In the second part of the study, the local BMD of 507 patients with either proximal humerus fractures or chronic shoulder instability was assessed by a single trauma surgeon. In both parts, the average HU values in standardized ROIs of the humeral head were automatically calculated after correcting for HU values below the water equivalent. A linear calibration equation was computed for the calculation from HU to BMD using a calibration device (EFP). The intra- and interobserver reliability was high (ICC > 0.95). Correlation coefficients between the local BMD of the proximal humerus and other anatomical sites were between 0.35 (lumbar spine) and 0.64 (forearm). We found a high correlation between the local BMD and age. The BMD in the fracture group was significantly lower than in the instability group. These patients were significantly older and more
Preoperative assessment of the cancellous bone mineral density of the proximal humerus using CT data
Energy Technology Data Exchange (ETDEWEB)
Krappinger, Dietmar; Roth, Tobias; Gschwentner, Martin; Suckert, Armin; Blauth, Michael; Hengg, Clemens; Kralinger, Franz [Innsbruck Medical University, Department of Trauma Surgery and Sports Medicine, Innsbruck (Austria)
2012-03-15
Osteoporotic fractures of the proximal humerus show an increasing incidence. Osteoporosis not only influences the fracture risk after low-energy trauma, but also affects the mechanical stability of internal fixation. Preoperative assessment of the local bone quality may be useful in the surgical treatment of patients sustaining these injuries. The aim of the present study was to present a method for the preoperative assessment of the local cancellous bone mineral density (BMD) of the proximal humerus using CT data. In the first part of the study, CT scans of 30 patients with unilateral fractures of the proximal humerus after low-energy trauma were used. The local BMD was assessed on the contralateral uninjured side. All 30 patients additionally underwent dual-emission X-ray absorptiometry (DXA) of the lumbar spine, proximal femur, and forearm of the side of the uninjured proximal humerus within 6 weeks after trauma. Three independent trauma surgeons performed measurements on the uninjured proximal humerus twice with a time interval of 4 weeks in order to assess the inter- and intraobserver reliability of the method. In the second part of the study, the local BMD of 507 patients with either proximal humerus fractures or chronic shoulder instability was assessed by a single trauma surgeon. In both parts, the average HU values in standardized ROIs of the humeral head were automatically calculated after correcting for HU values below the water equivalent. A linear calibration equation was computed for the calculation from HU to BMD using a calibration device (EFP). The intra- and interobserver reliability was high (ICC > 0.95). Correlation coefficients between the local BMD of the proximal humerus and other anatomical sites were between 0.35 (lumbar spine) and 0.64 (forearm). We found a high correlation between the local BMD and age. The BMD in the fracture group was significantly lower than in the instability group. These patients were significantly older and more
Restoration of regenerative ability of x-rayed newt limbs after grafting of proximal or distal skin
International Nuclear Information System (INIS)
Clarke, B.J.
1978-01-01
Studies were conducted in order to determine the role of skin in restoring regenerative ability of x-rayed newt limbs. Non-x-rayed skin from the hindlimb was grafted in four ways to x-rayed (2680R) forelimbs, stripped of their own skin: proximal hindlimb skin to the proximal forelimb, proximal hindlimb skin to the distal forelimb, distal hindlimb skin to the distal forelimb, and distal hindlimb skin to the proximal forelimb. The forelimbs were immediately amputated at the distal extent of the skin graft. Thirty-two of thirty-five (92%) x-rayed forelimbs that had received hindlimb skin regenerated. Of those that regenerated, 28.1% were hindlimbs as shown by the presence of five digits; 34.4% had four digits or less; 31.2% had an outgrowth, but no morphogenesis of digits and 6.3% had two hands. The level of the regenerate from x-rayed limbs was determined by the stump, not the hindlimb skin graft. Only proximal hindlimb skin grafts were able to promote the formation of single 5 digit regenerates. X-rayed forelimb skin was grafted onto x-rayed (2680R) hindlimbs after the hindlimb muscle and skin was removed. X-rayed hindlimbs that had received grafts of forelimb skin produced 5-digit regenerates in 6 of 11 cases (55%). Only 2 (18%) had four digits. The remaining animals (27%) exhibited bud-like regenerates. It is concluded that skin is capable of restoring regenerative ability of x-rayed limbs and that these limbs are able to participate in the production of the regenerate
Giant proximity effect in ferromagnetic bilayers
Ramos, Silvia; Charlton, Tim; Quintanilla, Jorge; Suter, Andreas; Moodera, Jagadeesh; Prokscha, Thomas; Salman, Zaher; Forgan, Ted
2013-03-01
The proximity effect is a phenomenon where an ordered state leaks from a material into an adjacent one over some finite distance, ξ. For superconductors, this distance is ~ the coherence length. Nevertheless much longer-range, ``giant'' proximity effects have been observed in cuprate junctions. This surprising effect can be understood as a consequence of critical opalescence. Since this occurs near all second order phase transitions, giant proximity effects should be very general and, in particular, they should be present in magnetic systems. The ferromagnetic proximity effect has the advantage that its order parameter (magnetization) can be observed directly. We investigate the above phenomenon in Co/EuS bilayer films, where both materials undergo ferromagnetic transitions but at rather different temperatures (bulk TC of 1400K for Co and 16.6K for EuS). A dramatic increase in the range of the proximity effect is expected near the TC of EuS. We present the results of our measurements of the magnetization profiles as a function of temperature, carried out using the complementary techniques of low energy muon rotation and polarized neutron reflectivity. Work supported by EPSRC, STFC and ONR grant N00014-09-1-0177 and NSF grant DMR 0504158.
Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa
Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C
2014-01-01
Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and
Kedzierska, Barbara; Lee, David J.; Węgrzyn, Grzegorz; Busby, Stephen J. W.; Thomas, Mark S.
2004-01-01
The bacteriophage λ CII protein stimulates the activity of three phage promoters, pE, pI and paQ, upon binding to a site overlapping the –35 element at each promoter. Here we used preparations of RNA polymerase carrying a DNA cleavage reagent attached to specific residues in the C-terminal domain of the RNA polymerase α subunit (αCTD) to demonstrate that one αCTD binds near position –41 at pE, whilst the other αCTD binds further upstream. The αCTD bound near position –41 is oriented such that its 261 determinant is in close proximity to σ70. The location of αCTD in CII-dependent complexes at the pE promoter is very similar to that found at many activator-independent promoters, and represents an alternative configuration for αCTD at promoters where activators bind sites overlapping the –35 region. We also used an in vivo alanine scan analysis to show that the DNA-binding determinant of αCTD is involved in stimulation of the pE promoter by CII, and this was confirmed by in vitro transcription assays. We also show that whereas the K271E substitution in αCTD results in a drastic decrease in CII-dependent activation of pE, the pI and paQ promoters are less sensitive to this substitution, suggesting that the role of αCTD at the three lysogenic promoters may be different. PMID:14762211
International Nuclear Information System (INIS)
Heller, E.J.
1996-01-01
It is well known that at long wavelengths λ an s-wave scatterer can have a scattering cross section σ on the order of λ 2 , much larger than its physical size, as measured by the range of its potential. Very interesting phenomena can arise when two or more identical scatterers are placed close together, well within one wavelength. We show that, for a pair of identical scatterers, an extremely narrow p-wave open-quote open-quote proximity close-quote close-quote resonance develops from a broader s-wave resonance of the individual scatterers. A new s-wave resonance of the pair also appears. The relation of these proximity resonances (so called because they appear when the scatterers are close together) to the Thomas and Efimov effects is discussed. copyright 1996 The American Physical Society
Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data
Directory of Open Access Journals (Sweden)
Tomasz Dzida
2017-09-01
Full Text Available We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα, RNA polymerase (Pol II and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.
Biazzo, Alessio; Cardile, Carlo; Brunelli, Luca; Ragni, Paolo; Clementi, Daniele
2017-04-28
The management of displaced 2- and 3-part fractures of the proximal humerus is controversial, both in younger and in elderly patients. The purpose of this paper is to evaluate the functional results of the Contours Proximal Humerus Plate (OrthofixR, Bussolengo,Verona, Italy), for the treatment of displaced 2- and 3-part fractures of the proximal humerus. We retrospectively reviewed 55 patients with proximal humerus fractures, who underwent osteosynthesis with Contours Proximal Humerus Plate from December 2011 to March 2015. We had 21 patients with 2-part fractures and with an average age of 67.1 years and 34 patients with 3-part fractures, with average age of 63.6 years. The average union time was 3 months. The mean Constant score was 67 for 2-part fracture group and 64.9 for 3-part fracture group. The difference was not statistically significant (p = 0.18). The overall complication rate was 14.5 %. Six patients underwent additional surgery (10.9%). The most frequent major complication was secondary loss of reduction following varus collapse of the fracture (2 cases). In these patients, there was loss of medial hinge integrity due to impaction and osteoporosis. The placement of the main locking screw in the calcar area to provide inferomedial support is the rational of the Contours Proximal Humerus Plate. Osteosynthesis with Contours Proximal Humerus Plate is a safe system for treating displaced 2- and 3-part fractures of the proximal humerus, with good functional results and complication rates comparable to those reported in the literature.
Factors influencing unsafe behaviors and accidents on construction sites: a review.
Khosravi, Yahya; Asilian-Mahabadi, Hassan; Hajizadeh, Ebrahim; Hassanzadeh-Rangi, Narmin; Bastani, Hamid; Behzadan, Amir H
2014-01-01
Construction is a hazardous occupation due to the unique nature of activities involved and the repetitiveness of several field behaviors. The aim of this methodological and theoretical review is to explore the empirical factors influencing unsafe behaviors and accidents on construction sites. In this work, results and findings from 56 related previous studies were investigated. These studies were categorized based on their design, type, methods of data collection, analytical methods, variables, and key findings. A qualitative content analysis procedure was used to extract variables, themes, and factors. In addition, all studies were reviewed to determine the quality rating and to evaluate the strength of provided evidence. The content analysis identified 8 main categories: (a) society, (b) organization, (c) project management, (d) supervision, (e) contractor, (f) site condition, (g) work group, and (h) individual characteristics. The review highlighted the importance of more distal factors, e.g., society and organization, and project management, that may contribute to reducing the likelihood of unsafe behaviors and accidents through the promotion of site condition and individual features (as proximal factors). Further research is necessary to provide a better understanding of the links between unsafe behavior theories and empirical findings, challenge theoretical assumptions, develop new applied theories, and make stronger recommendations.
DEFF Research Database (Denmark)
Løkkegaard, Ellen; Nielsen, A. K.
2014-01-01
was to describe the use of hormonal contraceptives among the Danish adolescent female population, focusing on age, period and cohort effects and including types of hormonal contraceptives. MATERIAL AND METHODS: All women aged 14-50 years during the 1995-2012 period were identified through the Central Person...... Register. Furthermore, the National Registry of Medicinal Products Statistics provided information on redeemed prescriptions for hormonal contraceptives characterised by Anatomical-Therapeutic-Chemical (ATC) classification codes. RESULTS: At the age of 17 years, more than 50% of the Danish adolescent......, adolescent girls have more pauses and shifts between types of hormonal contraceptives. Since 2010 there has been a shift toward use of second generation oral contraceptives away from third and fourth generation contraceptives. CONCLUSION: Adolescent girls tend to initiate their use of oral contraceptives...
DEFF Research Database (Denmark)
Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal
2013-01-01
, isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...
Yu, Xiaofang; Yu, Xiaobo; Wu, Shujie; Liu, Bo; Liu, Heng; Guan, Jingqi; Kan, Qiubin
2011-02-01
Acid-base bifunctional heterogeneous catalysts containing carboxylic and amine groups, which were immobilized at defined distance from one another on the mesoporous solid were synthesized by immobilizing lysine onto carboxyl-SBA-15. The obtained materials were characterized by X-ray diffraction (XRD), N 2 adsorption, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron micrographs (SEM), transmission electron micrographs (TEM), elemental analysis, and back titration. Proximal-C-A-SBA-15 with a proximal acid-base distance was more active than maximum-C-A-SBA-15 with a maximum acid-base distance in aldol condensation reaction between acetone and various aldehydes. It appears that the distance between acidic site and basic site immobilized on mesoporous solid should be an essential factor for catalysis optimization.
International Nuclear Information System (INIS)
Lee, Dong Won; Jin, Gong Yong; Oh, Hee Sul; Lim, Yeong Su; Lee, Sang Yong; Lee, Jeong Min; Kim, Chong Soo; Han, Young Min; Lee, Dong Geun
1998-01-01
To determine the effective embolic material and appropriate embolic site by comparing bowel changes after arterial embolization in dogs in which the proximal or distal level of the superior mesenteric artery had been occluded with gelfoam particles or a coil. Material and Methods : Using the coaxial catheter system,super selective arterial embolization was performed at sixteen sites in four dogs. In groups A and B, each site was occluded at the proximal or distal marginal artery, respectively, with gelfoam particles and in groups C and D, at the proximal or distal artery, respectively, with a coil. All dogs were sacrificed one day after the procedure, and gross and microscopic histologic findings were evaluated. Results : In all dogs, the procedure was successful. In group B, significant mucosal destruction, lymphocyte proliferation in submucosa and mucosa, and diffuse swelling in all layers of the intestine were found at all sites. The vessel in the submucosal layer was completely obstructed by red blood cells and gelfoam.At three sites, the intestine showed diffuse ischemic change, and at one other site, focal ischemic change was observed. In group D, exudation with destruction of mucosa and submucosal hemorrhage occurred at one site, but in groups A and C, intestinal layers were found to be normal. Conclusion :Using a coil, super selective arterial embolization was successful, even up to the distal level of the intestinal artery, and the intestine showed no ischemic change. Embolization with gelfoam must be performed carefully at the proximal level, and since it can cause severe intestinal necrosis, must be avoided at the distal level
Pedrana, Alisa; Hellard, Margaret; Gold, Judy; Ata, Nadine; Chang, Shanton; Howard, Steve; Asselin, Jason; Ilic, Olivia; Batrouney, Colin; Stoove, Mark
2013-02-07
A growing number of health promotion interventions are taking advantage of the popularity and interactivity of new social media platforms to foster and engage communities for health promotion. However, few health promotion interventions using social networking sites (SNS) have been rigorously evaluated. "Queer as F**k"(QAF) began as pilot project in 2010 to deliver sexual health promotion via short "webisodes" on SNS to gay men. Now in its fifth season, QAF is among the few published examples internationally to demonstrate the sexual health promotion potential of SNS. The objective of this evaluation is to assess reach, interactivity, and engagement generated by QAF to inform future health interventions and evaluations using SNS. We undertook a mixed method process evaluation using an uncontrolled longitudinal study design that compared multiple measurements over time to assess changes in reach and engagement. We adapted evaluation methods from the health promotion, information systems, and creative spheres. We incorporated online usage statistics, interviews informed by user diary-scrapbooks, and user focus groups to assess intervention reach and engagement. During Series 1-3 (April 2010 to April 2011), 32 webisodes were posted on the QAF Facebook and YouTube pages. These webisodes attracted over 30,000 views; ranging from 124-3092 views per individual episode. By April 2011, the QAF Facebook page had 2929 predominantly male fans. Interview and focus group participants supported the balance of education and entertainment. They endorsed the narrative "soap opera" format as an effective way to deliver sexual health messages in an engaging, informative, and accessible manner that encouraged online peer discussion of sexual health and promoted community engagement. QAF offers a successful example of exploiting the reach, interactivity, and engagement potential of SNS; findings from this process evaluation provide a model to inform the delivery and evaluation of future
Proximal Hamstring Tendinosis and Partial Ruptures.
Startzman, Ashley N; Fowler, Oliver; Carreira, Dominic
2017-07-01
Proximal hamstring tendinosis and partial hamstring origin ruptures are painful conditions of the proximal thigh and hip that may occur in the acute, chronic, or acute on chronic setting. Few publications exist related to their diagnosis and management. This systematic review discusses the incidence, treatment, and prognosis of proximal hamstring tendinosis and partial hamstring ruptures. Conservative treatment measures include nonsteroidal anti-inflammatory drugs, physical therapy, rest, and ice. If these measures fail, platelet-rich plasma or shockwave therapy may be considered. When refractory to conservative management, these injuries may be treated with surgical debridement and hamstring reattachment. [Orthopedics. 2017; 40(4):e574-e582.]. Copyright 2017, SLACK Incorporated.
Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich
2015-12-01
Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop. © 2015 American Society of Plant Biologists. All rights reserved.
Interference of transcription across H-NS binding sites and repression by H-NS.
Rangarajan, Aathmaja Anandhi; Schnetz, Karin
2018-05-01
Nucleoid-associated protein H-NS represses transcription by forming extended DNA-H-NS complexes. Repression by H-NS operates mostly at the level of transcription initiation. Less is known about how DNA-H-NS complexes interfere with transcription elongation. In vitro H-NS has been shown to enhance RNA polymerase pausing and to promote Rho-dependent termination, while in vivo inhibition of Rho resulted in a decrease of the genome occupancy by H-NS. Here we show that transcription directed across H-NS binding regions relieves H-NS (and H-NS/StpA) mediated repression of promoters in these regions. Further, we observed a correlation of transcription across the H-NS-bound region and de-repression. The data suggest that the transcribing RNA polymerase is able to remodel the H-NS complex and/or dislodge H-NS from the DNA and thus relieve repression. Such an interference of transcription and H-NS mediated repression may imply that poorly transcribed AT-rich loci are prone to be repressed by H-NS, while efficiently transcribed loci escape repression. © 2018 John Wiley & Sons Ltd.
Characterization of Rous sarcoma virus polyadenylation site use in vitro
International Nuclear Information System (INIS)
Maciolek, Nicole L.; McNally, Mark T.
2008-01-01
Polyadenylation of Rous sarcoma virus (RSV) RNA is inefficient, as approximately 15% of RSV RNAs represent read-through transcripts that use a downstream cellular polyadenylation site (poly(A) site). Read-through transcription has implications for the virus and the host since it is associated with oncogene capture and tumor induction. To explore the basis of inefficient RSV RNA 3'-end formation, we characterized RSV polyadenylation in vitro using HeLa cell nuclear extracts and HEK293 whole cell extracts. RSV polyadenylation substrates composed of the natural 3' end of viral RNA and various lengths of upstream sequence showed little or no polyadenylation, indicating that the RSV poly(A) site is suboptimal. Efficiently used poly(A) sites often have identifiable upstream and downstream elements (USEs and DSEs) in close proximity to the conserved AAUAAA signal. The sequences upstream and downstream of the RSV poly(A) site deviate from those found in efficiently used poly(A) sites, which may explain inefficient RSV polyadenylation. To assess the quality of the RSV USEs and DSEs, the well-characterized SV40 late USEs and/or DSEs were substituted for the RSV elements and vice versa, which showed that the USEs and DSEs from RSV are suboptimal but functional. CstF interacted poorly with the RSV polyadenylation substrate, and the inactivity of the RSV poly(A) site was at least in part due to poor CstF binding since tethering CstF to the RSV substrate activated polyadenylation. Our data are consistent with poor polyadenylation factor binding sites in both the USE and DSE as the basis for inefficient use of the RSV poly(A) site and point to the importance of additional elements within RSV RNA in promoting 3' end formation
Proximal Participation: A Pathway into Work
Chan, Selena
2013-01-01
In a longitudinal case study of apprentices, the term proximal participation was coined to describe the entry process of young people, with unclear career destinations, into the trade of baking. This article unravels the significance of proximal participation in the decision-making processes of young people who enter a trade through initial…
Ultimate and proximate explanations of strong reciprocity.
Vromen, Jack
2017-08-23
Strong reciprocity (SR) has recently been subject to heated debate. In this debate, the "West camp" (West et al. in Evol Hum Behav 32(4):231-262, 2011), which is critical of the case for SR, and the "Laland camp" (Laland et al. in Science, 334(6062):1512-1516, 2011, Biol Philos 28(5):719-745, 2013), which is sympathetic to the case of SR, seem to take diametrically opposed positions. The West camp criticizes advocates of SR for conflating proximate and ultimate causation. SR is said to be a proximate mechanism that is put forward by its advocates as an ultimate explanation of human cooperation. The West camp thus accuses advocates of SR for not heeding Mayr's original distinction between ultimate and proximate causation. The Laland camp praises advocates of SR for revising Mayr's distinction. Advocates of SR are said to replace Mayr's uni-directional view on the relation between ultimate and proximate causes by the bi-directional one of reciprocal causation. The paper argues that both the West camp and the Laland camp misrepresent what advocates of SR are up to. The West camp is right that SR is a proximate cause of human cooperation. But rather than putting forward SR as an ultimate explanation, as the West camp argues, advocates of SR believe that SR itself is in need of ultimate explanation. Advocates of SR tend to take gene-culture co-evolutionary theory as the correct meta-theoretical framework for advancing ultimate explanations of SR. Appearances notwithstanding, gene-culture coevolutionary theory does not imply Laland et al.'s notion of reciprocal causation. "Reciprocal causation" suggests that proximate and ultimate causes interact simultaneously, while advocates of SR assume that they interact sequentially. I end by arguing that the best way to understand the debate is by disambiguating Mayr's ultimate-proximate distinction. I propose to reserve "ultimate" and "proximate" for different sorts of explanations, and to use other terms for distinguishing
Directory of Open Access Journals (Sweden)
S. M. Issa
2012-07-01
Full Text Available Landfill sites receive 92% of total annual solid waste produced by municipalities in the emirate of Abu Dhabi. In this study, candidate sites for an appropriate landfill location for the Abu Dhabi municipal area are determined by integrating geographic information systems (GIS and multi-criteria evaluation (MCE analysis. To identify appropriate landfill sites, eight input map layers including proximity to urban areas, proximity to wells and water table depth, geology and topography, proximity to touristic and archeological sites, distance from roads network, distance from drainage networks, and land slope are used in constraint mapping. A final map was generated which identified potential areas showing suitability for the location of the landfill site. Results revealed that 30% of the study area was identified as highly suitable, 25% as suitable, and 45% as unsuitable. The selection of the final landfill site, however, requires further field research.
Berthelot, Charlotte; Leyval, Corinne; Foulon, Julie; Chalot, Michel; Blaudez, Damien
2016-10-01
Numerous studies address the distribution and the diversity of dark septate endophytes (DSEs) in the literature, but little is known about their ecological role and their effect on host plants, especially in metal-polluted soils. Seven DSE strains belonging to Cadophora, Leptodontidium, Phialophora and Phialocephala were isolated from roots of poplar trees from metal-polluted sites. All strains developed on a wide range of carbohydrates, including cell-wall-related compounds. The strains evenly colonized birch, eucalyptus and ryegrass roots in re-synthesis experiments. Root and shoot growth promotion was observed and was both plant and strain dependent. Two Phialophora and Leptodontidium strains particularly improved plant growth. However, there was no correlation between the level of root colonization by DSEs and the intensity of growth promotion. All strains produced auxin and six also stimulated plant growth through the release of volatile organic compounds (VOCs). SPME-GC/MS analyses revealed four major VOCs emitted by Cadophora and Leptodontidium The strains exhibited growth at high concentrations of several metals. The ability of metal-resistant DSE strains to produce both soluble and volatile compounds for plant growth promotion indicates interesting microbial resources with high potential to support sustainable production of bioenergy crops within the context of the phytomanagement of metal-contaminated sites. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Prosthetic replacement for proximal humeral fractures.
Kontakis, George; Tosounidis, Theodoros; Galanakis, Ioannis; Megas, Panagiotis
2008-12-01
The ideal management of complex proximal humeral fractures continues to be debatable. Evolution of proximal humeral fracture management, during the past decade, led to the implementation of many innovations in surgical treatment. Even though the pendulum of treatment seems to swing towards new trends such as locked plating, hemiarthroplasty remains a valid and reliable option that serves the patient's needs well. Hemiarthroplasty is indicated for complex proximal humeral fractures in elderly patients with poor bone stock and when internal fixation is difficult or unreliable. Hemiarthroplasty provides a better result when it is performed early post-injury. Stem height, retroversion and tuberosity positioning are technical aspects of utmost importance. Additionally reverse total shoulder arthroplasty is an alternative new modality that can be used as a primary solution in selected patients with proximal humeral fracture treatment. Failed hemiarthroplasty and fracture sequelae can be successfully managed with reverse total shoulder arthroplasty. Individual decision-making and tailored treatment that takes into consideration the personality of the fracture and the patient's characteristics should be used.
Industrial Computed Tomography using Proximal Algorithm
Zang, Guangming
2016-04-14
In this thesis, we present ProxiSART, a flexible proximal framework for robust 3D cone beam tomographic reconstruction based on the Simultaneous Algebraic Reconstruction Technique (SART). We derive the proximal operator for the SART algorithm and use it for minimizing the data term in a proximal algorithm. We show the flexibility of the framework by plugging in different powerful regularizers, and show its robustness in achieving better reconstruction results in the presence of noise and using fewer projections. We compare our framework to state-of-the-art methods and existing popular software tomography reconstruction packages, on both synthetic and real datasets, and show superior reconstruction quality, especially from noisy data and a small number of projections.
Kaiso Directs the Transcriptional Corepressor MTG16 to the Kaiso Binding Site in Target Promoters
Barrett, Caitlyn W.; Smith, J. Joshua; Lu, Lauren C.; Markham, Nicholas; Stengel, Kristy R.; Short, Sarah P.; Zhang, Baolin; Hunt, Aubrey A.; Fingleton, Barbara M.; Carnahan, Robert H.; Engel, Michael E.; Chen, Xi; Beauchamp, R. Daniel; Wilson, Keith T.; Hiebert, Scott W.; Reynolds, Albert B.; Williams, Christopher S.
2012-01-01
Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the ApcMin mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (4×KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co
Proximity sensor system development. CRADA final report
Energy Technology Data Exchange (ETDEWEB)
Haley, D.C. [Oak Ridge National Lab., TN (United States); Pigoski, T.M. [Merrit Systems, Inc. (United States)
1998-01-01
Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.
Proximity sensor system development. CRADA final report
International Nuclear Information System (INIS)
Haley, D.C.; Pigoski, T.M.
1998-01-01
Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors
Locking plate fixation for proximal humerus fractures.
LENUS (Irish Health Repository)
Burke, Neil G
2012-02-01
Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.
Proximal collagenous gastroenteritides:
DEFF Research Database (Denmark)
Nielsen, Ole Haagen; Riis, Lene Buhl; Danese, Silvio
2014-01-01
AIM: While collagenous colitis represents the most common form of the collagenous gastroenteritides, the collagenous entities affecting the proximal part of the gastrointestinal tract are much less recognized and possibly overlooked. The aim was to summarize the latest information through a syste...
Psychological responses to the proximity of climate change
Brügger, Adrian; Dessai, Suraje; Devine-Wright, Patrick; Morton, Thomas A.; Pidgeon, Nicholas F.
2015-12-01
A frequent suggestion to increase individuals' willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences, that is, those that are close in space and time. But previous studies that have tested this proximizing approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualization of the proximizing approach within established psychological research suggests that, depending on the particular theoretical perspective one takes on this issue, and on specific individual characteristics suggested by these perspectives, proximizing can bring about the intended positive effects, can have no (visible) effect or can even backfire. Thus, the effects of proximizing are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role that psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions.
Critical Proximity as a Methodological Move in Techno-Anthropology
DEFF Research Database (Denmark)
Birkbak, Andreas; Petersen, Morten Krogh; Elgaard Jensen, Torben
2015-01-01
proximity.’ Critical proximity offers an alternative to critical distance, especially with respect to avoiding premature references to abstract panoramas such as democratization and capitalist exploitation in the quest to conduct ‘critical’ analysis. Critical proximity implies, instead, granting the beings...
Directory of Open Access Journals (Sweden)
Sung Min Ju
2015-01-01
Full Text Available Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2 cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.
Infiltrating/sealing proximal caries lesions
DEFF Research Database (Denmark)
Martignon, S; Ekstrand, K R; Gomez, J
2012-01-01
This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...
What do health-promoting schools promote?
DEFF Research Database (Denmark)
Simovska, Venka
2012-01-01
-promotion interventions. Directly or indirectly the articles reiterate the idea that health promotion in schools needs to be linked with the core task of the school – education, and to the values inherent to education, such as inclusion, democracy, participation and influence, critical literacy and action competence......Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...
Hasan, Arif Ul; Kittikulsuth, Wararat; Yamaguchi, Fuminori; Musarrat Ansary, Tuba; Rahman, Asadur; Shibayama, Yuki; Nakano, Daisuke; Hitomi, Hirofumi; Tokuda, Masaaki; Nishiyama, Akira
2017-09-15
Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also increased the cellular cyclic adenosine monophosphate (cAMP) level. Luciferase assay showed that blocking of protein kinase A (PKA) using H89 reduced, while 8-Br-cAMP agonized the repression of HIF-1α promoter activity in hypoxic condition. Deletion of cAMP response element binding sites from the HIF-1α promoter abrogated the effect of IBMX. Western blot and immunofluorescent study confirmed that the CoCl 2 induced increased HIF-1α protein in whole cell lysate and in nucleus was reduced by the IBMX. Through this process, IBMX attenuated both CoCl 2 and hypoxia induced mRNA expressions of two pro-fibrogenic factors, platelet-derived growth factor B and lysyl oxidase. Moreover, IBMX reduced production of a mesenchymal transformation factor, β-catenin; as well as protected against hypoxia induced cell-death. Taken together, our study showed novel evidence that the PDE inhibitor IBMX can downregulate the transcription of HIF-1α, and thus may attenuate hypoxia induced renal fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Palm, Henrik; Teixidor, Jordi
2015-01-01
searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...
Directory of Open Access Journals (Sweden)
Cohn Steven M
2010-05-01
Full Text Available Abstract Background Intestinal cell kinase (ICK; GeneID 22858 is a conserved MAPK and CDK-like kinase that is widely expressed in human tissues. Data from the Cancer Genome Anatomy Project indicated ICK mRNA is increased in cancer, and that its expression correlated with expression of mRNA for an uncharacterized F-box protein, FBX9 (GeneID: 26268. ICK and FBX9 genes are arranged head-to-head on opposite strands, with start sites for transcription separated by ~3.3 kb. We hypothesized ICK and FBX9 are potentially important genes in cancer controlled by a bidirectional promoter. Results We assessed promoter activity of the intergenic region in both orientations in cancer cell lines derived from breast (AU565, SKBR3, colon (HCT-15, KM12, and stomach (AGS cancers, as well as in embryonic human kidney (HEK293T cells. The intergenic segment was active in both orientations in all of these lines, and ICK promoter activity was greater than FBX9 promoter activity. Results from deletions and truncations defined a minimal promoter for ICK, and revealed that repressors and enhancers differentially regulate ICK versus FBX9 promoter activity. The ICK promoter contains consensus motifs for several FOX-family transcription factors that align when mouse and human are compared using EMBOSS. FOXA1 and FOXA2 increase luciferase activity of a minimal promoter 10-20 fold in HEK293T cells. Consensus sites for TCF7L2 (TCF4 (Gene Id: 6934 are also present in both mouse and human. The expression of β-catenin increased activity of the minimal promoter ~10 fold. ICK reference mRNAs (NM_014920.3, NM_016513 are expressed in low copy number and increased in some breast cancers, using a ten base tag 5'-TCAACCTTAT-3' specific for both ICK transcripts. Conclusion ICK and FBX9 are divergently transcribed from a bidirectional promoter that is GC-rich and contains a CpG island. A minimal promoter for ICK contains functional sites for β-cateinin/TCF7L2 and FOXA. These data are
Calreticulin discriminates the proximal region at the N-glycosylation site of Glc1Man9GlcNAc2 ligand
Energy Technology Data Exchange (ETDEWEB)
Hirano, Makoto; Adachi, Yuka [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan); Ito, Yukishige [Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); ERATO, Japan Science and Technology Agency, Ito Glycotrilogy Project, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Totani, Kiichiro, E-mail: ktotani@st.seikei.ac.jp [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan)
2015-10-23
Calreticulin (CRT) is well known as a lectin-like chaperone that recognizes Glc1Man9GlcNAc2 (G1M9)-glycoproteins in the endoplasmic reticulum (ER). However, whether CRT can directly interact with the aglycone moiety (protein portion) of the glycoprotein remains controversial. To improve our understanding of CRT interactions, structure-defined G1M9-derivatives with different aglycones (–OH, –Gly–NH{sub 2}, and –Gly–Glu–{sup t}Bu) were used as CRT ligands, and their interactions with recombinant CRT were analyzed using thermal shift analysis. The results showed that CRT binds strongly to a G1M9-ligand in the order –Gly–Glu–{sup t}Bu > –Gly–NH{sub 2} > –OH, which is the same as that of the reglucosylation of Man9GlcNAc2 (M9)-derivatives by the folding sensor enzyme UGGT (UDP-glucose: glycoprotein glucosyltransferase). Our results indicate that, similar to UGGT, CRT discriminates the proximal region at the N-glycosylation site, suggesting a similar mechanism mediating the recognition of aglycone moieties in the ER glycoprotein quality control system. - Highlights: • Glc1Man9GlcNAc2 (G1M9) ligands with different aglycones were chemically prepared. • Calreticulin (CRT) discriminates the aglycone of Glc1Man9GlcNAc2 (G1M9) ligand. • CRT binds with G1M9 ligands in a similar manner to folding sensor enzyme.
Xin, Hongliang; Linic, Suljo
2016-06-01
Many commercial heterogeneous catalysts are complex structures that contain metal active sites promoted by multiple additives. Developing fundamental understanding about the impact of these perturbations on the local surface reactivity is crucial for catalyst development and optimization. In this contribution, we develop a general framework for identifying underlying mechanisms that control the changes in the surface reactivity of a metal site (more specifically the adsorbate-surface interactions) upon a perturbation in the local environment. This framework allows us to interpret fairly complex interactions on metal surfaces in terms of specific, physically transparent contributions that can be evaluated independently of each other. We use Cs-promoted dissociation of O2 as an example to illustrate our approach. We concluded that the Cs adsorbate affects the outcome of the chemical reaction through a strong alkali-induced electric field interacting with the static dipole moment of the O2/Ag(111) system.
GC content around splice sites affects splicing through pre-mRNA secondary structures
Directory of Open Access Journals (Sweden)
Chen Liang
2011-01-01
Full Text Available Abstract Background Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens, mice (Mus musculus, fruit flies (Drosophila melanogaster, and nematodes (Caenorhabditis elegans to further investigate this phenomenon. Results We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures. Conclusion All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.
Proximity correction of high-dosed frame with PROXECCO
Eisenmann, Hans; Waas, Thomas; Hartmann, Hans
1994-05-01
Usefulness of electron beam lithography is strongly related to the efficiency and quality of methods used for proximity correction. This paper addresses the above issue by proposing an extension to the new proximity correction program PROXECCO. The combination of a framing step with PROXECCO produces a pattern with a very high edge accuracy and still allows usage of the fast correction procedure. Making a frame with a higher dose imitates a fine resolution correction where the coarse part is disregarded. So after handling the high resolution effect by means of framing, an additional coarse correction is still needed. Higher doses have a higher contribution to the proximity effect. This additional proximity effect is taken into account with the help of the multi-dose input of PROXECCO. The dose of the frame is variable, depending on the deposited energy coming from backscattering of the proximity. Simulation proves the very high edge accuracy of the applied method.
Dual pathology proximal median nerve compression of the forearm.
LENUS (Irish Health Repository)
Murphy, Siun M
2013-12-01
We report an unusual case of synchronous pathology in the forearm- the coexistence of a large lipoma of the median nerve together with an osteochondroma of the proximal ulna, giving rise to a dual proximal median nerve compression. Proximal median nerve compression neuropathies in the forearm are uncommon compared to the prevalence of distal compression neuropathies (eg Carpal Tunnel Syndrome). Both neural fibrolipomas (Refs. 1,2) and osteochondromas of the proximal ulna (Ref. 3) in isolation are rare but well documented. Unlike that of a distal compression, a proximal compression of the median nerve will often have a definite cause. Neural fibrolipoma, also called fibrolipomatous hamartoma are rare, slow-growing, benign tumours of peripheral nerves, most often occurring in the median nerve of younger patients. To our knowledge, this is the first report of such dual pathology in the same forearm, giving rise to a severe proximal compression of the median nerve. In this case, the nerve was being pushed anteriorly by the osteochondroma, and was being compressed from within by the intraneural lipoma. This unusual case highlights the advantage of preoperative imaging as part of the workup of proximal median nerve compression.
Giant proximity effect and critical opalescence in EuS
Charlton, Timothy; Ramos, Silvia; Quintanilla, Jorge; Suter, Andreas; Moodera, Jagadeesh
2015-03-01
The proximity effect is a type of wetting phenomenon where an ordered state, usually magnetism or superconductivity, ``leaks'' from one material into an adjacent one over some finite distance. For superconductors, the characteristic range is of the order of the coherence length, usually hundreds of nm. Nevertheless much longer, ``giant'' proximity effects have been observed in cuprate perovskite junctions. Such giant proximity effects can be understood by taking into account the divergence of the pairing susceptibility in the non-superconducting material when it is itself close to a superconducting instability: a superconducting version of critical opalescence. Since critical opalescence occurs in all second order phase transitions, giant proximity effects are expected to be general, therefor there must be a giant ferromagnetic proximity effect. Compared to its superconducting counterpart, the giant ferromagnetic proximity effect has the advantage that the order parameter (magnetization) can be observed directly. We have fabricated Co/EuS thin films and measured the magnetization profiles as a function of temperature using the complementary techniques of low energy muon relaxation and polarized neutron reflectivity. Details of the proximity effect near TCEuS will be presented.
Strong Proximities on Smooth Manifolds and Vorono\\" i Diagrams
Peters, J. F.; Guadagni, C.
2015-01-01
This article introduces strongly near smooth manifolds. The main results are (i) second countability of the strongly hit and far-miss topology on a family $\\mathcal{B}$ of subsets on the Lodato proximity space of regular open sets to which singletons are added, (ii) manifold strong proximity, (iii) strong proximity of charts in manifold atlases implies that the charts have nonempty intersection. The application of these results is given in terms of the nearness of atlases and charts of proxim...
International Nuclear Information System (INIS)
1997-06-01
The Ecological Monitoring Program (EcMP) was designed to investigate the long-term ecological trends in terrestrial and aquatic ecosystems at the US Department of energy's (DOE's) Rocky Flats Environmental Technology Site (Site) (DOE 1993). Field sampling was conducted during 1993, 1994, and 1995, until the program was terminated in late 1995. This report presents the terrestrial vegetation data that were gathered by the EcMP. The site is located on the Colorado Piedmont, east of the Front Range, between Boulder and Golden, approximately 25 km (16 miles) northwest of Denver. The topography and proximity of the Site to the mountain front result in an interesting mixture of prairie and mountain plant species. The Site is one of the few large, relatively undisturbed areas of its kind that remains along the Colorado Piedmont. Until 1989, the primary mission of the Site was the production of nuclear weapons components (DOE 1993). After production ceased, Site personnel shifted their focus to cleanup and closure
Energy Technology Data Exchange (ETDEWEB)
NONE
1997-06-01
The Ecological Monitoring Program (EcMP) was designed to investigate the long-term ecological trends in terrestrial and aquatic ecosystems at the US Department of energy`s (DOE`s) Rocky Flats Environmental Technology Site (Site) (DOE 1993). Field sampling was conducted during 1993, 1994, and 1995, until the program was terminated in late 1995. This report presents the terrestrial vegetation data that were gathered by the EcMP. The site is located on the Colorado Piedmont, east of the Front Range, between Boulder and Golden, approximately 25 km (16 miles) northwest of Denver. The topography and proximity of the Site to the mountain front result in an interesting mixture of prairie and mountain plant species. The Site is one of the few large, relatively undisturbed areas of its kind that remains along the Colorado Piedmont. Until 1989, the primary mission of the Site was the production of nuclear weapons components (DOE 1993). After production ceased, Site personnel shifted their focus to cleanup and closure.
75 FR 5009 - Proximity Detection Systems for Underground Mines
2010-02-01
... Proximity Detection Systems for Underground Mines AGENCY: Mine Safety and Health Administration, Labor... information regarding whether the use of proximity detection systems would reduce the risk of accidents where... . Information on MSHA-approved proximity detection systems is available on the Internet at http://www.msha.gov...
Bimalleolar ankle fracture with proximal fibular fracture
Colenbrander, R. J.; Struijs, P. A. A.; Ultee, J. M.
2005-01-01
A 56-year-old female patient suffered a bimalleolar ankle fracture with an additional proximal fibular fracture. This is an unusual fracture type, seldom reported in literature. It was operatively treated by open reduction and internal fixation of the lateral malleolar fracture. The proximal fibular
Directory of Open Access Journals (Sweden)
Sakaki Yoshiyuki
2004-02-01
Full Text Available Abstract Background Gene expression is regulated mainly by transcription factors (TFs that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS using position weight matrices (PWMs that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. Results We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster, we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. Conclusion Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1 those that show TFBS clustered in promoters associated with CGI, and (2 those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in
Handcock, Rebecca N.; Gobbett, D. L.; González, Luciano A.; Bishop-Hurley, Greg J.; McGavin, Sharon L.
2016-08-01
Timely and accurate monitoring of pasture biomass and ground cover is necessary in livestock production systems to ensure productive and sustainable management. Interest in the use of proximal sensors for monitoring pasture status in grazing systems has increased, since data can be returned in near real time. Proximal sensors have the potential for deployment on large properties where remote sensing may not be suitable due to issues such as spatial scale or cloud cover. There are unresolved challenges in gathering reliable sensor data and in calibrating raw sensor data to values such as pasture biomass or vegetation ground cover, which allow meaningful interpretation of sensor data by livestock producers. Our goal was to assess whether a combination of proximal sensors could be reliably deployed to monitor tropical pasture status in an operational beef production system, as a precursor to designing a full sensor deployment. We use this pilot project to (1) illustrate practical issues around sensor deployment, (2) develop the methods necessary for the quality control of the sensor data, and (3) assess the strength of the relationships between vegetation indices derived from the proximal sensors and field observations across the wet and dry seasons. Proximal sensors were deployed at two sites in a tropical pasture on a beef production property near Townsville, Australia. Each site was monitored by a Skye SKR-four-band multispectral sensor (every 1 min), a digital camera (every 30 min), and a soil moisture sensor (every 1 min), each of which were operated over 18 months. Raw data from each sensor was processed to calculate multispectral vegetation indices. The data capture from the digital cameras was more reliable than the multispectral sensors, which had up to 67 % of data discarded after data cleaning and quality control for technical issues related to the sensor design, as well as environmental issues such as water incursion and insect infestations. We recommend
Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.
Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John
2014-01-01
Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and
Proximity functions for general right cylinders
International Nuclear Information System (INIS)
Kellerer, A.M.
1981-01-01
Distributions of distances between pairs of points within geometrical objects, or the closely related proximity functions and geometric reduction factors, have applications to dosimetric and microdosimetric calculations. For convex bodies these functions are linked to the chord-length distributions that result from random intersections by straight lines. A synopsis of the most important relations is given. The proximity functions and related functions are derived for right cylinders with arbitrary cross sections. The solution utilizes the fact that the squares of the distances between two random points are sums of independently distributed squares of distances parallel and perpendicular to the axis of the cylinder. Analogous formulas are derived for the proximity functions or geometric reduction factors for a cylinder relative to a point. This requires only a minor modification of the solution
Postpartum osteoporosis associated with proximal tibial stress fracture
Energy Technology Data Exchange (ETDEWEB)
Clemetson, I.A.; Anderson, S.E. [Department of Radiology, University Hospital of Bern, Inselspital, 3010, Bern (Switzerland); Popp, A.; Lippuner, K. [Department of Osteology, University Hospital of Bern, Inselspital, 3010, Bern (Switzerland); Ballmer, F. [Knee and Sports Medicine Unit, Lindenhofspital Bern, 3012, Bern (Switzerland)
2004-02-01
A 33-year-old woman presented with acute nonspecific knee pain, 6 months postpartum. MR imaging, computed tomography and radiography were performed and a proximal tibia plateau insufficiency fracture was detected. Bone densitometry demonstrated mild postpartum osteoporosis. To our knowledge these findings have not been described in this location and in this clinical setting. The etiology of the atraumatic fracture of the tibia is presumed to be due to a low bone mineral density. The bone loss was probably due to pregnancy, lactation and postpartum hormonal changes. There were no other inciting causes and the patient was normocalcemic. We discuss the presence of a postpartum stress fracture in a hitherto undescribed site in a patient who had lactated following an uncomplicated pregnancy and had no other identifiable cause for a stress fracture. (orig.)
Postpartum osteoporosis associated with proximal tibial stress fracture
International Nuclear Information System (INIS)
Clemetson, I.A.; Anderson, S.E.; Popp, A.; Lippuner, K.; Ballmer, F.
2004-01-01
A 33-year-old woman presented with acute nonspecific knee pain, 6 months postpartum. MR imaging, computed tomography and radiography were performed and a proximal tibia plateau insufficiency fracture was detected. Bone densitometry demonstrated mild postpartum osteoporosis. To our knowledge these findings have not been described in this location and in this clinical setting. The etiology of the atraumatic fracture of the tibia is presumed to be due to a low bone mineral density. The bone loss was probably due to pregnancy, lactation and postpartum hormonal changes. There were no other inciting causes and the patient was normocalcemic. We discuss the presence of a postpartum stress fracture in a hitherto undescribed site in a patient who had lactated following an uncomplicated pregnancy and had no other identifiable cause for a stress fracture. (orig.)
Proximity effect at Millikelvin temperatures
International Nuclear Information System (INIS)
Mota, A.C.
1986-01-01
Proximity effects have been studied extensively for the past 25 years. Typically, they are in films several thousand angstroms thick at temperatures not so far below T/sub CNS/, the transition temperature of the NS system. Interesting is, however, the proximity effect at temperatures much lower than T/sub CNS/. In this case, the Cooper-pair amplitudes are not small and very long pair penetration lengths into the normal metal can be expected. Thus, we have observed pair penetration lengths. For these investigations very suitable specimens are commercial wires of one filament of NbTi or Nb embedded in a copper matrix. The reasons are the high transmission coefficient at the interface between the copper and the superconductor and the fact that the copper in these commercial wires is rather clean with electron free paths between 5 to 10 μm long. In this paper, the magnetic properties of thick proximity systems in the range of temperatures between T/sub CNS/ and 5 x 10/sup -4/ T/sub CNS/ in both low and high magnetic fields are discussed
Dual pathology proximal median nerve compression of the forearm.
Murphy, Siun M; Browne, Katherine; Tuite, David J; O'Shaughnessy, Michael
2013-12-01
We report an unusual case of synchronous pathology in the forearm- the coexistence of a large lipoma of the median nerve together with an osteochondroma of the proximal ulna, giving rise to a dual proximal median nerve compression. Proximal median nerve compression neuropathies in the forearm are uncommon compared to the prevalence of distal compression neuropathies (eg Carpal Tunnel Syndrome). Both neural fibrolipomas (Refs. 1,2) and osteochondromas of the proximal ulna (Ref. 3) in isolation are rare but well documented. Unlike that of a distal compression, a proximal compression of the median nerve will often have a definite cause. Neural fibrolipoma, also called fibrolipomatous hamartoma are rare, slow-growing, benign tumours of peripheral nerves, most often occurring in the median nerve of younger patients. To our knowledge, this is the first report of such dual pathology in the same forearm, giving rise to a severe proximal compression of the median nerve. In this case, the nerve was being pushed anteriorly by the osteochondroma, and was being compressed from within by the intraneural lipoma. This unusual case highlights the advantage of preoperative imaging as part of the workup of proximal median nerve compression. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Promoter2.0: for the recognition of PolII promoter sequences
DEFF Research Database (Denmark)
Knudsen, Steen; Knudsen, Steen
1999-01-01
Motivation : A new approach to the prediction of eukaryotic PolII promoters from DNA sequence takesadvantage of a combination of elements similar to neural networks and genetic algorithms to recognize a set ofdiscrete subpatterns with variable separation as one pattern: a promoter. The neural...... of optimization, the algorithm was able todiscriminate between vertebrate promoter and non-promoter sequences in a test set with a correlationcoefficient of 0.63. In addition, all five known transcription start sites on the plus strand of the completeadenovirus genome were within 161 bp of 35 predicted...
Directory of Open Access Journals (Sweden)
Regina Augustin
2011-01-01
Full Text Available The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.
Tóth, P; Horváth, C; Ferencz, V; Tóth, B; Váradi, A; Szenci, O; Bodó, G
2013-01-01
Despite the fact that bone mineral density (BMD) is an important fracture risk predictor in human medicine, studies in equine orthopedic research are still lacking. We hypothesized that BMD correlates with bone failure and fatigue fractures of this bone. Thus, the objectives of this study were to measure the structural and mechanical properties of the proximal phalanx with dual energy X-ray absorptiometry (DXA), to correlate the data obtained from DXA and computer tomography (CT) measurements to those obtained by loading pressure examination and to establish representative region of interest (ROI) for in vitro BMD measurements of the equine proximal phalanx for predicting bone failure force. DXA was used to measure the whole bone BMD and additional three ROI sites in 14 equine proximal phalanges. Following evaluation of the bone density, whole bone, cortical width and area in the mid-diaphyseal plane were measured on CT images. Bones were broken using a manually controlled universal bone crusher to measure bone failure force and reevaluated for the site of fractures on follow-up CT images. Compressive load was applied at a constant displacement rate of 2 mm/min until failure, defined as the first clear drop in the load measurement. The lowest BMD was measured at the trabecular region (mean +/- SD: 1.52 +/- 0.12 g/cm2; median: 1.48 g/cm2; range: 1.38-1.83 g/cm2). There was a significant positive linear correlation between trabelcular BMD and the breaking strength (P = 0.023, r = 0.62). The trabecular region of the proximal phalanx appears to be the only significant indicator of failure of strength in vitro. This finding should be reassessed to further reveal the prognostic value of trabecular BMD in an in vivo fracture risk model.
Takabayashi, Yuki; Ishihara, Masayuki; Sumi, Yuki; Takikawa, Makoto; Nakamura, Shingo; Kiyosawa, Tomoharu
2015-01-01
Platelet-rich plasma (PRP) contains multiple growth factors, and fragmin-protamine micro-nanoparticles (F-P M-NPs) significantly enhance and stabilize growth factors. The purpose of this study was to evaluate the effects of PRP-containing F-P M-NPs (PRP&F-P M-NPs) on wound repair in split-thickness skin graft (STSG-) donor sites (DS). A total of 56 inbred male rats were anesthetized and split-thickness skin graft donor site (STSG-DS) were created with a Padgett dermatome. PRP&F-P M-NPs, F-P M-NPs, PRP, and saline (control) were then intradermally injected evenly into the STSG-DSs. On 3, 4, 5, 7, and 10 d after creation of STSG-DS, skin sample sections were stained with hematoxylin and eosin to evaluate reepithelialization and angiogenesis. Treatment of STSG-DS with PRP&F-P M-NPs effectively promoted epithelialization and new vessel formation compared with those treated with PRP, F-P M-NPs, and control (saline). The intradermal injection of PRP&F-P M-NPs promotes epithelialization and angiogenesis in STSG-DS wounds. Copyright © 2015 Elsevier Inc. All rights reserved.
Shim, Jaehong; Babu, A Giridhar; Velmurugan, Palanivel; Shea, Patrick J; Oh, Byung-Taek
2014-01-01
A bacterial strain (JH 70-4) exhibiting plant growth promoting characteristics (indoleacetic acid production and 1-aminocyclopropane-1-carboxylate deaminase activity), as well as heavy metal(loid) (HM) tolerance and Pb precipitation, was isolated from HM-contaminated soil at an abandoned mine site. The bacterium was identified as Pseudomonas fluorescens based on 16S rDNA sequencing. The JH 70-4 strain induced precipitation of Pb as PbS nanoparticles, confirmed by X-ray diffraction. Solution pH, incubation time, and Pb concentration influenced removal and PbS formation. Inoculating contaminated soil with JH 70-4 decreased Pb availability; exchangeable Pb decreased while organic- and sulphide-bound Pb increased. The toxicity characteristic leaching procedure showed a 65% decrease in Pb in leachate 60 d after inoculating soil with JH 70-4. Shoot and root lengths of Sudan grass grown in the inoculated soil were greater than in the uninoculated soil. Findings suggest that microbial Pb fixation is a viable strategy for remediating soil and promoting plant growth for phytostabilization of contaminated sites.
Social costs from proximity to hydraulic fracturing in New York State
International Nuclear Information System (INIS)
Popkin, Jennifer H.; Duke, Joshua M.; Borchers, Allison M.; Ilvento, Thomas
2013-01-01
The study reports data from an economic choice experiment to determine the likely welfare impacts of hydraulic fracturing, in this case using natural gas extracted by hydraulic fracturing for household electricity. Data were collected from an Internet survey of 515 residents of New York State. The welfare analysis indicated that on average households incur a welfare loss from in-state hydraulic fracturing as the source of their electricity. The evidence suggests that households in shale counties bear more costs from HF electricity than households out of shale counties. The average welfare loss is substantive, estimated at 40–46% of average household electric bills in shale counties and 16–20% of bills in counties without shale. The evidence also suggests that relative proximity to HF well sites also increases cost borne by households. -- Highlights: •New York households were surveyed to determine impacts of hydraulic fracturing. •Households on average lose welfare if hydraulic fracturing gas provides their electricity. •The average welfare loss is estimated to be 16–46% of respondents’ electricity bill. •The welfare impacts were heterogeneous, with some predicted to have welfare gain. •Proximity to hydraulic fracturing wells decreases welfare, on average
Steiner, Elisabeth; Holzmann, Klaus; Pirker, Christine; Elbling, Leonilla; Micksche, Michael; Berger, Walter
2004-04-23
The major vault protein (MVP) has been implicated in multidrug resistance, cellular transport, and malignant transformation. In this study we aimed to identify crucial MVP promoter elements that regulate MVP expression. By mutation as well as deletion analysis a conserved proximal GC-box element was demonstrated to be essential for basal human MVP promoter transactivation. Binding of Sp-family transcription factors but not AP2 to this element in vitro and in vivo was shown by EMSA and ChIP assays, respectively. Inhibition of GC-box binding by a dominant-negative Sp1-variant and by mithramycin A distinctly attenuated MVP promoter activity. In Sp-null Drosophila cells, the silent human MVP promoter was transactivated by several human Sp-family members. In human cells the MVP promoter was potently stimulated by the histone deacetylase (HDAC) inhibitors butyrate (NaB) and trichostatin A (TSA), resulting in enhanced MVP expression. This stimulation was substantially decreased by mutation of the single GC-box and by application of mithramycin A. Treatment with HDAC inhibitors led to a distinct decrease of Sp1 but increase of Sp3 binding in vivo to the respective promoter sequence as demonstrated by ChIP assays. Summarising, this study identifies variations in Sp-transcription factor binding to a single proximal GC-box element as critical for basal MVP promoter activation and its stimulation by HDAC inhibitors.
DEFF Research Database (Denmark)
Peng, Nan; Xia, Qiu; Chen, Zhengjun
2009-01-01
S gene encoding an arabinose binding protein was characterized using an Sulfolobus islandicus reporter gene system. The minimal active araS promoter (P(araS)) was found to be 59 nucleotides long and harboured four promoter elements: an ara-box, an upstream transcription factor B-responsive element (BRE......), a TATA-box and a proximal promoter element, each of which contained important nucleotides that either greatly decreased or completely abolished promoter activity upon mutagenesis. The basal araS promoter was virtually inactive due to intrinsically weak BRE element, and the upstream activating sequence...... (UAS) ara-box activated the basal promoter by recruiting transcription factor B to its BRE. While this UAS ensured a general expression from an inactive or weak basal promoter in the presence of other tested carbon resources, it exhibited a strong arabinose-responsive transcriptional activation. To our...
Uittenbogaard, Martine; Martinka, Debra L.; Johnson, Peter F.; Vinson, Charles; Chiaramello, Anne
2009-01-01
Expression of the bHLH transcription factor Nex1/MATH-2/NeuroD6, a member of the NeuroD subfamily, parallels overt neuronal differentiation and synaptogenesis during brain development. Our previous studies have shown that Nex1 is a critical effector of the NGF pathway and promotes neuronal differentiation and survival of PC12 cells in the absence of growth factors. In this study, we investigated the transcriptional regulation of the Nex1 gene during NGF-induced neuronal differentiation. We found that Nex1 expression is under the control of two conserved promoters, Nex1-P1 and Nex1-P2, located in two distinct non-coding exons. Both promoters are TATA-less with multiple transcription start sites, and are activated on NGF or cAMP exposure. Luciferase-reporter assays showed that the Nex1-P2 promoter activity is stronger than the Nex1-P1 promoter activity, which supports the previously reported differential expression levels of Nex1 transcripts throughout brain development. Using a combination of DNaseI footprinting, EMSA assays, and site-directed mutagenesis, we identified the essential regulatory elements within the first 2 kb of the Nex1 5′UTR. The Nex1-P1 promoter is mainly regulated by a conserved CRE element, whereas the Nex1-P2 promoter is under the control of a conserved C/EBP binding site. Overexpression of wild-type C/EBPβ resulted in increased Nex1-P2 promoter activity in NGF-differentiated PC12 cells. The fact that Nex1 is a target gene of C/EBPβ provides new insight into the C/EBP transcriptional cascade known to promote neurogenesis, while repressing gliogenesis. PMID:17075921
Guo, Lei; Rhen, Turk
2017-10-01
Sex is determined by temperature during embryogenesis in snapping turtles, Chelydra serpentina. Previous studies in this species show that dihydrotestosterone (DHT) induces ovarian development at temperatures that normally produce males or mixed sex ratios. The feminizing effect of DHT is associated with increased expression of FoxL2, suggesting that androgens regulate transcription of FoxL2. To test this hypothesis, we cloned the proximal promoter (1.6kb) and coding sequence for snapping turtle FoxL2 (tFoxL2) in frame with mCherry to produce a fluorescent reporter. The tFoxL2-mCherry fusion plasmid or mCherry control plasmid were stably transfected into mouse KK1 granulosa cells. These cells were then treated with 0, 1, 10, or 100nM DHT to assess androgen effects on tFoxL2-mCherry expression. In contrast to the main hypothesis, DHT did not alter expression of the tFoxL2-mCherry reporter. However, normal serum increased expression of tFoxL2-mCherry when compared to charcoal-stripped serum, indicating that the cloned region of tFoxL2 contains cis regulatory elements. We also used the tFoxL2-mCherry plasmid as an expression vector to test the hypothesis that DHT and tFoxL2 interact to regulate expression of endogenous genes in granulosa cells. While tFoxL2-mCherry and DHT had independent effects on mouse FoxL2, FshR, GnRHR, and StAR expression, tFoxL2-mCherry potentiated low concentration DHT effects on mouse aromatase expression. Further studies will be required to determine whether synergistic regulation of aromatase by DHT and FoxL2 also occurs in turtle gonads during the sex-determining period, which would explain the feminizing effect of DHT in this species. Copyright © 2017 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Schmitt, R.; Christopoulos, G.; Wagner, M.; Krimmer, H.; Fodor, S.; Schoonhoven, J. van; Prommersberger, K.J.
2011-01-01
Purpose: The purpose of this prospective study is to assess the diagnostic value of intravenously applied contrast agent for diagnosing osteonecrosis of the proximal fragment in scaphoid nonunion, and to compare the imaging results with intraoperative findings. Materials and methods: In 88 patients (7 women, 81 men) suffering from symptomatic scaphoid nonunion, preoperative MRI was performed (coronal PD-w FSE fs, sagittal-oblique T1-w SE nonenhanced and T1-w SE fs contrast-enhanced, sagittal T2*-w GRE). MRI interpretation was based on the intensity of contrast enhancement: 0 = none, 1 = focal, 2 = diffuse. Intraoperatively, the osseous viability was scored by means of bleeding points on the osteotomy site of the proximal scaphoid fragment: 0 = absent, 1 = moderate, 2 = good. Results: Intraoperatively, 17 necrotic, 29 compromised, and 42 normal proximal fragments were found. In nonenhanced MRI, bone viability was judged necrotic in 1 patient, compromised in 20 patients, and unaffected in 67 patients. Contrast-enhanced MRI revealed 14 necrotic, 21 compromised, and 53 normal proximal fragments. Judging surgical findings as the standard of reference, statistical analysis for nonenhanced MRI was: sensitivity 6.3%, specificity 100%, positive PV 100%, negative PV 82.6%, and accuracy 82.9%; statistics for contrast-enhanced MRI was: sensitivity 76.5%, specificity 98.6%, positive PV 92.9%, negative PV 94.6%, and accuracy 94.3%. Sensitivity for detecting avascular proximal fragments was significantly better (p < 0.001) in contrast-enhanced MRI in comparison to nonenhanced MRI. Conclusion: Viability of the proximal fragment in scaphoid nonunion can be significantly better assessed with the use of contrast-enhanced MRI as compared to nonenhanced MRI. Bone marrow edema is an inferior indicator of osteonecrosis. Application of intravenous gadolinium is recommended for imaging scaphoid nonunion.
Energy Technology Data Exchange (ETDEWEB)
Schmitt, R., E-mail: schmitt.radiologie@herzchirurgie.de [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Christopoulos, G.; Wagner, M. [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Krimmer, H. [Department of Hand Surgery, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Fodor, S. [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Schoonhoven, J. van; Prommersberger, K.J. [Department of Hand Surgery, Cardiovascular Center, Bad Neustadt an der Saale (Germany)
2011-02-15
Purpose: The purpose of this prospective study is to assess the diagnostic value of intravenously applied contrast agent for diagnosing osteonecrosis of the proximal fragment in scaphoid nonunion, and to compare the imaging results with intraoperative findings. Materials and methods: In 88 patients (7 women, 81 men) suffering from symptomatic scaphoid nonunion, preoperative MRI was performed (coronal PD-w FSE fs, sagittal-oblique T1-w SE nonenhanced and T1-w SE fs contrast-enhanced, sagittal T2*-w GRE). MRI interpretation was based on the intensity of contrast enhancement: 0 = none, 1 = focal, 2 = diffuse. Intraoperatively, the osseous viability was scored by means of bleeding points on the osteotomy site of the proximal scaphoid fragment: 0 = absent, 1 = moderate, 2 = good. Results: Intraoperatively, 17 necrotic, 29 compromised, and 42 normal proximal fragments were found. In nonenhanced MRI, bone viability was judged necrotic in 1 patient, compromised in 20 patients, and unaffected in 67 patients. Contrast-enhanced MRI revealed 14 necrotic, 21 compromised, and 53 normal proximal fragments. Judging surgical findings as the standard of reference, statistical analysis for nonenhanced MRI was: sensitivity 6.3%, specificity 100%, positive PV 100%, negative PV 82.6%, and accuracy 82.9%; statistics for contrast-enhanced MRI was: sensitivity 76.5%, specificity 98.6%, positive PV 92.9%, negative PV 94.6%, and accuracy 94.3%. Sensitivity for detecting avascular proximal fragments was significantly better (p < 0.001) in contrast-enhanced MRI in comparison to nonenhanced MRI. Conclusion: Viability of the proximal fragment in scaphoid nonunion can be significantly better assessed with the use of contrast-enhanced MRI as compared to nonenhanced MRI. Bone marrow edema is an inferior indicator of osteonecrosis. Application of intravenous gadolinium is recommended for imaging scaphoid nonunion.
Schmitt, R; Christopoulos, G; Wagner, M; Krimmer, H; Fodor, S; van Schoonhoven, J; Prommersberger, K J
2011-02-01
The purpose of this prospective study is to assess the diagnostic value of intravenously applied contrast agent for diagnosing osteonecrosis of the proximal fragment in scaphoid nonunion, and to compare the imaging results with intraoperative findings. In 88 patients (7 women, 81 men) suffering from symptomatic scaphoid nonunion, preoperative MRI was performed (coronal PD-w FSE fs, sagittal-oblique T1-w SE nonenhanced and T1-w SE fs contrast-enhanced, sagittal T2*-w GRE). MRI interpretation was based on the intensity of contrast enhancement: 0 = none, 1 = focal, 2 = diffuse. Intraoperatively, the osseous viability was scored by means of bleeding points on the osteotomy site of the proximal scaphoid fragment: 0=absent, 1 = moderate, 2 = good. Intraoperatively, 17 necrotic, 29 compromised, and 42 normal proximal fragments were found. In nonenhanced MRI, bone viability was judged necrotic in 1 patient, compromised in 20 patients, and unaffected in 67 patients. Contrast-enhanced MRI revealed 14 necrotic, 21 compromised, and 53 normal proximal fragments. Judging surgical findings as the standard of reference, statistical analysis for nonenhanced MRI was: sensitivity 6.3%, specificity 100%, positive PV 100%, negative PV 82.6%, and accuracy 82.9%; statistics for contrast-enhanced MRI was: sensitivity 76.5%, specificity 98.6%, positive PV 92.9%, negative PV 94.6%, and accuracy 94.3%. Sensitivity for detecting avascular proximal fragments was significantly better (p<0.001) in contrast-enhanced MRI in comparison to nonenhanced MRI. Viability of the proximal fragment in scaphoid nonunion can be significantly better assessed with the use of contrast-enhanced MRI as compared to nonenhanced MRI. Bone marrow edema is an inferior indicator of osteonecrosis. Application of intravenous gadolinium is recommended for imaging scaphoid nonunion. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
The developmental spectrum of proximal radioulnar synostosis
Energy Technology Data Exchange (ETDEWEB)
Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)
2010-01-15
Proximal radioulnar synostosis is a rare upper limb malformation. The elbow is first identifiable at 35 days (after conception), at which stage the cartilaginous anlagen of the humerus, radius and ulna are continuous. Subsequently, longitudinal segmentation produces separation of the distal radius and ulna. However, temporarily, the proximal ends are united and continue to share a common perichondrium. We investigated the hypothesis that posterior congenital dislocation of the radial head and proximal radioulnar fusion are different clinical manifestations of the same primary developmental abnormality. Records were searched for ''proximal radioulnar fusion/posterior radial head dislocation'' in patients followed at the local Children's Hospital and Rehabilitation Centre for Children. Relevant radiographic, demographic and clinical data were recorded. Ethics approval was obtained through the University Research Ethics Board. In total, 28 patients met the inclusion criteria. The majority of patients (16) had bilateral involvement; eight with posterior dislocation of the radial head only; five had posterior radial head dislocation with radioulnar fusion and two had radioulnar fusion without dislocation. One patient had bilateral proximal radioulnar fusion and posterior dislocation of the left radial head. Nine patients had only left-sided involvement, and three had only right-sided involvement.The degree of proximal fusion varied, with some patients showing 'complete' proximal fusion and others showing fusion that occurred slightly distal to the radial head: 'partially separated.' Associated disorders in our cohort included Poland syndrome (two patients), Cornelia de Lange syndrome, chromosome anomalies (including tetrasomy X) and Cenani Lenz syndactyly. The suggestion of a developmental relationship between posterior dislocation of the radial head and proximal radioulnar fusion is supported by the fact that both anomalies
Kenyon, Jonathan; Nickel-Meester, Gabrielle; Qing, Yulan; Santos-Guasch, Gabriela; Drake, Ellen; PingfuFu; Sun, Shuying; Bai, Xiaodong; Wald, David; Arts, Eric; Gerson, Stanton L
Normal human hematopoietic stem and progenitor cells (HPC) lose expression of MLH1 , an important mismatch repair (MMR) pathway gene, with age. Loss of MMR leads to replication dependent mutational events and microsatellite instability observed in secondary acute myelogenous leukemia and other hematologic malignancies. Epigenetic CpG methylation upstream of the MLH1 promoter is a contributing factor to acquired loss of MLH1 expression in tumors of the epithelia and proximal mucosa. Using single molecule high-throughput bisulfite sequencing we have characterized the CpG methylation landscape from -938 to -337 bp upstream of the MLH1 transcriptional start site (position +0), from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing MLH1 . We identify a correlation between MLH1 promoter methylation and loss of MLH1 expression. Additionally, using the CpG site methylation frequencies obtained in this study we were able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as has been previously described for many tumor cell types, we report for the first time a correlation between the loss of MLH1 expression and increased MLH1 promoter methylation in CFC derived from CD34 + selected hematopoietic stem and progenitor cells.
Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences
König, Sebastian L. B.; Huppert, Julian L.; Sigel, Roland K. O.; Evans, Amanda C.
2013-01-01
G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming regions. PMID:23771141
Directory of Open Access Journals (Sweden)
Chia-Ming Chang
2017-01-01
Full Text Available Objective: Despite its possible role in knee arthroplasty, the proximal-distal condylar length (PDCL of the femur has never been reported in the literature. We conducted an anatomic study of the proximal aspect of the medial femoral condyle to propose a method for measuring the PDCL. Materials and Methods: Inspection of dried bone specimens was carried out to assure the most proximal condylar margin (MPCM as the eligible starting point to measure the PDCL. Simulation surgery was performed on seven pairs of cadaveric knees to verify the clinical application of measuring the PDCL after locating the MPCM. Interobserver reliability of this procedure was also analyzed. Results: Observation of the bone specimens showed that the MPCM is a concavity formed by the junction of the distal end of the supracondylar ridge and the proximal margin of the medial condyle. This anatomically distinctive structure made the MPCM an unambiguous landmark. The cadaveric simulation surgical dissection demonstrated that the MPCM is easily accessed in a surgical setting, making the measurement of the PDCL plausible. The intraclass correlation coefficient was 0.78, indicating good interobserver reliability for this technique. Conclusion: This study has suggested that the PDCL can be measured based on the MPCM in a surgical setting. PDCL measurement might be useful in joint line position management, selection of femoral component sizes, and other applications related to the proximal-distal dimension of the knee. Further investigation is required.
CO Reduction to CH3OSiMe3: Electrophile-Promoted Hydride Migration at a Single Fe Site.
Deegan, Meaghan M; Peters, Jonas C
2017-02-22
One of the major challenges associated with developing molecular Fischer-Tropsch catalysts is the design of systems that promote the formation of C-H bonds from H 2 and CO while also facilitating the release of the resulting CO-derived organic products. To this end, we describe the synthesis of reduced iron-hydride/carbonyl complexes that enable an electrophile-promoted hydride migration process, resulting in the reduction of coordinated CO to a siloxymethyl (L n Fe-CH 2 OSiMe 3 ) group. Intramolecular hydride-to-CO migrations are extremely rare, and to our knowledge the system described herein is the first example where such a process can be accessed from a thermally stable M(CO)(H) complex. Further addition of H 2 to L n Fe-CH 2 OSiMe 3 releases CH 3 OSiMe 3 , demonstrating net four-electron reduction of CO to CH 3 OSiMe 3 at a single Fe site.
Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.
Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya
2015-12-01
Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation and Management of Proximal Humerus Fractures
Directory of Open Access Journals (Sweden)
Ekaterina Khmelnitskaya
2012-01-01
Full Text Available Proximal humerus fractures are common injuries, especially among older osteoporotic women. Restoration of function requires a thorough understanding of the neurovascular, musculotendinous, and bony anatomy. This paper addresses the relevant anatomy and highlights various management options, including indication for arthroplasty. In the vast majority of cases, proximal humerus fractures may be treated nonoperatively. In the case of displaced fractures, when surgical intervention may be pursued, numerous constructs have been investigated. Of these, the proximal humerus locking plate is the most widely used. Arthroplasty is generally reserved for comminuted 4-part fractures, head-split fractures, or fractures with significant underlying arthritic changes. Reverse total shoulder arthroplasty is reserved for patients with a deficient rotator cuff, or highly comminuted tuberosities.
The Life Saving Effects of Hospital Proximity
DEFF Research Database (Denmark)
Bertoli, Paola; Grembi, Veronica
We assess the lifesaving effect of hospital proximity using data on fatality rates of road-traffic accidents. While most of the literature on this topic is based on changes in distance to the nearest hospital triggered by hospital closures and use OLS estimates, our identification comes from......) increases the fatality rate by 13.84% on the sample average. This is equal to a 0.92 additional death per every 100 accidents. We show that OLS estimates provide a downward biased measure of the real effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity matters...... more when the road safety is low; the emergency service is not properly organized, and the nearest hospital has lower quality standards....
Promotion of Cultural Heritage in Batangas and Cavite
Directory of Open Access Journals (Sweden)
Dr. Dexter R. Buted
2014-06-01
Full Text Available – The study aimed to identify the commonly visited cultural heritage sites in Batangas and Cavite; to assess the cultural heritage sites in Batangas and Cavite in terms of physical, social and economic aspects; and to determine existing promotional patterns of Batangas and Cavite. Descriptive type of research was utilized in the study. Results showed that the most visited cultural heritage attraction in Taal, Batangas was Basilica of St. Martin de Tours while in Maragondon, Cavite the most visited was Andres Bonifacio Trial House . Blogs, Websites and Facebook are mostly used by the municipality of Taal in promoting their cultural heritage sites. While Cavite sticks to always using leaflets/flyers, brochures as their promotional materials. Cultural heritage sites in both Taal and Maragondon were perceived to have positive results in the assessments based on different aspects such as physical, social and economic aspects. The promotional materials of Taal and Maragondon are often used. A proposed plan of action was made to promote cultural attraction in Maragondon, Cavite and Taal, Batangas.
Lim, Megan S C; Wright, Cassandra J C; Carrotte, Elise R; Pedrana, Alisa E
2016-02-01
Issue addressed Social networking sites (SNS) are increasingly popular platforms for health promotion. Advancements in SNS health promotion require quality evidence; however, interventions are often not formally evaluated. This study aims to describe evaluation practices used in SNS health promotion. Methods A systematic review was undertaken of Medline, PsycINFO, Scopus, EMBASE, CINAHL Plus, Communication and Mass Media Complete, and Cochrane Library databases. Articles published between 2006 and 2013 describing any health promotion intervention delivered using SNS were included. Results Forty-seven studies were included. There were two main evaluation approaches: closed designs (n=23), which used traditional research designs and formal recruitment procedures; and open designs (n=19), which evaluated the intervention in a real-world setting, allowing unknown SNS users to interact with the content without enrolling in research. Closed designs were unable to assess reach and engagement beyond their research sample. Open designs often relied on weaker study designs with no use of objective outcome measures and yielded low response rates. Conclusions Barriers to evaluation included low participation rates, high attrition, unknown representativeness and lack of comparison groups. Acceptability was typically assessed among those engaged with the intervention, with limited population data available to accurately assess intervention reach. Few studies were able to assess uptake of the intervention in a real-life setting while simultaneously assessing effectiveness of interventions with research rigour. So what? Through use of quasi-experimental or well designed before-after evaluations, in combination with detailed engagement metrics, it is possible to balance assessment of effectiveness and reach to evaluate SNS health promotion.
International Nuclear Information System (INIS)
Erb, D.B.
2008-01-01
The Hanford Site's 200 Area Effluent Treatment Facility (ETF) processes contaminated aqueous wastes derived from Hanford Site facilities. The treated wastewater occasionally contains tritium, which cannot be removed by the ETF prior to the wastewater being discharged to the 200 Area State-Approved Land Disposal Site (SALDS). During the first 11 months of fiscal year 2008 (FY08) (September 1, 2007, to July 31, 2008), approximately 75.15 million L (19.85 million gal) of water were discharged to the SALDS. Groundwater monitoring for tritium and other constituents, as well as water-level measurements, is required for the SALDS by State Waste Discharge Permit Number ST-4500 (Ecology 2000). The current monitoring network consists of three proximal (compliance) monitoring wells and nine tritium-tracking wells. Quarterly sampling of the proximal wells occurred in October 2007 and in January/February 2008, April 2008, and August 2008. The nine tritium-tracking wells, including groundwater monitoring wells located upgradient and downgradient of the SALDS, were sampled in January through April 2008. Water-level measurements taken in the three proximal SALDS wells indicate that a small groundwater mound is present beneath the facility, which is a result of operational discharges. The mound increased in FY08 due to increased ETF discharges from treating groundwater from extraction wells at the 200-UP-l Operable Unit and the 241-T Tank Farm. Maximum tritium activities increased by an order of magnitude at well 699-48-77A (to 820,000 pCi/L in April 2008) but remained unchanged in the other two proximal wells. The increase was due to higher quantities of tritium in wastewaters that were treated and discharged in FY07 beginning to appear at the proximal wells. The FY08 tritium activities for the other two proximal wells were 68,000 pCi/L at well 699-48-77C (October 2007) and 120,000 pCi/L at well 699-48-77D (October 2007). To date, no indications of a tritium incursion from the
Lee, Kyung Ju; Lee, Kwang Youl; Lee, You Mie
2010-05-01
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a tumor suppressor and the suppression of RECK is induced by Ras or Her-2/neu oncogenes. However, regulation of RECK under hypoxic microenvironment is largely unknown. Here, we identified that hypoxia significantly downregulates RECK mRNA and protein expression using semiquantitative RT-PCR, real-time RT-PCR and western blot analysis. This repression was reversed by the HDAC inhibitor, trichostatin A (TSA) and HIF-1 inhibitor, YC-1. Hypoxia-induced downregulation of RECK was abolished by knockdown of HDAC1 and HIF-1alpha with respective small interfering RNAs (siRNAs), whereas overexpression of HDAC1 and HIF-1alpha suppressed RECK expression similar to the level under hypoxic conditions. Transfection of a deletion mutant of the second reverse HRE (rHRE2, -2345 to -2333) site of RECK promoter completely removed RECK suppression under hypoxia, indicating that the rHRE2 site is responsible for the inhibition of RECK. Chromatin immunoprecipitation and DNA affinity precipitation assays demonstrated that HDAC1 and HIF-1alpha were recruited to the rHRE2 region of RECK promoter under hypoxic conditions, but the treatment of TSA or YC-1 inhibited their binding to the rHRE2 site. Moreover, TSA and YC-1 inhibited hypoxia-induced cancer cell migration, invasion and MMPs secretion. Taken together, we can conclude that hypoxia induces RECK downregulation through the recruitment of HDAC1 and HIF-1alpha to the rHRE2 site in the promoter and the inhibition of hypoxic RECK silencing would be a therapeutic and preventive target for early tumorigenesis. Copyright 2010 Elsevier B.V. All rights reserved.
Proximal Focal Femoral Deficiency in Ibadan a Developing ...
African Journals Online (AJOL)
The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...
[Avulsion of the Proximal Hamstring Insertion. Case Reports].
Mizera, R; Harcuba, R; Kratochvíl, J
2016-01-01
Proximal hamstring avulsion is an uncommon muscle injury with a lack of consensus on indications and the timing and technique of surgery. Poor clinical symptoms and difficulties in the diagnostic process can lead to a false diagnosis. The authors present three cases of proximal hamstring avulsion, two complete and one partial ruptures of the biceps femoris muscle. MRI and ultrasound scans were used for optimal treatment alignment. Acute surgery reconstruction (hamstring strength. Two interesting systematic reviews published on the treatment of proximal hamstring avulsion are discussed in the final part of the paper. Key words: hamstring, rupture, avulsion.
A dual-mode proximity sensor with integrated capacitive and temperature sensing units
International Nuclear Information System (INIS)
Qiu, Shihua; Huang, Ying; He, Xiaoyue; Sun, Zhiguang; Liu, Ping; Liu, Caixia
2015-01-01
The proximity sensor is one of the most important devices in the field of robot application. It can accurately provide the proximity information to assistant robots to interact with human beings and the external environment safely. In this paper, we have proposed and demonstrated a dual-mode proximity sensor composed of capacitive and resistive sensing units. We defined the capacitive type proximity sensor perceiving the proximity information as C-mode and the resistive type proximity sensor detecting as R-mode. Graphene nanoplatelets (GNPs) were chosen as the R-mode sensing material because of its high performance. The dual-mode proximity sensor presents the following features: (1) the sensing distance of the dual-mode proximity sensor has been enlarged compared with the single capacitive proximity sensor in the same geometrical pattern; (2) experiments have verified that the proposed sensor can sense the proximity information of different materials; (3) the proximity sensing capability of the sensor has been improved by two modes perceive collaboratively, for a plastic block at a temperature of 60 °C: the R-mode will perceive the proximity information when the distance d between the sensor and object is 6.0–17.0 mm and the C-mode will do that when their interval is 0–2.0 mm; additionally two modes will work together when the distance is 2.0–6.0 mm. These features indicate our transducer is very valuable in skin-like sensing applications. (paper)
Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation
International Nuclear Information System (INIS)
Wu, Yanyuan; Alvarez, Monica; Slamon, Dennis J; Koeffler, Phillip; Vadgama, Jaydutt V
2010-01-01
Epigenetic changes associated with promoter DNA methylation results in silencing of several tumor suppressor genes that lead to increased risk for tumor formation and for progression of the cancer. Methylation specific PCR (MSP) and bisulfite sequencing were used for determination of proapoptotic gene Caspase 8 (CASP8) and the tumor suppressor gene maspin promoter methylation in four breast cancer and two non-tumorigenic breast cell lines. Involvement of histone H3 methylation in those cell lines were examined by CHIP assay. The CpG sites in the promoter region of CASP8 and maspin were methylated in all four breast cancer cell lines but not in two non-tumorigenic breast cell lines. Demethylation agent 5-aza-2'-deoxycytidine (5-aza-dc) selectively inhibits DNA methyltransferases, DNMT3a and DNMT3b, and restored CASP8 and maspin gene expression in breast cancer cells. 5-aza-dc also reduced histone H3k9me2 occupancy on CASP8 promoter in SKBR3cells, but not in MCF-7 cells. Combination of histone deacetylase inhibitor Trichostatin A (TSA) and 5-aza-dc significant decrease in nuclear expression of Di-methyl histone H3-Lys27 and slight increase in acetyl histone H3-Lys9 in MCF-7 cells. CASP8 mRNA and protein level in MCF-7 cells were increased by the 5-aza-dc in combination with TSA. Data from our study also demonstrated that treatment with 5-FU caused a significant increase in unmethylated CASP8 and in CASP8 mRNA in all 3 cancer lines. CASP8 and maspin expression were reduced in breast cancer cells due to promoter methylation. Selective application of demethylating agents could offer novel therapeutic opportunities in breast cancer
Dose ratio proton radiography using the proximal side of the Bragg peak
Energy Technology Data Exchange (ETDEWEB)
Doolan, P. J., E-mail: paul.doolan.09@ucl.ac.uk; Royle, G.; Gibson, A. [Department of Medical Physics and Bioengineering, University College London, London WC1E 6BT (United Kingdom); Lu, H.-M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Prieels, D.; Bentefour, E. H. [Ion Beam Applications (IBA), 3 Chemin du Cyclotron, Louvain la Neuve B-1348 (Belgium)
2015-04-15
Purpose: In recent years, there has been a movement toward single-detector proton radiography, due to its potential ease of implementation within the clinical environment. One such single-detector technique is the dose ratio method in which the dose maps from two pristine Bragg peaks are recorded beyond the patient. To date, this has only been investigated on the distal side of the lower energy Bragg peak, due to the sharp falloff. The authors investigate the limits and applicability of the dose ratio method on the proximal side of the lower energy Bragg peak, which has the potential to allow a much wider range of water-equivalent thicknesses (WET) to be imaged. Comparisons are made with the use of the distal side of the Bragg peak. Methods: Using the analytical approximation for the Bragg peak, the authors generated theoretical dose ratio curves for a range of energy pairs, and then determined how an uncertainty in the dose ratio would translate to a spread in the WET estimate. By defining this spread as the accuracy one could achieve in the WET estimate, the authors were able to generate lookup graphs of the range on the proximal side of the Bragg peak that one could reliably use. These were dependent on the energy pair, noise level in the dose ratio image and the required accuracy in the WET. Using these lookup graphs, the authors investigated the applicability of the technique for a range of patient treatment sites. The authors validated the theoretical approach with experimental measurements using a complementary metal oxide semiconductor active pixel sensor (CMOS APS), by imaging a small sapphire sphere in a high energy proton beam. Results: Provided the noise level in the dose ratio image was 1% or less, a larger spread of WETs could be imaged using the proximal side of the Bragg peak (max 5.31 cm) compared to the distal side (max 2.42 cm). In simulation, it was found that, for a pediatric brain, it is possible to use the technique to image a region with a
SREBP inhibits VEGF expression in human smooth muscle cells
Energy Technology Data Exchange (ETDEWEB)
Motoyama, Koka [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Fukumoto, Shinya [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Koyama, Hidenori [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Emoto, Masanori [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan); Shimano, Hitoshi [Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Maemura, Koji [Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Nishizawa, Yoshiki [Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan)
2006-03-31
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs.
SREBP inhibits VEGF expression in human smooth muscle cells
International Nuclear Information System (INIS)
Motoyama, Koka; Fukumoto, Shinya; Koyama, Hidenori; Emoto, Masanori; Shimano, Hitoshi; Maemura, Koji; Nishizawa, Yoshiki
2006-01-01
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs
Energy Technology Data Exchange (ETDEWEB)
Passos-Bueno, M.R.; Takata, R.I.; Rapaport, D.; Bakker, E.; Kneppers, A.L.J.; Dunnen, J.T. den; Ommen, J.B. van
1992-11-01
In about 65% of the cases of Duchenne muscular dystrophy (DMD) a partial gene deletion or duplication in the dystrophin gene can be detected. These mutations are clustered at two hot spots: 30% at the hot spot in the proximal part of the gene and about 70% at a more distal hot spot. Unexpectedly the authors observed a higher frequency of proximal gene rearrangements among proved germ line' mosaic cases. Of the 24 mosaic cases they are aware of, 19 (79%) have a proximal mutation, while only 5 (21%) have a distal mutation. This finding indicates that the mutations at the two hot spots in the dystrophin gene differ in origin. Independent support for the different mosaicism frequency was found by comparing the mutation spectra observed in isolated cases of DMD and familial cases (ratio 1:1). The authors conclude from these data that proximal deletions most likely occur early in embryonic development, causing them to have a higher chance of becoming familial, while distal deletions occur later and have a higher chance of causing only isolated cases. Finally, the findings have important consequences for the calculation of recurrence-risk estimates according to the site of the deletion: a [open quote]proximal[close quote] new mutant has an increased recurrence risk of approximately 30%, and a [open quote]distal[close quote] new mutant has a decreased recurrence risk of approximately 4%. 28 refs., 2 figs., 2 tabs.
A Regularized Algorithm for the Proximal Split Feasibility Problem
Directory of Open Access Journals (Sweden)
Zhangsong Yao
2014-01-01
Full Text Available The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.
Proximity approach to problems in topology and analysis
Naimpally, Somashekhar
2009-01-01
Dieses Buch konzentriert das aktuelle Gesamtwissen zum Proximity-Konzept und stellt es dem Leser in gut strukturierter Form dar. Hauptaugenmerk liegt auf den vielfältigen Möglichkeiten, die sich aus dem Proximity-Konzept der räumlichen Nähe und seiner Verallgemeinerung im Nearness-Konzept ergeben.
Proximity effects in ferromagnet/superconductor structures
International Nuclear Information System (INIS)
Yu, H.L.; Sun, G.Y.; Yang, L.Y.; Xing, D.Y.
2004-01-01
The Nambu spinor Green's function approach is applied to study proximity effects in ferromagnet/superconductor (FM/SC) structures. They include the induced superconducting order parameter and density of states (DOS) with superconducting feature on the FM side, and spin-dependent DOS within the energy gap on the SC side. The latter indicates an appearance of gapless superconductivity and a coexistence of ferromagnetism and superconductivity in a small regime near the interface. The influence of exchange energy in FM and barrier strength at interface on the proximity effects is discussed
Directory of Open Access Journals (Sweden)
Krasil'nikova Tatyana
2017-01-01
Full Text Available This paper discusses the problem associated with accidents in the aerial line (AL ultra-high voltage (UHV due to its big length. In lines with a voltage of 500-1150 kV the overwhelming proportion of trips (98% is caused by single-phase short circuit (SPSC. A substantial portion (70% single-phase short circuits is erratic arc accidents which can be successfully eliminated in a high-speed auto-reclosing (HSAR or single-phase auto-reclosing (SPAR. Success single-phase auto-reclosing (SPAR at liquidation by single-phase short circuit (SPSC, on the one hand, is determined by the characteristics of the secondary arc current, and on the other hand the effectiveness of ways to reduce secondary arc current and recovery voltage development. The minimum dead time, at a HSAR it is usually taken as 0.5 s., at single-phase autoreclosing (SPAR it depends on the current value of the arc support is in the range of 0.5-3.0 s. The article shows high efficiency of use single-phase auto reclosing (SPAR at liquidation SPSC in a single-chain AL voltage of 500 kV, the dependence of the bandwidth of transmission in maintaining the dynamic stability from the length of the pause SPAR.
Brünisholz, Hervé P; Hagen, Regine; Fürst, Anton E; Kuemmerle, Jan M
2015-10-01
To characterize the configuration of incomplete proximal fractures of the proximal phalanx (P1) in horses not used for racing and compare radiographic with computed tomography (CT) findings. Historical cohort. Twenty-four horses with incomplete fractures of P1. Medical records of horses not used for racing diagnosed with an incomplete proximal fracture of P1 based on clinical and radiographic examination and confirmed by CT between 2008 and 2013 were retrieved. Radiographs and CT studies of these horses were analyzed using a subjective grading system and by measuring variables that characterized fracture configuration. Twenty-four horses were included (20 Warmbloods) with a mean age of 9.5 years and mean body weight of 574 kg. Fourteen forelimbs and 10 hind limbs were affected. Mean duration of lameness was 8.7 weeks. Computed tomography was superior to radiography in both identifying the fracture and determining fracture size and location. On CT, 92% of fractures were located in the mid-sagittal plane. Mean proximodistal length of the fracture was 13 mm. Fractures were frequently not bicortical. Fractures in forelimbs were located significantly more dorsally than fractures in hind limbs. A distinct fracture pattern with 2 subchondral lines running parallel in close proximity to each other was identified in 54% of cases. Incomplete proximal fractures of P1 have significant variation in their configurations, especially their dorsopalmar/-plantar location. Computed tomography examination allowed clear identification of the fracture configurations and was superior to radiography. © Copyright 2015 by The American College of Veterinary Surgeons.
Cell Cycle Regulation by Alternative Polyadenylation of CCND1.
Wang, Qiong; He, Guopei; Hou, Mengmeng; Chen, Liutao; Chen, Shangwu; Xu, Anlong; Fu, Yonggui
2018-05-01
Global shortening of 3'UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA.
Directory of Open Access Journals (Sweden)
J. R. Patton
2013-04-01
Full Text Available Turbidite deposition along slope and trench settings is evaluated for the Cascadia and Sumatra–Andaman subduction zones. Source proximity, basin effects, turbidity current flow path, temporal and spatial earthquake rupture, hydrodynamics, and topography all likely play roles in the deposition of the turbidites as evidenced by the vertical structure of the final deposits. Channel systems tend to promote low-frequency components of the content of the current over longer distances, while more proximal slope basins and base-of-slope apron fan settings result in a turbidite structure that is likely influenced by local physiography and other factors. Cascadia's margin is dominated by glacial cycle constructed pathways which promote turbidity current flows for large distances. Sumatra margin pathways do not inherit these antecedent sedimentary systems, so turbidity currents are more localized.
Langenhan, Ronny; Bushuven, Stefanie; Reimers, Niklas; Probst, Axel
2018-04-01
The aim of this study was to conduct a re-evaluation of current strategies for peri-operative prophylaxis of infections in orthopaedic surgery of geriatric patients (≥65 years) with proximal femoral fractures (PFF). Between 01/2010 and 08/2014 all post-operative infections after stabilization of PFF of 1,089 geriatric patients were recorded retrospectively. All patients pre-operatively received a single dose of 1.5 g cefuroxime (group 1). These were compared to prospectively determined post-operative rates of surgical site infection (SSI) of 441 geriatric patients, which were operated on between 09/2014 and 03/2017 due to PFF. In this second group we investigated the urinary tract on admission. Bacteriuria was treated with the pre-operative single dose of 1.5 g cefuroxime along with ciprofloxacin for five days, beginning on admission. Level of significance was set to p infection. Multi-resistant pathogens were found in 15 patients and pathogens were cefuroxime-resistant in 37. The differences of SSI after at least three months were 2.1% in group 1 and 0.45% in group 2 for all patients with surgery of PFF (p < 0.02) and for those with arthroplasty (p < 0.037) significant. The immediate antibiotic therapy of a prevalent bacteriuria for five days decreases the risk of SSI after surgery of PFF. Our single-centre study can only point out the problem of prevalent reservoirs of pathogens and the need for treatment. Evidence-based therapy concepts (indications of antibiotics, classes, duration) have to be developed in multi-centric and prospective studies.
Social network sites: Indispensable or optional social tools?
DEFF Research Database (Denmark)
Shklovski, Irina
2012-01-01
Much research has enumerated potential benefits of online social network sites. Given the pervasiveness of these sites and the numbers of people that use them daily, both re-search and media tend to make the assumption that social network sites have become indispensible to their users. Based...... on the analysis of qualitative data from users of social network sites in Russia and Kazakhstan, this paper consid-ers under what conditions social network sites can become indispensable to their users and when these technologies remain on the periphery of life despite fulfilling useful func-tions. For some...... respondents, these sites had become indis-pensable tools as they were integrated into everyday rou-tines of communicating with emotionally important and proximal contacts and were often used for coordination of offline activities. For others social network sites remained spaces where they occasionally visited...
Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter
International Nuclear Information System (INIS)
Dahabieh, Matthew S.; Ooms, Marcel; Malcolm, Tom; Simon, Viviana; Sadowski, Ivan
2011-01-01
Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutations in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.
Robb, Nicole C.; Cordes, Thorben; Hwang, Ling Chin; Gryte, Kristofer; Duchi, Diego; Craggs, Timothy D.; Santoso, Yusdi; Weiss, Shimon; Ebright, Richard H.; Kapanidis, Achillefs N.
2013-01-01
Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts similar to 14 bp around the transcription start site and forms a single-stranded "transcription bubble" within a catalytically active RNAP-DNA open complex (RPo). There is significant flexibility in the
Directory of Open Access Journals (Sweden)
Zile Singh Kundu
2018-01-01
Full Text Available Background: Primary benign and malignant tumors of the proximal fibula are not very common. Upper fibula being an expendable bone; the majority of the primary bone tumors at this site are usually treated with en bloc proximal fibulectomy. There is scarce literature on functional results, difficulties faced during dissection when to preserve or sacrifice common peroneal nerve and importance of lateral collateral ligament repair after proximal fibulectomy. The present study attempts at assessing these variables. Materials and Methods: This retrospective study included 46 patients; 30 males and 16 females with age ranging from 12 to 44 years (average: 26 years operated between 2003 and 2014. There were 34 benign and 12 malignant tumors. All were treated with proximal en bloc fibulectomy as indicated and decided by the operating surgeon keeping in view its extent on magnetic resonance imaging. Peroneal nerve sacrifice or preservation was decided as per the type (benign/malignant, its involvement by the tumor and the extent of the tumor. In 14 (for 12 malignant and two benign giant cell tumors [GCTs] patients, the peroneal nerve required resection for the margins. Partial upper tibial resection was performed in cases of malignant tumors and three GCTs. The followup ranged between 24 and 120 months (median: 48 months. Results: Patients with peroneal nerve resection had inferior functional outcome than those without peroneal nerve resection. There was no higher risk of tibia fracture in patients with partial tibial resection. Lateral collateral reconstruction yielded better results and should be performed in all cases. Functional outcome was significantly better in patients with benign tumors than in patients with malignant tumors as these required neither resection of the peroneal nerve nor large amount of muscle excision. The functional results were evaluated using Musculoskeletal Tumor Society (MSTS score, and clinical outcomes were evaluated using
Characteristics of food industry web sites and "advergames" targeting children.
Culp, Jennifer; Bell, Robert A; Cassady, Diana
2010-01-01
To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A total of 290 Web pages and 247 unique games on 19 Internet sites were examined. Games, found on 81% of Web sites, were the most predominant promotion strategy used. All games had at least 1 brand identifier, with logos being most frequently used. On average Web sites contained 1 "healthful" message for every 45 exposures to brand identifiers. Food companies use Web sites to extend their television advertising to promote brand loyalty among children. These sites almost exclusively promoted food items high in sugar and fat. Health professionals need to monitor food industry marketing practices used in "new media." Published by Elsevier Inc.
Two-Step Proximal Gradient Algorithm for Low-Rank Matrix Completion
Directory of Open Access Journals (Sweden)
Qiuyu Wang
2016-06-01
Full Text Available In this paper, we propose a two-step proximal gradient algorithm to solve nuclear norm regularized least squares for the purpose of recovering low-rank data matrix from sampling of its entries. Each iteration generated by the proposed algorithm is a combination of the latest three points, namely, the previous point, the current iterate, and its proximal gradient point. This algorithm preserves the computational simplicity of classical proximal gradient algorithm where a singular value decomposition in proximal operator is involved. Global convergence is followed directly in the literature. Numerical results are reported to show the efficiency of the algorithm.
Directory of Open Access Journals (Sweden)
Scott F. Beers
2017-06-01
Full Text Available This study explored the effects of transcription on translation products and processes of adolescent students in grades 4 to 9 with and without persisting specific language disabilities in written language (SLDs—WL. To operationalize transcription ability (handwriting and spelling and transcription mode (by pen on digital tablet or by standard US keyboard, diagnostic groups contrasting in patterns of transcription ability were compared while composing autobiographical (personal narratives by handwriting or by keyboarding: Typically developing students (n=15, students with dyslexia (impaired word reading and spelling, n=20, and students with dysgraphia (impaired handwriting, n=19. They were compared on seven outcomes: total words composed, total composing time, words per minute, percent of spelling errors, average length of pauses, average number of pauses per minute, and average length of language bursts. They were also compared on automaticity of transcription modes—writing the alphabet from memory by handwriting or keyboarding (they could look at keys. Mixed ANOVAs yielded main effects for diagnostic group on percent of spelling errors, words per minute, and length of language burst. Main effects for transcription modes were found for automaticity of writing modes, total words composed, words per minute, and length of language bursts; there were no significant interactions. Regardless of mode, the dyslexia group had more spelling errors, showed a slower rate of composing, and produced shorter language bursts than the typical group. The total number of words, total time composing, words composed per minute, and pauses per minute were greater for keyboarding than handwriting, but length of language bursts was greater for handwriting. Implications of these results for conceptual models of composing and educational assessment practices are discussed.
The Contribution of SPECT/CT in the Diagnosis of Stress Fracture of the Proximal Tibia.
Okudan, Berna; Coşkun, Nazım; Arıcan, Pelin
2018-02-01
Stress fractures are injuries most commonly seen in the lower limbs and are usually caused by repetitive stress. While the distal and middle third of the tibia is the most frequent site for stress fractures (almost 50%), stress fractures of the proximal tibia is relatively rare and could be confused with other types of tibial fractures, thus altering management plans for the clinician. Early diagnosis of stress fractures is also important to avoid complications. Imaging plays an important role in the diagnosis of stress fractures, especially bone scan. Combined with single-photon emission computed tomography/computed tomography (SPECT/CT) it is an important imaging technique for stress fractures in both upper and lower extremities, and is widely preferred over other imaging techniques. In this case, we present the case of a 39-year-old male patient diagnosed with stress fracture of the proximal tibia and demonstrate the contribution of CT scan fused with SPECT imaging in the early diagnosis of stress fracture prior to other imaging modalities.
Electromagnetic properties of proximity systems
Kresin, Vladimir Z.
1985-07-01
Magnetic screening in the proximity system Sα-Mβ, where Mβ is a normal metal N, semiconductor (semimetal), or a superconductor, is studied. Main attention is paid to the low-temperature region where nonlocality plays an important role. The thermodynamic Green's-function method is employed in order to describe the behavior of the proximity system in an external field. The temperature and thickness dependences of the penetration depth λ are obtained. The dependence λ(T) differs in a striking way from the dependence in usual superconductors. The strong-coupling effect is taken into account. A special case of screening in a superconducting film backed by a size-quantizing semimetal film is considered. The results obtained are in good agreement with experimental data.
Electromagnetic properties of proximity systems
International Nuclear Information System (INIS)
Kresin, V.Z.
1985-01-01
Magnetic screening in the proximity system S/sub α/-M/sub β/, where M/sub β/ is a normal metal N, semiconductor (semimetal), or a superconductor, is studied. Main attention is paid to the low-temperature region where nonlocality plays an important role. The thermodynamic Green's-function method is employed in order to describe the behavior of the proximity system in an external field. The temperature and thickness dependences of the penetration depth lambda are obtained. The dependence lambda(T) differs in a striking way from the dependence in usual superconductors. The strong-coupling effect is taken into account. A special case of screening in a superconducting film backed by a size-quantizing semimetal film is considered. The results obtained are in good agreement with experimental data
Proximity operations concept design study, task 6
Williams, A. N.
1990-01-01
The feasibility of using optical technology to perform the mission of the proximity operations communications subsystem on Space Station Freedom was determined. Proximity operations mission requirements are determined and the relationship to the overall operational environment of the space station is defined. From this information, the design requirements of the communication subsystem are derived. Based on these requirements, a preliminary design is developed and the feasibility of implementation determined. To support the Orbital Maneuvering Vehicle and National Space Transportation System, the optical system development is straightforward. The requirements on extra-vehicular activity are such as to allow large fields of uncertainty, thus exacerbating the acquisition problem; however, an approach is given that could mitigate this problem. In general, it is found that such a system could indeed perform the proximity operations mission requirement, with some development required to support extra-vehicular activity.
Proximate analysis of Lentinus squarrosulus (Mont.) Singer and ...
African Journals Online (AJOL)
Each of the mushroom species was separated into its stipe and pileus and used for proximate analysis. There was a highly significant difference (p<0.01) in the proximate composition of the two species. P. atroumbonata had significantly higher crude protein, crude fibre and moisture content than L. squarrosulus while the ...
Genetics Home Reference: proximal 18q deletion syndrome
... characteristic features. Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a ... J, Fox PT, Stratton RF, Perry B, Hale DE. Recurrent interstitial deletions of proximal 18q: a new syndrome involving expressive speech delay. Am J Med Genet ...
Superconducting proximity effect in topological materials
Reeg, Christopher R.
In recent years, there has been a renewed interest in the proximity effect due to its role in the realization of topological superconductivity. In this dissertation, we discuss several results that have been obtained in the field of proximity-induced superconductivity and relate the results to the search for Majorana fermions. First, we show that repulsive electron-electron interactions can induce a non-Majorana zero-energy bound state at the interface between a conventional superconductor and a normal metal. We show that this state is very sensitive to disorder, owing to its lack of topological protection. Second, we show that Rashba spin-orbit coupling, which is one of the key ingredients in engineering a topological superconductor, induces triplet pairing in the proximity effect. When the spin-orbit coupling is strong (i.e., when the characteristic energy scale for spin-orbit coupling is comparable to the Fermi energy), the induced singlet and triplet pairing amplitudes can be comparable in magnitude. Finally, we discuss how the size of the proximity-induced gap, which appears in a low-dimensional material coupled to a superconductor, evolves as the thickness of the (quasi-)low-dimensional material is increased. We show that the induced gap can be comparable to the bulk energy gap of the underlying superconductor in materials that are much thicker than the Fermi wavelength, even in the presence of an interfacial barrier and strong Fermi surface mismatch. This result has important experimental consequences for topological superconductivity, as a sizable gap is required to isolate and detect the Majorana modes.
Estradiol represses Insulin-like 3 expression and promoter activity in MA-10 Leydig cells
International Nuclear Information System (INIS)
Lague, Eric; Tremblay, Jacques J.
2009-01-01
There are increasing evidence in the literature reporting the detrimental effects of endocrine disruptors on the development and function of the male reproductive system. One example is cryptorchidism, or undescended testis, caused by exposure to excessive estrogens. Estrogens, acting through the estrogen receptor α (ERα), have been shown to repress expression of the gene encoding insulin-like 3 (INSL3), a small peptide produced by testicular Leydig cells that is essential for normal testis descent. The molecular mechanism of estrogen/ER action on Insl3 expression, however, remains poorly understood. Here we report estradiol (E 2 ) represses Insl3 mRNA levels in MA-10 cells, a Leydig cell line model. We also found that E 2 represses the activity of the human and mouse Insl3 promoter in these cells. The E 2 -responsive region of the human INSL3 promoter was located to the proximal INSL3 promoter. This region does not contain a consensus estrogen response element indicating an indirect mechanism of action. In agreement with this, we found that E 2 -responsiveness was lost when two previously characterized binding sites for the nuclear receptors NUR77 and SF1 were mutated. Finally we show that the E 2 repressive effect could be overcome by cotreatment with testosterone, a positive regulator of Insl3 transcription. Collectively our data provide important new insights into the molecular mechanism of estrogen action in Insl3 transcription in Leydig cells
Keerthivasan, Shilpa; Aghajani, Katayoun; Dose, Marei; Molinero, Luciana; Khan, Mohammad W; Venkateswaran, Vysak; Weber, Christopher; Emmanuel, Akinola Olumide; Sun, Tianjao; Bentrem, David J; Mulcahy, Mary; Keshavarzian, Ali; Ramos, Elena M; Blatner, Nichole; Khazaie, Khashayarsha; Gounari, Fotini
2014-02-26
The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial. We recently reported that Tregs in colon cancer patients can become proinflammatory and tumor-promoting. These properties were directly linked with their expression of RORγt (retinoic acid-related orphan receptor-γt), the signature transcription factor of T(H)17 cells. We report that Wnt/β-catenin signaling in T cells promotes expression of RORγt. Expression of β-catenin was elevated in T cells, including Tregs, of patients with colon cancer. Genetically engineered activation of β-catenin in mouse T cells resulted in enhanced chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites genome-wide, induced expression of T(H)17 signature genes including RORγt, and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation of small intestine and colon and developed lesions indistinguishable from colitis-induced cancer. Activation of β-catenin only in Tregs was sufficient to produce inflammation and initiate cancer. On the basis of these findings, we conclude that activation of Wnt/β-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer.
Proximal focal femoral deficiency: A case report
Directory of Open Access Journals (Sweden)
Shashank Sharma
2015-01-01
Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.
Directory of Open Access Journals (Sweden)
Chun-Ming Chen
2008-02-01
Full Text Available Maxillary sinus enlargement often occurs in the maxillary posterior edentulous area and reduces the available bone height for implantation. Therefore, maxillary sinus lift and bone graft procedures are necessary to provide sufficient available bone. Autogenous bone grafting is the best base for implant osseointegration. Recently, tibial bone has been recognized as an alternative extraoral donor site. We present a case in which we used a proximal tibia bone graft for maxillary sinus augmentation under local anesthesia without sedation in the dental office. During a 4-year postoperative follow-up, gait was not disturbed and the scar on the donor site remained unremarkable.
Systemic calciphylaxis presenting as a painful, proximal myopathy.
Edelstein, C. L.; Wickham, M. K.; Kirby, P. A.
1992-01-01
A renal transplant patient who presented with a painful, proximal myopathy due to systemic calciphylaxis is described. The myopathy preceded the characteristic skin and soft tissue necrosis. Systemic calciphylaxis should be considered in a dialysis or a renal transplant patient presenting with a painful proximal myopathy even in the absence of necrotic skin lesions.
Anatomy and Biomechanics of the Finger Proximal Interphalangeal Joint.
Pang, Eric Quan; Yao, Jeffrey
2018-05-01
A complete understanding of the normal anatomy and biomechanics of the proximal interphalangeal joint is critical when treating pathology of the joint as well as in the design of new reconstructive treatments. The osseous anatomy dictates the principles of motion at the proximal interphalangeal joint. Subsequently, the joint is stabilized throughout its motion by the surrounding proximal collateral ligament, accessory collateral ligament, and volar plate. The goal of this article is to review the normal anatomy and biomechanics of the proximal interphalangeal joint and its associated structures, most importantly the proper collateral ligament, accessory collateral ligament, and volar plate. Copyright © 2017 Elsevier Inc. All rights reserved.
Origins and Impacts of New Mammalian Exons
Directory of Open Access Journals (Sweden)
Jason J. Merkin
2015-03-01
Full Text Available Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5′ UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5′ ends of genes enhances expression and that changes in 5′ end splicing alter gene expression between tissues and between species.
Chumphukam, O; Le, T T; Piletsky, S; Cass, A E G
2015-05-28
The ability to rapidly generate a pair of aptamers that bind independently to a protein target would greatly extend their use as reagents for two site ('sandwich') assays. We describe here a method to achieve this through proximity ligation. Using lysozyme as a target we demonstrate that under optimal conditions such a pair of aptamers, with nanomolar affinities, can be generated in a single round.
Context-Aware Community Construction in Proximity-Based Mobile Networks
Directory of Open Access Journals (Sweden)
Na Yu
2015-01-01
Full Text Available Sensor-equipped mobile devices have allowed users to participate in various social networking services. We focus on proximity-based mobile social networking environments where users can share information obtained from different places via their mobile devices when they are in proximity. Since people are more likely to share information if they can benefit from the sharing or if they think the information is of interest to others, there might exist community structures where users who share information more often are grouped together. Communities in proximity-based mobile networks represent social groups where connections are built when people are in proximity. We consider information influence (i.e., specify who shares information with whom as the connection and the space and time related to the shared information as the contexts. To model the potential information influences, we construct an influence graph by integrating the space and time contexts into the proximity-based contacts of mobile users. Further, we propose a two-phase strategy to detect and track context-aware communities based on the influence graph and show how the context-aware community structure improves the performance of two types of mobile social applications.
Proximal major limb amputations – a retrospective analysis of 45 oncological cases
Directory of Open Access Journals (Sweden)
Goertz Ole
2009-02-01
Full Text Available Abstract Background Proximal major limb amputations due to malignant tumors have become rare but are still a valuable treatment option in palliation and in some cases can even cure. The aim of this retrospective study was to analyse outcome in those patients, including the postoperative course, survival, pain, quality of life, and prosthesis usage. Methods Data of 45 consecutive patients was acquired from patient's charts and contact to patients, and general practitioners. Patients with interscapulothoracic amputation (n = 14, shoulder disarticulation (n = 13, hemipelvectomy (n = 3 or hip disarticulation (n = 15 were included. Results The rate of proximal major limb amputations in patients treated for sarcoma was 2.3% (37 out of 1597. Survival for all patients was 42.9% after one year and 12.7% after five years. Survival was significantly better in patients with complete tumor resections. Postoperative chemotherapy and radiation did not prolong survival. Eighteen percent of the patients with malignant disease developed local recurrence. In 44%, postoperative complications were observed. Different modalities of postoperative pain management and the site of the amputation had no significant influence on long-term pain assessment and quality of life. Eighty-seven percent suffered from phantom pain, 15.6% considered their quality of life worse than before the operation. Thirty-two percent of the patients who received a prosthesis used it regularly. Conclusion Proximal major limb amputations severely interfere with patients' body function and are the last, albeit valuable, option within the treatment concept of extremity malignancies or severe infections. Besides short survival, high complication rates, and postoperative pain, patients' quality of life can be improved for the time they have remaining.
A single-copy galK promoter cloning vector suitable for cloning strong promoters
DEFF Research Database (Denmark)
Dandanell, Gert; Court, Donald L.; Hammer, Karin
1986-01-01
We report the construction of lambda galK promoter cloning vectors for cloning and characterization of strong promoters. This phage, which contains a unique HindIII cloning site, was applied to the cloning and analysis of transcription initiations of the regulatory region of the deo-operon of...
Demographic statistics pertaining to nuclear power reactor sites
International Nuclear Information System (INIS)
1979-10-01
Population statistics are presented for 145 nuclear power plant sites. Summary tables and figures are included that were developed to aid in the evaluation of trends and general patterns associated with the various parameters of interest, such as the proximity of nuclear plant sites to centers of population. The primary reason for publishing this information at this time is to provide a factual basis for use in discussions on the subject of reactor siting policy. The report is a revised and updated version of a draft report published in December 1977. Errors in the population data base have been corrected and new data tabulations added
Hybrid external fixation of the proximal tibia: strategies to improve frame stability.
Roberts, Craig S; Dodds, James C; Perry, Kelvin; Beck, Dennis; Seligson, David; Voor, Michael J
2003-07-01
To determine the specific frame construction strategies that can increase the stability of hybrid (ring with tensioned wires proximally connected by bars to half-pins distally) external fixation of proximal tibia fractures. DESIGN Repeated measures biomechanical testing. Laboratory. Composite fiberglass tibias. Using the Heidelberg and Ilizarov systems, external fixators were tested on composite fiberglass tibias with a 1-cm proximal osteotomy (OTA fracture classification 41-A3.3) in seven frame configurations: unilateral frames with 5-mm diameter half-pins and 6-mm diameter half-pins; hybrid (as described above), with and without a 6-mm anterior proximal half-pin; a "box" hybrid (additional ring group distal to the fracture connected by symmetrically spaced bars to the proximal rings) with and without an anterior, proximal half-pin; and a full, four-ring configuration. Each configuration was loaded in four positions (central, medial, posterior, and posteromedial). Displacement at point of loading of proximal fragment. The "box" hybrid was stiffer than the standard hybrid for all loading positions. The addition of an anterior half-pin stiffened the standard hybrid and the "box" hybrid. The most dramatic improvements in the stability of hybrid frames used for proximal tibial fractures result from addition of an anterior, proximal half-pin.
Endomedullar nail of metacarpal and proximal phalanges
International Nuclear Information System (INIS)
Mendez Olaya, Francisco Javier; Sanchez Mesa, Pedro Antonio
2002-01-01
Prospective study, series of cases; it included patients with diaphysis fractures and union diaphysis-neck or union diaphysis-base of metacarpal and proximal phalanges, in whom was practiced anterograde intramedullary nailing previous closed reduction of the fracture, using prevent intramedullary nail of 1.6 mm. (cem 16) for the metacarpal fractures, and two nail prevent of 1.0 mm. (cem 10) for the proximal phalangeal fractures. Indications: transverse and oblique short fractures, spiral and with comminuting bicortical. Pursuit average is 5.7 months. Frequency surgical intervened patient: 2.2 each month, using this surgical technique a total of 20 (twenty) patients have been operated, 21 (twenty one) fractures; 16 (sixteen) metacarcal fractures and 5 (five) proximal phalangeal fractures, all of them tested using clinical and radiological parameters. Results: good 82%, regular 18%, and bad 0% obtaining bony consolidation and early rehabilitation with incorporation to their habitual works
Proximity to Woodland and Landscape Structure Drive Pollinator Visitation in Apple Orchard Ecosystem
Directory of Open Access Journals (Sweden)
Neelendra K Joshi
2016-04-01
Full Text Available Landscapes of farms and adjacent areas are known to influence abundance of various arthropods such as pollinators in commercial agricultural ecosystems. In this context, we examined the effect of heterogeneous landscapes surrounding and including commercial apple orchards on pollinator visitation and foraging distance during bloom period from 2011 to 2013 in Pennsylvania. Our results showed that the frequency of feral honeybees and solitary bee visits within an apple orchard depends on the proximity of the orchard to an unmanaged habitat (primarily comprised of forest. At the landscape scale, we found that the Mean Proximity Index, the Largest Patch Index and the Number of Patches positively correlated with the visitation rate of dominant bee taxa (Apis mellifera, Bombus spp. and solitary bees visiting apple flowers at low spatial scales (up to 500 m around the orchards. The Mean Proximity Index at 500 m was related to bee visitation patterns, especially for solitary bees and A. mellifera. Bees in all our study sites preferred to forage in areas with large homogenous patches up to 500 m around an apple orchard. This effect can be attributed to the mass flowering of apples that formed the largest proportion of the 500 m spatial scale. The Number of Patches at 250 m spatial scale was positively correlated with bee visitation, especially Bombus spp., probably because these areas had more habitats and more resources required by these bees. We conclude that retaining unmanaged habitats closer to commercial apple orchards will maintain biodiversity within the landscapes and insure pollination services to apples.
MR imaging of proximal femur: age-related changes
International Nuclear Information System (INIS)
Kim, Ju Heon; Jeon, Woo Jin; Sohn, Cheol Ho; Park, Mi Ok; Lee, Seong Mun; Joo, Yang Gu; Suh, Soo Jhi; Pyun, Young Sik
1995-01-01
The purpose of this study is to illustrate MR patterns of signal intensity of proximal femur in normal subjects according to the age distribution. T1-weighted MR images of the proximal femur in 125 subjects, aged 13 days to 25 years, were retrospectively analyzed. Age distribution was classified to 4 groups; below 4 months, 5 months to 4 years, 5 years to 14 years, and 15 years to 25 years. By the age of 4 months, the non-ossified femoral epiphysis was seen as intermediate-signal-intensity cartilage. At 5 months-4 years, the ossified femoral capital epiphysis was seen within intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow surrounded by a rim of low-signal-intensity cortical bone. At 5-14 years, the ossified femoral capital and greater trochanteric epiphysis were seen within the intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow. At 15-25 years, the proximal metaphyseal marrow showed increased signal intensity. Four patterns of the metaphyseal marrow were recognized by Ricci et al. The frequency of pattern 1 a progressively decreased with age. Pattern 2 and 3 were visible in the 15-25 years age group. An understanding of the spectrum of normal age-related change of the proximal femoral cartilage and marrow patterns serves as the foundation for interpretation of proximal femur pathologies
Topology of digital images visual pattern discovery in proximity spaces
Peters, James F
2014-01-01
This book carries forward recent work on visual patterns and structures in digital images and introduces a near set-based a topology of digital images. Visual patterns arise naturally in digital images viewed as sets of non-abstract points endowed with some form of proximity (nearness) relation. Proximity relations make it possible to construct uniform topolo- gies on the sets of points that constitute a digital image. In keeping with an interest in gaining an understanding of digital images themselves as a rich source of patterns, this book introduces the basics of digital images from a computer vision perspective. In parallel with a computer vision perspective on digital images, this book also introduces the basics of prox- imity spaces. Not only the traditional view of spatial proximity relations but also the more recent descriptive proximity relations are considered. The beauty of the descriptive proximity approach is that it is possible to discover visual set patterns among sets that are non-overlapping ...
Invertebrate communities of Arctic tundra ponds as related to proximity to drill site reserve pits
International Nuclear Information System (INIS)
Byron, E.; Williams, N.; Hoffman, R.; Elder, B.
1994-01-01
Aquatic invertebrate communities were assessed for diversity and abundance in North Slope tundra ponds of Prudhoe Bay, Alaska during the summer of 1992 as part of an evaluation of potential effects of exposure to petroleum drill site reserve pits (previously used for storing drill site wastes). The invertebrate communities of these shallow, tundra ponds provide abundant food for migratory, aquatic birds that use this area during the summer breeding season. The study was designed to compare abundance and diversity estimates of invertebrates in ponds surrounding the drill sites that differed in distance (and presumed exposure) to drill site reserve pits. The pits, themselves, were not sampled as part of this study. Invertebrate abundance and diversity estimates, assessed as standard biological criteria, were evaluated relative to water chemistry of the ponds, distance to the gravel pads or reserve pits, and pond morphometry. The results indicated the importance of pond morphometry in determining the structure of the invertebrate community. Shallow, exposed ponds tended to be dominated by different invertebrate communities than deeper, narrow ponds at the margins of frost polygons. In contrast, pond chemistry and relative exposure to drill sites were not predictive of invertebrate abundance or diversity
Donahue, Craig J.; Rais, Elizabeth A.
2009-01-01
This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…
Cellular specificity of HIV-1 replication can be controlled by LTR sequences
International Nuclear Information System (INIS)
Reed-Inderbitzin, Edward; Maury, Wendy
2003-01-01
Two well-established determinants of retroviral tropism are envelope sequences that regulate entry and LTR sequences that can regulate viral expression in a cell-specific manner. Studies with human immunodeficiency virus-1 (HIV-1) have demonstrated that tropism of this virus maps primarily to variable envelope sequences. Studies have demonstrated that T cell and macrophage-specific transcription factor binding motifs exist in the upstream region of the LTR U3; however, the ability of the core enhancer/promoter proximal elements (two NF-κB and three Sp1 sites) to function well in macrophages and T cells have led many to conclude that HIV LTR sequences are not primary determinants of HIV tropism. To determine if cellular specificity could be imparted to HIV by the core enhancer elements, the enhancer/promoter proximal region of the HIV LTR was substituted with motifs that control gene expression in a myeloid-specific manner. The enhancer region from equine infectious anemia virus (EIAV) when substituted for the HIV enhancer/promoter proximal region was found to drive expression in a macrophage-specific manner and was responsive to HIV Tat. The addition of a 5' methylation-dependent binding site (MDBP) and a promoter proximal Sp1 motif increased expression without altering cellular specificity. Spacing between the promoter proximal region and the TATA box was also found to influence LTR activity. Infectivity studies using chimeric LTRs within the context of a dual-tropic infectious molecular clone established that these LTRs directed HIV replication and production of infectious virions in macrophages but not primary T cells or T cell lines. This investigation demonstrates that cellular specificity can be imparted onto HIV-1 replication at the level of viral transcription and not entry
DEFF Research Database (Denmark)
Ekstrand, K R; Alloza, Alvaro Luna; Promisiero, L
2011-01-01
This study aimed to determine the reliability and accuracy of the ICDAS and radiographs in detecting and estimating the depth of proximal lesions on extracted teeth. The lesions were visible to the naked eye. Three trained examiners scored a total of 132 sound/carious proximal surfaces from 106 p...
Cancer rates after the Three Mile Island nuclear accident and proximity of residence to the plant.
Hatch, M C; Wallenstein, S; Beyea, J; Nieves, J W; Susser, M
1991-06-01
In the light of a possible link between stress and cancer promotion or progression, and of previously reported distress in residents near the Three Mile Island (TMI) nuclear power plant, we attempted to evaluate the impact of the March 1979 accident on community cancer rates. Proximity of residence to the plant, which related to distress in previous studies, was taken as a possible indicator of accident stress; the postaccident pattern in cancer rates was examined in 69 "study tracts" within a 10-mile radius of TMI, in relation to residential proximity. A modest association was found between postaccident cancer rates and proximity (OR = 1.4; 95% CI = 1.3, 1.6). After adjusting for a gradient in cancer risk prior to the accident, the odds ratio contrasting those closest to the plant with those living farther out was 1.2 (95% CI = 1.0, 1.4). A postaccident increase in cancer rates near the Three Mile Island plant was notable in 1982, persisted for another year, and then declined. Radiation emissions, as modeled mathematically, did not account for the observed increase. Interpretation in terms of accident stress is limited by the lack of an individual measure of stress and by uncertainty about whether stress has a biological effect on cancer in humans. An alternative mechanism for the cancer increase near the plant is through changes in care-seeking and diagnostic practice arising from postaccident concern.
Effects of Acids, Bases, and Heteroatoms on Proximal Radial Distribution Functions for Proteins.
Nguyen, Bao Linh; Pettitt, B Montgomery
2015-04-14
The proximal distribution of water around proteins is a convenient method of quantifying solvation. We consider the effect of charged and sulfur-containing amino acid side-chain atoms on the proximal radial distribution function (pRDF) of water molecules around proteins using side-chain analogs. The pRDF represents the relative probability of finding any solvent molecule at a distance from the closest or surface perpendicular protein atom. We consider the near-neighbor distribution. Previously, pRDFs were shown to be universal descriptors of the water molecules around C, N, and O atom types across hundreds of globular proteins. Using averaged pRDFs, a solvent density around any globular protein can be reconstructed with controllable relative error. Solvent reconstruction using the additional information from charged amino acid side-chain atom types from both small models and protein averages reveals the effects of surface charge distribution on solvent density and improves the reconstruction errors relative to simulation. Solvent density reconstructions from the small-molecule models are as effective and less computationally demanding than reconstructions from full macromolecular models in reproducing preferred hydration sites and solvent density fluctuations.
Correlation between social proximity and mobility similarity.
Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao
2017-09-20
Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.
Energy Technology Data Exchange (ETDEWEB)
Tony, G., E-mail: drgtony@gmail.com [Stafford General Hospital, Weston Road, Stafford, Staffordshire ST16 3SA (United Kingdom); Charran, A., E-mail: amandacharran@yahoo.com [Hillingdon Hospital, Pield Heath Rd, Uxbridge, Middlesex UB8 3NN (United Kingdom); Tins, B., E-mail: bernhard.tins@rjah.nhs.uk [Department of Diagnostic Imaging, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Lalam, R., E-mail: radhesh.lalam@rjah.nhs.uk [Department of Diagnostic Imaging, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Tyrrell, P.N.M., E-mail: prudencia.tyrrell@rjah.nhs.uk [Department of Diagnostic Imaging, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Singh, J., E-mail: jaspreet.singh@rjah.nhs.uk [Department of Diagnostic Imaging, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Cool, P., E-mail: paul.cool@rjah.nhs.uk [Orthopaedic Oncology, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Kiely, N., E-mail: nigel.kiely@rjah.nhs.uk [Paediatric Orthopaedics, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom); Cassar-Pullicino, V.N., E-mail: Victor.Pullicino@rjah.nhs.uk [Department of Diagnostic Imaging, Robert Jones and Agnes Hunt, Orthopaedic Hospital, Oswestry, Shropshire SY10 7 AG (United Kingdom)
2014-11-15
Highlights: • Purely intra-epiphyseal stress injuries of the proximal tibial epiphysis are described for the first time. • The variation in the MRI findings of these injuries depending on the stage of maturation is demonstrated. • We postulate a patho-mechanism to explain the variations in site and appearance of stress injuries in this region. - Abstract: Stress induced injuries affecting the physeal plate or cortical bone in children and adolescents, especially young athletes, have been well described. However, there are no reports in the current English language literature of stress injury affecting the incompletely ossified epiphyseal cartilage. We present four cases of stress related change to the proximal tibial epiphysis (PTE) along with their respective magnetic resonance imaging (MRI) appearances ranging from subtle oedema signal to a pseudo-tumour like appearance within the epiphyseal cartilage. The site and pattern of intra-epiphyseal injury is determined by the type of tissue that is affected, the maturity of the skeleton and the type of forces that are transmitted through the tissue. We demonstrate how an awareness of the morphological spectrum of MRI appearances in intra-epiphyseal stress injury and the ability to identify concomitant signs of stress in other nearby structures can help reduce misdiagnosis, avoid invasive diagnostic procedures like bone biopsy and reassure patients and their families.
International Nuclear Information System (INIS)
Tony, G.; Charran, A.; Tins, B.; Lalam, R.; Tyrrell, P.N.M.; Singh, J.; Cool, P.; Kiely, N.; Cassar-Pullicino, V.N.
2014-01-01
Highlights: • Purely intra-epiphyseal stress injuries of the proximal tibial epiphysis are described for the first time. • The variation in the MRI findings of these injuries depending on the stage of maturation is demonstrated. • We postulate a patho-mechanism to explain the variations in site and appearance of stress injuries in this region. - Abstract: Stress induced injuries affecting the physeal plate or cortical bone in children and adolescents, especially young athletes, have been well described. However, there are no reports in the current English language literature of stress injury affecting the incompletely ossified epiphyseal cartilage. We present four cases of stress related change to the proximal tibial epiphysis (PTE) along with their respective magnetic resonance imaging (MRI) appearances ranging from subtle oedema signal to a pseudo-tumour like appearance within the epiphyseal cartilage. The site and pattern of intra-epiphyseal injury is determined by the type of tissue that is affected, the maturity of the skeleton and the type of forces that are transmitted through the tissue. We demonstrate how an awareness of the morphological spectrum of MRI appearances in intra-epiphyseal stress injury and the ability to identify concomitant signs of stress in other nearby structures can help reduce misdiagnosis, avoid invasive diagnostic procedures like bone biopsy and reassure patients and their families
Bone mineral density of lumbar spine and proximal femur in healthy males
International Nuclear Information System (INIS)
Akin, S.; Isikli, S.; Korkusuz, F.; Ungan, M.; Senkoylu, A.
2004-01-01
Relationship between BMD and age at lumbar spine and proximal femur in Turkish males was investigated. Two hundred ninety healthy males (aged 20-59 years) were investigated. BMD of the lumbar spine had its peak at ages 30-39, however, the peak for the proximal femur was between the ages of 20 and 29. There was a significant decrease in BMD at proximal femur after these peak values with increasing age. There was a significant correlation between age and the proximal femoral BMD in males and age has a strong predictive power on proximal femur BMD score. (author)
Proximal soil sensors and data fusion for precision agriculture
Mahmood, H.S.
2013-01-01
different remote and proximal soil sensors are available today that can scan entire fields and give detailed information on various physical, chemical, mechanical and biological soil properties. The first objective of this thesis was to evaluate different proximal soil sensors available today and to
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation
DEFF Research Database (Denmark)
Hendriks, Ivo A; Lyon, David; Young, Clifford
2017-01-01
that were co-modified by ubiquitylation, acetylation and methylation. Notably, 9% of the identified SUMOylome occurred proximal to phosphorylation, and numerous SUMOylation sites were found to be fully dependent on prior phosphorylation events. SUMO-proximal phosphorylation occurred primarily in a proline......-directed manner, and inhibition of cyclin-dependent kinases dynamically affected co-modification. Collectively, we present a comprehensive analysis of the SUMOylated proteome, uncovering the structural preferences for SUMO and providing system-wide evidence for a remarkable degree of cross-talk between...
Proximal caries detection: Sirona Sidexis versus Kodak Ektaspeed Plus.
Khan, Emad A; Tyndall, Donald A; Ludlow, John B; Caplan, Daniel
2005-01-01
This study compared the accuracy of intraoral film and a charge-coupled device (CCD) receptor for proximal caries detection. Four observers evaluated images of the proximal surfaces of 40 extracted posterior teeth. The presence or absence of caries was scored using a five-point confidence scale. The actual status of each surface was determined from ground section histology. Responses were evaluated by means of receiver operating characteristic (ROC) analysis. Areas under ROC curves (Az) were assessed through a paired t-test. The performance of the CCD-based intraoral sensor was not different statistically from Ektaspeed Plus film in detecting proximal caries.
Atgl gene deletion predisposes to proximal tubule damage by impairing the fatty acid metabolism
International Nuclear Information System (INIS)
Chen, Wen; Zhang, Qiong; Cheng, Shiwu; Huang, Jie; Diao, Ge; Han, Jian
2017-01-01
Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl −/− mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr). In vitro experiments indicated that inhibition of ATGL in proximal tubular cell line HK-2 promoted intracellular lipid deposition, reactive oxygen species (ROS) accumulation and cell apoptosis. Both in vitro and in vivo experiments showed that ATGL inhibition decreased the renal peroxisome proliferator-activated receptorα(PPARα) expression, which implied the suppressed lipid metabolism. The antioxidant N-acetylcysteine (NAC) could partially reverse the effect of ROS accumulation and cell apoptosis, but could not restore the PPARαdecrease. These data raise the possibility that ATGL deficiency could impair the renal fatty acid metabolism though inhibiting PPARαexpression, which may lead to lipid deposition and cell apoptosis of PCT, and finally contribute to the renal fibrosis and dysfunction. - Highlights: • Atgl −/− mice develop tubulointerstitial damage and renal dysfunction. • ATGL deficiency results in lipid accumulation and apoptosis of proximal tubular cells. • ROS scavenger alleviates the ATGL-knockdown mediated lipid accumulation and apoptosis. • PPARαdown-regulation is the reason of ROS elevating in ATGL-knockdown HK-2 cells.
Diniz, Eva; DeSousa, Diogo; Koller, Silvia H; Volling, Brenda L
2016-05-01
Adolescent mothers often come from vulnerable backgrounds which might impact the quality of both maternal and infant behavior. Despite the negative impact of adolescent motherhood for maternal and infant behavior, social support may decrease the risks and promote maternal behavior toward the infant. The aim of this study was to investigate longitudinally the effects of proximal (maternal behavior) and distal (mother's perceived social support) variables on infant development in a sample of Brazilian adolescent mothers and their infants. Thirty-nine adolescent mothers (Mage=17.26years; SD=1.71) were observed interacting with their infants at 3 and 6 months postpartum and reported on social support. Results revealed that maternal and infant behavior were associated within and across times. Mothers' perceived social support at 3 months had an indirect effect on infant behavior at 6 months, totally mediated by maternal behavior at 6 months. Our findings revealed the mutual influence between maternal and infant behavior, revealing a proximal process. The results also underscored the importance of the passage of time in the interplay between mother-infant interactions and their developmental context. Copyright © 2016 Elsevier Inc. All rights reserved.
Soil monitoring in Pavlodar region adjoining to Semipalatinsk test site
International Nuclear Information System (INIS)
Tuleubaev, B.A.; Ramazanov, Zh.R.; Askarov, E.V.
2004-01-01
A problem of territory study and rehabilitation contaminated with man-caused radionuclides is an important task and it has economic, social, and ecology aspects. The problem is crucial for Pavlodar region due to real proximity and to partial location of Semipalatinsk Test Site on its territory. (author)
Xue, Hui; Veit, Christiane; Abas, Lindy; Tryfona, Theodora; Maresch, Daniel; Ricardi, Martiniano M; Estevez, José Manuel; Strasser, Richard; Seifert, Georg J
2017-08-01
Fasciclin-like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI-anchored, is highly N-glycosylated and carries two O-glycan epitopes previously associated with arabinogalactan proteins. The activity of FLA4 was resistant against deletion of the amino-proximal fasciclin 1 domain and was unaffected by removal of the GPI-modification signal, a highly conserved N-glycan or the deletion of predicted O-glycosylation sites. Nonetheless these structural changes dramatically decreased endoplasmic reticulum (ER)-exit and plasma membrane localization of FLA4, with N-glycosylation acting at the level of ER-exit and O-glycosylation influencing post-secretory fate. We show that FLA4 acts predominantly by molecular interactions involving its carboxy-proximal fasciclin 1 domain and that its amino-proximal fasciclin 1 domain is required for stabilization of plasma membrane localization. FLA4 functions as a soluble glycoprotein via its carboxy-proximal Fas1 domain and its normal cellular trafficking depends on N- and O-glycosylation. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.
Selective AR Modulators that Distinguish Proliferative from Differentiative Gene Promoters
2016-08-01
levels, and in some cases be useful in early stage disease or watchful waiting, and in other cases castration resistant prostate cancer (CRPC...dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Molecular endocrinology 13, 376 (Mar, 1999). 9...analyses and in mouse xenograft experiments, as planned. We will also continue to probe the molecular mechanism by which dox elicits these differential
DEFF Research Database (Denmark)
van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje
2016-01-01
, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...... in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were...
Harland, Karisa K; Greenan, Mitchell; Ramirez, Marizen
2014-09-01
Although approximately one-third of agricultural equipment-related crashes occur near town, these crashes are thought to be a rural problem. This analysis examines differences between agricultural equipment-related crashes by their urban-rural distribution and distance from a town. Agricultural equipment crashes were collected from nine Midwest Departments of Transportation (2005-2008). Crash zip code was assigned as urban or rural (large, small and isolated) using Rural-Urban Commuting Areas. Crash proximity to a town was estimated with ArcGIS. Multivariable logistic regression was used to estimate the odds of crashing in an urban versus rural zip codes and across rural gradients. ANOVA analysis estimated mean distance (miles) from a crash site to a town. Over four years, 4444 crashes involved agricultural equipment. About 30% of crashes occurred in urban zip codes. Urban crashes were more likely to be non-collisions (aOR=1.69[1.24-2.30]), involve ≥2 vehicles (2 vehicles: aOR=1.58[1.14-2.20], 3+ vehicles: aOR=1.68[0.98-2.88]), occur in a town (aOR=2.06[1.73-2.45]) and within one mile of a town (aOR=1.65[1.40-1.95]) than rural crashes. The proportion of crashes within a town differed significantly across rural gradients (Purban-rural distribution (Pagricultural equipment are unexpectedly common in urban areas and near towns and cities. Education among all roadway users, increased visibility of agricultural equipment and the development of complete rural roads are needed to increase road safety and prevent agricultural equipment-related crashes. Copyright © 2014 Elsevier Ltd. All rights reserved.
Computational proximity excursions in the topology of digital images
Peters, James F
2016-01-01
This book introduces computational proximity (CP) as an algorithmic approach to finding nonempty sets of points that are either close to each other or far apart. Typically in computational proximity, the book starts with some form of proximity space (topological space equipped with a proximity relation) that has an inherent geometry. In CP, two types of near sets are considered, namely, spatially near sets and descriptivelynear sets. It is shown that connectedness, boundedness, mesh nerves, convexity, shapes and shape theory are principal topics in the study of nearness and separation of physical aswell as abstract sets. CP has a hefty visual content. Applications of CP in computer vision, multimedia, brain activity, biology, social networks, and cosmology are included. The book has been derived from the lectures of the author in a graduate course on the topology of digital images taught over the past several years. Many of the students have provided important insights and valuable suggestions. The topics in ...
Poong, Y. S.; Yamaguchi, S.; Takada, J.
2013-07-01
This paper elucidates the current state of mobile technology readiness among young adults in higher education institution based on surveys and interviews. Although Lao PDR is ranked as low category in the ICT Index by International Telecommunication Union (ITU), findings show that there exists high level of readiness among the young adults. Recommendations for future research are developed to guide the development of mobile learning application with the aim to promote World Heritage Site preservation awareness.
E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling
Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V.
2016-01-01
Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a ...
The female geriatric proximal humeral fracture: protagonist for straight antegrade nailing?
Lindtner, Richard A; Kralinger, Franz S; Kapferer, Sebastian; Hengg, Clemens; Wambacher, Markus; Euler, Simon A
2017-10-01
Straight antegrade humeral nailing (SAHN) has become a standard technique for the surgical fixation of proximal humeral fractures, which predominantly affect elderly females. The nail's proximal anchoring point has been demonstrated to be critical to ensure reliable fixation in osteoporotic bone and to prevent iatrogenic damage to the superior rotator cuff bony insertion. Anatomical variations of the proximal humerus, however, may preclude satisfactory anchoring of the nail's proximal end and may bare the risk of rotator cuff violation, even though the nail is inserted as recommended. The aim of this study was to evaluate the anatomical suitability of proximal humeri of geriatric females aged 75 years and older for SAHN. Specifically, we sought to assess the proportion of humeri not anatomically amenable to SAHN for proximal humeral fracture. A total of 303 proximal humeri of 241 females aged 75 years and older (mean age 84.5 ± 5.0 years; range 75-102 years) were analyzed for this study. Multiplanar two-dimensional reformations (true ap, true lateral, and axial) were reconstructed from shoulder computed tomography (CT) data sets. The straight antegrade nail's ideal entry point, "critical point" (CP), and critical distance (CD; distance between ideal entry point and CP) were determined. The rate of proximal humeri not anatomically suitable for SAHN (critical type) was assessed regarding proximal reaming diameters of currently available straight antegrade humeral nails. Overall, 35.6% (108/303) of all proximal humeri were found to be "critical types" (CD straight antegrade nails currently in use. Moreover, 43.2% (131/303) of the humeri were considered "critical types" with regard to the alternatively used larger proximal reaming diameter of 11.5 mm. Mean CD was 9.0 ± 1.7 mm (range 3.5-13.5 mm) and did not correlate with age (r = -0.04, P = 0.54). No significant differences in CD and rate of "critical types" were found between left and right humeri
HEMATOMA OF THE PROXIMAL NAIL FOLD. REPORT OF 41 CASES
Directory of Open Access Journals (Sweden)
Chang Patricia
2011-04-01
Full Text Available Background: The proximal fold is an important part of the nail apparatus it contributes to the formation of the nail plate and through the cuticle acts as an impermeable barrier protecting it from any cause.Objective: To know the proximal nail fold hematoma caused by the use of pulse oximeter.Material and Methods: A descriptive study was conducted in 41 patients with proximal nail hematoma secondary to the use of oximetry in patients hospitalized in the Intermediate and Intensive Care Unit at the Hospital General de Enfermedades from December 1, 2007 to December 31, 2010.Results: We studied 41 patients with proximal nail fold hematoma secondary to the use of oximeter, 30 (73.1% were males and 11 (26.8% females. The numbers of fingers affected by pulse oximeter were in one digit. 30 (73.1% cases, in two digits 6 (14.6%, in three digits 3 (7.3%, in 4 digits 1 (2.4% and in 5 digits 1 (2.4% case. The most affected proximal nail fold was right index: 24 (58.5%, right middle 11 (26.8%, right ring 6 (14.6%, left index 12 (29.2%, and left middle 6 (14.6% cases.Conclusions: Hematomas of the proximal nail fold may be caused by different traumatisms. The use of pulse oximeter is one of them.
Directory of Open Access Journals (Sweden)
Walker Angela M
2009-04-01
Full Text Available Abstract Background The Pregnancy-associated glycoproteins (PAGs belong to a large family of aspartic peptidases expressed exclusively in the placenta of species in the Artiodactyla order. In cattle, the PAG gene family is comprised of at least 22 transcribed genes, as well as some variants. Phylogenetic analyses have shown that the PAG family segregates into 'ancient' and 'modern' groupings. Along with sequence differences between family members, there are clear distinctions in their spatio-temporal distribution and in their relative level of expression. In this report, 1 we performed an in silico analysis of the bovine genome to further characterize the PAG gene family, 2 we scrutinized proximal promoter sequences of the PAG genes to evaluate the evolution pressures operating on them and to identify putative regulatory regions, 3 we determined relative transcript abundance of selected PAGs during pregnancy and, 4 we performed preliminary characterization of the putative regulatory elements for one of the candidate PAGs, bovine (bo PAG-2. Results From our analysis of the bovine genome, we identified 18 distinct PAG genes and 14 pseudogenes. We observed that the first 500 base pairs upstream of the translational start site contained multiple regions that are conserved among all boPAGs. However, a preponderance of conserved regions, that harbor recognition sites for putative transcriptional factors (TFs, were found to be unique to the modern boPAG grouping, but not the ancient boPAGs. We gathered evidence by means of Q-PCR and screening of EST databases to show that boPAG-2 is the most abundant of all boPAG transcripts. Finally, we provided preliminary evidence for the role of ETS- and DDVL-related TFs in the regulation of the boPAG-2 gene. Conclusion PAGs represent a relatively large gene family in the bovine genome. The proximal promoter regions of these genes display differences in putative TF binding sites, likely contributing to observed
Inter-proximal enamel reduction in contemporary orthodontics.
Pindoria, J; Fleming, P S; Sharma, P K
2016-12-16
Inter-proximal enamel reduction has gained increasing prominence in recent years being advocated to provide space for orthodontic alignment, to refine contact points and to potentially improve long-term stability. An array of techniques and products are available ranging from hand-held abrasive strips to handpiece mounted burs and discs. The indications for inter-proximal enamel reduction and the importance of formal space analysis, together with the various techniques and armamentarium which may be used to perform it safely in both the labial and buccal segments are outlined.
Treatment of proximal ulna and olecranon fractures by dorsal plating
Kloen, Peter; Buijze, Geert A.
2009-01-01
OBJECTIVE : Anatomic reconstruction of proximal ulna and olecranon fractures allowing early mobilization and prevention of ulnohumeral arthritis. INDICATIONS : Comminuted olecranon or proximal ulna fractures (including Monteggia fractures), olecranon fractures extending distally from the coronoid
Office of Disease Prevention and Health Promotion
... Health Literacy Health Care Quality Healthy People healthfinder Office of Disease Prevention and Health Promotion Spotlight: This ... 16/2017 This site is coordinated by the Office of Disease Prevention and Health Promotion, Office of ...
Inexact proximal Newton methods for self-concordant functions
DEFF Research Database (Denmark)
Li, Jinchao; Andersen, Martin Skovgaard; Vandenberghe, Lieven
2016-01-01
with an application to L1-regularized covariance selection, in which prior constraints on the sparsity pattern of the inverse covariance matrix are imposed. In the numerical experiments the proximal Newton steps are computed by an accelerated proximal gradient method, and multifrontal algorithms for positive definite...... matrices with chordal sparsity patterns are used to evaluate gradients and matrix-vector products with the Hessian of the smooth component of the objective....
Proximity effects in topological insulator heterostructures
International Nuclear Information System (INIS)
Li Xiao-Guang; Wu Guang-Fen; Zhang Gu-Feng; Culcer Dimitrie; Zhang Zhen-Yu; Chen Hua
2013-01-01
Topological insulators (TIs) are bulk insulators that possess robust helical conducting states along their interfaces with conventional insulators. A tremendous research effort has recently been devoted to Tl-based heterostructures, in which conventional proximity effects give rise to a series of exotic physical phenomena. This paper reviews our recent studies on the potential existence of topological proximity effects at the interface between a topological insulator and a normal insulator or other topologically trivial systems. Using first-principles approaches, we have realized the tunability of the vertical location of the topological helical state via intriguing dual-proximity effects. To further elucidate the control parameters of this effect, we have used the graphene-based heterostructures as prototypical systems to reveal a more complete phase diagram. On the application side of the topological helical states, we have presented a catalysis example, where the topological helical state plays an essential role in facilitating surface reactions by serving as an effective electron bath. These discoveries lay the foundation for accurate manipulation of the real space properties of the topological helical state in TI-based heterostructures and pave the way for realization of the salient functionality of topological insulators in future device applications. (topical review - low-dimensional nanostructures and devices)
The Contribution of SPECT/CT in the Diagnosis of Stress Fracture of the Proximal Tibia
Directory of Open Access Journals (Sweden)
Berna Okudan
2018-02-01
Full Text Available Stress fractures are injuries most commonly seen in the lower limbs and are usually caused by repetitive stress. While the distal and middle third of the tibia is the most frequent site for stress fractures (almost 50%, stress fractures of the proximal tibia is relatively rare and could be confused with other types of tibial fractures, thus altering management plans for the clinician. Early diagnosis of stress fractures is also important to avoid complications. Imaging plays an important role in the diagnosis of stress fractures, especially bone scan. Combined with single-photon emission computed tomography/computed tomography (SPECT/CT it is an important imaging technique for stress fractures in both upper and lower extremities, and is widely preferred over other imaging techniques. In this case, we present the case of a 39-year-old male patient diagnosed with stress fracture of the proximal tibia and demonstrate the contribution of CT scan fused with SPECT imaging in the early diagnosis of stress fracture prior to other imaging modalities.
Work site stress management: national survey results.
Fielding, J E
1989-12-01
The National Survey of Work Site Health Promotion Activities established baseline data on the frequency of nine types of health promotion activity at private work sites with more than 50 employees in the United States. Stress management activities were provided at 26.6% of work sites. Types of activities at those work sites with some stress management activity included group counseling (58.5%), individual counseling (39.3%), follow-up counseling (25.9%), special events (11.5%), providing information about stress (80.7%), providing a place to relax (64.8%), and making organizational changes to reduce employee stress (81.2%). Frequency of activities varied by industry type and by region of the country. Incidence of most types of activities did not increase as work site size increased, although the likelihood of having any of these activities did increase with work site size. Stress management activities were more likely to be present at work sites with a medical staff or health educator. An increase in output, productivity, or quality was the most frequently cited benefit (46.5%). Negative effects were reported at 2.6% of the work sites. Other health promotion activities found at the work sites surveyed included smoking cessation (61.8%), treatment and control of high blood pressure (36.7%), and weight control (34.7%). Employee Assistance Programs were responsible for stress management at 62% of the work sites with an Employee Assistance Program.
Scaglioni, Mario F; Kuo, Yur-Ren; Chen, Yen-Chou
2016-03-01
The proximal peroneal artery perforator (PPAP) flap is a reliable, thin fasciocutaneous flap. The purpose of this article was to report our experience with the use of free PPAP flaps for reconstruction of defects of the distal hand and foot. From November 2012 to September 2013, 9 patients received reconstruction with 10 free PPAP flaps. The defect locations included the big toe (2 cases), metatarsophalangeal joint (5 cases), dorsal finger (2 cases) and volar finger (1 case). Flaps were raised based on proximal peroneal perforator vessels without sacrificing the peroneal artery. The first dorsal metatarsal artery (5 cases) and digital artery (5 cases) were dissected as recipient vessels. The flap sizes varied from 2.5 x 2 cm to 9 x 5 cm. All of flaps were survival after surgery. One flap suffered from venous thrombosis and was successfully salvaged by performing a venous thrombectomy and vein graft. The donor sites were all primarily closed with minimal morbidities. Follow-up observations were conducted for 7 to 20 months, and all patients had good functional recovery with satisfying cosmetic results. Perforators arising from the peroneal artery in the proximal lateral leg can be used to design small, pliable fasciocutaneous flaps. Although the pedicle is short, the vessel diameter is adequate for microvascular anastomosis to the distal foot and hand recipient vessels. The free PPAP flap may be a good option for reconstructing distal hand and foot defects. © 2014 Wiley Periodicals, Inc.
comparative proximate composition and antioxidant vitamins
African Journals Online (AJOL)
DR. AMINU
Keywords: Comparative, proximate composition, antioxidant vitamins, honey. INTRODUCTION ... solution of inverted sugars and complex mixture of other saccharides ... enzymatic browning in apple slices and grape juice. (Khan, 1985).
Zaridze, D G; Li, N; Men, T; Duffy, S W
1994-11-15
Rates of childhood cancer between 1981 and 1990 in the 4 administrative zones of Kazakhstan were studied to assess the relationship, if any, with distance from nuclear testing sites. Risk of various cancers among children aged 14 years or younger were estimated in relation to distance from (1) a site where testing in air was performed before 1963, (2) a site where underground testing took place thereafter, and (3) a reservoir, known as "Atom Lake," created by 4 nuclear explosions in 1965. Risk of acute leukaemia rose significantly with increasing proximity of residence to the testing areas, although the absolute value of the risk gradient was relatively small. The relative risk for those living less than 200 km from the air-testing site was 1.76 compared with those living 400 km or more away from the site. Similar relative risks were observed for the underground site and "Atom Lake." There was also some evidence of increased risk of brain tumours in association with proximity to the test sites. In 2 of the 4 zones studied, there was substantial regional variation in acute leukaemia rates which was not attributable to distance from the test site. The findings may be affected by potential confounders, notably urban/rural status and ethnic factors.
Mapping subsurface in proximity to newly-developed sinkhole along roadway.
2013-02-01
MS&T acquired electrical resistivity tomography profiles in immediate proximity to a newly-developed sinkhole in Nixa Missouri : The sinkhole has closed a well-traveled municipal roadway and threatens proximal infrastructure. The intent of this inves...
Kocsis, E; Trus, B L; Steer, C J; Bisher, M E; Steven, A C
1991-08-01
We have developed computational techniques that allow image averaging to be applied to electron micrographs of filamentous molecules that exhibit tight and variable curvature. These techniques, which involve straightening by cubic-spline interpolation, image classification, and statistical analysis of the molecules' curvature properties, have been applied to purified brain clathrin. This trimeric filamentous protein polymerizes, both in vivo and in vitro, into a wide range of polyhedral structures. Contrasted by low-angle rotary shadowing, dissociated clathrin molecules appear as distinctive three-legged structures, called "triskelions" (E. Ungewickell and D. Branton (1981) Nature 289, 420). We find triskelion legs to vary from 35 to 62 nm in total length, according to an approximately bell-shaped distribution (mu = 51.6 nm). Peaks in averaged curvature profiles mark hinges or sites of enhanced flexibility. Such profiles, calculated for each length class, show that triskelion legs are flexible over their entire lengths. However, three curvature peaks are observed in every case: their locations define a proximal segment of systematically increasing length (14.0-19.0 nm), a mid-segment of fixed length (approximately 12 nm), and a rather variable end-segment (11.6-19.5 nm), terminating in a hinge just before the globular terminal domain (approximately 7.3 nm diameter). Thus, two major factors contribute to the overall variability in leg length: (1) stretching of the proximal segment and (2) stretching of the end-segment and/or scrolling of the terminal domain. The observed elasticity of the proximal segment may reflect phosphorylation of the clathrin light chains.
Directory of Open Access Journals (Sweden)
Horel Scott A
2011-05-01
Full Text Available Abstract Objective The objective of this study is to examine the relationship between residential exposure to fast-food entrées, using two measures of potential spatial access: proximity (distance to the nearest location and coverage (number of different locations, and weekly consumption of fast-food meals. Methods Traditional fast-food restaurants and non-traditional fast-food outlets, such as convenience stores, supermarkets, and grocery stores, from the 2006 Brazos Valley Food Environment Project were linked with individual participants (n = 1409 who completed the nutrition module in the 2006 Brazos Valley Community Health Assessment. Results Increased age, poverty, increased distance to the nearest fast food, and increased number of different traditional fast-food restaurants, non-traditional fast-food outlets, or fast-food opportunities were associated with less frequent weekly consumption of fast-food meals. The interaction of gender and proximity (distance or coverage (number indicated that the association of proximity to or coverage of fast-food locations on fast-food consumption was greater among women and opposite of independent effects. Conclusions Results provide impetus for identifying and understanding the complex relationship between access to all fast-food opportunities, rather than to traditional fast-food restaurants alone, and fast-food consumption. The results indicate the importance of further examining the complex interaction of gender and distance in rural areas and particularly in fast-food consumption. Furthermore, this study emphasizes the need for health promotion and policy efforts to consider all sources of fast-food as part of promoting healthful food choices.
2011-01-01
Objective The objective of this study is to examine the relationship between residential exposure to fast-food entrées, using two measures of potential spatial access: proximity (distance to the nearest location) and coverage (number of different locations), and weekly consumption of fast-food meals. Methods Traditional fast-food restaurants and non-traditional fast-food outlets, such as convenience stores, supermarkets, and grocery stores, from the 2006 Brazos Valley Food Environment Project were linked with individual participants (n = 1409) who completed the nutrition module in the 2006 Brazos Valley Community Health Assessment. Results Increased age, poverty, increased distance to the nearest fast food, and increased number of different traditional fast-food restaurants, non-traditional fast-food outlets, or fast-food opportunities were associated with less frequent weekly consumption of fast-food meals. The interaction of gender and proximity (distance) or coverage (number) indicated that the association of proximity to or coverage of fast-food locations on fast-food consumption was greater among women and opposite of independent effects. Conclusions Results provide impetus for identifying and understanding the complex relationship between access to all fast-food opportunities, rather than to traditional fast-food restaurants alone, and fast-food consumption. The results indicate the importance of further examining the complex interaction of gender and distance in rural areas and particularly in fast-food consumption. Furthermore, this study emphasizes the need for health promotion and policy efforts to consider all sources of fast-food as part of promoting healthful food choices. PMID:21599955
Proximally exposed A-bomb survivors. 2
International Nuclear Information System (INIS)
Kamada, Nanao
1992-01-01
Methods for observing chromosomes can be chronologically divided into the era of non-differential staining technique (1962-1975) and the era of differential staining method (since 1976). This paper reviews the literature of chromosomal aberrations in bone marrow cells found in the two eras. Findings during the era of 1962-1975 include the frequency of chromosomal aberrations in bone marrow cells, comparison of chromosomal aberrations in bone marrow cells and T lymphocytes, and annual variation of chromosomal aberrations. The frequency of chromosomal aberrations was high in proximally exposed A-bomb survivors (90.5% and 52.6% in A-bomb survivors exposed within 500 m and at 501-1,000 m, respectively); on the contrary, it was low in those exposed far from 1,000 m (6.2% or less). The frequency of chromosomal aberrations in bone marrow cells was lower than that in T lymphocytes (21.5% vs 27.1% in those exposed within 500 m and 14.1% vs 23% in those exposed at 501-1,000 m). Annual analysis for chromosomal aberrations has shown the somewhat dependence upon medullary hematopoiesis and virus infection. The advent of differential staining technique since 1976 has made it possible to clarify the type of chromosomal aberrations and site of breakage. Of 710 bone marrow cells taken from 13 A-bomb survivors exposed within 1,000 m, 121 cells (from 11 A-bomb survivors) exhibited chromosomal aberrations. In differential staining analysis, all 121 cells but one were found to be of stable type, such as translocation and inversion. Furthermore, the site of breakage was found to be non-randomly distributed. Analysis of chromosomal aberrations in bone marrow cells has advantages of reflecting dynamic condition of these cells and determining gradual progression into leukemia. (N.K.)
Comparison of different proximity potentials for asymmetric colliding nuclei
International Nuclear Information System (INIS)
Dutt, Ishwar; Puri, Rajeev K.
2010-01-01
Using the different versions of phenomenological proximity potential as well as other parametrizations within the proximity concept, we perform a detailed comparative study of fusion barriers for asymmetric colliding nuclei with asymmetry parameter as high as 0.23. In all, 12 different proximity potentials are robust against the experimental data of 60 reactions. Our detailed study reveals that the surface energy coefficient as well as radius of the colliding nuclei depend significantly on the asymmetry parameter. All models are able to explain the fusion barrier heights within ±10% on the average. The potentials due to Bass 80, AW 95, and Denisov DP explain nicely the fusion cross sections at above- as well as below-barrier energies.
Fractures of the proximal humerus involving the intertubercular groove
International Nuclear Information System (INIS)
Ahovuo, J.; Paavolainen, P.; Bjoerkenheim, J.M.; Helsinki Univ. Central Hospital
1989-01-01
The purpose of this study was to analyse the involvement of the gliding surface of the biceps tendon in fractures of the proximal humerus. Fifteen patients had a fracture of the proximal humerus verified with antero-posterior and axillary radiographs. Tangential radiographs of the intertubercular groove, obtained from the shoulder joint, showed involvement of the intertubercular groove in 13 patients (87%), which could not be shown with other projections. Groove radiographs revealed in 3 patients a dislocation of the fragments of the greater tuberosity large enough to require surgical treatment, but which had not been found using conventional techniques. Therefore, a groove radiograph should be used to precise fractures of the proximal humerus. (orig.)
Denver radium site's - Case history
International Nuclear Information System (INIS)
Topolski, T.T.
1985-01-01
In developing this case history of the Denver radium sites, an attempt is made to establish the Colorado carnotite connection from the point of discovery to early development and its eventual role in the inception of the National Radium Institute and Denver's radium legacy. Early exploitive mining activities and the exportation of the highest grades of uranium ore to Europe greatly disturbed key officials at the U.S. Bureau of Mines. With its proximity to known carnotite deposits and industrial capacity, Denver's destiny as one of America's early radium production centers became a reality by 1914. With African pitchblend discoveries, Belgium competition spelled the beginning of the end of Denver's romance with radium by 1920. The sites where Denver made or used its radium were lost in obscurity for 60 years and rediscovered in 1979. Thirty one sites and a characterization of their radioactive impact are now a part of the Superfund National Priorities listing for eventual cleanup
Proximity effects on the spin density waves in X/Cr(001) multilayers (X = Sn, V, and Mn)
Energy Technology Data Exchange (ETDEWEB)
Amitouche, F. [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-Ouzou, B.P. No17 RP, 15000 Tizi-Ouzou (Algeria); Bouarab, S., E-mail: bouarab_said@mail.ummto.d [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-Ouzou, B.P. No17 RP, 15000 Tizi-Ouzou (Algeria); Tazibt, S. [Laboratoire de Physique et Chimie Quantique, Universite Mouloud Mammeri de Tizi-Ouzou, B.P. No17 RP, 15000 Tizi-Ouzou (Algeria); Vega, A. [Departamento de Fisica Teorica, Atomica y Optica, Universidad de Valladolid, Prado de la Magdalena s/n, E-47011 Valladolid (Spain); Demangeat, C. [Institut de Physique, 3 rue de l' Universite 67000 Strasbourg (France)
2011-01-03
We present ab initio density functional calculations of the electronic structure and magnetic properties of X{sub 2}/Cr{sub 36}(001) and X{sub 1}/Cr{sub 37}(001) multilayers, with X = Sn, V and Mn, to investigate the impact of the proximity effects of the X layers on the spin density waves of the Cr slab. We find different magnetic profiles corresponding to the spin density wave and to the layered antiferromagnetic configurations. The nature of the different magnetic solutions is discussed in terms of the different interfacial environments in the proximity of Sn, V or Mn. The magnetic behavior at the interface is discussed in connection with the electronic structure through the density of electronic states projected at the interfacial X and Cr sites. We compare the results with those previously obtained for Fe{sub 3}/X{sub 1}/Cr{sub 37}/X{sub 1}(001) multilayers to analyze the role played by the ferromagnetic iron slab.
Proximity effects on the spin density waves in X/Cr(001) multilayers (X = Sn, V, and Mn)
International Nuclear Information System (INIS)
Amitouche, F.; Bouarab, S.; Tazibt, S.; Vega, A.; Demangeat, C.
2011-01-01
We present ab initio density functional calculations of the electronic structure and magnetic properties of X 2 /Cr 36 (001) and X 1 /Cr 37 (001) multilayers, with X = Sn, V and Mn, to investigate the impact of the proximity effects of the X layers on the spin density waves of the Cr slab. We find different magnetic profiles corresponding to the spin density wave and to the layered antiferromagnetic configurations. The nature of the different magnetic solutions is discussed in terms of the different interfacial environments in the proximity of Sn, V or Mn. The magnetic behavior at the interface is discussed in connection with the electronic structure through the density of electronic states projected at the interfacial X and Cr sites. We compare the results with those previously obtained for Fe 3 /X 1 /Cr 37 /X 1 (001) multilayers to analyze the role played by the ferromagnetic iron slab.
Geographic proximity to coal plants and U.S. public support for extending the Production Tax Credit
International Nuclear Information System (INIS)
Goldfarb, Jillian L.; Buessing, Marric; Kriner, Douglas L.
2016-01-01
The Production Tax Credit (PTC) is an important policy instrument through which the federal government promotes renewable energy development in the United States. However, the efficacy of the PTC is hampered by repeated expirations and short-term extensions, and by the general uncertainty surrounding its future status. We examine the factors driving variation in public support for the extension of the PTC using a nationally representative, internet-based survey. Americans living near a coal-fired power plant are significantly more likely to support extending the PTC than are their peers who are more insulated from the externalities of burning coal. The evidence for this dynamic was strongest and most statistically significant among subjects experimentally primed to think about the adverse health effects of burning coal. Raising awareness of the public health ramifications of generating electricity from fossil fuels holds the potential to increase support for renewable energy policies among those living in proximity to coal plants, even in a highly politicized policy debate. - Highlights: • Proximity to coal power plant increases support for Production Tax Credit. • Attitudes toward global warming influence support for PTC. • Raising awareness of health threat increases PTC support if living near coal plant.
Energy Technology Data Exchange (ETDEWEB)
Shin, Ji Hoon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology (Korea, Republic of); Angle, John F.; Park, Auh Whan; Anderson, Curtis; Sabri, Saher S.; Turba, Ulku C. [University of Virginia Health System, Division of Angiography, Interventional Radiology and Special Procedures, Department of Radiology (United States); Kern, John A.; Cherry, Kenneth J. [University of Virginia Health System, Department of Surgery (United States); Matsumoto, Alan H., E-mail: ahm4d@virginia.edu [University of Virginia Health System, Division of Angiography, Interventional Radiology and Special Procedures, Department of Radiology (United States)
2012-12-15
Purpose: To present the computed tomographic (CT) imaging findings and their relevance to clinical outcomes related to stent graft placement in patients with penetrating aortic ulcers (PAUs). Methods: Medical and imaging records and imaging studies were reviewed for consecutive patients who underwent stent graft repair of a PAU. The distribution and characteristics of the PAU, technical success of stent graft repair, procedure-related complications, associated aortic wall abnormalities, and outcomes of the PAUs at follow-up CT scans were evaluated. Results: Fifteen patients underwent endovascular treatment for PAU. A total of 87% of the PAUs were in the proximal (n = 8) or distal (n = 5) descending thoracic aorta. There was a broad spectrum of PAU depth (mean, 7.9 {+-} 5.6 mm; range 1.5-25.0 mm) and diameter (mean, 13.5 {+-} 9.7 mm; range 2.2-41.0 mm). Atherosclerosis of the thoracic aorta and intramural hematoma were associated in 53 and 93% of the patients, respectively. Technical success was achieved in 100%. Two or more stent grafts were used in five patients. Endoleaks were observed in two patients within 2 weeks of the procedure, both of which resolved spontaneously. At follow-up CT scanning, regression and thrombosis of the PAUs were observed in all patients. The average patient survival was 61.8 months, with an overall mortality of 13% (2 of 15) at follow-up. Neither death was related to the endograft device or the PAU. Conclusion: Endovascular stent graft placement was safe and effective in causing regression and thrombosis of PAUs in this small series of patients. Two or more stent grafts were used in five patients (33%) with associated long-segmental atherosclerotic changes of the thoracic aorta or intramural hematoma.
International Nuclear Information System (INIS)
Shin, Ji Hoon; Angle, John F.; Park, Auh Whan; Anderson, Curtis; Sabri, Saher S.; Turba, Ulku C.; Kern, John A.; Cherry, Kenneth J.; Matsumoto, Alan H.
2012-01-01
Purpose: To present the computed tomographic (CT) imaging findings and their relevance to clinical outcomes related to stent graft placement in patients with penetrating aortic ulcers (PAUs). Methods: Medical and imaging records and imaging studies were reviewed for consecutive patients who underwent stent graft repair of a PAU. The distribution and characteristics of the PAU, technical success of stent graft repair, procedure-related complications, associated aortic wall abnormalities, and outcomes of the PAUs at follow-up CT scans were evaluated. Results: Fifteen patients underwent endovascular treatment for PAU. A total of 87% of the PAUs were in the proximal (n = 8) or distal (n = 5) descending thoracic aorta. There was a broad spectrum of PAU depth (mean, 7.9 ± 5.6 mm; range 1.5–25.0 mm) and diameter (mean, 13.5 ± 9.7 mm; range 2.2–41.0 mm). Atherosclerosis of the thoracic aorta and intramural hematoma were associated in 53 and 93% of the patients, respectively. Technical success was achieved in 100%. Two or more stent grafts were used in five patients. Endoleaks were observed in two patients within 2 weeks of the procedure, both of which resolved spontaneously. At follow-up CT scanning, regression and thrombosis of the PAUs were observed in all patients. The average patient survival was 61.8 months, with an overall mortality of 13% (2 of 15) at follow-up. Neither death was related to the endograft device or the PAU. Conclusion: Endovascular stent graft placement was safe and effective in causing regression and thrombosis of PAUs in this small series of patients. Two or more stent grafts were used in five patients (33%) with associated long-segmental atherosclerotic changes of the thoracic aorta or intramural hematoma.
Souza, E M; Pedrosa, F O; Rigo, L U; Machado, H B; Yates, M G
2000-06-01
The nifA promoter of Herbaspirillum seropedicae contains potential NtrC, NifA and IHF binding sites together with a -12/-24 sigma(N)-dependent promoter. This region has now been investigated by deletion mutagenesis for the effect of NtrC and NifA on the expression of a nifA::lacZ fusion. A 5' end to the RNA was identified at position 641, 12 bp downstream from the -12/-24 promoter. Footprinting experiments showed that the G residues at positions -26 and -9 are hypermethylated, and that the region from -10 to +10 is partially melted under nitrogen-fixing conditions, confirming that this is the active nifA promoter. In H. seropedicae nifA expression from the sigma(N)-dependent promoter is repressed by fixed nitrogen but not by oxygen and is probably activated by the NtrC protein. NifA protein is apparently not essential for nifA expression but it can still bind the NifA upstream activating sequence.
Directory of Open Access Journals (Sweden)
Christine R Langlois
2016-11-01
Full Text Available Prions are a group of proteins that can adopt a spectrum of metastable conformations in vivo. These alternative states change protein function and are self-replicating and transmissible, creating protein-based elements of inheritance and infectivity. Prion conformational flexibility is encoded in the amino acid composition and sequence of the protein, which dictate its ability not only to form an ordered aggregate known as amyloid but also to maintain and transmit this structure in vivo. But, while we can effectively predict amyloid propensity in vitro, the mechanism by which sequence elements promote prion propagation in vivo remains unclear. In yeast, propagation of the [PSI+] prion, the amyloid form of the Sup35 protein, has been linked to an oligopeptide repeat region of the protein. Here, we demonstrate that this region is composed of separable functional elements, the repeats themselves and a repeat proximal region, which are both required for efficient prion propagation. Changes in the numbers of these elements do not alter the physical properties of Sup35 amyloid, but their presence promotes amyloid fragmentation, and therefore maintenance, by molecular chaperones. Rather than acting redundantly, our observations suggest that these sequence elements make complementary contributions to prion propagation, with the repeat proximal region promoting chaperone binding to and the repeats promoting chaperone processing of Sup35 amyloid.
Qu, Wei-Min; Yue, Xiao-Fang; Sun, Yu; Fan, Kun; Chen, Chang-Rui; Hou, Yi-Ping; Urade, Yoshihiro; Huang, Zhi-Li
2012-10-01
Decoctions of the Chinese herb houpu contain honokiol and are used to treat a variety of mental disorders, including depression. Depression commonly presents alongside sleep disorders and sleep disturbances, which appear to be a major risk factor for depression. Here, we have evaluated the somnogenic effect of honokiol and the mechanisms involved. Honokiol was administered i.p. at 20:00 h in mice. Flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor, was administered i.p. 15 min before honokiol. The effects of honokiol were measured by EEG and electromyogram (EMG), c-Fos expression and in vitro electrophysiology. Honokiol (10 and 20 mg·kg⁻¹) significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of NREM sleep. Honokiol increased the number of state transitions from wakefulness to NREM sleep and, subsequently, from NREM sleep to wakefulness. However, honokiol had no effect on either the amount of REM sleep or EEG power density of both NREM and REM sleep. Honokiol increased c-Fos expression in ventrolateral preoptic area (VLPO) neurons, as examined by immunostaining, and excited sleep-promoting neurons in the VLPO by whole-cell patch clamping in the brain slice. Pretreatment with flumazenil abolished the somnogenic effects and activation of the VLPO neurons by honokiol. Honokiol promoted NREM sleep by modulating the benzodiazepine site of the GABA(A) receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Directory of Open Access Journals (Sweden)
Ema T Crooks
2015-05-01
Full Text Available Eliciting broad tier 2 neutralizing antibodies (nAbs is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs expressing trimers (trimer VLP sera and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs. Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype rendered 50% or 16.7% (n = 18 of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.
Exploiting Proximity-Based Mobile Apps for Large-Scale Location Privacy Probing
Directory of Open Access Journals (Sweden)
Shuang Zhao
2018-01-01
Full Text Available Proximity-based apps have been changing the way people interact with each other in the physical world. To help people extend their social networks, proximity-based nearby-stranger (NS apps that encourage people to make friends with nearby strangers have gained popularity recently. As another typical type of proximity-based apps, some ridesharing (RS apps allowing drivers to search nearby passengers and get their ridesharing requests also become popular due to their contribution to economy and emission reduction. In this paper, we concentrate on the location privacy of proximity-based mobile apps. By analyzing the communication mechanism, we find that many apps of this type are vulnerable to large-scale location spoofing attack (LLSA. We accordingly propose three approaches to performing LLSA. To evaluate the threat of LLSA posed to proximity-based mobile apps, we perform real-world case studies against an NS app named Weibo and an RS app called Didi. The results show that our approaches can effectively and automatically collect a huge volume of users’ locations or travel records, thereby demonstrating the severity of LLSA. We apply the LLSA approaches against nine popular proximity-based apps with millions of installations to evaluate the defense strength. We finally suggest possible countermeasures for the proposed attacks.
Vickers, Timothy A; Crooke, Stanley T
2012-07-01
While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.
Mammalian RNA polymerase II core promoters: insights from genome-wide studies
DEFF Research Database (Denmark)
Sandelin, Albin; Carninci, Piero; Lenhard, Boris
2007-01-01
The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing...... in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing...
Bull, Sheana Salyers; Gillette, Cynthia; Glasgow, Russell E; Estabrooks, Paul
2003-10-01
Information on external validity of work site health promotion research is essential to translate research findings to practice. The authors provide a literature review of work site health behavior interventions. Using the RE-AIM framework, they summarize characteristics and results of these studies to document reporting of intervention reach, adoption, implementation, and maintenance. The authors reviewed a total of 24 publications from 11 leading health behavior journals. They found that participation rates among eligible employees were reported in 87.5% of studies; only 25% of studies reported on intervention adoption. Data on characteristics of participants versus nonparticipants were reported in fewer than 10% of studies. Implementation data were reported in 12.5% of the studies. Only 8% of studies reported any type of maintenance data. Stronger emphasis is needed on representativeness of employees, work site settings studied, and longer term results. Examples of how this can be done are provided.
Comparative morphometric analysis of the proximal femur of African hominids and felids
Directory of Open Access Journals (Sweden)
Andrew Gallagher
2015-09-01
Full Text Available Size and shape of the mammalian proximal femur and taxon-specific distinctions in the relative proportions of the proximal articulation, the femoral neck and the proximal femoral diaphysis, are critical determinants in its adaptation to differential biomechanical stresses and observed locomotor habitus in different taxa. The morphometrics of the proximal femur are considered equally critical in the assessment of locomotor habitus of extinct fossil mammals, particularly extinct Miocene anthropoids and Plio-Pleistocene hominins. Analyses of size and shape of k=10 dimensions of the proximal femur were undertaken for a large sample series of two extant mammal families the Felidae and Hominidae using conventional multivariate statistical procedures, commonly used size-correction methods, and post-hoc tests of significance. While significant differences in form do exist, there are equally striking convergences in the functional morphology of extant hominid and felid taxa. Multivariate and bivariate allometric analyses confirm that the proximal femur of these two mammalian families share a common underlying structure manifest in a shared first common principal component. Nevertheless, while considerable convergences in general form of the proximal femur of African hominids and large-bodied felids are apparent, there exist equally discreet distinctions which are consistent with the differential structural demands imposed by their distinct locomotor and behavioural habitus.
Detailed investigations of proximal tubular function in Imerslund-Grasbeck syndrome
DEFF Research Database (Denmark)
Storm, Tina; Zeitz, Christina; Cases, Olivier
2013-01-01
expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers...
Does subchondral bone of the equine proximal phalanx adapt to race training?
Noble, Phillipa; Singer, Ellen R; Jeffery, Nathan S
2016-07-01
Sagittal fractures of the first phalanx are a common, potentially catastrophic injury in racehorses. These fractures are often linked to an acute, one time, biomechanical event; however, recent evidence implies that chronic exposure to stress can lead to the accumulation of bony changes that affect the structural integrity of the bone and increase the likelihood of fracture. The aim of the study was to compare variations of two common metrics of bone adaptation - subchondral bone density and thickness across the proximal articular surface of the first phalanx in Thoroughbred horses that (1) raced but never experienced a first phalanx fracture (Raced Control); (2) raced and had experienced fracture of the contralateral first phalanx (Contralateral to Fracture); (3) had never raced or experienced a first phalanx fracture (Unraced Control). A total of 22 first phalangeal bones were sampled post-mortem and imaged using micro-computed tomography calibrated for mineral density measures. Measurements of volumetric subchondral bone mineral density and thickness were taken from images at five sites from medial to lateral, in three coronal planes (25, 50 and 75% dorsal-palmar). At each of the 15 sites, measurements were repeated and averaged across 10 adjacent micro-computed tomography slices of bone, spanning 0.75 mm. The magnitude and variance of these measurements were compared between sites and between cohorts with non-parametric statistical tests. Across the proximal osteochondral surface of the first phalanx, the pattern of subchondral bone volumetric bone mineral density and thickness varied with each coronal section studied. The subchondral bone thickness was greater for the central and dorsal coronal sections, compared with the palmar section. For the race-fit groups (Raced Control and Contralateral to Fracture), the highest volumetric bone mineral density was in the central sagittal groove. The volumetric bone mineral density was significantly greater in the
Eren, M; Painter, C A; Gleaves, L A; Schoenhard, J A; Atkinson, J B; Brown, N J; Vaughan, D E
2003-11-01
Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal -2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-beta1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-beta1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal -2.9 kb promoter.
Singh, Ashutosh Kumar; Narsaria, Nidi; G R, Arun; Srivastava, Vivek
Unstable trochanteric femur fractures are common fractures that are difficult to manage. We conducted a prospective study to compare functional outcomes and complications of 2 different implant designs, proximal femur nail (PFN) and proximal femur locking compression plate (PFLCP), used in internal fixation of unstable trochanteric femur fractures. On hospital admission, 48 patients with unstable trochanteric fractures were randomly assigned (using a sealed envelope method) to treatment with either PFN (24 patients) or PFLCP (24 patients). Perioperative data and complications were recorded. All cases were followed up for 2 years. The groups did not differ significantly (P > .05) in operative time, reduction quality, complications, hospital length of stay, union rate, or time to union. Compared with the PFLCP group, the PFN group had shorter incisions and less blood loss. Regarding functional outcomes, there was no significant difference in mean Harris Hip Score (P = .48) or Palmer and Parker mobility score (P = .58). Both PFN and PFLCP are effective in internal fixation of unstable trochanteric femur fractures.
Two Stages repair of proximal hypospadias: Review of 33 cases
African Journals Online (AJOL)
HussamHassan
Background/Purpose: Proximal hypospadias with chordee is the most challenging variant of hypospadias to reconstruct. During the last 10 years, the approach to sever hypospadias has been controversial. Materials & Methods: During the period from June 2002 to December 2009, I performed 33 cases with proximal.
Dual-energy X-ray absorptiometry in the lumbar spine, proximal femur and distal radius in children
International Nuclear Information System (INIS)
Tsukahara, H.; Sudo, M.; Umezaki, M.; Hiraoka, M.; Yamamoto, K.; Ishii, Y.; Haruki, S.
1992-01-01
Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) in the lumbar spine, proximal femur and distal radius in 48 Japanese children aged 3-18 years. In the normal children (n=32), BMD increased with age in all locations, with a nearly twofold increase from preschool age to adolescence. Most of the children with chronic diseases known to affect bone metabolism (e.g., steroid osteoporosis) (n=16) had low BMD in every region, indicating that these disease states probably affect multiple sites of the skeleton in children. (orig.)
Jefferis, R; Lund, J; Pound, J D
1998-06-01
The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.
Enhancement of RNA synthesis by promoter duplication in tombusviruses
International Nuclear Information System (INIS)
Panavas, T.; Panaviene, Z.; Pogany, J.; Nagy, P.D.
2003-01-01
Replication of tombusviruses, small plus-strand RNA viruses of plants, is regulated by cis-acting elements present in the viral RNA. The role of cis-acting elements can be studied in vitro by using a partially purified RNA-dependent RNA polymerase (RdRp) preparation obtained from tombusvirus-infected plants , Virology 276, 279- 288). Here, we demonstrate that the minus-strand RNA of tombusviruses contains, in addition to the 3'-terminal minimal plus-strand initiation promoter, a second cis-acting element, termed the promoter proximal enhancer (PPE). The PPE element enhanced RNA synthesis by almost threefold from the adjacent minimal promoter in the in vitro assay. The sequence of the PPE element is 70% similar to the minimal promoter, suggesting that sequence duplication of the minimal promoter may have been the mechanism leading to the generation of the PPE. Consistent with this proposal, replacement of the PPE element with the minimal promoter, which resulted in a perfectly duplicated promoter region, preserved its enhancer-like function. In contrast, mutagenesis of the PPE element or its replacement with an artificial G/C-rich sequence abolished its stimulative effect on initiation of RNA synthesis in vitro. In vivo experiments are also consistent with the role of the PPE element in enhancement of tombusvirus replication. Sequence comparison of several tombusviruses and related carmoviruses further supports the finding that duplication of minimal promoter sequences may have been an important mechanism during the evolution of cis-acting elements in tombusviruses and related RNA viruses
The biology of eukaryotic promoter prediction - a review
DEFF Research Database (Denmark)
Pedersen, Anders Gorm; Baldi, Pierre; Chauvin, Yves
1999-01-01
between functional promoters has been estimated to be in the range of 30-40 kilobases. Although it is conceivable that some of these predicted promoters correspond to cryptic initiation sites that are used in vivo, it is likely that most are false positives. This suggests that it is important to carefully......Computational prediction of eukaryotic promoters from the nucleotide sequence is one of the most attractive problems in sequence analysis today, but it is also a very difficult one. Thus, current methods predict in the order of one promoter per kilobase in human DNA, while the average distance...... reconsider the biological data that forms the basis of current algorithms, and we here present a review of data that may be useful in this regard. The review covers the following topics: (1) basal transcription and core promoters, (2) activated transcription and transcription factor binding sites, (3) Cp...
Physical constraints determine the logic of bacterial promoter architectures
Ezer, Daphne; Zabet, Nicolae Radu; Adryan, Boris
2014-01-01
Site-specific transcription factors (TFs) bind to their target sites on the DNA, where they regulate the rate at which genes are transcribed. Bacterial TFs undergo facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA) when searching for their target sites. Using computer simulations of this search process, we show that the organization of the binding sites, in conjunction with TF copy number and binding site affinity, plays an important role in determining not only the steady state of promoter occupancy, but also the order at which TFs bind. These effects can be captured by facilitated diffusion-based models, but not by standard thermodynamics. We show that the spacing of binding sites encodes complex logic, which can be derived from combinations of three basic building blocks: switches, barriers and clusters, whose response alone and in higher orders of organization we characterize in detail. Effective promoter organizations are commonly found in the E. coli genome and are highly conserved between strains. This will allow studies of gene regulation at a previously unprecedented level of detail, where our framework can create testable hypothesis of promoter logic. PMID:24476912
Correction of Misclassifications Using a Proximity-Based Estimation Method
Directory of Open Access Journals (Sweden)
Shmulevich Ilya
2004-01-01
Full Text Available An estimation method for correcting misclassifications in signal and image processing is presented. The method is based on the use of context-based (temporal or spatial information in a sliding-window fashion. The classes can be purely nominal, that is, an ordering of the classes is not required. The method employs nonlinear operations based on class proximities defined by a proximity matrix. Two case studies are presented. In the first, the proposed method is applied to one-dimensional signals for processing data that are obtained by a musical key-finding algorithm. In the second, the estimation method is applied to two-dimensional signals for correction of misclassifications in images. In the first case study, the proximity matrix employed by the estimation method follows directly from music perception studies, whereas in the second case study, the optimal proximity matrix is obtained with genetic algorithms as the learning rule in a training-based optimization framework. Simulation results are presented in both case studies and the degree of improvement in classification accuracy that is obtained by the proposed method is assessed statistically using Kappa analysis.
A micropuncture study of proximal tubular transport of lithium during osmotic diuresis
DEFF Research Database (Denmark)
Leyssac, P P; Holstein-Rathlou, N H; Skøtt, P
1990-01-01
Lithium and sodium are normally reabsorbed in parallel with water by the renal proximal tubule whereby their tubular fluid-to-plasma concentration ratios (TF/P) remain close to unity throughout the proximal convoluted segment. During osmotic diuresis, the late proximal (TF/P)Na is known to decrease....... The present experiments were undertaken to study whether the late proximal TF/P for Li decreases like that of Na during osmotic diuresis. Data were obtained in a control period (C) and in two successive periods during mannitol diuresis (P1, P2). Glomerular filtration rate decreased gradually during osmotic...
Inter-organizational proximity in the context of logistics – research challenges
Directory of Open Access Journals (Sweden)
Patrycja Klimas
2015-03-01
Full Text Available Background: One of major areas of modern research econnected with management issues covers inter-organizational networks (including supply chains and cooperation processes aimed at improvement of the effectiveness of their performance to be found in such networks. The logistics is the main factor responsible for effectiveness of the supply chain. A possible and a quite new direction of research in the area of the performance of processes of the inter-organizational cooperation is the proximity hypothesis that is considered in five dimensions (geographical, organizational, social, cognitive, and institutional. However, according to many authors, there is a lack of research on supply chains conducted from the logistics point of view. The proximity hypothesis in this area of research can be seen as a kind of novum. Therefore, this paper presents the proximity concept from the perspective of the management science, the overview of prior research covering the inter-organizational proximity with supply chain from the logistics point of view as well as the possible future directions of the empirical efforts. Methods: The aim of this paper is to present previous theoretical and empirical results of research covering inter-organizational proximity in logistics and to show current and up-to-date research challenges in this area. The method of the critical analysis of literature is used to realize the goal constructed this way. Results: Knowledge about the influence of the inter-organizational proximity on the performance of supply chains is rather limited, and the research conducted so far, is rather fragmentary and not free of limitations of the conceptual and methodological nature. Additional rationales for further research in this area include knowledge and cognitive gaps indentified in this paper. According to authors the aim of future empirical research should be as follows: (1 unification and update of used conceptual and methodological approaches
Muratori, Rosangela; Mandolesi, Daniele; Galaverni, Maria Cristina; Azzaroli, Francesco
2017-06-01
Postoperative benign biliary stricture in the anastomotic site is one of the most common complications of biliary-enteric anastomosis, with a rate of 6.87% after 2-13 years of follow-up. If untreated, biliary strictures can induce other complications such as recurrent cholangitis, intrahepatic stones, pancreatitis and secondary biliary cirrhosis. We report our experience with extracorporeal shock wave lithotripsy (ESWL) in a patient with a massive symptomatic stone proximal to an anastomotic biliary stricture.
Proximal-type epithelioid sarcoma - Case report Sarcoma epitelióide tipo proximal - Relato de caso
Directory of Open Access Journals (Sweden)
Luciana Mendes dos Santos
2013-06-01
Full Text Available Epithelioid sarcoma, first described by Enzinger in 1970, is a rare soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. In 1997, Guillou et al. described a different type of epithelioid sarcoma, called proximal-type epithelioid sarcoma, which is found mostly in the pelvic and perineal regions and genital tracts of young to middle-aged adults. It is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. In this paper we present a case of proximal-type epithelioid sarcoma with an aggressive clinical course, including distant metastasis and death nine months after diagnosis.O sarcoma epitelióide, primeiramente descrito por Enzinger, em 1970, é uma neoplasia de partes moles que ocorre principalmente nas extremidades distais de adolescentes e adultos jovens. Em 1997, Guillou e cols. descreveram um tipo diferente de sarcoma epitelióide, que afetava frequentemente a região pélvica, períneo e áreas genitais de pacientes de média idade, com exame histológico caracterizado pela proliferação de células com aspecto epitelióide. Neste trabalho, descreve-se caso de paciente que apresentava há três meses duas lesões na região glútea, cujo exame histológico confirmou diagnóstico de sarcoma epitelioide do tipo proximal, já com presença de metástases pulmonares e cerebrais e que foi a óbito nove meses após o diagnóstico.
Rodriguez, Manuel; Wilder, David A.; Therrien, Kelly; Wine, Byron; Miranti, Reylissa; Daratany, Kenneth; Salume, Gloria; Baranovsky, Greg; Rodriquez, Matias
2006-01-01
The performance diagnostic checklist (PDC) was administered to examine the variables influencing the offering of promotional stamps by employees at two sites of a restaurant franchise. PDC results suggested that a lack of appropriate antecedents, equipment and processes, and consequences were responsible for the deficits. Based on these results,…
The shape of the hominoid proximal femur: a geometric morphometric analysis
Harmon, Elizabeth H
2007-01-01
As part of the hip joint, the proximal femur is an integral locomotor component. Although a link between locomotion and the morphology of some aspects of the proximal femur has been identified, inclusive shapes of this element have not been compared among behaviourally heterogeneous hominoids. Previous analyses have partitioned complex proximal femoral morphology into discrete features (e.g. head, neck, greater trochanter) to facilitate conventional linear measurements. In this study, three-dimensional geometric morphometrics are used to examine the shape of the proximal femur in hominoids to determine whether femoral shape co-varies with locomotor category. Fourteen landmarks are recorded on adult femora of Homo, Pan, Gorilla, Pongo and Hylobates. Generalized Procrustes analysis (GPA) is used to adjust for position, orientation and scale among landmark configurations. Principal components analysis is used to collapse and compare variation in residuals from GPA, and thin-plate spline analysis is used to visualize shape change among taxa. The results indicate that knucklewalking African apes are similar to one another in femoral shape, whereas the more suspensory Asian apes diverge from the African ape pattern. The shape of the human and orangutan proximal femur converge, a result that is best explained in terms of the distinct requirements for locomotion in each group. These findings suggest that the shape of the proximal femur is brought about primarily by locomotor behaviour. PMID:17310545
International Nuclear Information System (INIS)
Bhasin, S.; Zlatkin, M.B.; Sartoris, D.J.; Andre, M.; Resnick, D.
1987-01-01
Integrated cancellous, cortical, and total bone density in the femoral neck and inter-trochanteric region was measured bilaterally in 25 women aged 35-90 years (mean age, 65). Contiguous-section (1-cm-thick) data were analyzed using three-dimensional histogram software on a Cemax 1000 image processor. Single-section quantitative CT was used to determine mean mineral equivalent values for vertebral cancellous bone from T-11 to L-3 in each woman. Significant correlation was found between cancellous bone density at the two sites. Cortical and total bone densities in the proximal femur were predicted less well with vertebral cancellous data, suggesting a greater dependence on weight-bearing and activity factors
Energy Technology Data Exchange (ETDEWEB)
Kim, Ha Youn; Park, Sung Tae; Bae, Won Kyoung; Goo, Dong Erk [Dept. of Radiology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)
2014-12-15
We studied the influence of proximal geometry on the results of computational fluid dynamics (CFD). We made five models of different proximal geometry from three dimensional angiography of 63-year-old women with intracranial aneurysm. CFD results were analyzed as peak systolic velocity (PSV) at inlet and outlet as well as flow velocity profile at proximal level of internal carotid artery (ICA) aneurysm. Modified model of cavernous one with proximal tubing showed faster PSV at outlet than that at inlet. The PSV of outlets of other models were slower than that of inlets. The flow velocity profiles at immediate proximal to ICA aneurysm showed similar patterns in all models, suggesting that proximal vessel geometries could affect CFD results.
Soundarrajan, Dhanasekaran; Rajkumar, Natesan; Dhanasekararaja, Palanisamy; Rajasekaran, Shanmuganathan
2018-01-01
Proximal tibia stress fractures with knee osteoarthritis pose a challenging situation. We evaluated the radiological and functional outcome of one-stage total knee arthroplasty (TKA) and long stem for patients with varied grades of knee arthritis and proximal tibia stress fractures. Methods: We analysed 20 patients from April 2012 to March 2017 with proximal tibia stress fractures associated with knee osteoarthritis of varied grades. Out of 20 patients, five were acute fresh fractures. The mean age was 64 years (range, 52-78) which includes three men and 17 women. Previous surgery in the same limb, rheumatoid arthritis, valgus deformity were excluded. All patients were treated with posterior stabilised TKA with long stem, of which, four patients had screw augmentation for medial tibial bone defect and two patients with malunited fracture at stress fracture site required osteotomy, plating and bone grafting. Two patients had two level stress fracture of tibia in the same leg. The mean follow-up period was 28 (range, 6-60) months. The mean tibiofemoral angle improved from 18.27° varus to 1.8° valgus. The mean knee society score improved from 21.9 (range, -10 to 45) to 82.8 (range, 15-99) [p fractures got united at the last follow-up. One patient had infection and wound dehiscence at six months for which debridement done and had poor functional outcome. TKA with long stem gives excellent outcome, irrespective of severity of arthritis associated with stress fracture. By restoring limb alignment and bypassing the fracture site, it facilitates fracture healing. Early detection and prompt intervention is necessary to prevent the progression to recalcitrant non-union or malunion. © The Authors, published by EDP Sciences, 2018.
Proximate analysis of female population of wild feather back fish ...
African Journals Online (AJOL)
User
2011-05-09
May 9, 2011 ... Key words: Body composition, Notopterus notopterus, condition factor, wild fish. INTRODUCTION. Proximate body composition is the analysis of water, fat, protein and ash contents of the fish (Love, 1980). Proximate composition is a good indicator of physiology which is needed for routine analysis of ...
Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs
Directory of Open Access Journals (Sweden)
Lei Du
2016-01-01
Full Text Available Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses (0.7 V, 5 Hz were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oculomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.
Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.
Kageyama, R; Merlino, G T; Pastan, I
1989-09-15
Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.
International Nuclear Information System (INIS)
Farwell, Andrea J.; Vesely, Susanne; Nero, Vincent; Rodriguez, Hilda; McCormack, Kimberley; Shah, Saleh; Dixon, D. George; Glick, Bernard R.
2007-01-01
The growth of transgenic canola (Brassica napus) expressing a gene for the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase was compared to non-transformed canola exposed to flooding and elevated soil Ni concentration, in situ. In addition, the ability of the plant growth-promoting bacterium Pseudomonas putida UW4, which also expresses ACC deaminase, to facilitate the growth of non-transformed and transgenic canola under the above mentioned conditions was examined. Transgenic canola and/or canola treated with P. putida UW4 had greater shoot biomass compared to non-transformed canola under low flood-stress conditions. Under high flood-stress conditions, shoot biomass was reduced and Ni accumulation was increased in all instances relative to low flood-stress conditions. This is the first field study to document the increase in plant tolerance utilizing transgenic plants and plant growth-promoting bacteria exposed to multiple stressors. - Using transgenic plants and plant growth-promoting bacteria as phytoremediation methods increased plant tolerance at a metal-contaminated field site under low flood conditions
High-throughput determination of RNA structure by proximity ligation.
Ramani, Vijay; Qiu, Ruolan; Shendure, Jay
2015-09-01
We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA proximity ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures.
Proximate, Mineral and Phytochemical Composition of Dioscorea ...
African Journals Online (AJOL)
ADOWIE PERE
Keywords: Dioscorea dumetorum, proximate composition, mineral analysis, phytochemical screening ... were analyzed using atomic absorption ... determined using a Hack Dr/200 Spectrophotometer. ... Lead Acetate. +. +. + .... cosmetics.
Proximate composition and antinutrient content of pumpkin ...
African Journals Online (AJOL)
Proximate composition and antinutrient content of pumpkin ( Cucurbita pepo ) and sorghum ( Sorghum bicolor ) flour blends fermented with Lactobacillus plantarum , Aspergillus niger and Bacillus subtilis.