Improvements on non-equilibrium and transport Green function techniques: The next-generation TRANSIESTA

NASA Astrophysics Data System (ADS)

Papior, Nick; Lorente, Nicolás; Frederiksen, Thomas; García, Alberto; Brandbyge, Mads

2017-03-01

We present novel methods implemented within the non-equilibrium Green function code (NEGF) TRANSIESTA based on density functional theory (DFT). Our flexible, next-generation DFT-NEGF code handles devices with one or multiple electrodes (Ne ≥ 1) with individual chemical potentials and electronic temperatures. We describe its novel methods for electrostatic gating, contour optimizations, and assertion of charge conservation, as well as the newly implemented algorithms for optimized and scalable matrix inversion, performance-critical pivoting, and hybrid parallelization. Additionally, a generic NEGF "post-processing" code (TBTRANS/PHTRANS) for electron and phonon transport is presented with several novelties such as Hamiltonian interpolations, Ne ≥ 1 electrode capability, bond-currents, generalized interface for user-defined tight-binding transport, transmission projection using eigenstates of a projected Hamiltonian, and fast inversion algorithms for large-scale simulations easily exceeding 106 atoms on workstation computers. The new features of both codes are demonstrated and bench-marked for relevant test systems.

Inferring a District-Based Hierarchical Structure of Social Contacts from Census Data

PubMed Central

Yu, Zhiwen; Liu, Jiming; Zhu, Xianjun

2015-01-01

Researchers have recently paid attention to social contact patterns among individuals due to their useful applications in such areas as epidemic evaluation and control, public health decisions, chronic disease research and social network research. Although some studies have estimated social contact patterns from social networks and surveys, few have considered how to infer the hierarchical structure of social contacts directly from census data. In this paper, we focus on inferring an individual’s social contact patterns from detailed census data, and generate various types of social contact patterns such as hierarchical-district-structure-based, cross-district and age-district-based patterns. We evaluate newly generated contact patterns derived from detailed 2011 Hong Kong census data by incorporating them into a model and simulation of the 2009 Hong Kong H1N1 epidemic. We then compare the newly generated social contact patterns with the mixing patterns that are often used in the literature, and draw the following conclusions. First, the generation of social contact patterns based on a hierarchical district structure allows for simulations at different district levels. Second, the newly generated social contact patterns reflect individuals social contacts. Third, the newly generated social contact patterns improve the accuracy of the SEIR-based epidemic model. PMID:25679787

A domain-centric solution to functional genomics via dcGO Predictor

PubMed Central

2013-01-01

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

Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation.

PubMed

Kobayashi, Toshihiro; Kato-Itoh, Megumi; Nakauchi, Hiromitsu

2015-01-15

Generation of functional organs from patients' own cells is one of the ultimate goals of regenerative medicine. As a novel approach to creation of organs from pluripotent stem cells (PSCs), we employed blastocyst complementation in organogenesis-disabled animals and successfully generated PSC-derived pancreas and kidneys. Blastocyst complementation, which exploits the capacity of PSCs to participate in forming chimeras, does not, however, exclude contribution of PSCs to the development of tissues-including neural cells or germ cells-other than those specifically targeted by disabling of organogenesis. This fact provokes ethical controversy if human PSCs are to be used. In this study, we demonstrated that forced expression of Mix-like protein 1 (encoded by Mixl1) can be used to guide contribution of mouse embryonic stem cells to endodermal organs after blastocyst injection. We then succeeded in applying this method to generate functional pancreas in pancreatogenesis-disabled Pdx1 knockout mice using a newly developed tetraploid-based organ-complementation method. These findings hold promise for targeted organ generation from patients' own PSCs in livestock animals.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

PubMed Central

KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

PubMed Central

Weiss, Andy; Broach, William H.; Wiemels, Richard E.; Mogen, Austin B.; Rice, Kelly C.

2016-01-01

ABSTRACT In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. PMID:26861020

Clinical characteristics and beta cell function in Chinese patients with newly diagnosed type 2 diabetes mellitus with different levels of serum triglyceride.

PubMed

Zheng, Shuang; Zhou, Huan; Han, Tingting; Li, Yangxue; Zhang, Yao; Liu, Wei; Hu, Yaomin

2015-04-29

To explore clinical characteristics and beta cell function in Chinese patients with newly diagnosed drug naive type 2 diabetes mellitus (T2DM) with different levels of serum triglyceride (TG). Patients with newly diagnosed T2DM (n = 624) were enrolled and divided into different groups according to levels of serum TG. All patients underwent oral glucose tolerance tests and insulin releasing tests. Demographic data, lipid profiles, glucose levels, and insulin profiles were compared between different groups. Basic insulin secretion function index (homeostasis model assessment for beta cell function index, HOMA-β), modified beta cell function index (MBCI), glucose disposition indices (DI), and early insulin secretion function index (insulinogenic index, IGI) were used to evaluate the beta cell function. Patients of newly diagnosed T2DM with hypertriglyceridemia were younger, fatter and had worse lipid profiles, glucose profiles, and high insulin levels than those with normal TG. There is no difference in early phase insulin secretion among groups of newly diagnosed T2DM patients with different TG levels. The basal beta cell function (HOMA-β and MBCI) initially increased along rising TG levels and then decreased as the TG levels rose further. The insulin sensitivity was relatively high in patients with a low level of TG and low with a high level of TG. Hypertriglyceridemia influences clinical characteristics and β cell function of Chinese patients with newly diagnosed T2DM. A better management of dyslipidemia may, to some extent, reduce the effect of lipotoxicity, thereby improving glucose homeostasis in patients with newly diagnosed T2DM.

Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

PubMed Central

Deshpande, Aditi; Bergami, Matteo; Ghanem, Alexander; Conzelmann, Karl-Klaus; Lepier, Alexandra; Götz, Magdalena; Berninger, Benedikt

2013-01-01

Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit. PMID:23487772

Analysis of Taiwan patents for the medicinal mushroom "Niu-Chang- Chih".

PubMed

Chen, Yu-Fen; Lu, Wen-Ling; Wu, Ming-Der; Yuan, Gwo-Fang

2013-04-01

"Niu-Chang-Chih" (Antrodia cinnanomea) is a medicinal mushroom that has only been collected from the aromatic tree, Cinnamomum kanehirai, which is native to Taiwan. A total of 105 Taiwan patent applications and patents for "Niu-Chang-Chih" were collected and analyzed. Patent applications and granted patents claiming newly identified functional components from "Niu-Chang-Chih," biologically pure cultures of the mushroom strain, and cultivation of "Niu-Chang-Chih" were examined. Several applications and patents claim identified active compounds from "Niu-Chang- Chih," which provide better patent protection. These newly identified functional compounds include cyclohexanones, maleic and succinic acid derivatives, labdane diterpenoids, and benzenoids. Newly identified functional proteins include a glutathione-dependent formaldehyde dehydrogenase (GFD), a glycoprotein named ACA1, and a laccase. Newly identified functional polysaccharides include ACP1, ACP2, and ACP3. The number of patents for newly identified compounds and their uses are expected to continue growing.

Extension of Ko Straight-Beam Displacement Theory to Deformed Shape Predictions of Slender Curved Structures

NASA Technical Reports Server (NTRS)

Ko, William L.; Fleischer, Van Tran

2011-01-01

The Ko displacement theory originally developed for shape predictions of straight beams is extended to shape predictions of curved beams. The surface strains needed for shape predictions were analytically generated from finite-element nodal stress outputs. With the aid of finite-element displacement outputs, mathematical functional forms for curvature-effect correction terms are established and incorporated into straight-beam deflection equations for shape predictions of both cantilever and two-point supported curved beams. The newly established deflection equations for cantilever curved beams could provide quite accurate shape predictions for different cantilever curved beams, including the quarter-circle cantilever beam. Furthermore, the newly formulated deflection equations for two-point supported curved beams could provide accurate shape predictions for a range of two-point supported curved beams, including the full-circular ring. Accuracy of the newly developed curved-beam deflection equations is validated through shape prediction analysis of curved beams embedded in the windward shallow spherical shell of a generic crew exploration vehicle. A single-point collocation method for optimization of shape predictions is discussed in detail

Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury☆

PubMed Central

Jiang, Jindou; Bu, Xingyao; Liu, Meng; Cheng, Peixun

2012-01-01

Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury. PMID:25806058

Quantitative chemical proteomics profiling of de novo protein synthesis during starvation-mediated autophagy

PubMed Central

Wang, Jigang; Zhang, Jianbin; Lee, Yew-Mun; Koh, Pin-Lang; Ng, Shukie; Bao, Feichao; Lin, Qingsong; Shen, Han-Ming

2016-01-01

ABSTRACT Autophagy is an intracellular degradation mechanism in response to nutrient starvation. Via autophagy, some nonessential cellular constituents are degraded in a lysosome-dependent manner to generate biomolecules that can be utilized for maintaining the metabolic homeostasis. Although it is known that under starvation the global protein synthesis is significantly reduced mainly due to suppression of MTOR (mechanistic target of rapamycin serine/threonine kinase), emerging evidence demonstrates that de novo protein synthesis is involved in the autophagic process. However, characterizing these de novo proteins has been an issue with current techniques. Here, we developed a novel method to identify newly synthesized proteins during starvation-mediated autophagy by combining bio-orthogonal noncanonical amino acid tagging (BONCAT) and isobaric tags for relative and absolute quantitation (iTRAQTM). Using bio-orthogonal metabolic tagging, L-azidohomoalanine (AHA) was incorporated into newly synthesized proteins which were then enriched with avidin beads after a click reaction between alkyne-bearing biotin and AHA's bio-orthogonal azide moiety. The enriched proteins were subjected to iTRAQ labeling for protein identification and quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Via the above approach, we identified and quantified a total of 1176 proteins and among them 711 proteins were found to meet our defined criteria as de novo synthesized proteins during starvation-mediated autophagy. The characterized functional profiles of the 711 newly synthesized proteins by bioinformatics analysis suggest their roles in ensuring the prosurvival outcome of autophagy. Finally, we performed validation assays for some selected proteins and found that knockdown of some genes has a significant impact on starvation-induced autophagy. Thus, we think that the BONCAT-iTRAQ approach is effective in the identification of newly synthesized proteins and provides useful insights to the molecular mechanisms and biological functions of autophagy. PMID:27463841

Effects of levetiracetam monotherapy on sperm parameters and sex hormones: Data from newly diagnosed patients with epilepsy.

PubMed

Ceylan, Mustafa; Yalcin, Ahmet; Bayraktutan, Omer Faruk; Karabulut, Ibrahim; Sonkaya, Ali Rıza

2016-10-01

Epilepsy has an impact on the reproductive system. Males with epilepsy have lower fertility rates, hypo-sexuality and reduced potency compared with the general population. Anti-epileptic drugs and epilepsy itself are thought to be responsible for this reduced fertility. LEV is a second-generation anti-epileptic agent with low incidences of both adverse effects and drug-drug interactions. In this study, we have investigated the effects of LEV treatment on sex hormones and sperm parameters in newly diagnosed epilepsy patients. We recruited 26 males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were divided into two groups depending on whether they had partial or generalized seizures. We acquired the results of pre- and post-treatment sperm analyses and serum sex hormone levels. We also recorded the maximum dose, daily dose and treatment duration for each individual. Pre- and post-treatment comparisons and correlations between both sperm and sex hormone parameters and both treatment duration and dose were determined. Pre- and post-treatment sex hormone levels were not significantly different. The total sperm count, percentage of normal morphology and functional sperm count tested after treatment were significantly lower in both groups compared with pre-treatment values (p<0.05). There was a moderate correlation between daily dose and reduction in functional sperm count (r: 0.41, p: 0.034). Our findings confirm that LEV treatment of newly diagnosed epilepsy patients decreases sperm parameters without altering sex hormone levels. Our results may guide the choice of anti-epileptic drug treatment among men with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Quantitative chemical proteomics profiling of de novo protein synthesis during starvation-mediated autophagy.

PubMed

Wang, Jigang; Zhang, Jianbin; Lee, Yew-Mun; Koh, Pin-Lang; Ng, Shukie; Bao, Feichao; Lin, Qingsong; Shen, Han-Ming

2016-10-02

Autophagy is an intracellular degradation mechanism in response to nutrient starvation. Via autophagy, some nonessential cellular constituents are degraded in a lysosome-dependent manner to generate biomolecules that can be utilized for maintaining the metabolic homeostasis. Although it is known that under starvation the global protein synthesis is significantly reduced mainly due to suppression of MTOR (mechanistic target of rapamycin serine/threonine kinase), emerging evidence demonstrates that de novo protein synthesis is involved in the autophagic process. However, characterizing these de novo proteins has been an issue with current techniques. Here, we developed a novel method to identify newly synthesized proteins during starvation-mediated autophagy by combining bio-orthogonal noncanonical amino acid tagging (BONCAT) and isobaric tags for relative and absolute quantitation (iTRAQ TM ). Using bio-orthogonal metabolic tagging, L-azidohomoalanine (AHA) was incorporated into newly synthesized proteins which were then enriched with avidin beads after a click reaction between alkyne-bearing biotin and AHA's bio-orthogonal azide moiety. The enriched proteins were subjected to iTRAQ labeling for protein identification and quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Via the above approach, we identified and quantified a total of 1176 proteins and among them 711 proteins were found to meet our defined criteria as de novo synthesized proteins during starvation-mediated autophagy. The characterized functional profiles of the 711 newly synthesized proteins by bioinformatics analysis suggest their roles in ensuring the prosurvival outcome of autophagy. Finally, we performed validation assays for some selected proteins and found that knockdown of some genes has a significant impact on starvation-induced autophagy. Thus, we think that the BONCAT-iTRAQ approach is effective in the identification of newly synthesized proteins and provides useful insights to the molecular mechanisms and biological functions of autophagy.

A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing

PubMed Central

Davidsson, Marcus; Diaz-Fernandez, Paula; Schwich, Oliver D.; Torroba, Marcos; Wang, Gang; Björklund, Tomas

2016-01-01

Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries. The libraries are designed to enable the production of viral vector preparations assessing coding or non-coding RNA function in vivo. When generating high diversity libraries, it is a challenge to achieve efficient cloning, unambiguous barcoding and detailed characterization using low-cost sequencing technologies. With the presented protocol, diversity of above 3 million uniquely barcoded adeno-associated viral (AAV) plasmids can be achieved in a single reaction through a process achievable in any molecular biology laboratory. This approach opens up for a multitude of in vivo assessments from the evaluation of enhancer and promoter regions to the optimization of genome editing. The generated plasmid libraries are also useful for validation of sequencing clustering algorithms and we here validate the newly presented message passing clustering process named Starcode. PMID:27874090

An alternative extragradient projection method for quasi-equilibrium problems.

PubMed

Chen, Haibin; Wang, Yiju; Xu, Yi

2018-01-01

For the quasi-equilibrium problem where the players' costs and their strategies both depend on the rival's decisions, an alternative extragradient projection method for solving it is designed. Different from the classical extragradient projection method whose generated sequence has the contraction property with respect to the solution set, the newly designed method possesses an expansion property with respect to a given initial point. The global convergence of the method is established under the assumptions of pseudomonotonicity of the equilibrium function and of continuity of the underlying multi-valued mapping. Furthermore, we show that the generated sequence converges to the nearest point in the solution set to the initial point. Numerical experiments show the efficiency of the method.

Changes in cell migration and survival in the olfactory bulb of the pcd/pcd mouse.

PubMed

Valero, J; Weruaga, E; Murias, A R; Recio, J S; Curto, G G; Gómez, C; Alonso, J R

2007-06-01

Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals, progenitor cells from the rostral migratory stream (RMS) differentiate into bulbar interneurons that modulate MC activity. In the present work, we studied changes in proliferation, tangential migration, radial migration patterns, and the survival of these newly generated neurons in this neurodegeneration animal model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months before killing in order to label neuroblast incorporation into the OB and to analyze the survival of these cells after differentiation, respectively. Both the organization and cellular composition of the RMS and the differentiation of the newly generated neurons in the OB were studied using specific markers of glial cells, neuroblasts, and mature neurons. No changes were observed in the cell proliferation rate nor in their tangential migration through the RMS, indicating that migrating neuroblasts are only weakly responsive to the alteration in their target region, the OB. However, the absence of MC does elicit differences in the final destination of the newly generated interneurons. Moreover, the loss of MC also produces changes in the survival of the newly generated interneurons, in accordance with the dramatic decrease in the number of synaptic targets available.

Evidence that proliferation of golgi apparatus depends on both de novo generation from the endoplasmic reticulum and formation from pre-existing stacks during the growth of tobacco BY-2 cells.

PubMed

Abiodun, Moses Olabiyi; Matsuoka, Ken

2013-04-01

In higher plants, the numbers of cytoplasmic-distributed Golgi stacks differ based on function, age and cell type. It has not been clarified how the numbers are controlled, whether all the Golgi apparatus in a cell function equally and whether the increase in Golgi number is a result of the de novo formation from the endoplasmic reticulum (ER) or fission of pre-existing stacks. A tobacco prolyl 4-hydroxylase (NtP4H1.1), which is a cis-Golgi-localizing type II membrane protein, was tagged with a photoconvertible fluorescent protein, mKikGR (monomeric Kikume green red), and expressed in tobacco bright yellow 2 (BY-2) cells. Transformed cells were exposed to purple light to convert the fluorescence from green to red. A time-course analysis after the conversion revealed a progressive increase in green puncta and a decrease in the red puncta. From 3 to 6 h, we observed red, yellow and green fluorescent puncta corresponding to pre-existing Golgi; Golgi containing both pre-existing and newly synthesized protein; and newly synthesized Golgi. Analysis of the number and fluorescence of Golgi at different phases of the cell cycle suggested that an increase in Golgi number with both division and de novo synthesis occurred concomitantly with DNA replication. Investigation with different inhibitors suggested that the formation of new Golgi and the generation of Golgi containing both pre-existing and newly synthesized protein are mediated by different machineries. These results and modeling based on quantified results indicate that the Golgi apparatuses in tobacco BY-2 cells are not uniform and suggest that both de novo synthesis from the ER and Golgi division contribute almost equally to the increase in proliferating cells.

The Effect of Structural Modifications on Ionic Conductivity in Newly-Designed Polyester Electrolytes

NASA Astrophysics Data System (ADS)

Pesko, Danielle; Jung, Yuki; Coates, Geoff; Balsara, Nitash

2015-03-01

Gaining a fundamental understanding of the relationship between molecular structure and ionic conductivity of polymer electrolytes is an essential step toward designing next generation materials for battery applications. In this study, we use a systematic set of newly-designed polyesters with varying side-chain lengths and oxygen functional groups to elucidate the effects of structural modifications on the conductive properties of the corresponding electrolytes. Mixtures of polyesters and lithium bis(trifluromethanesulfonyl)imide (LiTFSI) were characterized using ac impedance spectroscopy to measure the ionic conductivity at various temperatures and salt concentrations. The relative conductivities of these electrolytes in the dilute limit are directly comparable to results of molecular dynamics simulations performed using the same polymers. The simulations correspond well with the experimental results, and provide molecular level insight about the solvation environment of the lithium ions and how the ions transport through these polyesters.

How Schools Can Promote Healthy Development for Newly Arrived Immigrant and Refugee Adolescents: Research Priorities.

PubMed

McNeely, Clea A; Morland, Lyn; Doty, S Benjamin; Meschke, Laurie L; Awad, Summer; Husain, Altaf; Nashwan, Ayat

2017-02-01

The US education system must find creative and effective ways to foster the healthy development of the approximately 2 million newly arrived immigrant and refugee adolescents, many of whom contend with language barriers, limited prior education, trauma, and discrimination. We identify research priorities for promoting the school success of these youth. The study used the 4-phase priority-setting method of the Child Health and Nutrition Research Initiative. In the final stage, 132 researchers, service providers, educators, and policymakers based in the United States were asked to rate the importance of 36 research options. The highest priority research options (range 1 to 5) were: evaluating newcomer programs (mean = 4.44, SD = 0.55), identifying how family and community stressors affect newly arrived immigrant and refugee adolescents' functioning in school (mean = 4.40, SD = 0.56), identifying teachers' major stressors in working with this population (mean = 4.36, SD = 0.72), and identifying how to engage immigrant and refugee families in their children's education (mean = 4.35, SD = 0.62). These research priorities emphasize the generation of practical knowledge that could translate to immediate, tangible benefits for schools. Funders, schools, and researchers can use these research priorities to guide research for the highest benefit of schools and the newly arrived immigrant and refugee adolescents they serve. © 2017, American School Health Association.

Electron beam mask writer EBM-9500 for logic 7nm node generation

NASA Astrophysics Data System (ADS)

Matsui, Hideki; Kamikubo, Takashi; Nakahashi, Satoshi; Nomura, Haruyuki; Nakayamada, Noriaki; Suganuma, Mizuna; Kato, Yasuo; Yashima, Jun; Katsap, Victor; Saito, Kenichi; Kobayashi, Ryoei; Miyamoto, Nobuo; Ogasawara, Munehiro

2016-10-01

Semiconductor scaling is slowing down because of difficulties of device manufacturing below logic 7nm node generation. Various lithography candidates which include ArF immersion with resolution enhancement technology (like Inversed Lithography technology), Extreme Ultra Violet lithography and Nano Imprint lithography are being developed to address the situation. In such advanced lithography, shot counts of mask patterns are estimated to increase explosively in critical layers, and then it is hoped that multi beam mask writer (MBMW) is released to handle them within realistic write time. However, ArF immersion technology with multiple patterning will continue to be a mainstream lithography solution for most of the layers. Then, the shot counts in less critical layers are estimated to be stable because of the limitation of resolution in ArF immersion technology. Therefore, single beam mask writer (SBMW) can play an important role for mask production still, relative to MBMW. Also the demand of SBMW seems actually strong for the logic 7nm node. To realize this, we have developed a new SBMW, EBM-9500 for mask fabrication in this generation. A newly introduced electron beam source enables higher current density of 1200A/cm2. Heating effect correction function has also been newly introduced to satisfy the requirements for both pattern accuracy and throughput. In this paper, we will report the configuration and performance of EBM-9500.

Natural and lesion-induced decrease in cell proliferation in the medial nucleus of the trapezoid body during hearing development.

PubMed

Saliu, Aminat; Adise, Shana; Xian, Sandy; Kudelska, Kamila; Rodríguez-Contreras, Adrián

2014-04-01

The functional interactions between neurons and glial cells that are important for nervous system function are presumably established during development from the activity of progenitor cells. In this study we examined proliferation of progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in the rat auditory brainstem. We performed DNA synthesis labeling experiments to demonstrate changes in cell proliferation activity during postnatal stages of development. An increase in cell proliferation correlated with MNTB growth and the presence of S100β-positive astrocytes among MNTB neurons. In additional experiments we analyzed the fate of newly born cells. At perinatal ages, newly born cells colabeled with the astrocyte marker S100β in higher numbers than when cells were generated at postnatal day 6. Furthermore, we identified newly born cells that were colabeled with caspase-3 immunohistochemistry and performed comparative experiments to demonstrate that there is a natural decrease in cell proliferation activity during postnatal development in rats, mice, gerbils, and ferrets. Lastly, we found that there is a stronger decrease in MNTB cell proliferation after performing bilateral lesions of the auditory periphery in rats. Altogether, these results identify important stages in the development of astrocytes in the MNTB and provide evidence that the proliferative activity of the progenitor cells is developmentally regulated. We propose that the developmental reduction in cell proliferation may reflect coordinated signaling between the auditory brainstem and the auditory periphery. Copyright © 2013 The Authors. Wiley Periodicals, Inc.

Rosiglitazone Promotes White Matter Integrity and Long-Term Functional Recovery After Focal Cerebral Ischemia.

PubMed

Han, Lijuan; Cai, Wei; Mao, Leilei; Liu, Jia; Li, Peiying; Leak, Rehana K; Xu, Yun; Hu, Xiaoming; Chen, Jun

2015-09-01

Oligodendrogenesis is essential for white matter repair after stroke. Although agonists of peroxisome proliferator-activated receptors γ confer neuroprotection in models of cerebral ischemia, it is not known whether this effect extends to white matter protection. This study tested the hypothesis that the peroxisome proliferator-activated receptors γ agonist rosiglitazone enhances oligodendrogenesis and improves long-term white matter integrity after ischemia/reperfusion. Male adult C57/BL6 mice (25-30 g) were subjected to 60-minute middle cerebral artery occlusion and reperfusion. Rosiglitazone (3 mg/kg) was injected intraperitoneally once daily for 14 days beginning 2 hours after reperfusion. Sensorimotor and cognitive functions were evaluated ≤21 days after middle cerebral artery occlusion. Immunostaining was used to assess infarct volume, myelin loss, and microglial activation. Bromodeoxyuridine (BrdU) was injected for measurements of proliferating NG2(+) oligodendrocyte precursor cells (OPCs) and newly generated adenomatous polyposis coli(+) oligodendrocytes. Mixed glial cultures were used to confirm the effect of rosiglitazone on oligodendrocyte differentiation and microglial polarization. Rosiglitazone significantly reduced brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions for at least 21 days after middle cerebral artery occlusion. Rosiglitazone enhanced OPC proliferation and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion. Rosiglitazone treatment also reduced the numbers of Iba1(+)/CD16(+) M1 microglia and increased the numbers of Iba1(+)/CD206(+) M2 microglia after stroke. Glial culture experiments confirmed that rosiglitazone promoted oligodendrocyte differentiation, perhaps by promoting microglial M2 polarization. Rosiglitazone treatment improves long-term white matter integrity after cerebral ischemia, at least, in part, by promoting oligodendrogenesis and facilitating microglial polarization toward the beneficial M2 phenotype. © 2015 American Heart Association, Inc.

Study of cognitive functions in newly diagnosed cases of subclinical and clinical hypothyroidism.

PubMed

Sharma, Kirti; Behera, Joshil Kumar; Sood, Sushma; Rajput, Rajesh; Satpal; Praveen, Prashant

2014-01-01

Hypothyroidism is associated with significant neurocognitive deficits because hypothyroidism prevents the brain from adequately sustaining the energy consuming processes needed for neurotransmission, memory, and other higher brain functions. Hence, the study was done to assess the cognitive functions of newly diagnosed subclinical and clinical hypothyroid patients by evoked response potential P300. 75 patients each of newly diagnosed subclinical and clinical hypothyroid patients attending endocrinology clinic and 75 healthy age and sex matched euthyroid controls were considered for the study. P300 was recorded with Record Medicare System Polyrite, Chandigarh using auditory "oddball paradigm". The data was analyzed using ANOVA followed by post Tukey's test. Newly diagnosed clinical hypothyroid patients showed a significant increase in P300 latency compared to control (P < 0.05) and subclinical cases (P < 0.01) while there was no significant difference between the P300 latency of subclinical cases and control group. Also, there was no significant difference in P300 amplitude among the three groups. P300 latency in case of newly diagnosed hypothyroid clinical cases is significantly increased compared to newly diagnosed subclinical cases and control.

Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits

PubMed Central

Tirone, Felice; Farioli-Vecchioli, Stefano; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca

2013-01-01

Within the hippocampal circuitry, the basic function of the dentate gyrus is to transform the memory input coming from the enthorinal cortex into sparse and categorized outputs to CA3, in this way separating related memory information. New neurons generated in the dentate gyrus during adulthood appear to facilitate this process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying this model has been gathered essentially by ablating the newly adult-generated neurons. This approach, however, does not allow monitoring of the integration of new neurons into memory circuits and is likely to set in motion compensatory circuits, possibly leading to an underestimation of the role of new neurons. Here we review the background of the basic function of the hippocampus and of the known properties of new adult-generated neurons. In this context, we analyze the cognitive performance in mouse models generated by us and others, with modified expression of the genes Btg2 (PC3/Tis21), Btg1, Pten, BMP4, etc., where new neurons underwent a change in their differentiation rate or a partial decrease of their proliferation or survival rate rather than ablation. The effects of these modifications are equal or greater than full ablation, suggesting that the architecture of circuits, as it unfolds from the interaction between existing and new neurons, can have a greater functional impact than the sheer number of new neurons. We propose a model which attempts to measure and correlate the set of cellular changes in the process of neurogenesis with the memory function. PMID:23734097

Curved Displacement Transfer Functions for Geometric Nonlinear Large Deformation Structure Shape Predictions

NASA Technical Reports Server (NTRS)

Ko, William L.; Fleischer, Van Tran; Lung, Shun-Fat

2017-01-01

For shape predictions of structures under large geometrically nonlinear deformations, Curved Displacement Transfer Functions were formulated based on a curved displacement, traced by a material point from the undeformed position to deformed position. The embedded beam (depth-wise cross section of a structure along a surface strain-sensing line) was discretized into multiple small domains, with domain junctures matching the strain-sensing stations. Thus, the surface strain distribution could be described with a piecewise linear or a piecewise nonlinear function. The discretization approach enabled piecewise integrations of the embedded-beam curvature equations to yield the Curved Displacement Transfer Functions, expressed in terms of embedded beam geometrical parameters and surface strains. By entering the surface strain data into the Displacement Transfer Functions, deflections along each embedded beam can be calculated at multiple points for mapping the overall structural deformed shapes. Finite-element linear and nonlinear analyses of a tapered cantilever tubular beam were performed to generate linear and nonlinear surface strains and the associated deflections to be used for validation. The shape prediction accuracies were then determined by comparing the theoretical deflections with the finiteelement- generated deflections. The results show that the newly developed Curved Displacement Transfer Functions are very accurate for shape predictions of structures under large geometrically nonlinear deformations.

GENERIC VERIFICATION PROTOCOL: DISTRIBUTED GENERATION AND COMBINED HEAT AND POWER FIELD TESTING PROTOCOL

EPA Science Inventory

This report is a generic verification protocol by which EPA’s Environmental Technology Verification program tests newly developed equipment for distributed generation of electric power, usually micro-turbine generators and internal combustion engine generators. The protocol will ...

Rapid production of functionalized recombinant proteins: marrying ligation independent cloning and in vitro protein ligation.

PubMed

Kushnir, Susanna; Marsac, Yoann; Breitling, Reinhard; Granovsky, Igor; Brok-Volchanskaya, Vera; Goody, Roger S; Becker, Christian F W; Alexandrov, Kirill

2006-01-01

Functional genomics and proteomics have been very active fields since the sequencing of several genomes was completed. To assign a physiological role to the newly discovered coding genes with unknown function, new generic methods for protein production, purification, and targeted functionalization are needed. This work presents a new vector, pCYSLIC, that allows rapid generation of Escherichia coli expression constructs via ligation-independent cloning (LIC). The vector is designed to facilitate protein purification by either Ni-NTA or GSH affinity chromatography. Subsequent proteolytic removal of affinity tags liberates an N-terminal cysteine residue that is then used for covalent modification of the target protein with different biophysical probes via protein ligation. The described system has been tested on 36 mammalian Rab GTPases, and it was demonstrated that recombinant GTPases produced with pCYSLIC could be efficiently modified with fluorescein or biotin in vitro. Finally, LIC was compared with the recently developed In-Fusion cloning method, and it was demonstrated that In-Fusion provides superior flexibility in choice of expression vector. By the application of In-Fusion cloning Cys-Rab6A GTPase with an N-terminal cysteine residue was generated employing unmodified pET30a vector and TVMV protease.

High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

PubMed

Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

2017-08-01

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus.

PubMed

Stevens, Hanna E; Jiang, Ginger Y; Schwartz, Michael L; Vaccarino, Flora M

2012-06-15

Fibroblast growth factor (FGF) signaling controls self-renewal of neural stem cells during embryonic telencephalic development. FGF receptor 2 (FGFR2) has a significant role in the production of cortical neurons during embryogenesis, but its role in the hippocampus during development and in adulthood has not been described. Here we dissociate the role of FGFR2 in the hippocampus during development and during adulthood with the use of embryonic knockout and inducible knockout mice. Embryonic knockout of FGFR2 causes a reduction of hippocampal volume and impairment in adult spatial memory in mice. Spatial reference memory, as assessed by performance on the water maze probe trial, was correlated with reduced hippocampal parvalbumin+ cells, whereas short-term learning was correlated with reduction in immature neurons in the dentate gyrus. Furthermore, short-term learning and newly generated neurons in the dentate gyrus were deficient even when FGFR2 was lacking only in adulthood. Taken together, these findings support a dual role for FGFR2 in hippocampal short-term learning and long-term reference memory, which appear to depend on the abundance of two separate cellular components, parvalbumin interneurons and newly generated granule cells in the hippocampus. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of molecular packing in organic crystals on singlet fission with ab initio many body perturbation theory

NASA Astrophysics Data System (ADS)

Haber, Jonah; Refaely-Abramson, Sivan; da Jornada, Felipe H.; Louie, Steven G.; Neaton, Jeffrey B.

Multi-exciton generation processes, in which multiple charge carriers are generated from a single photon, are mechanisms of significant interest for achieving efficiencies beyond the Shockley-Queisser limit of conventional p-n junction solar cells. One well-studied multiexciton process is singlet fission, whereby a singlet decays into two spin-correlated triplet excitons. Here, we use a newly developed computational approach to calculate singlet-fission coupling terms and rates with an ab initio Green's function formalism based on many-body perturbation theory (MBPT) within the GW approximation and the Bethe-Salpeter equation approach. We compare results for crystalline pentacene and TIPS-pentacene and explore the effect of molecular packing on the singlet fission mechanism. This work is supported by the Department of Energy.

Time for Genome Editing: Next-Generation Attenuated Malaria Parasites.

PubMed

Singer, Mirko; Frischknecht, Friedrich

2017-03-01

Immunization with malaria parasites that developmentally arrest in or immediately after the liver stage is the only way currently known to confer sterilizing immunity in both humans and rodent models. There are various ways to attenuate parasite development resulting in different timings of arrest, which has a significant impact on vaccination efficiency. To understand what most impacts vaccination efficiency, newly developed gain-of-function methods can now be used to generate a wide array of differently attenuated parasites. The combination of multiple attenuation approaches offers the potential to engineer efficiently attenuated Plasmodium parasites and learn about their fascinating biology at the same time. Here we discuss recent studies and the potential of targeted parasite manipulation using genome editing to develop live attenuated malaria vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Power Generation Evaluated on a Bismuth Telluride Unicouple Module

NASA Astrophysics Data System (ADS)

Hu, Xiaokai; Nagase, Kazuo; Jood, Priyanka; Ohta, Michihiro; Yamamoto, Atsushi

2015-06-01

The power generated by a thermoelectric unicouple module made of Bi2Te3 alloy was evaluated by use of a newly developed instrument. An electrical load was connected to the module, and the terminal voltage and output power of the module were obtained by altering electric current. Water flow was used to cool the cold side of the module and for heat flow measurement, by monitoring inlet and outlet temperatures. When the electric current was increased, heat flow was enhanced as a result of the Peltier effect and Joule heating. Voltage, power, heat flow, and efficiency as functions of current were determined for hot-side temperatures from 50 to 220°C. Maximum power output and peak conversion efficiency could thus be easily derived for each temperature.

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

PubMed

Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard

2016-11-30

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Retinovascular physiology and pathophysiology: new experimental approach/new insights

PubMed Central

Puro, Donald G.

2012-01-01

An important challenge in visual neuroscience is understand the physiology and pathophysiology of the intra-retinal vasculature, whose function is required for ophthalmoception by humans and most other mammals. In the quest to learn more about this highly specialized portion of the circulatory system, a newly developed method for isolating vast microvascular complexes from the rodent retina has opened the way for using techniques such as patch-clamping, fluorescence imaging and time-lapse photography to elucidate the functional organization of a capillary network and its pre-capillary arteriole. For example, the ability to obtain dual perforated-patch recordings from well-defined sites within an isolated microvascular complex permitted the first characterization of the electrotonic architecture of a capillary/arteriole unit. This analysis revealed that this operational unit is not simply a homogenous synctium, but has a complex functional organization that is dynamically modulated by extracellular signals such as angiotensin II. Another recent discovery is that a capillary and its pre-capillary arteriole have distinct physiological differences; capillaries have an abundance of ATP-sensitive potassium (KATP) channels and a dearth of voltage-dependent calcium channels (VDCCs) while the converse is true for arterioles. In addition, voltage transmission between abluminal cells and the endothelium is more efficient in the capillaries. Thus, the capillary network is well-equipped to generate and transmit voltages, and the pre-capillary arteriole is well-adapted to transduce a capillary-generated voltage into a change in abluminal cell calcium and thereby, a vasomotor response. Use of microvessels isolated from the diabetic retina has led to new insights concerning retinal vascular pathophysiology. For example, soon after the onset of diabetes, the efficacy of voltage transmission through the endothelium is diminished; arteriolar VDCCs is inhibited, and there is increased vulnerability to purinergic vasotoxicity, which is a newly identified pathobiological mechanism. Other recent studies reveal that KATP channels not only have an essential physiological role in generating vasomotor responses, but their activation substantially boosts the lethality of hypoxia. Thus, the pathophysiology of the retinal microvasculature is closely linked with its physiology. PMID:22333041

Newly Elaborated Multipurpose Polymer Electrolyte Encompassing RTILs for Smart Energy-Efficient Devices.

PubMed

Nair, Jijeesh R; Porcarelli, Luca; Bella, Federico; Gerbaldi, Claudio

2015-06-17

Profoundly ion-conducting, self-standing, and tack-free ethylene oxide-based polymer electrolytes encompassing a room-temperature ionic liquid (RTIL) with specific amounts of lithium salt are successfully prepared via a rapid and easily upscalable process including a UV irradiation step. All prepared materials are thoroughly characterized in terms of their physical, chemical, and morphological properties and eventually galvanostatically cycled in lab-scale lithium batteries (LIBs) exploiting a novel direct polymerization procedure to get intimate electrode/electrolyte interfacial characteristics. The promising multipurpose characteristics of the newly elaborated materials are demonstrated by testing them in dye-sensitized solar cells (DSSCs), where the introduction of the iodine/iodide-based redox mediator in the polymer matrix assured the functioning of a lab-scale test cell with conversion efficiency exceeding 6% at 1 sun. The reported results enlighten the promising prospects of the material to be successfully implemented as stable, durable, and efficient electrolyte in next-generation energy conversion and storage devices.

Understanding the Cellular Function of TRPV2 Channel through Generation of Specific Monoclonal Antibodies

PubMed Central

Cohen, Matthew R.; Huynh, Kevin W.; Cawley, Daniel; Moiseenkova-Bell, Vera Y.

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function. PMID:24392006

Understanding the cellular function of TRPV2 channel through generation of specific monoclonal antibodies.

PubMed

Cohen, Matthew R; Huynh, Kevin W; Cawley, Daniel; Moiseenkova-Bell, Vera Y

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca(2+)-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function.

Alternative polyadenylation: New insights from global analyses

PubMed Central

Shi, Yongsheng

2012-01-01

Recent studies have revealed widespread mRNA alternative polyadenylation (APA) in eukaryotes and its dynamic spatial and temporal regulation. APA not only generates proteomic and functional diversity, but also plays important roles in regulating gene expression. Global deregulation of APA has been demonstrated in a variety of human diseases. Recent exciting advances in the field have been made possible in a large part by high throughput analyses using newly developed experimental tools. Here I review the recent progress in global studies of APA and the insights that have emerged from these and other studies that use more conventional methods. PMID:23097429

View generation for 3D-TV using image reconstruction from irregularly spaced samples

NASA Astrophysics Data System (ADS)

Vázquez, Carlos

2007-02-01

Three-dimensional television (3D-TV) will become the next big step in the development of advanced TV systems. One of the major challenges for the deployment of 3D-TV systems is the diversity of display technologies and the high cost of capturing multi-view content. Depth image-based rendering (DIBR) has been identified as a key technology for the generation of new views for stereoscopic and multi-view displays from a small number of views captured and transmitted. We propose a disparity compensation method for DIBR that does not require spatial interpolation of the disparity map. We use a forward-mapping disparity compensation with real precision. The proposed method deals with the irregularly sampled image resulting from this disparity compensation process by applying a re-sampling algorithm based on a bi-cubic spline function space that produces smooth images. The fact that no approximation is made on the position of the samples implies that geometrical distortions in the final images due to approximations in sample positions are minimized. We also paid attention to the occlusion problem. Our algorithm detects the occluded regions in the newly generated images and uses simple depth-aware inpainting techniques to fill the gaps created by newly exposed areas. We tested the proposed method in the context of generation of views needed for viewing on SynthaGram TM auto-stereoscopic displays. We used as input either a 2D image plus a depth map or a stereoscopic pair with the associated disparity map. Our results show that this technique provides high quality images to be viewed on different display technologies such as stereoscopic viewing with shutter glasses (two views) and lenticular auto-stereoscopic displays (nine views).

Enhancing biodegradation and energy generation via roughened surface graphite electrode in microbial desalination cell.

PubMed

Ebrahimi, Atieh; Yousefi Kebria, Daryoush; Najafpour Darzi, Ghasem

2017-09-01

The microbial desalination cell (MDC) is known as a newly developed technology for water and wastewater treatment. In this study, desalination rate, organic matter removal and energy production in the reactors with and without desalination function were compared. Herein, a new design of plain graphite called roughened surface graphite (RSG) was used as the anode electrode in both microbial fuel cell (MFC) and MDC reactors for the first time. Among the three type of anode electrodes investigated in this study, RSG electrode produced the highest power density and salt removal rate of 10.81 W/m 3 and 77.6%, respectively. Such a power density was 2.33 times higher than the MFC reactor due to the junction potential effect. In addition, adding the desalination function to the MFC reactor enhanced columbic efficiency from 21.8 to 31.4%. These results provided a proof-of-concept that the use of MDC instead of MFC would improve wastewater treatment efficiency and power generation, with an added benefit of water desalination. Furthermore, RSG can successfully be employed in an MDC or MFC, enhancing the bio-electricity generation and salt removal.

Polymorphic SSR markers for Plasmopara obducens (Peronosporaceae), the newly emergent downy mildew pathogen of Impatiens (Balsaminaceae)

USDA-ARS?s Scientific Manuscript database

Premise of the study: Microsatellite markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 151.2 Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identi...

Swarming differentiation and swimming motility in Bacillus subtilis are controlled by swrA, a newly identified dicistronic operon.

PubMed

Calvio, Cinzia; Celandroni, Francesco; Ghelardi, Emilia; Amati, Giuseppe; Salvetti, Sara; Ceciliani, Fabrizio; Galizzi, Alessandro; Senesi, Sonia

2005-08-01

The number and disposition of flagella harbored by eubacteria are regulated by a specific trait successfully maintained over generations. The genes governing the number of flagella in Bacillus subtilis have never been identified, although the ifm locus has long been recognized to influence the motility phenotype of this microorganism. The characterization of a spontaneous ifm mutant of B. subtilis, displaying diverse degrees of cell flagellation in both liquid and solid media, raised the question of how the ifm locus governs the number and assembly of functional flagella. The major finding of this investigation is the characterization of a newly identified dicistronic operon, named swrA, that controls both swimming motility and swarming differentiation in B. subtilis. Functional analysis of the swrA operon allowed swrAA (previously named swrA [D. B. Kearns, F. Chu, R. Rudner, and R. Losick, Mol. Microbiol. 52:357-369, 2004]) to be the first gene identified in B. subtilis that controls the number of flagella in liquid environments and the assembly of flagella in response to cell contact with solid surfaces. Evidence is given that the second gene of the operon, swrAB, is essential for enabling the surface-adhering cells to undergo swarming differentiation. Preliminary data point to a molecular interaction between the two gene products.

Random number generators for large-scale parallel Monte Carlo simulations on FPGA

NASA Astrophysics Data System (ADS)

Lin, Y.; Wang, F.; Liu, B.

2018-05-01

Through parallelization, field programmable gate array (FPGA) can achieve unprecedented speeds in large-scale parallel Monte Carlo (LPMC) simulations. FPGA presents both new constraints and new opportunities for the implementations of random number generators (RNGs), which are key elements of any Monte Carlo (MC) simulation system. Using empirical and application based tests, this study evaluates all of the four RNGs used in previous FPGA based MC studies and newly proposed FPGA implementations for two well-known high-quality RNGs that are suitable for LPMC studies on FPGA. One of the newly proposed FPGA implementations: a parallel version of additive lagged Fibonacci generator (Parallel ALFG) is found to be the best among the evaluated RNGs in fulfilling the needs of LPMC simulations on FPGA.

Neutrophil-derived chemokines on the road to immunity.

PubMed

Tecchio, Cristina; Cassatella, Marco A

2016-04-01

During recent years, it has become clear that polymorphonuclear neutrophils are remarkably versatile cells, whose functions go far beyond phagocytosis and killing. In fact, besides being involved in primary defense against infections-mainly through phagocytosis, generation of toxic molecules, release of toxic enzymes and formation of extracellular traps-neutrophils have been shown to play a role in finely regulating the development and the evolution of inflammatory and immune responses. These latter neutrophil-mediated functions occur by a variety of mechanisms, including the production of newly manufactured cytokines. Herein, we provide a general overview of the chemotactic cytokines/chemokines that neutrophils can potentially produce, either under inflammatory/immune reactions or during their activation in more prolonged processes, such as in tumors. We highlight recent observations generated from studying human or rodent neutrophils in vitro and in vivo models. We also discuss the biological significance of neutrophil-derived chemokines in the context of infectious, neoplastic and immune-mediated diseases. The picture that is emerging is that, given their capacity to produce and release chemokines, neutrophils exert essential functions in recruiting, activating and modulating the activities of different leukocyte populations. Copyright © 2016. Published by Elsevier Ltd.

Ontogeny of the Maize Shoot Apical Meristem[W][OA

PubMed Central

Takacs, Elizabeth M.; Li, Jie; Du, Chuanlong; Ponnala, Lalit; Janick-Buckner, Diane; Yu, Jianming; Muehlbauer, Gary J.; Schnable, Patrick S.; Timmermans, Marja C.P.; Sun, Qi; Nettleton, Dan; Scanlon, Michael J.

2012-01-01

The maize (Zea mays) shoot apical meristem (SAM) arises early in embryogenesis and functions during stem cell maintenance and organogenesis to generate all the aboveground organs of the plant. Despite its integral role in maize shoot development, little is known about the molecular mechanisms of SAM initiation. Laser microdissection of apical domains from developing maize embryos and seedlings was combined with RNA sequencing for transcriptomic analyses of SAM ontogeny. Molecular markers of key events during maize embryogenesis are described, and comprehensive transcriptional data from six stages in maize shoot development are generated. Transcriptomic profiling before and after SAM initiation indicates that organogenesis precedes stem cell maintenance in maize; analyses of the first three lateral organs elaborated from maize embryos provides insight into their homology and to the identity of the single maize cotyledon. Compared with the newly initiated SAM, the mature SAM is enriched for transcripts that function in transcriptional regulation, hormonal signaling, and transport. Comparisons of shoot meristems initiating juvenile leaves, adult leaves, and husk leaves illustrate differences in phase-specific (juvenile versus adult) and meristem-specific (SAM versus lateral meristem) transcript accumulation during maize shoot development. This study provides insight into the molecular genetics of SAM initiation and function in maize. PMID:22911570

Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression

PubMed Central

Sharma, Manju; Dearth, Andrea; Smith, Benjamin; Braun, Robert E.

2015-01-01

The Y-box proteins YBX2 and YBX3 bind RNA and DNA and are required for metazoan development and fertility. However, possible functional redundancy between YBX2 and YBX3 has prevented elucidation of their molecular function as RNA masking proteins and identification of their target RNAs. To investigate possible functional redundancy between YBX2 and YBX3, we attempted to construct Ybx2 -/- ;Ybx3 -/- double mutants using a previously reported Ybx2 -/- model and a newly generated global Ybx3 -/- model. Loss of YBX3 resulted in reduced male fertility and defects in spermatid differentiation. However, homozygous double mutants could not be generated as haploinsufficiency of both Ybx2 and Ybx3 caused sterility characterized by extensive defects in spermatid differentiation. RNA sequence analysis of mRNP and polysome occupancy in single and compound Ybx2/3 heterozygotes revealed loss of translational repression almost exclusively in the compound Ybx2/3 heterozygotes. RNAseq analysis also demonstrated that Y-box protein dose-dependent loss of translational regulation was inversely correlated with the presence of a Y box recognition target sequence, suggesting that Y box proteins bind RNA hierarchically to modulate translation in a range of targets. PMID:26646932

Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

PubMed

Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

2017-08-01

Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

Immunological Applications of Stem Cells in Type 1 Diabetes

PubMed Central

Voltarelli, Julio; Zavazava, Nicholas

2011-01-01

Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs. PMID:21862682

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design.

PubMed

Paula, Carine; Motta, Adriana; Schmitz, Carla; Nunes, Claudia P; Souza, Ana Paula; Bonorino, Cristina

2009-02-01

It is known that immune system functions decrease with age, and that adaptive immune responses, especially CD4+ T cell function, seem to be the main affected point in immunity with aging. Dendritic cells (DC) are the major antigen presenting cell (APC), and at least part of the defects observed in adaptive immunity of aged individuals could be due to diminished potential of bone marrow to generate new DC, or defects in DC function. In this study, we investigated if the ability of aged bone marrow (BM) to generate new DC in vitro, as well as aged BM-derived DC responses to lypopolysaccharide (LPS). Because DC are important tools in newly developing anti-tumor therapies, we also studied the ability of aged DC to phagocytose and present antigen from necrotic tumor cells. We found that aged BM generated fewer DC in vitro compared to young BM. While LPS-induced DC maturation is reduced in DC of aged mice, a high TNF-alpha production is observed in aged DC even without LPS stimulation. While phagocytosis of tumor cells is not affected by age, and DC derived from aged BM show a higher TNF-alpha production in response to phagocytosis, presentation of tumor antigens was decreased in aged DC. Because class II upregulation in response to phagocytosis was similar between aged and young DC, this could indicate an age associated processing defect in the exogenous pathway. These findings suggest that age of BM used to generate DC does not impair their phagocytic ability or TNF-alpha production, however leads to a decreased yield in mature DC, reduced response to LPS, and diminished antigen processing/presentation potential. Our results are relevant to optimization DC-based vaccine design for aged populations.

Comparison of glycemic control and β-cell function in new onset T2DM patients with PCOS of metformin and saxagliptin monotherapy or combination treatment.

PubMed

Tao, Tao; Wu, Peihong; Wang, Yuying; Liu, Wei

2018-02-27

Impaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China. A total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study. All patients received treatment for 24 weeks with metformin, saxagliptin, or their combination. Patients were allocated to one of three treatment groups by a computer-generated code that facilitated equal patient distribution of 25 patients per group. The primary outcome was a change in glycemic control and β-cell function. A total of 63 patients completed the study (n = 21, for each group). The reduction in hemoglobin A1c was significant in the combination group, compared to the monotherapy groups (saxagliptin vs. combination treatment vs. metformin: - 1.1 vs. -1.3 vs. -1.1%, P = 0.016), whereas it was comparable between the metformin and saxagliptin groups (P > 0.05). Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P < 0.01 for all). However, no significant change was observed in the homeostasis model assessment- β-cell function among the metformin and combination groups, and no significant changes were observed in the insulinogenic index among all three groups (P > 0.05 for all). In addition, saxagliptin and metformin treatments significantly reduced body mass index and high-sensitivity C-reactive protein levels (P < 0.01 for both). Saxagliptin and metformin were comparably effective in regulating weight loss, glycemic control, and β-cell function, improving lipid profiles, and reducing inflammation in newly diagnosed type 2 diabetes mellitus patients with polycystic ovary syndrome. ChiCTR-IPR-17011120 (retrospectively registered on 2017-04-12).

Effects of Mediterranean diet on sexual function in people with newly diagnosed type 2 diabetes: The MÈDITA trial.

PubMed

Maiorino, Maria Ida; Bellastella, Giuseppe; Caputo, Mariangela; Castaldo, Filomena; Improta, Maria Rosaria; Giugliano, Dario; Esposito, Katherine

To assess the long-term effect of Mediterranean diet, as compared with low-fat diet, on sexual function in patients with newly diagnosed type 2 diabetes. In a randomized clinical trial, with a total follow-up of 8.1years, 215 men and women with newly diagnosed type 2 diabetes were assigned to Mediterranean diet (n=108) or a low-fat diet (n=107). The primary outcome measures were changes of erectile function (IIEF) in diabetic men and of female sexual function (FSFI) in diabetic women. There was no difference in baseline sexual function in men (n=54 vs 52) or women (n=54 vs 55) randomized to Mediterranean diet or low-fat diet, respectively (P=0.287, P=0.815). Over the entire follow-up, the changes of the primary outcomes were significantly lower in the Mediterranean diet group compared with the low-fat group: IIEF and FSFI showed a significantly lesser decrease (1.22 and 1.18, respectively, P=0.024 and 0.019) with the Mediterranean diet. Baseline C-reactive protein levels predicted erectile dysfunction in men but not female sexual dysfunction in women. Among persons with newly diagnosed type 2 diabetes, a Mediterranean diet reduced the deterioration of sexual function over time in both sexes. Copyright © 2016 Elsevier Inc. All rights reserved.

Replication-coupled chromatin assembly of newly synthesized histones: distinct functions for the histone tail domains.

PubMed

Ejlassi-Lassallette, Aïda; Thiriet, Christophe

2012-02-01

The maintenance of the genome during replication requires the assembly of nucleosomes with newly synthesized histones. Achieving the deposition of newly synthesized histones in chromatin implies their transport from the cytoplasm to the nucleus at the replication sites. Several lines of evidence have revealed critical functions of the histone tail domains in these conserved cellular processes. In this review, we discuss the role of the amino termini of the nucleosome building blocks, H2A/H2B and H3/H4, in different model systems. The experimental data showed that H2A/H2B tails and H3/H4 tails display distinct functions in nuclear import and chromatin assembly. Furthermore, we describe recent studies exploiting the unique properties of the slime mold, Physarum polycephalum , that have advanced understanding of the function of the highly conserved replication-dependent diacetylation of H4.

Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.

PubMed

Francipane, Maria Giovanna; Lagasse, Eric

2016-09-01

In recent years, functional three-dimensional (3D) tissue generation in vitro has been significantly advanced by tissue-engineering methods, achieving better reproduction of complex native organs compared to conventional culture systems. This review will discuss traditional 3D cell culture techniques as well as newly developed technology platforms. These recent techniques provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the development of patient-specific, transplantable tissues and organs on demand.

RADON GENERATION AND TRANSPORT IN AGED CONCRETE

EPA Science Inventory

The report gives results of a characterization of radon generation and transport in Florida concretes sampled from 12- to 45-year-old residential slabs. It also compares measurements from old concrete samples to previous measurements on newly poured Florida residential concretes....

Shear viscosity coefficient of liquid lanthanides

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

Patel, H. P., E-mail: patel.harshal2@gmail.com; Thakor, P. B., E-mail: pbthakore@rediffmail.com; Prajapati, A. V., E-mail: anand0prajapati@gmail.com

2015-05-15

Present paper deals with the computation of shear viscosity coefficient (η) of liquid lanthanides. The effective pair potential v(r) is calculated through our newly constructed model potential. The Pair distribution function g(r) is calculated from PYHS reference system. To see the influence of local field correction function, Hartree (H), Tailor (T) and Sarkar et al (S) local field correction function are used. Present results are compared with available experimental as well as theoretical data. Lastly, we found that our newly constructed model potential successfully explains the shear viscosity coefficient (η) of liquid lanthanides.

Shear viscosity coefficient of liquid lanthanides

NASA Astrophysics Data System (ADS)

Patel, H. P.; Sonvane, Y. A.; Thakor, P. B.; Prajapati, A. V.

2015-05-01

Present paper deals with the computation of shear viscosity coefficient (η) of liquid lanthanides. The effective pair potential v(r) is calculated through our newly constructed model potential. The Pair distribution function g(r) is calculated from PYHS reference system. To see the influence of local field correction function, Hartree (H), Tailor (T) and Sarkar et al (S) local field correction function are used. Present results are compared with available experimental as well as theoretical data. Lastly, we found that our newly constructed model potential successfully explains the shear viscosity coefficient (η) of liquid lanthanides.

Understanding Value as a Key Concept in Sustaining the Perioperative Nursing Workforce.

PubMed

Kapaale, Chaluza C

2018-03-01

Perioperative nursing is faced with a staffing crisis attributed in part to minimal numbers of newly graduated nurses choosing a career in this specialty. This article analyzes and applies the concept of value to explore how to maintain an adequate perioperative nursing workforce; recruit newly graduated nurses; and encourage career professional, nurse educator, and student collaboration to generate meaningful value for perioperative nursing. This analysis revealed that value co-creation for perioperative nursing could lead to newly graduated nurses increasingly choosing perioperative nursing as a career, and enjoying satisfying perioperative nursing careers while providing high-quality patient care. © AORN, Inc, 2018.

Gas-Phase Functionalization of Macroscopic Carbon Nanotube Fiber Assemblies: Reaction Control, Electrochemical Properties, and Use for Flexible Supercapacitors.

PubMed

Iglesias, Daniel; Senokos, Evgeny; Alemán, Belén; Cabana, Laura; Navío, Cristina; Marcilla, Rebeca; Prato, Maurizio; Vilatela, Juan J; Marchesan, Silvia

2018-02-14

The assembly of aligned carbon nanotubes (CNTs) into fibers (CNTFs) is a convenient approach to exploit and apply the unique physico-chemical properties of CNTs in many fields. CNT functionalization has been extensively used for its implementation into composites and devices. However, CNTF functionalization is still in its infancy because of the challenges associated with preservation of CNTF morphology. Here, we report a thorough study of the gas-phase functionalization of CNTF assemblies using ozone which was generated in situ from a UV source. In contrast with liquid-based oxidation methods, this gas-phase approach preserves CNTF morphology, while notably increasing its hydrophilicity. The functionalized material is thoroughly characterized by Raman spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and scanning electron microscopy. Its newly acquired hydrophilicity enables CNTF electrochemical characterization in aqueous media, which was not possible for the pristine material. Through comparison of electrochemical measurements in aqueous electrolytes and ionic liquids, we decouple the effects of functionalization on pseudocapacitive reactions and quantum capacitance. The functionalized CNTF assembly is successfully used as an active material and a current collector in all-solid supercapacitor flexible devices with an ionic liquid-based polymer electrolyte.

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.

PubMed

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days' implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days' implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

Postmortem procedures in the emergency department: using the recently dead to practise and teach.

PubMed Central

Iserson, K V

1993-01-01

In generations past, it was common practice for doctors to learn lifesaving technical skills on patients who had recently died. But this practice has lately been criticised on religious, legal, and ethical grounds, and has fallen into disuse in many hospitals and emergency departments. This paper uses four questions to resolve whether doctors in emergency departments should practise and teach non-invasive and minimally invasive procedures on the newly dead: Is it ethically and legally permissible to practise and teach non-invasive and minimally invasive procedures on the newly dead emergency-department patient? What are the alternatives or possible consequences of not practising non-invasive and minimally invasive procedures on newly dead patients? Is consent from relatives required? Should doctors in emergency departments allow or even encourage this use of newly dead patients? PMID:8331644

Effect of Continuous Cropping Generations on Each Component Biomass of Poplar Seedlings during Different Growth Periods

PubMed Central

Xia, Jiangbao; Zhang, Shuyong; Li, Tian; Liu, Xia; Zhang, Ronghua; Zhang, Guangcan

2014-01-01

In order to investigate the change rules and response characteristics of growth status on each component of poplar seedling followed by continuous cropping generations and growth period, we clear the biomass distribution pattern of poplar seedling, adapt continuous cropping, and provide theoretical foundation and technical reference on cultivation management of poplar seedling, the first generation, second generation, and third generation continuous cropping poplar seedlings were taken as study objects, and the whole poplar seedling was harvested to measure and analyze the change of each component biomass on different growth period poplar leaves, newly emerging branches, trunks and root system, and so forth. The results showed that the whole biomass of poplar seedling decreased significantly with the leaf area and its ratio increased, and the growth was inhibited obviously. The biomass aboveground was more than that underground. The ratios of leaf biomass and newly emerging branches biomass of first continuous cropping poplar seedling were relatively high. With the continuous cropping generations and growth cycle increasing, poplar seedling had a growth strategy to improve the ratio of root-shoot and root-leaf to adapt the limited soil nutrient of continuous cropping. PMID:25401150

Effects of IAA, IBA, NAA, and GA3 on rooting and morphological features of Melissa officinalis L. stem cuttings.

PubMed

Sevik, Hakan; Guney, Kerim

2013-01-01

This study analyzed the potential of producing Melissa officinalis L. using stem cuttings. Four different hormones (IAA, IBA, NAA, and GA3) were applied to the cuttings, with and without buds, in two doses (1000 mg/L and 5000 mg/L), and after 60 days, 10 morphological characteristics of newly generated plants were detected, and a statistical analysis was carried out. The results of the study show that the cuttings with at least one bud must be used in order to produce M. officinalis using stem cuttings. Even though the auxin group hormones (IAA, IBA, and NAA) do not have an apparent effect on rooting percentage, these hormones were detected to affect the morphological characteristics of the newly generated plants, especially root generation. GA3 application has a considerable effect on stem height.

Dynamics of growth zone patterning in the milkweed bug Oncopeltus fasciatus

PubMed Central

Weiss, Aryeh; Williams, Terri A.; Nagy, Lisa M.

2017-01-01

We describe the dynamic process of abdominal segment generation in the milkweed bug Oncopeltus fasciatus. We present detailed morphological measurements of the growing germband throughout segmentation. Our data are complemented by cell division profiles and expression patterns of key genes, including invected and even-skipped as markers for different stages of segment formation. We describe morphological and mechanistic changes in the growth zone and in nascent segments during the generation of individual segments and throughout segmentation, and examine the relative contribution of newly formed versus existing tissue to segment formation. Although abdominal segment addition is primarily generated through the rearrangement of a pool of undifferentiated cells, there is nonetheless proliferation in the posterior. By correlating proliferation with gene expression in the growth zone, we propose a model for growth zone dynamics during segmentation in which the growth zone is functionally subdivided into two distinct regions: a posterior region devoted to a slow rate of growth among undifferentiated cells, and an anterior region in which segmental differentiation is initiated and proliferation inhibited. PMID:28432218

Accuracy enhancement of point triangulation probes for linear displacement measurement

NASA Astrophysics Data System (ADS)

Kim, Kyung-Chan; Kim, Jong-Ahn; Oh, SeBaek; Kim, Soo Hyun; Kwak, Yoon Keun

2000-03-01

Point triangulation probes (PTBs) fall into a general category of noncontact height or displacement measurement devices. PTBs are widely used for their simple structure, high resolution, and long operating range. However, there are several factors that must be taken into account in order to obtain high accuracy and reliability; measurement errors from inclinations of an object surface, probe signal fluctuations generated by speckle effects, power variation of a light source, electronic noises, and so on. In this paper, we propose a novel signal processing algorithm, named as EASDF (expanded average square difference function), for a newly designed PTB which is composed of an incoherent source (LED), a line scan array detector, a specially selected diffuse reflecting surface, and several optical components. The EASDF, which is a modified correlation function, is able to calculate displacement between the probe and the object surface effectively even if there are inclinations, power fluctuations, and noises.

Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

PubMed

Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

2014-10-13

A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

Adult Mammalian Neurogenesis and Motivated Behaviors.

PubMed

Jorgensen, Claudia

2018-05-31

Adult neurogenesis continues to captivate the curiosity of the scientific community; and researchers seem to have a particular interest in identifying the functional implications of such plasticity. While the majority of research focuses on the association between adult neurogenesis and learning and memory (including spatial learning associated with hippocampal neurogenesis and olfactory discrimination associated with neurogenesis in the olfactory system), the following review will explore the link to motivated behaviors. In particular, goal-directed behaviors such as sociosexual, parental, aggressive, as well as depression- and anxiety-like behaviors and their reciprocal association to adult neurogenesis will be evaluated. The review will detail research in humans and other mammalian species. Furthermore, the potential mechanisms underlying these neurogenic alterations will be highlighted. Lastly, the review will conclude with a discussion on the functional significance of these newly generated cells in mediating goal-directed behaviors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair.

PubMed

Lam, Yung C; Akhter, Shamima; Gu, Peili; Ye, Jing; Poulet, Anaïs; Giraud-Panis, Marie-Josèphe; Bailey, Susan M; Gilson, Eric; Legerski, Randy J; Chang, Sandy

2010-07-07

Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo(-/-)ATM(-/-) MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5'-3' exonuclease function of SNM1B/Apollo in the generation of 3' single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.

The Pacific White Shrimp β-actin Promoter: Functional Properties and the Potential Application for Transduction System Using Recombinant Baculovirus.

PubMed

Shi, Yingli; Xiang, Jianhai; Zhou, Guangzhou; Ron, Tetsuzan Benny; Tong, Hsin-I; Kang, Wen; Sun, Si; Lu, Yuanan

2016-06-01

A newly isolated Pacific white shrimp (Litopenaeus vannamei) beta-actin promoter SbaP and its derivative compact construct SbaP (ENX) have recently been demonstrated to promote ectopic gene expression in vitro and in vivo. To further explore the potential transduction application, this newly isolated shrimp promoter SbaP was comparatively tested with cytomegalovirus (CMV), simian virus 40 (SV40), polyhedrin (Polh), and white spot syndrome virus immediate early gene 1 (WSSV ie1) four constitutive promoters and a beta-actin promoter (TbaP) from tilapia fish to characterize its promoting function in eight different cell lines. Luciferase quantitation assays revealed that SbaP can drive luciferase gene expression in all eight cell lines including sf21 (insect), PAC2 (zebrafish), EPC (carp), CHSE-214 (chinook salmon), GSTEF (green sea turtle), MS-1 (monk seal), 293T (human), and HeLa (human), but at different levels. Comparative analysis revealed that the promoting activity of SbaP was lower (≤10-fold) than CMV but higher (2-20 folds) than Polh in most of these cell lines tested. Whereas, SbaP mediated luciferase expression in sf21 cells was over 20-fold higher than CMV, SV40, Polh, and TbaP promoter. Compared to the SbaP, SbaP (ENX), which was constructed on the basis of SbaP by deletion of two "negative" regulatory elements, exhibited no significant change of promoting activity in EPC and PAC2 cells, but a 5 and 16 % lower promoting effect in 293T and HeLa cells, respectively. Additionally, a recombinant baculovirus was constructed under the control of SbaP (ENX), and efficient promoter activity of newly generated baculoviral vector was detected both in vitro of infected sf21 cells and in vivo of injected indicator shrimp. These results warrant the potential application of SbaP, particularly SbaP (ENX) in ectopic gene expression in future.

Left ventricular functions in children with newly diagnosed Graves' disease. A single-center study from Upper Egypt.

PubMed

Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman

2018-01-01

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

Landscape heterogeneity shapes predation in a newly restored predator-prey system.

PubMed

Kauffman, Matthew J; Varley, Nathan; Smith, Douglas W; Stahler, Daniel R; MacNulty, Daniel R; Boyce, Mark S

2007-08-01

Because some native ungulates have lived without top predators for generations, it has been uncertain whether runaway predation would occur when predators are newly restored to these systems. We show that landscape features and vegetation, which influence predator detection and capture of prey, shape large-scale patterns of predation in a newly restored predator-prey system. We analysed the spatial distribution of wolf (Canis lupus) predation on elk (Cervus elaphus) on the Northern Range of Yellowstone National Park over 10 consecutive winters. The influence of wolf distribution on kill sites diminished over the course of this study, a result that was likely caused by territorial constraints on wolf distribution. In contrast, landscape factors strongly influenced kill sites, creating distinct hunting grounds and prey refugia. Elk in this newly restored predator-prey system should be able to mediate their risk of predation by movement and habitat selection across a heterogeneous risk landscape.

Landscape heterogeneity shapes predation in a newly restored predator-prey system

USGS Publications Warehouse

Kauffman, M.J.; Varley, N.; Smith, D.W.; Stahler, D.R.; MacNulty, D.R.; Boyce, M.S.

2007-01-01

Because some native ungulates have lived without top predators for generations, it has been uncertain whether runaway predation would occur when predators are newly restored to these systems. We show that landscape features and vegetation, which influence predator detection and capture of prey, shape large-scale patterns of predation in a newly restored predator-prey system. We analysed the spatial distribution of wolf (Canis lupus) predation on elk (Cervus elaphus) on the Northern Range of Yellowstone National Park over 10 consecutive winters. The influence of wolf distribution on kill sites diminished over the course of this study, a result that was likely caused by territorial constraints on wolf distribution. In contrast, landscape factors strongly influenced kill sites, creating distinct hunting grounds and prey refugia. Elk in this newly restored predator-prey system should be able to mediate their risk of predation by movement and habitat selection across a heterogeneous risk landscape. ?? 2007 Blackwell Publishing Ltd/CNRS.

High precision multi-genome scale reannotation of enzyme function by EFICAz

PubMed Central

Arakaki, Adrian K; Tian, Weidong; Skolnick, Jeffrey

2006-01-01

Background The functional annotation of most genes in newly sequenced genomes is inferred from similarity to previously characterized sequences, an annotation strategy that often leads to erroneous assignments. We have performed a reannotation of 245 genomes using an updated version of EFICAz, a highly precise method for enzyme function prediction. Results Based on our three-field EC number predictions, we have obtained lower-bound estimates for the average enzyme content in Archaea (29%), Bacteria (30%) and Eukarya (18%). Most annotations added in KEGG from 2005 to 2006 agree with EFICAz predictions made in 2005. The coverage of EFICAz predictions is significantly higher than that of KEGG, especially for eukaryotes. Thousands of our novel predictions correspond to hypothetical proteins. We have identified a subset of 64 hypothetical proteins with low sequence identity to EFICAz training enzymes, whose biochemical functions have been recently characterized and find that in 96% (84%) of the cases we correctly identified their three-field (four-field) EC numbers. For two of the 64 hypothetical proteins: PA1167 from Pseudomonas aeruginosa, an alginate lyase (EC 4.2.2.3) and Rv1700 of Mycobacterium tuberculosis H37Rv, an ADP-ribose diphosphatase (EC 3.6.1.13), we have detected annotation lag of more than two years in databases. Two examples are presented where EFICAz predictions act as hypothesis generators for understanding the functional roles of hypothetical proteins: FLJ11151, a human protein overexpressed in cancer that EFICAz identifies as an endopolyphosphatase (EC 3.6.1.10), and MW0119, a protein of Staphylococcus aureus strain MW2 that we propose as candidate virulence factor based on its EFICAz predicted activity, sphingomyelin phosphodiesterase (EC 3.1.4.12). Conclusion Our results suggest that we have generated enzyme function annotations of high precision and recall. These predictions can be mined and correlated with other information sources to generate biologically significant hypotheses and can be useful for comparative genome analysis and automated metabolic pathway reconstruction. PMID:17166279

AACSD: An atomistic analyzer for crystal structure and defects

NASA Astrophysics Data System (ADS)

Liu, Z. R.; Zhang, R. F.

2018-01-01

We have developed an efficient command-line program named AACSD (Atomistic Analyzer for Crystal Structure and Defects) for the post-analysis of atomic configurations generated by various atomistic simulation codes. The program has implemented not only the traditional filter methods like the excess potential energy (EPE), the centrosymmetry parameter (CSP), the common neighbor analysis (CNA), the common neighborhood parameter (CNP), the bond angle analysis (BAA), and the neighbor distance analysis (NDA), but also the newly developed ones including the modified centrosymmetry parameter (m-CSP), the orientation imaging map (OIM) and the local crystallographic orientation (LCO). The newly proposed OIM and LCO methods have been extended for all three crystal structures including face centered cubic, body centered cubic and hexagonal close packed. More specially, AACSD can be easily used for the atomistic analysis of metallic nanocomposite with each phase to be analyzed independently, which provides a unique pathway to capture their dynamic evolution of various defects on the fly. In this paper, we provide not only a throughout overview on various theoretical methods and their implementation into AACSD program, but some critical evaluations, specific testing and applications, demonstrating the capability of the program on each functionality.

Experimental validation of Critical Temperature-Pressure theory of scuffing

NASA Astrophysics Data System (ADS)

Lee, Si C.; Chen, Huanliang

1995-07-01

A series of experiments was conducted for validating a newly developed theory of scuffing. The Critical temperature-Pressure (CTP) theory is based on the physisorption behavior of lubricants and is capable of predicting the onset of scuffing failures over a wide range of operating conditions, including the contacts operating in the boundary lubrication and in the partial elastohydrodynamic lubrication (EHL) regimes. According to the CTP theory, failures occur when the contact temperature exceeds a certain critical value which is a function of the lubricant pressure generated by the hydrodynamic action of the EHL contact. A special device capable of simulating the ambient conditions of the partial EHL conjunctions (of contact temperature, pressure, and the lubricant pressure) was constructed. A ball-on-flat type wear tester was put inside a pressure vessel, completely immersed in a highly pressurized bath of mineral oil. The temperature on the flat specimen was gradually increased while the ball was slowly traversed. At a certain critical temmperature, the friction force abruptly jumped indicating the incipiency of the lubrication breakdown. This experiment was repeated for several levels of hydrostatic pressure and the corresponding critical temperatures were obtained. The test results showed an excellent correlation with the newly developed CTP theory.

Newly-graduated midwives transcending barriers: a grounded theory study.

PubMed

Barry, Michele J; Hauck, Yvonne L; O'Donoghue, Thomas; Clarke, Simon

2013-12-01

Midwifery has developed its own philosophy to formalise its unique identity as a profession. Newly-graduated midwives are taught, and ideally embrace, this philosophy during their education. However, embarking in their career within a predominantly institutionalised and the medically focused health-care model may challenge this application. The research question guiding this study was as follows: 'How do newly graduated midwives deal with applying the philosophy of midwifery in their first six months of practice?' The aim was to generate a grounded theory around this social process. This Western Australian grounded theory study is conceptualised within the social theory of symbolic interactionism. Data were collected by means of in-depth, semi-structured interviews with 11 recent midwifery graduates. Participant and interviewer's journals provided supplementary data. The 'constant comparison' approach was used for data analysis. The substantive theory of transcending barriers was generated. Three stages in transcending barriers were identified: Addressing personal attributes, Understanding the 'bigger picture', and finally, 'Evaluating, planning and acting' to provide woman-centred care. An overview of these three stages provides the focus of this article. The theory of transcending barriers provides a new perspective on how newly-graduated midwives deal with applying the philosophy of midwifery in their first six months of practice. A number of implications for pre and post registration midwifery education and policy development are suggested, as well as recommendations for future research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional Mobility Testing: A Novel Method to Create Suit Design Requirements

NASA Technical Reports Server (NTRS)

England, Scott A.; Benson, Elizabeth A.; Rajulu, Sudhakar L.

2008-01-01

This study was performed to aide in the creation of design requirements for the next generation of space suits that more accurately describe the level of mobility necessary for a suited crewmember through the use of an innovative methodology utilizing functional mobility. A novel method was utilized involving the collection of kinematic data while 20 subjects (10 male, 10 female) performed pertinent functional tasks that will be required of a suited crewmember during various phases of a lunar mission. These tasks were selected based on relevance and criticality from a larger list of tasks that may be carried out by the crew. Kinematic data was processed through Vicon BodyBuilder software to calculate joint angles for the ankle, knee, hip, torso, shoulder, elbow, and wrist. Maximum functional mobility was consistently lower than maximum isolated mobility. This study suggests that conventional methods for establishing design requirements for human-systems interfaces based on maximal isolated joint capabilities may overestimate the required mobility. Additionally, this method provides a valuable means of evaluating systems created from these requirements by comparing the mobility available in a new spacesuit, or the mobility required to use a new piece of hardware, to this newly established database of functional mobility.

Molecular Level Characterization of the Structure and Interactions in Peptide-Functionalized Metal-Organic Frameworks.

PubMed

Todorova, Tanya K; Rozanska, Xavier; Gervais, Christel; Legrand, Alexandre; Ho, Linh N; Berruyer, Pierrick; Lesage, Anne; Emsley, Lyndon; Farrusseng, David; Canivet, Jérôme; Mellot-Draznieks, Caroline

2016-11-07

We use density functional theory, newly parameterized molecular dynamics simulations, and last generation 15 N dynamic nuclear polarization surface enhanced solid-state NMR spectroscopy (DNP SENS) to understand graft-host interactions and effects imposed by the metal-organic framework (MOF) host on peptide conformations in a peptide-functionalized MOF. Focusing on two grafts typified by MIL-68-proline (-Pro) and MIL-68-glycine-proline (-Gly-Pro), we identified the most likely peptide conformations adopted in the functionalized hybrid frameworks. We found that hydrogen bond interactions between the graft and the surface hydroxyl groups of the MOF are essential in determining the peptides conformation(s). DNP SENS methodology shows unprecedented signal enhancements when applied to these peptide-functionalized MOFs. The calculated chemical shifts of selected MIL-68-NH-Pro and MIL-68-NH-Gly-Pro conformations are in a good agreement with the experimentally obtained 15 N NMR signals. The study shows that the conformations of peptides when grafted in a MOF host are unlikely to be freely distributed, and conformational selection is directed by strong host-guest interactions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrative Identification of Arabidopsis Mitochondrial Proteome and Its Function Exploitation through Protein Interaction Network

PubMed Central

Cui, Jian; Liu, Jinghua; Li, Yuhua; Shi, Tieliu

2011-01-01

Mitochondria are major players on the production of energy, and host several key reactions involved in basic metabolism and biosynthesis of essential molecules. Currently, the majority of nucleus-encoded mitochondrial proteins are unknown even for model plant Arabidopsis. We reported a computational framework for predicting Arabidopsis mitochondrial proteins based on a probabilistic model, called Naive Bayesian Network, which integrates disparate genomic data generated from eight bioinformatics tools, multiple orthologous mappings, protein domain properties and co-expression patterns using 1,027 microarray profiles. Through this approach, we predicted 2,311 candidate mitochondrial proteins with 84.67% accuracy and 2.53% FPR performances. Together with those experimental confirmed proteins, 2,585 mitochondria proteins (named CoreMitoP) were identified, we explored those proteins with unknown functions based on protein-protein interaction network (PIN) and annotated novel functions for 26.65% CoreMitoP proteins. Moreover, we found newly predicted mitochondrial proteins embedded in particular subnetworks of the PIN, mainly functioning in response to diverse environmental stresses, like salt, draught, cold, and wound etc. Candidate mitochondrial proteins involved in those physiological acitivites provide useful targets for further investigation. Assigned functions also provide comprehensive information for Arabidopsis mitochondrial proteome. PMID:21297957

Update on the MRI Core of the Alzheimer's Disease Neuroimaging Initiative

PubMed Central

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; DeCarli, Charles S; Dale, Anders M; Weiner, Michael W

2010-01-01

Functions of the ADNI MRI core fall into three categories: (1) those of the central MRI core lab at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data, and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present (“ADNI-GO”) and future (“ADNI-2”, if funded) MRI protocol will be to maintain MRI methodological consistency in previously enrolled “ADNI-1” subjects who are followed longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor specific pilot sub-studies of arterial spin labeling perfusion, resting state functional connectivity and diffusion tensor imaging. One each of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multi-center (but single vendor) setting for these three emerging MRI applications. PMID:20451869

Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative.

PubMed

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; Decarli, Charles S; Dale, Anders M; Carmichael, Owen W; Tosun, Duygu; Weiner, Michael W

2010-05-01

Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications. Copyright 2010 The Alzheimer

An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex

PubMed Central

Chen, Kenian; Sloan, Steven A.; Bennett, Mariko L.; Scholze, Anja R.; O'Keeffe, Sean; Phatnani, Hemali P.; Guarnieri, Paolo; Caneda, Christine; Ruderisch, Nadine; Deng, Shuyun; Liddelow, Shane A.; Zhang, Chaolin; Daneman, Richard; Maniatis, Tom; Barres, Ben A.

2014-01-01

The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain. PMID:25186741

Network-wide reorganization of procedural memory during NREM sleep revealed by fMRI

PubMed Central

Vahdat, Shahabeddin; Fogel, Stuart; Benali, Habib; Doyon, Julien

2017-01-01

Sleep is necessary for the optimal consolidation of newly acquired procedural memories. However, the mechanisms by which motor memory traces develop during sleep remain controversial in humans, as this process has been mainly investigated indirectly by comparing pre- and post-sleep conditions. Here, we used functional magnetic resonance imaging and electroencephalography during sleep following motor sequence learning to investigate how newly-formed memory traces evolve dynamically over time. We provide direct evidence for transient reactivation followed by downscaling of functional connectivity in a cortically-dominant pattern formed during learning, as well as gradual reorganization of this representation toward a subcortically-dominant consolidated trace during non-rapid eye movement (NREM) sleep. Importantly, the putamen functional connectivity within the consolidated network during NREM sleep was related to overnight behavioral gains. Our results demonstrate that NREM sleep is necessary for two complementary processes: the restoration and reorganization of newly-learned information during sleep, which underlie human motor memory consolidation. DOI: http://dx.doi.org/10.7554/eLife.24987.001 PMID:28892464

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

PubMed Central

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration. PMID:25709432

The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

PubMed Central

Szalay, Balázs; Cseh, Áron; Mészáros, Gergő; Kovács, László; Balog, Attila; Vásárhelyi, Barna

2014-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca2+ level, mitochondrial Ca2+ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca2+ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca2+ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca2+ level was higher than controls at baseline. The cytoplasmic Ca2+ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca2+ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. PMID:25098248

Complications Associated with Long-Term Disposition of Newly-Generated Transuranic Waste: A National Laboratory Perspective

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

B.J. Orchard; L.A. Harvego; T.L. Carlson

The Idaho National Laboratory (INL) is a multipurpose national laboratory delivering specialized science and engineering solutions for the U.S. Department of Energy (DOE). Sponsorship of INL was formally transferred to the DOE Office of Nuclear Energy, Science and Technology (NE) by Secretary Spencer Abraham in July 2002. The move to NE, and designation as the DOE lead nuclear energy laboratory for reactor technology, supports the nation’s expanding nuclear energy initiatives, placing INL at the center of work to develop advanced Generation IV nuclear energy systems; nuclear energy/hydrogen coproduction technology; advanced nuclear energy fuel cycle technologies; and providing national security answersmore » to national infrastructure needs. As a result of the Laboratory’s NE mission, INL generates both contact-handled and remote-handled transuranic (TRU) waste from ongoing operations. Generation rates are relatively small and fluctuate based on specific programs and project activities being conducted; however, the Laboratory will continue to generate TRU waste well into the future in association with the NE mission. Currently, plans and capabilities are being established to transfer INL’s contact-handled TRU waste to the Advanced Mixed Waste Treatment Plant (AMWTP) for certification and disposal to the Waste Isolation Pilot Plant (WIPP). Remote-handled TRU waste is currently placed in storage at the Materials and Fuels Complex (MFC). In an effort to minimize future liabilities associated with the INL NE mission, INL is evaluating and assessing options for the management and disposition of all its TRU waste on a real-time basis at time of generation. This paper summarizes near-term activities to minimize future re handling of INL’s TRU waste, as well as, potential complications associated with the long-term disposition of newly-generated TRU waste. Potential complications impacting the disposition of INL newly-generated TRU waste include, but are not limited to: 1) required remote-handled TRU packaging configuration(s) vs. current facility capabilities, 2) long-term NE mission activities, 3) WIPP certification requirements, and 4) budget considerations.« less

Regulatory Concerns on the In-Containment Water Storage System of the Korean Next Generation Reactor

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

Ahn, Hyung-Joon; Lee, Jae-Hun; Bang, Young-Seok

2002-07-15

The in-containment water storage system (IWSS) is a newly adopted system in the design of the Korean Next Generation Reactor (KNGR). It consists of the in-containment refueling water storage tank, holdup volume tank, and cavity flooding system (CFS). The IWSS has the function of steam condensation and heat sink for the steam release from the pressurizer and provides cooling water to the safety injection system and containment spray system in an accident condition and to the CFS in a severe accident condition. With the progress of the KNGR design, the Korea Institute of Nuclear Safety has been developing Safety andmore » Regulatory Requirements and Guidances for safety review of the KNGR. In this paper, regarding the IWSS of the KNGR, the major contents of the General Safety Criteria, Specific Safety Requirements, Safety Regulatory Guides, and Safety Review Procedures were introduced, and the safety review items that have to be reviewed in-depth from the regulatory viewpoint were also identified.« less

Improving Vector Evaluated Particle Swarm Optimisation by Incorporating Nondominated Solutions

PubMed Central

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm. PMID:23737718

Improving Vector Evaluated Particle Swarm Optimisation by incorporating nondominated solutions.

PubMed

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm.

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

2010-01-01

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

New activity pattern in human interactive dynamics

NASA Astrophysics Data System (ADS)

Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

2015-09-01

We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

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

Omet, M.; Michizono, S.; Matsumoto, T.

We report the development and implementation of four FPGA-based predistortion-type klystron linearization algorithms. Klystron linearization is essential for the realization of ILC, since it is required to operate the klystrons 7% in power below their saturation. The work presented was performed in international collaborations at the Fermi National Accelerator Laboratory (FNAL), USA and the Deutsches Elektronen Synchrotron (DESY), Germany. With the newly developed algorithms, the generation of correction factors on the FPGA was improved compared to past algorithms, avoiding quantization and decreasing memory requirements. At FNAL, three algorithms were tested at the Advanced Superconducting Test Accelerator (ASTA), demonstrating a successfulmore » implementation for one algorithm and a proof of principle for two algorithms. Furthermore, the functionality of the algorithm implemented at DESY was demonstrated successfully in a simulation.« less

Theoretical Investigation of Phonon Dispersion Relation of 3d Liquid Transition Metals

NASA Astrophysics Data System (ADS)

Thakor, P. B.; Sonvane, Y. A.; Gajjar, P. N.; Jani, A. R.

2011-12-01

The phonon dispersion relations of 3d liquid transition metals have been obtained in the present study. We have used Hubbard and Beeby (HB) method to generate phonon dispersion relation of liquid metals. To describe the structural information, the structure factor S(q) due to the Percus-Yevick hard sphere (PYHS) reference systems is used along with our newly constructed parameter free model potential. The influence of exchange and correlation effect on the phonon dispersion relation of 3d liquid transition metals is examined explicitly, which reflects the varying effects of screening. We have used different local field correction functions like Hartree (H), Taylor (T) and Sarkar et al (S). Present results have found good in agreement with available experimental data.

LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells.

PubMed

Pan, Di; Li, Wei; Miao, Hanchi; Yao, Jing; Li, Zhiyu; Wei, Libin; Zhao, Li; Guo, Qinglong

2014-02-15

In this study, the anticancer effect of LW-214, a newly synthesized flavonoid, against MCF-7 human breast cancer cells and the underlying mechanisms were investigated. LW-214 triggered the mitochondrial apoptotic pathway by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm) and caspase-9 activation, degradation of poly (ADP-ribose) polymerase (PARP), cytochrome c (Cyt c) release and apoptosis-inducing factor (AIF) transposition. Further research revealed that both the reactive oxygen species (ROS) generation and the apoptosis signal regulating kinase 1 (ASK1) activation by LW-214 were induced by down-regulating the thioredoxin-1 (Trx-1) expression. The ROS elevation and ASK1 activation induced a sustained phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125, as known as JNK inhibitor, almost reversed LW-214-induced apoptosis in MCF-7 cells. Overexpression of Trx-1 in MCF-7 cells attenuated LW-214-mediated apoptosis as well as the JNK activation and reversed the expression of mitochondrial apoptosis-related protein. Accordingly, the in vivo study showed that LW-214 exhibited a potential antitumor effect in BALB/c species mice inoculated MCF-7 tumor with low systemic toxicity, and the mechanism was the same as in vitro study. Taken together, these findings indicated that LW-214 may down-regulated Trx-1 function, causing intracellular ROS generation and releasing the ASK1, and lead to JNK activation, which consequently induced the mitochondrial apoptosis in vitro and in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Design of new genome- and gene-sourced primers and identification of QTL for seed oil content in a specially high-oil Brassica napus cultivar.

PubMed

Sun, Meiyu; Hua, Wei; Liu, Jing; Huang, Shunmou; Wang, Xinfa; Liu, Guihua; Wang, Hanzhong

2012-01-01

Rapeseed (Brassica napus L.) is one of most important oilseed crops in the world. There are now various rapeseed cultivars in nature that differ in their seed oil content because they vary in oil-content alleles and there are high-oil alleles among the high-oil rapeseed cultivars. For these experiments, we generated doubled haploid (DH) lines derived from the cross between the specially high-oil cultivar zy036 whose seed oil content is approximately 50% and the specially low-oil cultivar 51070 whose seed oil content is approximately 36%. First, to address the deficiency in polymorphic markers, we designed 5944 pairs of newly developed genome-sourced primers and 443 pairs of newly developed primers related to oil-content genes to complement the 2244 pairs of publicly available primers. Second, we constructed a new DH genetic linkage map using 527 molecular markers, consisting of 181 publicly available markers, 298 newly developed genome-sourced markers and 48 newly developed markers related to oil-content genes. The map contained 19 linkage groups, covering a total length of 2,265.54 cM with an average distance between markers of 4.30 cM. Third, we identified quantitative trait loci (QTL) for seed oil content using field data collected at three sites over 3 years, and found a total of 12 QTL. Of the 12 QTL associated with seed oil content identified, 9 were high-oil QTL which derived from the specially high-oil cultivar zy036. Two high-oil QTL on chromosomes A2 and C9 co-localized in two out of three trials. By QTL mapping for seed oil content, we found four candidate genes for seed oil content related to four gene markers: GSNP39, GSSR161, GIFLP106 and GIFLP046. This information will be useful for cloning functional genes correlated with seed oil content in the future.

Design of New Genome- and Gene-Sourced Primers and Identification of QTL for Seed Oil Content in a Specially High-Oil Brassica napus Cultivar

PubMed Central

Liu, Jing; Huang, Shunmou; Wang, Xinfa; Liu, Guihua; Wang, Hanzhong

2012-01-01

Rapeseed (Brassica napus L.) is one of most important oilseed crops in the world. There are now various rapeseed cultivars in nature that differ in their seed oil content because they vary in oil-content alleles and there are high-oil alleles among the high-oil rapeseed cultivars. For these experiments, we generated doubled haploid (DH) lines derived from the cross between the specially high-oil cultivar zy036 whose seed oil content is approximately 50% and the specially low-oil cultivar 51070 whose seed oil content is approximately 36%. First, to address the deficiency in polymorphic markers, we designed 5944 pairs of newly developed genome-sourced primers and 443 pairs of newly developed primers related to oil-content genes to complement the 2244 pairs of publicly available primers. Second, we constructed a new DH genetic linkage map using 527 molecular markers, consisting of 181 publicly available markers, 298 newly developed genome-sourced markers and 48 newly developed markers related to oil-content genes. The map contained 19 linkage groups, covering a total length of 2,265.54 cM with an average distance between markers of 4.30 cM. Third, we identified quantitative trait loci (QTL) for seed oil content using field data collected at three sites over 3 years, and found a total of 12 QTL. Of the 12 QTL associated with seed oil content identified, 9 were high-oil QTL which derived from the specially high-oil cultivar zy036. Two high-oil QTL on chromosomes A2 and C9 co-localized in two out of three trials. By QTL mapping for seed oil content, we found four candidate genes for seed oil content related to four gene markers: GSNP39, GSSR161, GIFLP106 and GIFLP046. This information will be useful for cloning functional genes correlated with seed oil content in the future. PMID:23077542

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

PubMed

Del Prete, Gregory Q; Ailers, Braiden; Moldt, Brian; Keele, Brandon F; Estes, Jacob D; Rodriguez, Anthony; Sampias, Marissa; Oswald, Kelli; Fast, Randy; Trubey, Charles M; Chertova, Elena; Smedley, Jeremy; LaBranche, Celia C; Montefiori, David C; Burton, Dennis R; Shaw, George M; Markowitz, Marty; Piatak, Michael; KewalRamani, Vineet N; Bieniasz, Paul D; Lifson, Jeffrey D; Hatziioannou, Theodora

2014-09-10

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of pancreaticoduodenectomy on endocrine and exocrine pancreatic function: A prospective cohort study based on pre- and postoperative function tests.

PubMed

Roeyen, Geert; Jansen, Miet; Hartman, Vera; Chapelle, Thiery; Bracke, Bart; Ysebaert, Dirk; De Block, Christophe

Studies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy. Between 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively. In 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T 30 (p = 0.037). A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively. Although deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

High resolution microtomography for density and spatial infomation about wood structures

Treesearch

Barbara Illman; Betsy Dowd

1999-01-01

Microtomography has successfully been used to characterize loss of structural integrity of wood. Tomographic images were generated with the newly developed third generation x-ray computed microtomography (XCMT) instrument at the X27A beamline at the national Synchrotron Light source (NSLS). The beamline is equipped with high-flux x-ray monochromator based on multilayer...

Pupal abnormalities among laboratory-reared gypsy moths

Treesearch

Richard W. Hansen

1991-01-01

Gypsy moth cohorts from 10 near-wild strains (one to six previous generations in culture), six wild strains (field-collected egg masses), and the standard "New Jersey" lab strain (34th and 35th generation in culture) were reared on Otis wheat germ-based artificial diet, in a constant environment. Rearings were begun with newly-hatched first instars; pupae...

Shear Viscosity Coefficient of 5d Liquid Transition Metals

NASA Astrophysics Data System (ADS)

Thakor, P. B.; Sonvane, Y. A.; Gajjar, P. N.; Jani, A. R.

2011-07-01

In the present paper we have calculated shear viscosity coefficient (η) of 5 d liquid transition metals. To calculate effective pair potential ν(r) and pair distribution function g(r) we have used our own newly constructed model potential and Percus- Yevick hard sphere (PYHS) structure factor S(q) respectively. We have also investigated the effect of different correction function like Hartree (H), Taylor (T) and Sarkar et al. (S) on shear viscosity coefficient (η). Our newly constructed model potential successfully explains the shear viscosity coefficient (η) of 5 d liquid transition metals.

Analysis of Expressed Sequence Tags (EST) in Date Palm.

PubMed

Al-Faifi, Sulieman A; Migdadi, Hussein M; Algamdi, Salem S; Khan, Mohammad Altaf; Al-Obeed, Rashid S; Ammar, Megahed H; Jakse, Jerenj

2017-01-01

Expressed sequence tags (EST) were generated from a normalized cDNA library of the date palm Sukkari cv. to understand the high-quality and better field performance of this well-known commercial cultivar. A total of 6943 high-quality ESTs were generated, out of them 6671 are submitted to the GenBank dbEST (LIBEST_028537). The generated ESTs were assembled into 6362 unigenes, consisting of 494 (14.4%) contigs and 5868 (84.53%) singletons. The functional annotation shows that the majority of the ESTs are associated with binding (44%), catalytic (40%), transporter (5%), and structural molecular (5%) activities. The blastx results show that 73% of unigenes are significantly similar to known plant genes and 27% are novel. The latter could be of particular interest in date palm genetic studies. Further analysis shows that some ESTs are categorized as stress/defense- and fruit development-related genes. These newly generated ESTs could significantly enhance date palm EST databases in the public domain and are available to scientists and researchers across the globe. This knowledge will facilitate the discovery of candidate genes that govern important developmental and agronomical traits in date palm. It will provide important resources for developing genetic tools, comparative genomics, and genome evolution among date palm cultivars.

Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope.

PubMed

Shonat, R D; Wachman, E S; Niu, W; Koretsky, A P; Farkas, D L

1997-09-01

A newly developed microscope using acousto-optic tunable filters (AOTFs) was used to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in the cerebral cortex of mice. SO2 maps were generated from the spectral analysis of reflected absorbance images collected at different wavelengths, and PO2 maps were generated from the phosphorescence lifetimes of an injected palladium-porphyrin compound using a frequency-domain measurement. As the inspiratory O2 was stepped from hypoxia (10% O2), through normoxia (21% O2), to hyperoxia (60% O2), measured SO2 and PO2 levels rose accordingly and predictably throughout. A plot of SO2 versus PO2 in different arterial and venous regions of the pial vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation curve, providing further validation of the two mapping procedures. The study demonstrates the versatility of the AOTF microscope for in vivo physiologic investigation, allowing for the generation of nearly simultaneous SO2 and PO2 maps in the cerebral cortex, and the frequency-domain detection of phosphorescence lifetimes. This class of study opens up exciting new possibilities for investigating the dynamics of hemoglobin and O2 binding during functional activation of neuronal tissues.

Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope.

PubMed Central

Shonat, R D; Wachman, E S; Niu, W; Koretsky, A P; Farkas, D L

1997-01-01

A newly developed microscope using acousto-optic tunable filters (AOTFs) was used to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in the cerebral cortex of mice. SO2 maps were generated from the spectral analysis of reflected absorbance images collected at different wavelengths, and PO2 maps were generated from the phosphorescence lifetimes of an injected palladium-porphyrin compound using a frequency-domain measurement. As the inspiratory O2 was stepped from hypoxia (10% O2), through normoxia (21% O2), to hyperoxia (60% O2), measured SO2 and PO2 levels rose accordingly and predictably throughout. A plot of SO2 versus PO2 in different arterial and venous regions of the pial vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation curve, providing further validation of the two mapping procedures. The study demonstrates the versatility of the AOTF microscope for in vivo physiologic investigation, allowing for the generation of nearly simultaneous SO2 and PO2 maps in the cerebral cortex, and the frequency-domain detection of phosphorescence lifetimes. This class of study opens up exciting new possibilities for investigating the dynamics of hemoglobin and O2 binding during functional activation of neuronal tissues. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 6 PMID:9284290

Coping strategies among patients with newly diagnosed amyotrophic lateral sclerosis.

PubMed

Jakobsson Larsson, Birgitta; Nordin, Karin; Askmark, Håkan; Nygren, Ingela

2014-11-01

To prospectively identify different coping strategies among newly diagnosed amyotrophic lateral sclerosis patients and whether they change over time and to determine whether physical function, psychological well-being, age and gender correlated with the use of different coping strategies. Amyotrophic lateral sclerosis is a fatal disease with impact on both physical function and psychological well-being. Different coping strategies are used to manage symptoms and disease progression, but knowledge about coping in newly diagnosed amyotrophic lateral sclerosis patients is scarce. This was a prospective study with a longitudinal and descriptive design. A total of 33 patients were included and evaluation was made at two time points, one to three months and six months after diagnosis. Patients were asked to complete the Motor Neuron Disease Coping Scale and the Hospital Anxiety and Depression Scale. Physical function was estimated using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. The most commonly used strategies were support and independence. Avoidance/venting and information seeking were seldom used at both time points. The use of information seeking decreased between the two time points. Men did not differ from women, but patients ≤64 years used positive action more often than older patients. Amyotrophic Lateral Sclerosis Functional Rating Scale was positively correlated with positive action at time point 1, but not at time point 2. Patients' psychological well-being was correlated with the use of different coping strategies. Support and independence were the most used coping strategies, and the use of different strategies changed over time. Psychological well-being was correlated with different coping strategies in newly diagnosed amyotrophic lateral sclerosis patients. The knowledge about coping strategies in early stage of the disease may help the nurses to improve and develop the care and support for these patients. © 2014 John Wiley & Sons Ltd.

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

Yu, Kuang; Libisch, Florian; Carter, Emily A., E-mail: eac@princeton.edu

We report a new implementation of the density functional embedding theory (DFET) in the VASP code, using the projector-augmented-wave (PAW) formalism. Newly developed algorithms allow us to efficiently perform optimized effective potential optimizations within PAW. The new algorithm generates robust and physically correct embedding potentials, as we verified using several test systems including a covalently bound molecule, a metal surface, and bulk semiconductors. We show that with the resulting embedding potential, embedded cluster models can reproduce the electronic structure of point defects in bulk semiconductors, thereby demonstrating the validity of DFET in semiconductors for the first time. Compared to ourmore » previous version, the new implementation of DFET within VASP affords use of all features of VASP (e.g., a systematic PAW library, a wide selection of functionals, a more flexible choice of U correction formalisms, and faster computational speed) with DFET. Furthermore, our results are fairly robust with respect to both plane-wave and Gaussian type orbital basis sets in the embedded cluster calculations. This suggests that the density functional embedding method is potentially an accurate and efficient way to study properties of isolated defects in semiconductors.« less

Functional Implications of Novel Human Acid Sphingomyelinase Splice Variants

PubMed Central

Rhein, Cosima; Tripal, Philipp; Seebahn, Angela; Konrad, Alice; Kramer, Marcel; Nagel, Christine; Kemper, Jonas; Bode, Jens; Mühle, Christiane; Gulbins, Erich; Reichel, Martin; Becker, Cord-Michael; Kornhuber, Johannes

2012-01-01

Background Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. Methodology/Principal Findings We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. Conclusions/Significance These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. PMID:22558155

Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

PubMed Central

Figueres-Oñate, Maria; López-Mascaraque, Laura

2016-01-01

Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

Functional Tooth Restoration by Allogeneic Mesenchymal Stem Cell-Based Bio-Root Regeneration in Swine

PubMed Central

Wei, Fulan; Song, Tieli; Ding, Gang; Xu, Junji; Liu, Yi; Liu, Dayong; Fan, Zhipeng; Zhang, Chunmei

2013-01-01

Our previous proof-of-concept study showed the feasibility of regenerating the dental stem cell-based bioengineered tooth root (bio-root) structure in a large animal model. Here, we used allogeneic dental mesenchymal stem cells to regenerate bio-root, and then installed a crown on the bio-root to restore tooth function. A root shape hydroxyapatite tricalcium phosphate scaffold containing dental pulp stem cells was covered by a Vc-induced periodontal ligament stem cell sheet and implanted into a newly generated jaw bone implant socket. Six months after implantation, a prefabricated porcelain crown was cemented to the implant and subjected to tooth function. Clinical, radiological, histological, ultrastructural, systemic immunological evaluations and mechanical properties were analyzed for dynamic changes in the bio-root structure. The regenerated bio-root exhibited characteristics of a normal tooth after 6 months of use, including dentinal tubule-like and functional periodontal ligament-like structures. No immunological response to the bio-roots was observed. We developed a standard stem cell procedure for bio-root regeneration to restore adult tooth function. This study is the first to successfully regenerate a functional bio-root structure for artificial crown restoration by using allogeneic dental stem cells and Vc-induced cell sheet, and assess the recipient immune response in a preclinical model. PMID:23363023

Ebolaviruses: New roles for old proteins.

PubMed

Cantoni, Diego; Rossman, Jeremy S

2018-05-01

In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Many of these new functions appear to be unrelated to the protein's primary function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity.

Ebolaviruses: New roles for old proteins

PubMed Central

2018-01-01

In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subsequent humanitarian effort spurred extensive research, significantly enhancing our understanding of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. These newly discovered roles are revealing new mechanisms of virus replication and pathogenicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral protein (VP). Many of these new functions appear to be unrelated to the protein’s primary function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity. PMID:29723187

Visualizing Microbial Biogeochemistry: NanoSIMS and Stable Isotope Probing (Invited)

NASA Astrophysics Data System (ADS)

Pett-Ridge, J.; Weber, P. K.

2009-12-01

Linking phylogenetic information to function in microbial communities is a key challenge for microbial ecology. Isotope-labeling experiments provide a useful means to investigate the ecophysiology of microbial populations and cells in the environment and allow measurement of nutrient transfers between cell types, symbionts and consortia. The combination of Nano-Secondary Ion Mass Spectrometry (NanoSIMS) analysis, in situ labeling and high resolution microscopy allows isotopic analysis to be linked to phylogeny and morphology and holds great promise for fine-scale studies of microbial systems. In NanoSIMS analysis, samples are sputtered with an energetic primary beam (Cs+, O-) liberating secondary ions that are separated by the mass spectrometer and detected in a suite of electron multipliers. Five isotopic species may be analyzed concurrently with spatial resolution as fine as 50nm. A high sensitivity isotope ratio ‘map’ can then be generated for the analyzed area. NanoSIMS images of 13C, 15N and Mo (a nitrogenase co-factor) localization in diazotrophic cyanobacteria show how cells differentially allocate resources within filaments and allow calculation of nutrient uptake rates on a cell by cell basis. Images of AM fungal hyphae-root and cyanobacteria-rhizobia associations indicate the mobilization and sharing (stealing?) of newly fixed C and N. In a related technique, “El-FISH”, stable isotope labeled biomass is probed with oligonucleotide-elemental labels and then imaged by NanoSIMS. In microbial consortia and cyanobacterial mats, this technique helps link microbial structure and function simultaneously even in systems with unknown and uncultivated microbes. Finally, the combination of re-engineered universal 16S oligonucleotide microarrays with NanoSIMS analyses may allow microbial identity to be linked to functional roles in complex systems such as mats and cellulose degrading hindgut communities. These newly developed methods provide correlated oligonucleotide, functional enzyme and metabolic image data and should help unravel the metabolic processes of complex microbial communities in soils, biofilms and aquatic systems.

Bulimic symptoms and interpersonal functioning among college students.

PubMed

Kwan, Mun Yee; Minnich, Allison M; Douglas, Valerie; Gordon, Kathryn H; Castro, Yessenia

2017-11-01

Integrating interpersonal theory and the stress generation hypothesis, two studies investigated the association between bulimic symptoms and interpersonal distress and the mechanism underlying this association. In Study 1, 36 pairs of female roommates completed self-report questionnaires in a laboratory while Study 2 recruited 539 undergraduate men and women to participate in a longitudinal online study by completing self-report measures at two time points. Multilevel modeling revealed that targets' bulimic symptoms predicted roommates' intention to continue living with them in Study 1. Greater bulimic symptoms predicted lower intention. In Study 2, bulimic symptoms had a direct and an indirect effect on interpersonal distress, with reassurance-seeking as a mediator in the indirect effect. Findings replicated previous studies showing that bulimic symptoms generate further distress and, in our studies, interpersonal distress specifically. Moreover, reassurance-seeking was a newly identified mechanism underlying this association. These findings provide support for the usefulness of interpersonal theory and the stress generation hypothesis as a framework for understanding bulimic symptomatology. Clinicians may find it useful to target reassurance-seeking behaviors during the treatment of bulimic symptoms in order to improve treatment outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus.

PubMed

Carroll, Ronan K; Weiss, Andy; Broach, William H; Wiemels, Richard E; Mogen, Austin B; Rice, Kelly C; Shaw, Lindsey N

2016-02-09

In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. Despite a large number of studies identifying regulatory or small RNA (sRNA) genes in Staphylococcus aureus, their annotation is notably lacking in available genome files. In addition to this, there has been a considerable lack of cross-referencing in the wealth of studies identifying these elements, often leading to the same sRNA being identified multiple times and bearing multiple names. In this work, we have consolidated and curated known sRNA genes from the literature and mapped them to their position on the S. aureus genome, creating new genome annotation files. These files can now be used by the scientific community at large in experiments to search for previously undiscovered sRNA genes and to monitor sRNA gene expression by transcriptome sequencing (RNA-seq). We demonstrate this application, identifying 39 new sRNAs and studying their expression during S. aureus growth in human serum. Copyright © 2016 Carroll et al.

Efficient CRISPR/Cas9-mediated gene editing in Arabidopsis thaliana and inheritance of modified genes in the T2 and T3 generations.

PubMed

Jiang, WenZhi; Yang, Bing; Weeks, Donald P

2014-01-01

The newly developed CRISPR/Cas9 system for targeted gene knockout or editing has recently been shown to function in plants in both transient expression systems as well as in primary T1 transgenic plants. However, stable transmission of genes modified by the Cas9/single guide RNA (sgRNA) system to the T2 generation and beyond has not been demonstrated. Here we provide extensive data demonstrating the efficiency of Cas9/sgRNA in causing modification of a chromosomally integrated target reporter gene during early development of transgenic Arabidopsis plants and inheritance of the modified gene in T2 and T3 progeny. Efficient conversion of a nonfunctional, out-of-frame GFP gene to a functional GFP gene was confirmed in T1 plants by the observation of green fluorescent signals in leaf tissues as well as the presence of mutagenized DNA sequences at the sgRNA target site within the GFP gene. All GFP-positive T1 transgenic plants and nearly all GFP-negative plants examined contained mutagenized GFP genes. Analyses of 42 individual T2 generation plants derived from 6 different T1 progenitor plants showed that 50% of T2 plants inherited a single T-DNA insert. The efficiency of the Cas9/sgRNA system and stable inheritance of edited genes point to the promise of this system for facile editing of plant genes.

Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator.

PubMed

Cao, Ning; Song, Seung Hyun; Maleki, Teimour; Shaffer, Michael; Stantz, Keith M; Cao, Minsong; Kao, Chinghai; Mendonca, Marc S; Ziaie, Babak; Ko, Song-Chu

2016-04-01

Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.

Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

PubMed

Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

2016-01-01

Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.

Newly graduated nurses' use of knowledge sources: a meta-ethnography.

PubMed

Voldbjerg, Siri Lygum; Grønkjaer, Mette; Sørensen, Erik Elgaard; Hall, Elisabeth O C

2016-08-01

To advance evidence on newly graduated nurses' use of knowledge sources. Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use of knowledge sources are increasing though generated from scattered healthcare contexts. Therefore, a metasynthesis of qualitative research on what knowledge sources new graduates use in decision-making was conducted. Meta-ethnography. Nineteen reports, representing 17 studies, published from 2000-2014 were identified from iterative searches in relevant databases from May 2013-May 2014. Included reports were appraised for quality and Noblit and Hare's meta-ethnography guided the interpretation and synthesis of data. Newly graduated nurses' use of knowledge sources during their first 2-year postgraduation were interpreted in the main theme 'self and others as knowledge sources,' with two subthemes 'doing and following' and 'knowing and doing,' each with several elucidating categories. The metasynthesis revealed a line of argument among the report findings underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions. The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources. © 2016 John Wiley & Sons Ltd.

A state-of-the-art compact SiC photovoltaic inverter with maximum power point tracking function

NASA Astrophysics Data System (ADS)

Ando, Yuji; Oku, Takeo; Yasuda, Masashi; Ushijima, Kazufumi; Matsuo, Hiroshi; Murozono, Mikio

2018-01-01

We have developed a 150-W SiC-based photovoltaic (PV)-inverter with the maximum power point tracking (MPPT) function. The newly developed inverter achieved a state-of-the-art combination of the weight (0.79 kg) and the volume (790 mm3) as a 150-250 W class PV-inverter. As compared to the original version that we have previously reported, the weight and volume were decreased by 37% and 38%, respectively. This compactness originated from the optimized circuit structure and the increased density of a wiring circuit. Conversion efficiencies of the MPPT charge controller and the direct current (DC)-alternating current (AC) converter reached 96.4% and 87.6%, respectively. These efficiency values are comparable to those for the original version. We have developed a PV power generation system consisting of this inverter, a spherical Si solar cell module, and a 15-V Li-ion laminated battery. The total weight of the system was below 6 kg. The developed system exhibited stable output power characteristics, even when the weather conditions were fluctuated. These compactness, high efficiencies, and excellent stability clearly indicated the feasibility of SiC power devices even for sub-kW class PV power generation systems.

Inferring muscle functional roles of the ostrich pelvic limb during walking and running using computer optimization.

PubMed

Rankin, Jeffery W; Rubenson, Jonas; Hutchinson, John R

2016-05-01

Owing to their cursorial background, ostriches (Struthio camelus) walk and run with high metabolic economy, can reach very fast running speeds and quickly execute cutting manoeuvres. These capabilities are believed to be a result of their ability to coordinate muscles to take advantage of specialized passive limb structures. This study aimed to infer the functional roles of ostrich pelvic limb muscles during gait. Existing gait data were combined with a newly developed musculoskeletal model to generate simulations of ostrich walking and running that predict muscle excitations, force and mechanical work. Consistent with previous avian electromyography studies, predicted excitation patterns showed that individual muscles tended to be excited primarily during only stance or swing. Work and force estimates show that ostrich gaits are partially hip-driven with the bi-articular hip-knee muscles driving stance mechanics. Conversely, the knee extensors acted as brakes, absorbing energy. The digital extensors generated large amounts of both negative and positive mechanical work, with increased magnitudes during running, providing further evidence that ostriches make extensive use of tendinous elastic energy storage to improve economy. The simulations also highlight the need to carefully consider non-muscular soft tissues that may play a role in ostrich gait. © 2016 The Authors.

World's Cheapest Readout Electronics for Kinetic Inductance Detector by Using RedPitaya

NASA Astrophysics Data System (ADS)

Tomita, N.; Jeong, H.; Choi, J.; Ishitsuka, H.; Mima, S.; Nagasaki, T.; Oguri, S.; Tajima, O.

2016-07-01

The kinetic inductance detector (KID) is a cutting-edge superconducting detector. The number of KID developers is growing. Most of them have switched from their previous study to superconducting technologies. Therefore, infrastructures for the fabrication of KIDs and cooling systems for their tests have already been established. However, readout electronics have to be newly prepared. Neither a commercial system nor low-cost standard electronics are available despite various attempts to create a standard one. We suggest the use of RedPitaya as readout electronics for the initial step of KID development, which is low cost (≈ 400 USD) and easy to set up. The RedPitaya consists of an all-programmable FPGA-CPU module and a dual-channel 14 bit DAC (ADC) to generate (measure) fast analog signals with 125 MSpS. Each port can be synchronized in-phase or quadrature-phase, and functions for generating and sampling analog signal are prepared. It is straightforward to construct vector network analyzer-like logic by using a combination of these default functions. Up-conversion and down-conversion of its frequency range are also possible by using commercial equipment, i.e., mixers, couplers, and a local oscillator. We implemented direct down-conversion logic on the RedPitaya, and successfully demonstrated KID signal measurements.

Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes

PubMed Central

Kawahara, Hiroyuki; Kasahara, Masanori; Nishiyama, Atsuya; Ohsumi, Keita; Goto, Tetsuya; Kishimoto, Takeo; Saeki, Yasushi; Yokosawa, Hideyoshi; Shimbara, Naoki; Murata, Shigeo; Chiba, Tomoki; Suzuki, Koichi; Tanaka, Keiji

2000-01-01

The 26S proteasome is a multisubunit protein- destroying machinery that degrades ubiquitin-tagged proteins. To date only a single species of Rpn10, which possibly functions as a multiubiquitin chain-binding subunit, has been identified in various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single gene by developmentally regulated, alternative splicing. Rpn10a is ubiquitously expressed, whereas Rpn10e is expressed only in embryos, with the highest levels of expression in the brain. Both forms of Rpn10 are components of the 26S proteasome, with an apparently similar affinity for multiubiquitylated [125I]lysozyme in vitro. However, they exert markedly divergent effects on the destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome occurs in at least two functionally distinct forms: one containing a ubiquitously expressed Rpn10a and the other a newly identified, embryo-specific Rpn10e. While the former is thought to perform proteolysis constitutively in a wide variety of cells, the latter may play a specialized role in early embryonic development. PMID:10921894

Sentence processing in the cerebral cortex.

PubMed

Sakai, K L; Hashimoto, R; Homae, F

2001-01-01

Human language is a unique faculty of the mind. It has been the ultimate mystery throughout the history of neuroscience. Despite many aphasia and functional imaging studies, the exact correlation between cortical language areas and subcomponents of the linguistic system has not been established. One notable drawback is that most functional imaging studies have tested language tasks at the word level, such as lexical decision and word generation tasks, thereby neglecting the syntactic aspects of the language faculty. As proposed by Chomsky, the critical knowledge of language involves universal grammar (UG), which governs the syntactic structure of sentences. In this article, we will review recent advances made by functional neuroimaging studies of language, focusing especially on sentence processing in the cerebral cortex. We also present the recent results of our functional magnetic resonance imaging (fMRI) study intended to identify cortical areas specifically involved in syntactic processing. A study of sentence processing that employs a newly developed technique, optical topography (OT), is also presented. Based on these findings, we propose a modular specialization of Broca's area, Wernicke's area, and the angular gyrus/supramarginal gyrus. The current direction of research in neuroscience is beginning to establish the existence of distinct modules responsible for our knowledge of language.

Photochemical Properties and Reactivity of a Ru Compound Containing an NAD/NADH-Functionalized 1,10-Phenanthroline Ligand.

PubMed

Kobayashi, Katsuaki; Ohtsu, Hideki; Nozaki, Koichi; Kitagawa, Susumu; Tanaka, Koji

2016-03-07

An NAD/NADH-functionalized ligand, benzo[b]pyrido[3,2-f][1,7]-phenanthroline (bpp), was newly synthesized. A Ru compound containing the bpp ligand, [Ru(bpp)(bpy)2](2+), underwent 2e(-) and 2H(+) reduction, generating the NADH form of the compound, [Ru(bppHH)(bpy)2](2+), in response to visible light irradiation in CH3CN/TEA/H2O (8/1/1). The UV-vis and fluorescent spectra of both [Ru(bpp)(bpy)2](2+) and [Ru(bppHH)(bpy)2](2+) resembled the spectra of [Ru(bpy)3](2+). Both complexes exhibited strong emission, with quantum yields of 0.086 and 0.031, respectively; values that are much higher than those obtained from the NAD/NADH-functionalized complexes [Ru(pbn)(bpy)2](2+) and [Ru(pbnHH)(bpy)2](2+) (pbn = (2-(2-pyridyl)benzo[b]-1.5-naphthyridine, pbnHH = hydrogenated form of pbn). The reduction potential of the bpp ligand in [Ru(bpp)(bpy)2](2+) (-1.28 V vs SCE) is much more negative than that of the pbn ligand in [Ru(pbn)(bpy)2](2+) (-0.74 V), although the oxidation potentials of bppHH and pbnHH are essentially equal (0.95 V). These results indicate that the electrochemical oxidation of the dihydropyridine moiety in the NADH-type ligand was independent of the π system, including the Ru polypyridyl framework. [Ru(bppHH)(bpy)2](2+) allowed the photoreduction of oxygen, generating H2O2 in 92% yield based on [Ru(bppHH)(bpy)2](2+). H2O2 production took place via singlet oxygen generated by the energy transfer from excited [Ru(bppHH)(bpy)2](2+) to triplet oxygen.

Work stress among newly graduated nurses in relation to workplace and clinical group supervision.

PubMed

Blomberg, Karin; Isaksson, Ann-Kristin; Allvin, Renée; Bisholt, Birgitta; Ewertsson, Mona; Kullén Engström, Agneta; Ohlsson, Ulla; Sundler Johansson, Annelie; Gustafsson, Margareta

2016-01-01

The aim was to investigate occupational stress among newly graduated nurses in relation to the workplace and clinical group supervision. Being a newly graduated nurse is particularly stressful. What remains unclear is whether the workplace and clinical group supervision affect the stress. A cross-sectional comparative study was performed in 2012. Data were collected by means of a numerical scale measuring occupational stress, questions about workplace and clinical group supervision. One hundred and thirteen nurses who had recently graduated from three Swedish universities were included in the study. The stress was high among the newly graduated nurses but it differed significantly between workplaces, surgical departments generating the most stress. Nurses who had received clinical group supervision reported significantly less stress. The stress between workplaces remained significant also when participation in clinical group supervision was taken into account. Newly graduated nurses experience great stress and need support, especially those in surgical departments. Nurses participating in clinical group supervision reported significantly less stress. It is important to develop strategies that help to adapt the work situation so as to give nurses the necessary support. Clinical group supervision should be considered as an option for reducing stress. © 2014 John Wiley & Sons Ltd.

A study examining senior nursing students' expectations of work and the workforce.

PubMed

Saber, Deborah A; Anglade, Debbie; Schirle, Lori M

2016-03-01

This study explored traditional and accelerated Bachelor of Science nursing students' expectations of nursing work and the workforce. Role transition difficulty is blamed for much of the 15-60% newly licensed registered nurse turnover in their first 3 years of employment. This qualitative study consisted of 14 focus groups (n = 98) to determine Bachelor of Science nursing students' expectations of work as newly licensed registered nurses. Two overriding themes for accelerated and traditional students emerged: stressors and coping strategies. Students believe four stressors will affect their progression into the newly licensed registered nurse role and have developed coping strategies. This study suggests that students have experienced stressors in the clinical environment and anticipate them in the newly licensed registered nurse role. During transition, strategies such as 'fitting in' and 'staying safe' will be employed to ensure work success. Younger generations value a healthy work-life balance and a positive working environment. These nurses will not tolerate positions that do not align with their values. With the aging of citizens in the USA and the predicted nursing shortage, nursing management needs to employ strategies to retain newly licensed registered nurses. © 2015 John Wiley & Sons Ltd.

Pressure generation to 50 GPa in Kawai-type multianvil apparatus using newly developed tungsten carbide anvils

NASA Astrophysics Data System (ADS)

Kunimoto, Takehiro; Irifune, Tetsuo; Tange, Yoshinori; Wada, Kouhei

2016-04-01

A pressure generation test for Kawai-type multianvil apparatus (KMA) has been made using second-stage anvils of a newly developed ultra-hard tungsten carbide composite. Superb performance of the new anvil with significantly less plastic deformation was confirmed as compared to those commonly used for the KMA experiments. A maximum pressure of ∼48 GPa was achieved using the new anvils with a truncation edge length (TEL) of 1.5 mm, based on in situ X-ray diffraction measurements. Further optimization of materials and sizes of the pressure medium/gasket should lead to pressures even higher than 50 GPa in KMA using this novel tungsten carbide composite, which may also be used for expansion of the pressure ranges in other types of high pressure apparatus operated in large volume press.

Translational genomics for plant breeding with the genome sequence explosion.

PubMed

Kang, Yang Jae; Lee, Taeyoung; Lee, Jayern; Shim, Sangrea; Jeong, Haneul; Satyawan, Dani; Kim, Moon Young; Lee, Suk-Ha

2016-04-01

The use of next-generation sequencers and advanced genotyping technologies has propelled the field of plant genomics in model crops and plants and enhanced the discovery of hidden bridges between genotypes and phenotypes. The newly generated reference sequences of unstudied minor plants can be annotated by the knowledge of model plants via translational genomics approaches. Here, we reviewed the strategies of translational genomics and suggested perspectives on the current databases of genomic resources and the database structures of translated information on the new genome. As a draft picture of phenotypic annotation, translational genomics on newly sequenced plants will provide valuable assistance for breeders and researchers who are interested in genetic studies. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

PubMed

Giannakopoulos, Aris; Katelaris, Anni; Noni, Maria; Karakonstantakis, Theodore; Kanaka-Gantenbein, Christina; Doudounakis, Stavros

2018-05-01

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Inhomogeneity induced and appropriately parameterized semilocal exchange and correlation energy functionals in two-dimensions.

PubMed

Patra, Abhilash; Jana, Subrata; Samal, Prasanjit

2018-04-07

The construction of meta generalized gradient approximations based on the density matrix expansion (DME) is considered as one of the most accurate techniques to design semilocal exchange energy functionals in two-dimensional density functional formalism. The exchange holes modeled using DME possess unique features that make it a superior entity. Parameterized semilocal exchange energy functionals based on the DME are proposed. The use of different forms of the momentum and flexible parameters is to subsume the non-uniform effects of the density in the newly constructed semilocal functionals. In addition to the exchange functionals, a suitable correlation functional is also constructed by working upon the local correlation functional developed for 2D homogeneous electron gas. The non-local effects are induced into the correlation functional by a parametric form of one of the newly constructed exchange energy functionals. The proposed functionals are applied to the parabolic quantum dots with a varying number of confined electrons and the confinement strength. The results obtained with the aforementioned functionals are quite satisfactory, which indicates why these are suitable for two-dimensional quantum systems.

Inhomogeneity induced and appropriately parameterized semilocal exchange and correlation energy functionals in two-dimensions

NASA Astrophysics Data System (ADS)

Patra, Abhilash; Jana, Subrata; Samal, Prasanjit

2018-04-01

The construction of meta generalized gradient approximations based on the density matrix expansion (DME) is considered as one of the most accurate techniques to design semilocal exchange energy functionals in two-dimensional density functional formalism. The exchange holes modeled using DME possess unique features that make it a superior entity. Parameterized semilocal exchange energy functionals based on the DME are proposed. The use of different forms of the momentum and flexible parameters is to subsume the non-uniform effects of the density in the newly constructed semilocal functionals. In addition to the exchange functionals, a suitable correlation functional is also constructed by working upon the local correlation functional developed for 2D homogeneous electron gas. The non-local effects are induced into the correlation functional by a parametric form of one of the newly constructed exchange energy functionals. The proposed functionals are applied to the parabolic quantum dots with a varying number of confined electrons and the confinement strength. The results obtained with the aforementioned functionals are quite satisfactory, which indicates why these are suitable for two-dimensional quantum systems.

Geospatial Standards and the Knowledge Generation Lifescycle

NASA Technical Reports Server (NTRS)

Khalsa, Siri Jodha S.; Ramachandran, Rahul

2014-01-01

Standards play an essential role at each stage in the sequence of processes by which knowledge is generated from geoscience observations, simulations and analysis. This paper provides an introduction to the field of informatics and the knowledge generation lifecycle in the context of the geosciences. In addition we discuss how the newly formed Earth Science Informatics Technical Committee is helping to advance the application of standards and best practices to make data and data systems more usable and interoperable.

REM sleep selectively prunes and maintains new synapses in development and learning.

PubMed

Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao

2017-03-01

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

DOUBLE SHELL TANK (DST) HYDROXIDE DEPLETION MODEL FOR CARBON DIOXIDE ABSORPTION

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

OGDEN DM; KIRCH NW

2007-10-31

This document generates a supernatant hydroxide ion depletion model based on mechanistic principles. The carbon dioxide absorption mechanistic model is developed in this report. The report also benchmarks the model against historical tank supernatant hydroxide data and vapor space carbon dioxide data. A comparison of the newly generated mechanistic model with previously applied empirical hydroxide depletion equations is also performed.

Virtual phantom magnetic resonance imaging (ViP MRI) on a clinical MRI platform.

PubMed

Saint-Jalmes, Hervé; Bordelois, Alejandro; Gambarota, Giulio

2018-01-01

The purpose of this study was to implement Virtual Phantom Magnetic Resonance Imaging (ViP MRI), a technique that allows for generating reference signals in MR images using radiofrequency (RF) signals, on a clinical MR system and to test newly designed virtual phantoms. MRI experiments were conducted on a 1.5 T MRI scanner. Electromagnetic modelling of the ViP system was done using the principle of reciprocity. The ViP RF signals were generated using a compact waveform generator (dimensions of 26 cm × 18 cm × 16 cm), connected to a homebuilt 25 mm-diameter RF coil. The ViP RF signals were transmitted to the MRI scanner bore, simultaneously with the acquisition of the signal from the object of interest. Different types of MRI data acquisition (2D and 3D gradient-echo) as well as different phantoms, including the Shepp-Logan phantom, were tested. Furthermore, a uniquely designed virtual phantom - in the shape of a grid - was generated; this newly proposed phantom allows for the investigations of the vendor distortion correction field. High quality MR images of virtual phantoms were obtained. An excellent agreement was found between the experimental data and the inverse cube law, which was the expected functional dependence obtained from the electromagnetic modelling of the ViP system. Short-term time stability measurements yielded a coefficient of variation in the signal intensity over time equal to 0.23% and 0.13% for virtual and physical phantom, respectively. MR images of the virtual grid-shaped phantom were reconstructed with the vendor distortion correction; this allowed for a direct visualization of the vendor distortion correction field. Furthermore, as expected from the electromagnetic modelling of the ViP system, a very compact coil (diameter ~ cm) and very small currents (intensity ~ mA) were sufficient to generate a signal comparable to that of physical phantoms in MRI experiments. The ViP MRI technique was successfully implemented on a clinical MR system. One of the major advantages of ViP MRI over previous approaches is that the generation and transmission of RF signals can be achieved with a self-contained apparatus. As such, the ViP MRI technique is transposable to different platforms (preclinical and clinical) of different vendors. It is also shown here that ViP MRI could be used to generate signals whose characteristics cannot be reproduced by physical objects. This could be exploited to assess MRI system properties, such as the vendor distortion correction field. © 2017 American Association of Physicists in Medicine.

Reconsideration of the Detection and Fluorescence Mechanism of a Pyrene-Based Chemosensor for TNT.

PubMed

Lu, Meiheng; Zhou, Panwang; Ma, Yinhua; Tang, Zhe; Yang, Yanqiang; Han, Keli

2018-02-08

The rapid detection of chemical explosives is crucial for national security and public safety, and the investigation of sensing mechanisms is important for designing highly efficient chemosensors. This study theoretically investigates the detection and fluorescence mechanism of a newly synthesized pyrene-based chemosensor for the detection of trinitrotoluene (TNT) through density-functional-theory (DFT) and time-dependent density-functional-theory (TDDFT) methods and suggests a different interaction product of the probe and TNT from previously reported ones [ Mosca et al. J. Am. Chem. Soc. 2015 , 137 , 7967 ]. Instead of forming Meisenheimer complexes, the energies of which are beyond those of the reactants, a low-energy product generated by a π-π-stacking interaction is more rational and favorable. The fluorescence-quenching property further confirms that the π-π-stacking product is the predicted one rather than luminescent Meisenheimer complexes. Frontier-molecular-orbital (FMO)-analysis results show that photoinduced electron transfer (PET) is the mechanism underlying the luminescence quenching of the probe upon exposure to TNT.

Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity

PubMed Central

Farsi, Zohreh; Rammner, Burkhard; Woehler, Andrew; Lafer, Eileen M; Mim, Carsten; Jahn, Reinhard

2018-01-01

Newly-formed synaptic vesicles (SVs) are rapidly acidified by vacuolar adenosine triphosphatases (vATPases), generating a proton electrochemical gradient that drives neurotransmitter loading. Clathrin-mediated endocytosis is needed for the formation of new SVs, yet it is unclear when endocytosed vesicles acidify and refill at the synapse. Here, we isolated clathrin-coated vesicles (CCVs) from mouse brain to measure their acidification directly at the single vesicle level. We observed that the ATP-induced acidification of CCVs was strikingly reduced in comparison to SVs. Remarkably, when the coat was removed from CCVs, uncoated vesicles regained ATP-dependent acidification, demonstrating that CCVs contain the functional vATPase, yet its function is inhibited by the clathrin coat. Considering the known structures of the vATPase and clathrin coat, we propose a model in which the formation of the coat surrounds the vATPase and blocks its activity. Such inhibition is likely fundamental for the proper timing of SV refilling. PMID:29652249

Development of a functional thyroid model based on an organoid culture system.

PubMed

Saito, Yoshiyuki; Onishi, Nobuyuki; Takami, Hiroshi; Seishima, Ryo; Inoue, Hiroyoshi; Hirata, Yuki; Kameyama, Kaori; Tsuchihashi, Kenji; Sugihara, Eiji; Uchino, Shinya; Ito, Koichi; Kawakubo, Hirofumi; Takeuchi, Hiroya; Kitagawa, Yuko; Saya, Hideyuki; Nagano, Osamu

2018-03-04

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRAS Q61R ) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

NBodyLab Simulation Experiments with GRAPE-6a AND MD-GRAPE2 Acceleration

NASA Astrophysics Data System (ADS)

Johnson, V.; Ates, A.

2005-12-01

NbodyLab is an astrophysical N-body simulation testbed for student research. It is accessible via a web interface and runs as a backend framework under Linux. NbodyLab can generate data models or perform star catalog lookups, transform input data sets, perform direct summation gravitational force calculations using a variety of integration schemes, and produce analysis and visualization output products. NEMO (Teuben 1994), a popular stellar dynamics toolbox, is used for some functions. NbodyLab integrators can optionally utilize two types of low-cost desktop supercomputer accelerators, the newly available GRAPE-6a (125 Gflops peak) and the MD-GRAPE2 (64-128 Gflops peak). The initial version of NBodyLab was presented at ADASS 2002. This paper summarizes software enhancements developed subsequently, focusing on GRAPE-6a related enhancements, and gives examples of computational experiments and astrophysical research, including star cluster and solar system studies, that can be conducted with the new testbed functionality.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

PubMed Central

Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

PubMed Central

Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

2014-01-01

A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

Improvements in Spectrum's fit to program data tool.

PubMed

Mahiane, Severin G; Marsh, Kimberly; Grantham, Kelsey; Crichlow, Shawna; Caceres, Karen; Stover, John

2017-04-01

The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round. In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty. The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better. Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling

PubMed Central

Steinfeld, Jörg; Steinfeld, Ichie; Bausch, Alexander; Coronato, Nicola; Hampel, Meggi-Lee; Depner, Heike; Layer, Paul G.

2017-01-01

ABSTRACT In vertebrates, the retinal pigment epithelium (RPE) and photoreceptors of the neural retina (NR) comprise a functional unit required for vision. During vertebrate eye development, a conversion of the RPE into NR can be induced by growth factors in vivo at optic cup stages, but the reverse process, the conversion of NR tissue into RPE, has not been reported. Here, we show that bone morphogenetic protein (BMP) signalling can reprogram the NR into RPE at optic cup stages in chick. Shortly after BMP application, expression of Microphthalmia-associated transcription factor (Mitf) is induced in the NR and selective cell death on the basal side of the NR induces an RPE-like morphology. The newly induced RPE differentiates and expresses Melanosomalmatrix protein 115 (Mmp115) and RPE65. BMP-induced Wnt2b expression is observed in regions of the NR that become pigmented. Loss of function studies show that conversion of the NR into RPE requires both BMP and Wnt signalling. Simultaneous to the appearance of ectopic RPE tissue, BMP application reprogrammed the proximal RPE into multi-layered retinal tissue. The newly induced NR expresses visual segment homeobox-containing gene (Vsx2), and the ganglion and photoreceptor cell markers Brn3α and Visinin are detected. Our results show that high BMP concentrations are required to induce the conversion of NR into RPE, while low BMP concentrations can still induce transdifferentiation of the RPE into NR. This knowledge may contribute to the development of efficient standardized protocols for RPE and NR generation for cell replacement therapies. PMID:28546339

Limits to ground control in autonomous spacecraft

NASA Technical Reports Server (NTRS)

Wan, Alfred D. M.; Braspenning, Peter J.; Vreeswijk, Gerrard A. W.

1995-01-01

In this paper the autonomy concept used by ESA and NASA is critically evaluated. Moreover, a more proper ground control/spacecraft organizational structure is proposed on the basis of a new, more elaborated concept of autonomy. In an extended theoretical discussion its definitional properties and functionalities are established. The rather basic property of adaptivity leads to the categorization of behaviour into the modes of satisfaction and avoidance behaviour. However, the autonomy property with the most profound consequences is goal-robustness. The mechanism that implements goal-robustness tests newly generated goals and externally received goals on consistency with high-level goals. If goals appear not to be good instantiations or more acceptable replacements of existing goals, they are rejected. This means that ground control has to cooperate with the spacecraft instead of (intermittently) commanding it.

The third-generation turbocharged engine for the Audi 5000 CS and 5000 CS Quattro

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

Stock, D.

In September 1985 the new Audi 5000 CS Quattro was introduced to the American market. This luxurious high performance touring sedan has been equipped with a more advanced turbocharged engine with intercooler and electronic engine management giving improved performance, excellent torque, faster response and better fuel economy. The basic engine is the tried-and-tested Audi 5-cylinder unit. The turbocharged engine's ancillary systems, the electronic ignition control and fuel injection have all been newly developed, carefully optimized and well matched in the special demands of a turbocharged engine. The ignition system controls the engine and fuel injection and delivers analog and digitalmore » signals to the car's instrument panel display. The system also has an integrated self-diagnostic function.« less

FPGA-based Klystron linearization implementations in scope of ILC

DOE PAGES

Omet, M.; Michizono, S.; Matsumoto, T.; ...

2015-01-23

We report the development and implementation of four FPGA-based predistortion-type klystron linearization algorithms. Klystron linearization is essential for the realization of ILC, since it is required to operate the klystrons 7% in power below their saturation. The work presented was performed in international collaborations at the Fermi National Accelerator Laboratory (FNAL), USA and the Deutsches Elektronen Synchrotron (DESY), Germany. With the newly developed algorithms, the generation of correction factors on the FPGA was improved compared to past algorithms, avoiding quantization and decreasing memory requirements. At FNAL, three algorithms were tested at the Advanced Superconducting Test Accelerator (ASTA), demonstrating a successfulmore » implementation for one algorithm and a proof of principle for two algorithms. Furthermore, the functionality of the algorithm implemented at DESY was demonstrated successfully in a simulation.« less

Anomaly of Transmission Properties in Pre-Cantor Dielectric Multilayers

NASA Astrophysics Data System (ADS)

Kaino, Keimei; Sonoda, Jun

2008-02-01

Using the transmission-line theory, we investigate wave propagation in a pre-Cantor multilayer. Transmission spectra of the low stages of pre-Cantor media show good agreement with those of numerical calculation of Maxwell's equations using the FDTD method. Numerical results obtained using the FDTD method show that the electric field at the midpoint of the nth stage pre-Cantor medium has sharp resonance and broad attenuation at transmission bands that are newly generated in attenuation bands of the (n-1)th stage. Using an expression of transmittance of the high stage of pre-Cantor multilayer, we show that the transmittance t becomes a two-valued function of t = 0/1 and the collection of points for t = 1 is a power set of positive integers whose cardinal number is 3ℵ0.

Rgs13 constrains early B cell responses and limits germinal center sizes.

PubMed

Hwang, Il-Young; Hwang, Kyung-Sun; Park, Chung; Harrison, Kathleen A; Kehrl, John H

2013-01-01

Germinal centers (GCs) are microanatomic structures that develop in secondary lymphoid organs in response to antigenic stimulation. Within GCs B cells clonally expand and their immunoglobulin genes undergo class switch recombination and somatic hypermutation. Transcriptional profiling has identified a number of genes that are prominently expressed in GC B cells. Among them is Rgs13, which encodes an RGS protein with a dual function. Its canonical function is to accelerate the intrinsic GTPase activity of heterotrimeric G-protein α subunits at the plasma membrane, thereby limiting heterotrimeric G-protein signaling. A unique, non-canonical function of RGS13 occurs following translocation to the nucleus, where it represses CREB transcriptional activity. The functional role of RGS13 in GC B cells is unknown. To create a surrogate marker for Rgs13 expression and a loss of function mutation, we inserted a GFP coding region into the Rgs13 genomic locus. Following immunization GFP expression rapidly increased in activated B cells, persisted in GC B cells, but declined in newly generated memory B and plasma cells. Intravital microscopy of the inguinal lymph node (LN) of immunized mice revealed the rapid appearance of GFP(+) cells at LN interfollicular regions and along the T/B cell borders, and eventually within GCs. Analysis of WT, knock-in, and mixed chimeric mice indicated that RGS13 constrains extra-follicular plasma cell generation, GC size, and GC B cell numbers. Analysis of select cell cycle and GC specific genes disclosed an aberrant gene expression profile in the Rgs13 deficient GC B cells. These results indicate that RGS13, likely acting at cell membranes and in nuclei, helps coordinate key decision points during the expansion and differentiation of naive B cells.

The Newly Qualified Teacher: A Leader and a Professional? A Norwegian Study

ERIC Educational Resources Information Center

Grimsath, Gerd; Nordvik, Grete; Bergsvik, Eli

2008-01-01

This article is based on a Norwegian study. The focus is two-fold, including the views of both new teachers and leaders on the issue of leadership and professionalism. First, the focus is on the way newly qualified teachers describe how they function in the school and kindergarten organizations. The discussion explores how new teachers' meetings…

Demonstration of flexible multicasting and aggregation functionality for TWDM-PON

NASA Astrophysics Data System (ADS)

Chen, Yuanxiang; Li, Juhao; Zhu, Paikun; Zhu, Jinglong; Tian, Yu; Wu, Zhongying; Peng, Huangfa; Xu, Yongchi; Chen, Jingbiao; He, Yongqi; Chen, Zhangyuan

2017-06-01

The time- and wavelength-division multiplexed passive optical network (TWDM-PON) has been recognized as an attractive solution to provide broadband access for the next-generation networks. In this paper, we propose flexible service multicasting and aggregation functionality for TWDM-PON utilizing multiple-pump four-wave-mixing (FWM) and cyclic arrayed waveguide grating (AWG). With the proposed scheme, multiple TWDM-PON links share a single optical line terminal (OLT), which can greatly reduce the network deployment expense and achieve efficient network resource utilization by load balancing among different optical distribution networks (ODNs). The proposed scheme is compatible with existing TDM-PON infrastructure with fixed-wavelength OLT transmitter, thus smooth service upgrade can be achieved. Utilizing the proposed scheme, we demonstrate a proof-of-concept experiment with 10-Gb/s OOK and 10-Gb/s QPSK orthogonal frequency division multiplexing (OFDM) signal multicasting and aggregating to seven PON links. Compared with back-to-back (BTB) channel, the newly generated multicasting OOK signal and OFDM signal have power penalty of 1.6 dB and 2 dB at the BER of 10-3, respectively. For the aggregation of multiple channels, no obvious power penalty is observed. What is more, to verify the flexibility of the proposed scheme, we reconfigure the wavelength selective switch (WSS) and adjust the number of pumps to realize flexible multicasting functionality. One to three, one to seven, one to thirteen and one to twenty-one multicasting are achieved without modifying OLT structure.

OK-432 synergizes with IFN-γ to confer dendritic cells with enhanced antitumor immunity.

PubMed

Pan, Ke; Lv, Lin; Zheng, Hai-xia; Zhao, Jing-jing; Pan, Qiu-zhong; Li, Jian-jun; Weng, De-sheng; Wang, Dan-dan; Jiang, Shan-shan; Chang, Alfred E; Li, Qiao; Xia, Jian-chuan

2014-03-01

Generation of functional dendritic cells (DCs) with boosted immunity after the withdrawal of initial activation/maturation conditions remains a significant challenge. In this study, we investigated the impact of a newly developed maturation cocktail consisting of OK-432 and interferon-gamma (IFN-γ) on the function of human monocyte-derived DCs (MoDCs). We found that OK-432 plus IFN-γ stimulation could induce significantly stronger expression of surface molecules, production of cytokines, as well as migration of DCs compared with OK-432 stimulation alone. Most importantly, DCs matured with OK-432 plus IFN-γ-induced maintained secretion of interleukin-12 (IL-12)p70 in secondary culture after stimulus withdrawal. Functionally, OK-432 plus IFN-γ-conditioned DCs induce remarkable Th1 and Tc1 responses more effectively than OK-432 alone, even more than the use of α-type-1 cytokine cocktail. As a result, DCs matured with OK-432 plus IFN-γ can prime stronger cytotoxic lymphocyte (CTL) and natural killer (NK) cell response against tumor cells in vitro. Peripheral blood mononuclear cells activated by DCs matured with OK-432 plus IFN-γ also showed greater tumor growth inhibition in vivo in null mice. Molecular mechanistic analysis showed that DC maturation using IFN-γ in concert with OK-432 involves the activation of p38 and nuclear factor-kappa B (NF-κB) pathways. This study provided a novel strategy to generate more potent immune segments in DC vaccine.

Prediction of Broadband Shock-Associated Noise Including Propagation Effects Originating NASA

NASA Technical Reports Server (NTRS)

Miller, Steven; Morris, Philip J.

2012-01-01

An acoustic analogy is developed based on the Euler equations for broadband shock-associated noise (BBSAN) that directly incorporates the vector Green s function of the linearized Euler equations and a steady Reynolds-Averaged Navier-Stokes solution (SRANS) to describe the mean flow. The vector Green s function allows the BBSAN propagation through the jet shear layer to be determined. The large-scale coherent turbulence is modeled by two-point second order velocity cross-correlations. Turbulent length and time scales are related to the turbulent kinetic energy and dissipation rate. An adjoint vector Green s function solver is implemented to determine the vector Green s function based on a locally parallel mean flow at different streamwise locations. The newly developed acoustic analogy can be simplified to one that uses the Green s function associated with the Helmholtz equation, which is consistent with a previous formulation by the authors. A large number of predictions are generated using three different nozzles over a wide range of fully-expanded jet Mach numbers and jet stagnation temperatures. These predictions are compared with experimental data from multiple jet noise experimental facilities. In addition, two models for the so-called fine-scale mixing noise are included in the comparisons. Improved BBSAN predictions are obtained relative to other models that do not include propagation effects.

Computer-aided US diagnosis of breast lesions by using cell-based contour grouping.

PubMed

Cheng, Jie-Zhi; Chou, Yi-Hong; Huang, Chiun-Sheng; Chang, Yeun-Chung; Tiu, Chui-Mei; Chen, Kuei-Wu; Chen, Chung-Ming

2010-06-01

To develop a computer-aided diagnostic algorithm with automatic boundary delineation for differential diagnosis of benign and malignant breast lesions at ultrasonography (US) and investigate the effect of boundary quality on the performance of a computer-aided diagnostic algorithm. This was an institutional review board-approved retrospective study with waiver of informed consent. A cell-based contour grouping (CBCG) segmentation algorithm was used to delineate the lesion boundaries automatically. Seven morphologic features were extracted. The classifier was a logistic regression function. Five hundred twenty breast US scans were obtained from 520 subjects (age range, 15-89 years), including 275 benign (mean size, 15 mm; range, 5-35 mm) and 245 malignant (mean size, 18 mm; range, 8-29 mm) lesions. The newly developed computer-aided diagnostic algorithm was evaluated on the basis of boundary quality and differentiation performance. The segmentation algorithms and features in two conventional computer-aided diagnostic algorithms were used for comparative study. The CBCG-generated boundaries were shown to be comparable with the manually delineated boundaries. The area under the receiver operating characteristic curve (AUC) and differentiation accuracy were 0.968 +/- 0.010 and 93.1% +/- 0.7, respectively, for all 520 breast lesions. At the 5% significance level, the newly developed algorithm was shown to be superior to the use of the boundaries and features of the two conventional computer-aided diagnostic algorithms in terms of AUC (0.974 +/- 0.007 versus 0.890 +/- 0.008 and 0.788 +/- 0.024, respectively). The newly developed computer-aided diagnostic algorithm that used a CBCG segmentation method to measure boundaries achieved a high differentiation performance. Copyright RSNA, 2010

Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis

PubMed Central

Starikova, Irina; Al-Haroni, Mohammed; Werner, Guido; Roberts, Adam P.; Sørum, Vidar; Nielsen, Kaare M.; Johnsen, Pål J.

2013-01-01

Objectives To determine the fitness effects of various mobile genetic elements (MGEs) in Enterococcus faecium and Enterococcus faecalis when newly acquired. We also tested the hypothesis that the biological cost of vancomycin resistance plasmids could be mitigated during continuous growth in the laboratory. Methods Different MGEs, including two conjugative transposons (CTns) of the Tn916 family (18 and 33 kb), a pathogenicity island (PAI) of 200 kb and vancomycin-resistance (vanA) plasmids (80–200 kb) of various origins and classes, were transferred into common ancestral E. faecium and E. faecalis strains by conjugation assays and experimentally evolved (vanA plasmids only). Transconjugants were characterized by PFGE, S1 nuclease assays and Southern blotting hybridization analyses. Single specific primer PCR was performed to determine the target sites for the insertion of the CTns. The fitness costs of various MGEs in E. faecium and E. faecalis were estimated in head-to-head competition experiments, and evolved populations were generated in serial transfer assays. Results The biological cost of a newly acquired PAI and two CTns were both host- and insertion-locus-dependent. Newly acquired vanA plasmids may severely reduce host fitness (25%–27%), but these costs were rapidly mitigated after only 400 generations of continuous growth in the absence of antibiotic selection. Conclusions Newly acquired MGEs may impose an immediate biological cost in E. faecium. However, as demonstrated for vanA plasmids, the initial costs of MGE carriage may be mitigated during growth and beneficial plasmid–host association can rapidly emerge. PMID:23833178

Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

PubMed Central

Azekawa, Takaharu; Ohashi, Shizuko; Itami, Akira

2011-01-01

Background Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting. Methods Using a retrospective cohort study design, we screened all outpatients (n = 7936) who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703) diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic. Results Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant. Conclusion Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder. PMID:22128254

Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder.

PubMed

Azekawa, Takaharu; Ohashi, Shizuko; Itami, Akira

2011-01-01

Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting. Using a retrospective cohort study design, we screened all outpatients (n = 7936) who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703) diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic. Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant. Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.

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

Adachi, T.; The Graduate University for Advanced Studies, Hayama, Miura, Kanagawa 240-0193; Arai, T.

A new type of pulse chopper called an Einzel lens chopper is described. An Einzel lens placed immediately after an electron cyclotron resonance ion source is driven by high-voltage pulses generated by a newly developed solid-state Marx generator. A rectangular negative barrier pulse-voltage is controlled in time, and the barrier pulse is turned on only when a beam pulse is required. The results of successful experiments are reported herein.

Comparison of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus.

PubMed

Fang, Fu-Sheng; Gong, Yan-Ping; Li, Chun-Lin; Li, Jian; Tian, Hui; Huang, Wei; Wang, Liang-Chen; Li, Lin

2014-06-01

We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). In this 15-week, open-labelled, parallel-controlled, randomised study, 60 Chinese drug-naive patients with newly diagnosed T2DM were randomised (2:1) to receive repaglinide or metformin monotherapy. Primary endpoint was change in HbA1c from baseline to the end of the trial. Secondary endpoints included changes in glycaemic variability, insulin sensitivity and β-cell function. Patients in both repaglinide and metformin groups achieved significant reductions in HbA1c (-1.8 ± 1.5 vs -1.6 ± 1.5%), FPG (fasting blood glucose) (-1.7 ± 1.7 vs -2.1 ± 1.7  mmol/l) and 2-h PPG (post-prandial glucose) (-3.8 ± 3.1 vs -3.8 ± 3.6  mmol/l), with no statistical differences between the groups. Glycaemic variability, glucose infusion rate and β-cell function were all significantly improved from baseline in the two groups (all P<0.05), without any statistical differences in the improvement between the groups. Repaglinide and metformin achieved comparable efficacy in improving glycaemic control, reducing glycaemic variability, enhancing insulin sensitivity and ameliorating β-cell function. Therefore, repaglinide is an optional agent for initial therapy in Chinese patients with newly diagnosed T2DM. © 2014 European Society of Endocrinology.

Maternal Forced Swimming Reduces Cell Proliferation in the Postnatal Dentate Gyrus of Mouse Offspring

PubMed Central

Wasinski, Frederick; Estrela, Gabriel R.; Arakaki, Aline M.; Bader, Michael; Alenina, Natalia; Klempin, Friederike; Araújo, Ronaldo C.

2016-01-01

Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring. PMID:27621701

Being a team leader: newly registered nurses relate their experiences.

PubMed

Ekström, Louise; Idvall, Ewa

2015-01-01

This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way. © 2013 John Wiley & Sons Ltd.

Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death

PubMed Central

Yan, Bing Chun; Park, Joon Ha; Chen, Bai Hui; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae-Chul; Hwang, In Koo; Cho, Jun Hwi; Lee, Yun Lyul; Kang, Il-Jun; Won, Moo-Ho

2014-01-01

Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death. PMID:25422633

deepTools: a flexible platform for exploring deep-sequencing data.

PubMed

Ramírez, Fidel; Dündar, Friederike; Diehl, Sarah; Grüning, Björn A; Manke, Thomas

2014-07-01

We present a Galaxy based web server for processing and visualizing deeply sequenced data. The web server's core functionality consists of a suite of newly developed tools, called deepTools, that enable users with little bioinformatic background to explore the results of their sequencing experiments in a standardized setting. Users can upload pre-processed files with continuous data in standard formats and generate heatmaps and summary plots in a straight-forward, yet highly customizable manner. In addition, we offer several tools for the analysis of files containing aligned reads and enable efficient and reproducible generation of normalized coverage files. As a modular and open-source platform, deepTools can easily be expanded and customized to future demands and developments. The deepTools webserver is freely available at http://deeptools.ie-freiburg.mpg.de and is accompanied by extensive documentation and tutorials aimed at conveying the principles of deep-sequencing data analysis. The web server can be used without registration. deepTools can be installed locally either stand-alone or as part of Galaxy. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

A Recurrent Germline Mutation in the 5'UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation.

PubMed

Hornig, Nadine C; de Beaufort, Carine; Denzer, Friederike; Cools, Martine; Wabitsch, Martin; Ukat, Martin; Kulle, Alexandra E; Schweikert, Hans-Udo; Werner, Ralf; Hiort, Olaf; Audi, Laura; Siebert, Reiner; Ammerpohl, Ole; Holterhus, Paul-Martin

2016-01-01

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5' untranslated region (5'-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5'UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5'UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general.

A Recurrent Germline Mutation in the 5’UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation

PubMed Central

Hornig, Nadine C.; de Beaufort, Carine; Denzer, Friederike; Cools, Martine; Wabitsch, Martin; Ukat, Martin; Kulle, Alexandra E.; Schweikert, Hans-Udo; Werner, Ralf; Hiort, Olaf; Audi, Laura; Siebert, Reiner; Ammerpohl, Ole; Holterhus, Paul-Martin

2016-01-01

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5’ untranslated region (5’-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5′UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5′UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general. PMID:27110943

Development and Assessment of Transgenic Rodent Parasites for the Preclinical Evaluation of Malaria Vaccines.

PubMed

Espinosa, Diego A; Radtke, Andrea J; Zavala, Fidel

2016-01-01

Rodent transgenic parasites are useful tools for the preclinical evaluation of malaria vaccines. Over the last decade, several studies have reported the development of transgenic rodent parasites expressing P. falciparum antigens for the assessment of vaccine-induced immune responses, which traditionally have been limited to in vitro assays. However, the genetic manipulation of rodent Plasmodium species can have detrimental effects on the parasite's infectivity and development. In this chapter, we present a few guidelines for designing transfection plasmids, which should improve transfection efficiency and facilitate the generation of functional transgenic parasite strains. In addition, we provide a transfection protocol for the development of transgenic P. berghei parasites as well as practical methods to assess the viability and infectivity of these newly generated strains throughout different stages of their life cycle. These techniques should allow researchers to develop novel rodent malaria parasites expressing antigens from human malaria species and to determine whether these transgenic strains are fully infectious and thus represent stringent platforms for the in vivo evaluation of malaria vaccine candidates.

Exploiting conformational dynamics in drug discovery: design of C-terminal inhibitors of Hsp90 with improved activities

PubMed Central

Moroni, Elisabetta; Zhao, Huiping; Blagg, Brian S.J.; Colombo, Giorgio

2014-01-01

The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between a protein and the ligand as a source for new opportunities in ligand design. Analysis of the formation/disappearance of protein pockets produced in response to a first-generation inhibitor assisted in the identification of functional groups that could be introduced onto scaffolds to facilitate optimal binding, which allowed for increased binding with previously uncharacterized regions. MD simulations were used to elucidate primary changes that occur in the Hsp90 C-terminal binding pocket in the presence of first-generation ligands. This data was then used to design ligands that adapt to these receptor conformations, which provides access to an energy landscape that is not visible in a static model. The newly synthesized compounds demonstrated anti-proliferative activity at ~150 nanomolar concentration. The method identified herein may be used to design chemical probes that provide additional information on structural variations of Hsp90 C-terminal binding site. PMID:24397468

4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage

NASA Astrophysics Data System (ADS)

Zhong, Guannan; Zhao, Qunfei; Zhang, Qinglin; Liu, Wen

2017-07-01

γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C-C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.

Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India.

PubMed

Bondre, Vijay P; Sankararaman, Vasudha; Andhare, Vijaysinh; Tupekar, Manisha; Sapkal, Gajanan N

2016-11-01

Human herpes simplex virus 1 (HSV-1) is the most common cause of sporadic encephalitis in humans that contributes to >10 per cent of the encephalitis cases occurring worldwide. Availability of limited full genome sequences from a small number of isolates resulted in poor understanding of host and viral factors responsible for variable clinical outcome. In this study genetic relationship, extent and source of recombination using full-length genome sequence derived from a newly isolated HSV-1 isolate was studied in comparison with those sampled from patients with varied clinical outcome. Full genome sequence of HSV-1 isolated from cerebrospinal fluid (CSF) of a patient with acute encephalitis syndrome (AES) by inoculation in baby hamster kidney-21 (BHK-21) cells was determined using next-generation sequencing (NGS) technology. Phylogenetic analysis of the newly generated sequence in comparison with 33 additional full-length genomes defined genetic relationship with worldwide distributed strains. The bootscan and similarity plot analysis defined recombination crossovers and similarities between newly isolated Indian HSV-1 with six Asian and a total of 34 worldwide isolated strains. Mapping of 376,332 reads amplified from HSV-1 DNA by NGS generated full-length genome of 151,024 bp from newly isolated Indian HSV-1. Phylogenetic analysis classified worldwide distributed strains into three major evolutionary lineages correlating to their geographic distribution. Lineage 1 containing strains were isolated from America and Europe; lineage 2 contained all the strains from Asian countries along with the North American KOS and RE strains whereas the South African isolates were distributed into two groups under lineage 3. Recombination analysis confirmed events of recombination in Indian HSV-1 genome resulting from mixing of different strains evolved in Asian countries. Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections.

Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India

PubMed Central

Bondre, Vijay P.; Sankararaman, Vasudha; Andhare, Vijaysinh; Tupekar, Manisha; Sapkal, Gajanan N.

2016-01-01

Background & objectives: Human herpes simplex virus 1 (HSV-1) is the most common cause of sporadic encephalitis in humans that contributes to >10 per cent of the encephalitis cases occurring worldwide. Availability of limited full genome sequences from a small number of isolates resulted in poor understanding of host and viral factors responsible for variable clinical outcome. In this study genetic relationship, extent and source of recombination using full-length genome sequence derived from a newly isolated HSV-1 isolate was studied in comparison with those sampled from patients with varied clinical outcome. Methods: Full genome sequence of HSV-1 isolated from cerebrospinal fluid (CSF) of a patient with acute encephalitis syndrome (AES) by inoculation in baby hamster kidney-21 (BHK-21) cells was determined using next-generation sequencing (NGS) technology. Phylogenetic analysis of the newly generated sequence in comparison with 33 additional full-length genomes defined genetic relationship with worldwide distributed strains. The bootscan and similarity plot analysis defined recombination crossovers and similarities between newly isolated Indian HSV-1 with six Asian and a total of 34 worldwide isolated strains. Results: Mapping of 376,332 reads amplified from HSV-1 DNA by NGS generated full-length genome of 151,024 bp from newly isolated Indian HSV-1. Phylogenetic analysis classified worldwide distributed strains into three major evolutionary lineages correlating to their geographic distribution. Lineage 1 containing strains were isolated from America and Europe; lineage 2 contained all the strains from Asian countries along with the North American KOS and RE strains whereas the South African isolates were distributed into two groups under lineage 3. Recombination analysis confirmed events of recombination in Indian HSV-1 genome resulting from mixing of different strains evolved in Asian countries. Interpretation & conclusions: Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections. PMID:28361829

Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays.

PubMed

Le Quellec, Sandra; Paris, Mickaël; Nougier, Christophe; Sobas, Frédéric; Rugeri, Lucia; Girard, Sandrine; Bordet, Jean-Claude; Négrier, Claude; Dargaud, Yesim

2017-05-01

Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS). Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling. The turnaround time was reduced by 31% (p<0.001) with the use of PTS. No statistically significant difference was observed for most routine haematology assays including PFT, and ROTEM® analysis. A statistically significant, but not clinically relevant, shortening of the APTT after sample transport by PTS was found (mean±SD: 30s±1.8 vs. 29.5s±2.1 for NPTS). D-dimer levels were 7.4% higher after transport through PTS but were not discordant. A statistically significant increase of thrombin generation was found in both platelet poor- and platelet rich- plasma samples after PTS transport compared to NPTS transport. PTS is suitable for the transport of samples prior to routine haematology assays including PFT, but should not be used for samples intended for thrombin generation measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors Influencing Generation Y African Americans in Their Choice for College Education: An Empirical Case Study of Fort Valley State University Students

ERIC Educational Resources Information Center

Gyapong, Samuel K.; Smith, Thomas

2012-01-01

In an effort to assist a newly appointed Public Relations Officer to determine the most effective way to promote the institution to college-bound Generation Y African-Americans we offered to conduct a survey research of our current students. The results were very revealing and have been used successfully to increase enrollment to historically high…

Stiffness-generated rigid-body mode shapes for Lanczos eigensolution with SUPORT DOF by way of a MSC/NASTRAN DMAP alter

NASA Technical Reports Server (NTRS)

Abdallah, Ayman A.; Barnett, Alan R.; Widrick, Timothy W.; Manella, Richard T.; Miller, Robert P.

1994-01-01

When using all MSC/NASTRAN eigensolution methods except Lanczos, the analyst can replace the coupled system rigid-body modes calculated within DMAP module READ with mass orthogonalized and normalized rigid-body modes generated from the system stiffness. This option is invoked by defining MSC/NASTRAN r-set degrees of freedom via the SUPORT bulk data card. The newly calculated modes are required if the rigid-body modes calculated by the eigensolver are not 'clean' due to numerical roundoffs in the solution. When performing transient structural dynamic load analysis, the numerical roundoffs can result in inaccurate rigid-body accelerations which affect steady-state responses. Unfortunately, when using the Lanczos method and defining r-set degrees of freedom, the rigid-body modes calculated within DMAP module REIGL are retained. To overcome this limitation and to allow MSC/NASTRAN to handle SUPORT degrees of freedom identically for all eigensolvers, a DMAP Alter has been written which replaces Lanczos-calculated rigid-body modes with stiffness-generated rigid-body modes. The newly generated rigid-body modes are normalized with respect to the system mass and orthogonalized using the Gram-Schmidt technique. This algorithm has been implemented as an enhancement to an existing coupled loads methodology.

REM sleep selectively prunes and maintains new synapses in development and learning

PubMed Central

Li, Wei; Ma, Lei; Yang, Guang; Gan, Wenbiao

2017-01-01

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly-formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation in development and when a new motor task is learned, indicating a role of REM sleep in pruning to balance the number of new spines formed over time. In addition, REM sleep also strengthens and maintains some newly-formed spines that are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening of new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning, and memory consolidation by selectively eliminating and maintaining newly-formed synapses via dendritic calcium spike-dependent mechanisms. PMID:28092659

A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue.

PubMed

Elsayed, Maha; Magistretti, Pierre J

2015-01-01

Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

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

Wang, Weizhou, E-mail: wzw@lynu.edu.cn, E-mail: ybw@gzu.edu.cn; Zhang, Yu; Sun, Tao

High-level coupled cluster singles, doubles, and perturbative triples [CCSD(T)] computations with up to the aug-cc-pVQZ basis set (1924 basis functions) and various extrapolations toward the complete basis set (CBS) limit are presented for the sandwich, T-shaped, and parallel-displaced benzene⋯naphthalene complex. Using the CCSD(T)/CBS interaction energies as a benchmark, the performance of some newly developed wave function and density functional theory methods has been evaluated. The best performing methods were found to be the dispersion-corrected PBE0 functional (PBE0-D3) and spin-component scaled zeroth-order symmetry-adapted perturbation theory (SCS-SAPT0). The success of SCS-SAPT0 is very encouraging because it provides one method for energy componentmore » analysis of π-stacked complexes with 200 atoms or more. Most newly developed methods do, however, overestimate the interaction energies. The results of energy component analysis show that interaction energies are overestimated mainly due to the overestimation of dispersion energy.« less

A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

PubMed Central

Elsayed, Maha; Magistretti, Pierre J.

2015-01-01

Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment. PMID:26733803

Short-term load and wind power forecasting using neural network-based prediction intervals.

PubMed

Quan, Hao; Srinivasan, Dipti; Khosravi, Abbas

2014-02-01

Electrical power systems are evolving from today's centralized bulk systems to more decentralized systems. Penetrations of renewable energies, such as wind and solar power, significantly increase the level of uncertainty in power systems. Accurate load forecasting becomes more complex, yet more important for management of power systems. Traditional methods for generating point forecasts of load demands cannot properly handle uncertainties in system operations. To quantify potential uncertainties associated with forecasts, this paper implements a neural network (NN)-based method for the construction of prediction intervals (PIs). A newly introduced method, called lower upper bound estimation (LUBE), is applied and extended to develop PIs using NN models. A new problem formulation is proposed, which translates the primary multiobjective problem into a constrained single-objective problem. Compared with the cost function, this new formulation is closer to the primary problem and has fewer parameters. Particle swarm optimization (PSO) integrated with the mutation operator is used to solve the problem. Electrical demands from Singapore and New South Wales (Australia), as well as wind power generation from Capital Wind Farm, are used to validate the PSO-based LUBE method. Comparative results show that the proposed method can construct higher quality PIs for load and wind power generation forecasts in a short time.

Thymus function in drug-induced lupus.

PubMed

Rubin, R L; Salomon, D R; Guerrero, R S

2001-01-01

Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.

Microscopically based energy density functionals for nuclei using the density matrix expansion: Implementation and pre-optimization

NASA Astrophysics Data System (ADS)

Stoitsov, M.; Kortelainen, M.; Bogner, S. K.; Duguet, T.; Furnstahl, R. J.; Gebremariam, B.; Schunck, N.

2010-11-01

In a recent series of articles, Gebremariam, Bogner, and Duguet derived a microscopically based nuclear energy density functional by applying the density matrix expansion (DME) to the Hartree-Fock energy obtained from chiral effective field theory two- and three-nucleon interactions. Owing to the structure of the chiral interactions, each coupling in the DME functional is given as the sum of a coupling constant arising from zero-range contact interactions and a coupling function of the density arising from the finite-range pion exchanges. Because the contact contributions have essentially the same structure as those entering empirical Skyrme functionals, a microscopically guided Skyrme phenomenology has been suggested in which the contact terms in the DME functional are released for optimization to finite-density observables to capture short-range correlation energy contributions from beyond Hartree-Fock. The present article is the first attempt to assess the ability of the newly suggested DME functional, which has a much richer set of density dependencies than traditional Skyrme functionals, to generate sensible and stable results for nuclear applications. The results of the first proof-of-principle calculations are given, and numerous practical issues related to the implementation of the new functional in existing Skyrme codes are discussed. Using a restricted singular value decomposition optimization procedure, it is found that the new DME functional gives numerically stable results and exhibits a small but systematic reduction of our test χ2 function compared to standard Skyrme functionals, thus justifying its suitability for future global optimizations and large-scale calculations.

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P  = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P  = .001), respectively (between subjects P  = .631). There was no significant difference between PRGF and HA groups in patients' satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.

Root tips moving through soil

PubMed Central

Curlango-Rivera, Gilberto

2011-01-01

Root elongation occurs by the generation of new cells from meristematic tissue within the apical 1–2 mm region of root tips. Therefore penetration of the soil environment is carried out by newly synthesized plant tissue, whose cells are inherently vulnerable to invasion by pathogens. This conundrum, on its face, would seem to reflect an intolerable risk to the successful establishment of root systems needed for plant life. Yet root tip regions housing the meristematic tissues repeatedly have been found to be free of microbial infection and colonization. Even when spore germination, chemotaxis, and/or growth of pathogens are stimulated by signals from the root tip, the underlying root tissue can escape invasion. Recent insights into the functions of root border cells, and the regulation of their production by transient exposure to external signals, may shed light on long-standing observations. PMID:21455030

A dynamic model of soil salinity and drainage generation in irrigated agriculture: A framework for policy analysis

NASA Astrophysics Data System (ADS)

Dinar, Ariel; Aillery, Marcel P.; Moore, Michael R.

1993-06-01

This paper presents a dynamic model of irrigated agriculture that accounts for drainage generation and salinity accumulation. Critical model relationships involving crop production, soil salinity, and irrigation drainage are based on newly estimated functions derived from lysimeter field tests. The model allocates land and water inputs over time based on an intertemporal profit maximization objective function and soil salinity accumulation process. The model is applied to conditions in the San Joaquin Valley of California, where environmental degradation from irrigation drainage has become a policy issue. Findings indicate that in the absence of regulation, drainage volumes increase over time before reaching a steady state as increased quantities of water are allocated to leaching soil salts. The model is used to evaluate alternative drainage abatement scenarios involving drainage quotas and taxes, water supply quotas and taxes, and irrigation technology subsidies. In our example, direct drainage policies are more cost-effective in reducing drainage than policies operating indirectly through surface water use, although differences in cost efficiency are relatively small. In some cases, efforts to control drainage may result in increased soil salinity accumulation, with implications for long-term cropland productivity. While policy adjustments may alter the direction and duration of convergence to a steady state, findings suggest that a dynamic model specification may not be necessary due to rapid convergence to a comon steady state under selected scenarios.

Toward an understanding of agonist binding to human Orexin-1 and Orexin-2 receptors with G-protein-coupled receptor modeling and site-directed mutagenesis.

PubMed

Heifetz, Alexander; Barker, Oliver; Morris, G Benjamin; Law, Richard J; Slack, Mark; Biggin, Philip C

2013-11-19

The class A G-protein-coupled receptors (GPCRs) Orexin-1 (OX1) and Orexin-2 (OX2) are located predominantly in the brain and are linked to a range of different physiological functions, including the control of feeding, energy metabolism, modulation of neuro-endocrine function, and regulation of the sleep-wake cycle. The natural agonists for OX1 and OX2 are two neuropeptides, Orexin-A and Orexin-B, which have activity at both receptors. Site-directed mutagenesis (SDM) has been reported on both the receptors and the peptides and has provided important insight into key features responsible for agonist activity. However, the structural interpretation of how these data are linked together is still lacking. In this work, we produced and used SDM data, homology modeling followed by MD simulation, and ensemble-flexible docking to generate binding poses of the Orexin peptides in the OX receptors to rationalize the SDM data. We also developed a protein pairwise similarity comparing method (ProS) and a GPCR-likeness assessment score (GLAS) to explore the structural data generated within a molecular dynamics simulation and to help distinguish between different GPCR substates. The results demonstrate how these newly developed methods of structural assessment for GPCRs can be used to provide a working model of neuropeptide-Orexin receptor interaction.

GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis.

PubMed

Zheng, Qi; Wang, Xiu-Jie

2008-07-01

Gene Ontology (GO) analysis has become a commonly used approach for functional studies of large-scale genomic or transcriptomic data. Although there have been a lot of software with GO-related analysis functions, new tools are still needed to meet the requirements for data generated by newly developed technologies or for advanced analysis purpose. Here, we present a Gene Ontology Enrichment Analysis Software Toolkit (GOEAST), an easy-to-use web-based toolkit that identifies statistically overrepresented GO terms within given gene sets. Compared with available GO analysis tools, GOEAST has the following improved features: (i) GOEAST displays enriched GO terms in graphical format according to their relationships in the hierarchical tree of each GO category (biological process, molecular function and cellular component), therefore, provides better understanding of the correlations among enriched GO terms; (ii) GOEAST supports analysis for data from various sources (probe or probe set IDs of Affymetrix, Illumina, Agilent or customized microarrays, as well as different gene identifiers) and multiple species (about 60 prokaryote and eukaryote species); (iii) One unique feature of GOEAST is to allow cross comparison of the GO enrichment status of multiple experiments to identify functional correlations among them. GOEAST also provides rigorous statistical tests to enhance the reliability of analysis results. GOEAST is freely accessible at http://omicslab.genetics.ac.cn/GOEAST/

Earthworm populations and functional traits in a land-use gradient of annual, perennial and permanent grassland systems in a heterogenic agricultural landscape

NASA Astrophysics Data System (ADS)

Emmerling, Christoph; Ruf, Thorsten

2017-04-01

Soil use is the key driving factor for the composition of the detritus food webs, for SOM quantity and quality, and related soil properties. Many studies have identified land-use change as a major driver affecting soil biodiversity, which severely influences soil functioning and the ecosystem services they deliver. The overall intention of the study was to gain insights in future trends of soil ecology in a changing land-use towards bioenergy production. Therefor we investigated earthworm responses to different land-use intensities, such as rotational cropping with maize (1G), cultivation of perennial crops (2G), like Szarvasi, Silphie, Igniscum and Miscanthus, and permanent grasslands at landscape scale in Western Germany. We analyzed species composition, individual numbers and biomass, and earthworm functional traits. We can conclude that on average the investigated earthworm parameters of the newly introduced second generation bioenergy crops took a medium position between annual maize and permanent grassland sites. In addition, the experiments clearly emphasized that some results were in a clear trend, but others were site-depended and to some extend indifferent. We will critically discuss the ecological significance of perennial land-use systems from a soil biodiversity and soil functioning point of view.

Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia

PubMed Central

Panopoulos, Athanasia D.; Stirzaker, Roslynn A.; Hacking, Douglas F.; Tahtamouni, Lubna H.; Willson, Tracy A.; Mielke, Lisa A.; Henley, Katya J.; Zhang, Jian-Guo; Wicks, Ian P.; Stevenson, William S.; Nurden, Paquita; Watowich, Stephanie S.; Justice, Monica J.

2007-01-01

A pivotal mediator of actin dynamics is the protein cofilin, which promotes filament severing and depolymerization, facilitating the breakdown of existing filaments, and the enhancement of filament growth from newly created barbed ends. It does so in concert with actin interacting protein 1 (Aip1), which serves to accelerate cofilin's activity. While progress has been made in understanding its biochemical functions, the physiologic processes the cofilin/Aip1 complex regulates, particularly in higher organisms, are yet to be determined. We have generated an allelic series for WD40 repeat protein 1 (Wdr1), the mammalian homolog of Aip1, and report that reductions in Wdr1 function produce a dramatic phenotype gradient. While severe loss of function at the Wdr1 locus causes embryonic lethality, macrothrombocytopenia and autoinflammatory disease develop in mice carrying hypomorphic alleles. Macrothrombocytopenia is the result of megakaryocyte maturation defects, which lead to a failure of normal platelet shedding. Autoinflammatory disease, which is bone marrow–derived yet nonlymphoid in origin, is characterized by a massive infiltration of neutrophils into inflammatory lesions. Cytoskeletal responses are impaired in Wdr1 mutant neutrophils. These studies establish an essential requirement for Wdr1 in megakaryocytes and neutrophils, indicating that cofilin-mediated actin dynamics are critically important to the development and function of both cell types. PMID:17515402

INDIGO – INtegrated Data Warehouse of MIcrobial GenOmes with Examples from the Red Sea Extremophiles

PubMed Central

Alam, Intikhab; Antunes, André; Kamau, Allan Anthony; Ba alawi, Wail; Kalkatawi, Manal; Stingl, Ulrich; Bajic, Vladimir B.

2013-01-01

Background The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. Results We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. Conclusions We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo. PMID:24324765

INDIGO - INtegrated data warehouse of microbial genomes with examples from the red sea extremophiles.

PubMed

Alam, Intikhab; Antunes, André; Kamau, Allan Anthony; Ba Alawi, Wail; Kalkatawi, Manal; Stingl, Ulrich; Bajic, Vladimir B

2013-01-01

The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.

Global and Regional Brain Non-Gaussian Diffusion Changes in Newly Diagnosed Patients with Obstructive Sleep Apnea.

PubMed

Tummala, Sudhakar; Palomares, Jose; Kang, Daniel W; Park, Bumhee; Woo, Mary A; Harper, Ronald M; Kumar, Rajesh

2016-01-01

Obstructive sleep apnea (OSA) patients show brain structural injury and functional deficits in autonomic, affective, and cognitive regulatory sites, as revealed by mean diffusivity (MD) and other imaging procedures. The time course and nature of gray and white matter injury can be revealed in more detail with mean kurtosis (MK) procedures, which can differentiate acute from chronic injury, and better show extent of damage over MD procedures. Our objective was to examine global and regional MK changes in newly diagnosed OSA, relative to control subjects. Two diffusion kurtosis image series were collected from 22 recently-diagnosed, treatment-naïve OSA and 26 control subjects using a 3.0-Tesla MRI scanner. MK maps were generated, normalized to a common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance (covariates; age, sex). No age or sex differences appeared, but body mass index, sleep, neuropsychologic, and cognitive scores significantly differed between groups. MK values were significantly increased globally in OSA over controls, and in multiple localized sites, including the basal forebrain, extending to the hypothalamus, hippocampus, thalamus, insular cortices, basal ganglia, limbic regions, cerebellar areas, parietal cortices, ventral temporal lobe, ventrolateral medulla, and midline pons. Multiple sites, including the insular cortices, ventrolateral medulla, and midline pons showed more injury over previously identified damage with MD procedures, with damage often lateralized. Global mean kurtosis values are significantly increased in obstructive sleep apnea (OSA), suggesting acute tissue injury, and these changes are principally localized in critical sites mediating deficient functions in the condition. The mechanisms for injury likely include altered perfusion and hypoxemia-induced processes, leading to acute tissue changes in recently diagnosed OSA. © 2016 Associated Professional Sleep Societies, LLC.

Factors and trade-offs with rehabilitation effectiveness and efficiency in newly disabled older persons.

PubMed

Chow, Patsy; Chen, Cynthia; Cheong, Angela; Fong, Ngan Phoon; Chan, Kin Ming; Tan, Boon Yeow; Menon, Edward; Ee, Chye Hua; Lee, Kok Keng; Koh, David; Koh, Gerald C

2014-08-01

To determine the factors for rehabilitation effectiveness (REs) and rehabilitation efficiency (REy) among newly disabled older persons and if there is any trade-off between REs and REy. Retrospective cohort study. Rehabilitation hospitals. Patients (N=8828) aged ≥65 years admitted for inpatient rehabilitation from 1996 to 2005. Not applicable. Independent factors affecting REs and REy were determined. The median rank ratios of REs to REy for each admission Barthel Index (BI) unit and number of days of stay were generated. The ideal ranges of admission BI score and length of stay (LOS) that corresponded to the REs to REy median rank ratio of 1 (both REs and REy optimized) were identified. Factors associated with poorer REs and REy were older age, Malay ethnicity, delayed admission, admission diagnosis of amputation, and comorbidities of dementia and stroke. An increase of 10 in admission BI score was associated with an increase of 3.47% in REs but a decrease of 1.1 per 30 days in REy; and an increase in LOS of 2.7 days was associated with an increase of 28% in REs but a decrease of 5.2 per 30 days in REy. A trade-off relation between REs and REy with respect to admission functional status and LOS was observed. The range, which optimized both REs and REy, was 50 to 59 units for admission BI score and 37 to 46 days for LOS. There are trade-offs between REs and REy with respect to admission functional status and LOS. Clinicians, policymakers, patients, and other stakeholders should be aware of such trade-offs when they make joint policy decisions about rehabilitation services. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Mental and physical health-related functioning mediates between psychological job demands and sickness absence among nurses.

PubMed

Roelen, Corné; van Rhenen, Willem; Schaufeli, Wilmar; van der Klink, Jac; Magerøy, Nils; Moen, Bente; Bjorvatn, Bjørn; Pallesen, Ståle

2014-08-01

To investigate whether health-related functioning mediates the effect of psychological job demands on sickness absence in nurses. Nurses face high job demands that can have adverse health effects resulting in sickness absence. Prospective cohort study with 1-year follow-up. Data for 2964 Norwegian nurses were collected in the period 2008-2010. At baseline, psychological job demands were measured with the Demand-Control-Support Questionnaire. Health-related functioning was assessed by the Mental Composite Score and the Physical Composite Score of the SF-12 Health Survey (2nd version). Sickness absence (no = 0, yes = 1) was self-reported at 1-year follow-up. Interaction and mediation analyses were conducted stratified by tenure (<1-year, 1-2 years, 3-6 years, >6 years) as a registered nurse. A total of 2180 nurses (74%) with complete data were eligible for analysis. A significant three-way interaction between job demands, control and support was found in newly licensed nurses (tenure <1-year). Baseline psychological job demands were positively associated with sickness absence at 1-year follow-up. This association was substantially weakened when Mental Composite Score and Physical Composite Score were introduced as mediator variables, indicating a partial mediation effect that was particularly pronounced in newly licensed nurses. Psychological job demands did not modify the effect of health-related functioning on sickness absence. Both mental and physical health-related functioning mediated between psychological job demands and sickness absence. Nurse managers should pay attention to health-related functioning, because poor health-related functioning may predict sickness absence, especially in newly licensed nurses. © 2013 John Wiley & Sons Ltd.

A New Generation of Leaching Tests – The Leaching Environmental Assessment Framework

EPA Science Inventory

Provides an overview of newly released leaching tests that provide a more accurate source term when estimating environmental release of metals and other constituents of potential concern (COPCs). The Leaching Environmental Assessment Framework (LEAF) methods have been (1) develo...

Successful In Vitro Expansion and Differentiation of Cord Blood Derived CD34+ Cells into Early Endothelial Progenitor Cells Reveals Highly Differential Gene Expression

PubMed Central

Topcic, Denijal; Haviv, Izhak; Merivirta, Ruusu-Maaria; Agrotis, Alexander; Leitner, Ephraem; Jowett, Jeremy B.; Bode, Christoph; Lappas, Martha; Peter, Karlheinz

2011-01-01

Endothelial progenitor cells (EPCs) can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU) assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP), PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15) or pro-angiogenic (galectin-3) properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP) was the most up-regulated gene. PMID:21858032

Competitive Genomic Screens of Barcoded Yeast Libraries

PubMed Central

Urbanus, Malene; Proctor, Michael; Heisler, Lawrence E.; Giaever, Guri; Nislow, Corey

2011-01-01

By virtue of advances in next generation sequencing technologies, we have access to new genome sequences almost daily. The tempo of these advances is accelerating, promising greater depth and breadth. In light of these extraordinary advances, the need for fast, parallel methods to define gene function becomes ever more important. Collections of genome-wide deletion mutants in yeasts and E. coli have served as workhorses for functional characterization of gene function, but this approach is not scalable, current gene-deletion approaches require each of the thousands of genes that comprise a genome to be deleted and verified. Only after this work is complete can we pursue high-throughput phenotyping. Over the past decade, our laboratory has refined a portfolio of competitive, miniaturized, high-throughput genome-wide assays that can be performed in parallel. This parallelization is possible because of the inclusion of DNA 'tags', or 'barcodes,' into each mutant, with the barcode serving as a proxy for the mutation and one can measure the barcode abundance to assess mutant fitness. In this study, we seek to fill the gap between DNA sequence and barcoded mutant collections. To accomplish this we introduce a combined transposon disruption-barcoding approach that opens up parallel barcode assays to newly sequenced, but poorly characterized microbes. To illustrate this approach we present a new Candida albicans barcoded disruption collection and describe how both microarray-based and next generation sequencing-based platforms can be used to collect 10,000 - 1,000,000 gene-gene and drug-gene interactions in a single experiment. PMID:21860376

Slow Joining of Newly Replicated DNA Chains in DNA Polymerase I-Deficient Escherichia coli Mutants*

PubMed Central

Okazaki, Reiji; Arisawa, Mikio; Sugino, Akio

1971-01-01

In Escherichia coli mutants deficient in DNA polymerase I, newly replicated short DNA is joined at about 10% of the rate in the wild-type strains. It is postulated that DNA polymerase I normally functions in filling gaps between the nascent short segments synthesized by the replication complex. Possible implications of the finding are discussed in relation to other abnormal properties of these mutants. PMID:4943548

Atmospheric radiation modeling of galactic cosmic rays using LRO/CRaTER and the EMMREM model with comparisons to balloon and airline based measurements

NASA Astrophysics Data System (ADS)

Joyce, C. J.; Schwadron, N. A.; Townsend, L. W.; deWet, W. C.; Wilson, J. K.; Spence, H. E.; Tobiska, W. K.; Shelton-Mur, K.; Yarborough, A.; Harvey, J.; Herbst, A.; Koske-Phillips, A.; Molina, F.; Omondi, S.; Reid, C.; Reid, D.; Shultz, J.; Stephenson, B.; McDevitt, M.; Phillips, T.

2016-09-01

We provide an analysis of the galactic cosmic ray radiation environment of Earth's atmosphere using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) together with the Badhwar-O'Neil model and dose lookup tables generated by the Earth-Moon-Mars Radiation Environment Module (EMMREM). This study demonstrates an updated atmospheric radiation model that uses new dose tables to improve the accuracy of the modeled dose rates. Additionally, a method for computing geomagnetic cutoffs is incorporated into the model in order to account for location-dependent effects of the magnetosphere. Newly available measurements of atmospheric dose rates from instruments aboard commercial aircraft and high-altitude balloons enable us to evaluate the accuracy of the model in computing atmospheric dose rates. When compared to the available observations, the model seems to be reasonably accurate in modeling atmospheric radiation levels, overestimating airline dose rates by an average of 20%, which falls within the uncertainty limit recommended by the International Commission on Radiation Units and Measurements (ICRU). Additionally, measurements made aboard high-altitude balloons during simultaneous launches from New Hampshire and California provide an additional comparison to the model. We also find that the newly incorporated geomagnetic cutoff method enables the model to represent radiation variability as a function of location with sufficient accuracy.

Technobabble: Photoshop 6 Converges Web, Print Photograph-Editing Capabilities.

ERIC Educational Resources Information Center

Communication: Journalism Education Today, 2001

2001-01-01

Discusses the newly-released Adobe Photoshop 6, and its use in student publications. Notes its refined text-handling capabilities, a more user-friendly interface, integrated vector functions, easier preparation of Web images, and new and more powerful layer functions. (SR)

Predictive model for CO2 generation and decay in building envelopes

NASA Astrophysics Data System (ADS)

Aglan, Heshmat A.

2003-01-01

Understanding carbon dioxide generation and decay patterns in buildings with high occupancy levels is useful to identify their indoor air quality, air change rates, percent fresh air makeup, occupancy pattern, and how a variable air volume system to off-set undesirable CO2 level can be modulated. A mathematical model governing the generation and decay of CO2 in building envelopes with forced ventilation due to high occupancy is developed. The model has been verified experimentally in a newly constructed energy efficient healthy house. It was shown that the model accurately predicts the CO2 concentration at any time during the generation and decay processes.

Evidence for a distributed respiratory rhythm generating network in the goldfish (Carsssius auratus).

PubMed

Duchcherer, Maryana; Kottick, Andrew; Wilson, R J A

2010-01-01

Central pattern generators located in the brainstem regulate ventilatory behaviors in vertebrates. The development of the isolated brainstem preparation has allowed these neural networks to be characterized in a number of aquatic species. The aim of this study was to explore the architecture of the respiratory rhythm-generating site in the goldfish (Carassius auratus) and to determine the utility of a newly developed isolated brainstem preparation, the Sheep Dip. Here we provide evidence for a distributed organization of respiratory rhythm generating neurons along the rostrocaudal axis of the goldfish brainstem and outline the advantages of the Sheep Dip as a tool used to survey neural networks.

Genome-wide analysis of short interspersed nuclear elements SINES revealed high sequence conservation, gene association and retrotranspositional activity in wheat

PubMed Central

Ben-David, Smadar; Yaakov, Beery; Kashkush, Khalil

2013-01-01

Short interspersed nuclear elements (SINEs) are non-autonomous non-LTR retroelements that are present in most eukaryotic species. While SINEs have been intensively investigated in humans and other animal systems, they are poorly studied in plants, especially in wheat (Triticum aestivum). We used quantitative PCR of various wheat species to determine the copy number of a wheat SINE family, termed Au SINE, combined with computer-assisted analyses of the publicly available 454 pyrosequencing database of T. aestivum. In addition, we utilized site-specific PCR on 57 Au SINE insertions, transposon methylation display and transposon display on newly formed wheat polyploids to assess retrotranspositional activity, epigenetic status and genetic rearrangements in Au SINE, respectively. We retrieved 3706 different insertions of Au SINE from the 454 pyrosequencing database of T. aestivum, and found that most of the elements are inserted in A/T-rich regions, while approximately 38% of the insertions are associated with transcribed regions, including known wheat genes. We observed typical retrotransposition of Au SINE in the second generation of a newly formed wheat allohexaploid, and massive hypermethylation in CCGG sites surrounding Au SINE in the third generation. Finally, we observed huge differences in the copy numbers in diploid Triticum and Aegilops species, and a significant increase in the copy numbers in natural wheat polyploids, but no significant increase in the copy number of Au SINE in the first four generations for two of three newly formed allopolyploid species used in this study. Our data indicate that SINEs may play a prominent role in the genomic evolution of wheat through stress-induced activation. PMID:23855320

Genome-wide analysis of short interspersed nuclear elements SINES revealed high sequence conservation, gene association and retrotranspositional activity in wheat.

PubMed

Ben-David, Smadar; Yaakov, Beery; Kashkush, Khalil

2013-10-01

Short interspersed nuclear elements (SINEs) are non-autonomous non-LTR retroelements that are present in most eukaryotic species. While SINEs have been intensively investigated in humans and other animal systems, they are poorly studied in plants, especially in wheat (Triticum aestivum). We used quantitative PCR of various wheat species to determine the copy number of a wheat SINE family, termed Au SINE, combined with computer-assisted analyses of the publicly available 454 pyrosequencing database of T. aestivum. In addition, we utilized site-specific PCR on 57 Au SINE insertions, transposon methylation display and transposon display on newly formed wheat polyploids to assess retrotranspositional activity, epigenetic status and genetic rearrangements in Au SINE, respectively. We retrieved 3706 different insertions of Au SINE from the 454 pyrosequencing database of T. aestivum, and found that most of the elements are inserted in A/T-rich regions, while approximately 38% of the insertions are associated with transcribed regions, including known wheat genes. We observed typical retrotransposition of Au SINE in the second generation of a newly formed wheat allohexaploid, and massive hypermethylation in CCGG sites surrounding Au SINE in the third generation. Finally, we observed huge differences in the copy numbers in diploid Triticum and Aegilops species, and a significant increase in the copy numbers in natural wheat polyploids, but no significant increase in the copy number of Au SINE in the first four generations for two of three newly formed allopolyploid species used in this study. Our data indicate that SINEs may play a prominent role in the genomic evolution of wheat through stress-induced activation. © 2013 Ben-Gurion University The Plant Journal © 2013 John Wiley & Sons Ltd.

Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling.

PubMed

Altmann, Christine; Vasic, Verica; Hardt, Stefanie; Heidler, Juliana; Häussler, Annett; Wittig, Ilka; Schmidt, Mirko H H; Tegeder, Irmgard

2016-10-22

Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues. Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve. Oppositely, progranulin deficient mice have long-lasting deficits in motor function tests after nerve injury due to enhanced losses of motor neurons and stronger microglia activation in the ventral horn of the spinal cord. Deep proteome and gene ontology (GO) enrichment analysis revealed that the proteins upregulated in progranulin overexpressing mice were involved in 'regulation of transcription' and 'response to insulin' (GO terms). Transcription factor prediction pointed to activation of Notch signaling and indeed, co-immunoprecipitation studies revealed that progranulin bound to the extracellular domain of Notch receptors, and this was functionally associated with higher expression of Notch target genes in the dorsal root ganglia of transgenic mice with neuronal progranulin overexpression. Functionally, these transgenic mice recovered normal gait and running, which was not achieved by controls and was stronger impaired in progranulin deficient mice. We infer that progranulin activates Notch signaling pathways, enhancing thereby the regenerative capacity of partially injured neurons, which leads to improved motor function recovery.

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

PubMed Central

Abrous, Djoher Nora; Wojtowicz, Jan Martin

2015-01-01

During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes. PMID:26032718

Accuracy of available methods for quantifying the heat power generation of nanoparticles for magnetic hyperthermia.

PubMed

Andreu, Irene; Natividad, Eva

2013-12-01

In magnetic hyperthermia, characterising the specific functionality of magnetic nanoparticle arrangements is essential to plan the therapies by simulating maximum achievable temperatures. This functionality, i.e. the heat power released upon application of an alternating magnetic field, is quantified by means of the specific absorption rate (SAR), also referred to as specific loss power (SLP). Many research groups are currently involved in the SAR/SLP determination of newly synthesised materials by several methods, either magnetic or calorimetric, some of which are affected by important and unquantifiable uncertainties that may turn measurements into rough estimates. This paper reviews all these methods, discussing in particular sources of uncertainties, as well as their possible minimisation. In general, magnetic methods, although accurate, do not operate in the conditions of magnetic hyperthermia. Calorimetric methods do, but the easiest to implement, the initial-slope method in isoperibol conditions, derives inaccuracies coming from the lack of matching between thermal models, experimental set-ups and measuring conditions, while the most accurate, the pulse-heating method in adiabatic conditions, requires more complex set-ups.

A new memetic algorithm for mitigating tandem automated guided vehicle system partitioning problem

NASA Astrophysics Data System (ADS)

Pourrahimian, Parinaz

2017-11-01

Automated Guided Vehicle System (AGVS) provides the flexibility and automation demanded by Flexible Manufacturing System (FMS). However, with the growing concern on responsible management of resource use, it is crucial to manage these vehicles in an efficient way in order reduces travel time and controls conflicts and congestions. This paper presents the development process of a new Memetic Algorithm (MA) for optimizing partitioning problem of tandem AGVS. MAs employ a Genetic Algorithm (GA), as a global search, and apply a local search to bring the solutions to a local optimum point. A new Tabu Search (TS) has been developed and combined with a GA to refine the newly generated individuals by GA. The aim of the proposed algorithm is to minimize the maximum workload of the system. After all, the performance of the proposed algorithm is evaluated using Matlab. This study also compared the objective function of the proposed MA with GA. The results showed that the TS, as a local search, significantly improves the objective function of the GA for different system sizes with large and small numbers of zone by 1.26 in average.

Polymorphic SSR Markers for Plasmopara obducens (Peronosporaceae), the Newly Emergent Downy Mildew Pathogen of Impatiens (Balsaminaceae)

DOE PAGES

Salgado-Salazar, Catalina; Rivera, Yazmín; Veltri, Daniel; ...

2015-11-10

Premise of the study: Simple sequence repeat (SSR) markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 202-Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identify 13,483 SSR motifs. Primers were synthesized for 62 marker candidates, of which 37 generated reliable PCR products. Testing of the 37 markers using 96 P. obducens samples showed 96% of the markers were polymorphic, with 2-6 alleles observed. Observed and expected heterozygosity ranged from 0.000-0.892 and 0.023-0.746, respectively. Just 17 markers were sufficientmore » to identify all multilocus genotypes. Conclusions: These are the first SSR markers available for this pathogen, and one of the first molecular resources. These markers will be useful in assessing variation in pathogen populations and determining the factors contributing to the emergence of destructive impatiens downy mildew disease.« less

A collaborative filtering approach for protein-protein docking scoring functions.

PubMed

Bourquard, Thomas; Bernauer, Julie; Azé, Jérôme; Poupon, Anne

2011-04-22

A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions. In this work, we introduce a new procedure for conformation ranking. We previously developed a set of scoring functions where learning was performed using a genetic algorithm. These functions were used to assign a rank to each possible conformation. We now have a refined rank using different classifiers (decision trees, rules and support vector machines) in a collaborative filtering scheme. The scoring function newly obtained is evaluated using 10 fold cross-validation, and compared to the functions obtained using either genetic algorithms or collaborative filtering taken separately. This new approach was successfully applied to the CAPRI scoring ensembles. We show that for 10 targets out of 12, we are able to find a near-native conformation in the 10 best ranked solutions. Moreover, for 6 of them, the near-native conformation selected is of high accuracy. Finally, we show that this function dramatically enriches the 100 best-ranking conformations in near-native structures.

A Collaborative Filtering Approach for Protein-Protein Docking Scoring Functions

PubMed Central

Bourquard, Thomas; Bernauer, Julie; Azé, Jérôme; Poupon, Anne

2011-01-01

A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions. In this work, we introduce a new procedure for conformation ranking. We previously developed a set of scoring functions where learning was performed using a genetic algorithm. These functions were used to assign a rank to each possible conformation. We now have a refined rank using different classifiers (decision trees, rules and support vector machines) in a collaborative filtering scheme. The scoring function newly obtained is evaluated using 10 fold cross-validation, and compared to the functions obtained using either genetic algorithms or collaborative filtering taken separately. This new approach was successfully applied to the CAPRI scoring ensembles. We show that for 10 targets out of 12, we are able to find a near-native conformation in the 10 best ranked solutions. Moreover, for 6 of them, the near-native conformation selected is of high accuracy. Finally, we show that this function dramatically enriches the 100 best-ranking conformations in near-native structures. PMID:21526112

FAST TRACK COMMUNICATION High rate straining of tantalum and copper

NASA Astrophysics Data System (ADS)

Armstrong, R. W.; Zerilli, F. J.

2010-12-01

High strain rate measurements reported recently for several tantalum and copper crystal/polycrystal materials are shown to follow dislocation mechanics-based constitutive relations, first at lower strain rates, for dislocation velocity control of the imposed plastic deformations and, then at higher rates, transitioning to nano-scale dislocation generation control by twinning or slip. For copper, there is the possibility of added-on slip dislocation displacements to be accounted for from the newly generated dislocations.

The effects of short-term continuous subcutaneous insulin infusion treatment on fasting glucagon-like peptide-1 concentrations in newly diagnosed type 2 diabetes.

PubMed

Huang, Xiaofei; Li, Sha; Yang, Mei; Fu, Xuquan; Li, Huaqi; Yan, Tong; Liu, Yidong; Chen, Lihong; Lan, Lingsheng; Li, Libo; Zhong, Xiaowei

2018-04-01

Early short-term intensive insulin therapy in newly diagnosed type 2 diabetes patients shows benefit in glycemic control and β-cell function. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose metabolism and development of type 2 diabetes. We did a study to observe the changes of GLP-1 and β-cell function after short-term continuous subcutaneous insulin infusion (CSII) treatment. A total of 66 subjects were enrolled, including 30 normal glucose tolerance controls (NGT) and 36 patients with newly diagnosed type 2 diabetes between October 2015 and July 2016. Fasting plasma glucose (FPG), insulin, and GLP-1 were measured in each subject. The patients underwent CSII treatment for 2 weeks, and then FBG, insulin, and GLP-1 were measured. HOMA-IR and HOMA-B were then calculated. All patients achieved target glycemic control in two weeks. HOMA-IR and HOMA-B improved significantly after intensive interventions (p < 0.05). The GLP-1 concentration increased significantly in patients after treatment (p < 0.05). When grouped according to bodyweight and age in all patients, the HOMA-IR changed significantly in overweight and old age subgroups, the HOMA-B increased significantly in normal weight, overweight and middle age subgroups, and the GLP-1 concentration also increased significantly in overweight and middle age subgroups respectively (p < 0.05). Short-term CSII treatment can obtain glycemic control target and recover β-cell function and GLP-1 secretion in newly diagnosed type 2 diabetes patients. The overweight and middle-aged patients may get more benefit from this treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Time- and polarity-dependent proteomic changes associated with homeostatic scaling at central synapses

PubMed Central

Schanzenbächer, Christoph T

2018-01-01

In homeostatic scaling at central synapses, the depth and breadth of cellular mechanisms that detect the offset from the set-point, detect the duration of the offset and implement a cellular response are not well understood. To understand the time-dependent scaling dynamics we treated cultured rat hippocampal cells with either TTX or bicucculline for 2 hr to induce the process of up- or down-scaling, respectively. During the activity manipulation we metabolically labeled newly synthesized proteins using BONCAT. We identified 168 newly synthesized proteins that exhibited significant changes in expression. To obtain a temporal trajectory of the response, we compared the proteins synthesized within 2 hr or 24 hr of the activity manipulation. Surprisingly, there was little overlap in the significantly regulated newly synthesized proteins identified in the early- and integrated late response datasets. There was, however, overlap in the functional categories that are modulated early and late. These data indicate that within protein function groups, different proteomic choices can be made to effect early and late homeostatic responses that detect the duration and polarity of the activity manipulation. PMID:29447110

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication.

PubMed

Koo, Seong Joo; Fernández-Montalván, Amaury E; Badock, Volker; Ott, Christopher J; Holton, Simon J; von Ahsen, Oliver; Toedling, Joern; Vittori, Sarah; Bradner, James E; Gorjánácz, Mátyás

2016-10-25

ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.

Five isomers of C 60 generated in microwave plasma of chloroform

NASA Astrophysics Data System (ADS)

Xie, Su-Yuan; Deng, Shun-Liu; Huang, Rong-Bin; Yu, La-Jia; Zheng, Lan-Sun

2001-08-01

In addition to Ih symmetry buckminsterfullerene, four other isomers of C 60 were generated in a microwave plasma of chloroform. The newly observed isomers, separated and identified by a high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), were found to be stable at room temperature but transform to buckminsterfullerene when heated. With regards to the generation of various fully chlorinated carbon clusters as well as the C 60 isomers, which may be attributed to the rapidly cooling of the synthetic reaction, a modified Pentagon Road scheme is suggested for fullerene formation.

Positive Approaches to Business Management: Conference Proceedings.

ERIC Educational Resources Information Center

LaVire, Willis A., Ed.

In August 1970, an institute for newly appointed junior college business managers was planned around the business management function. This function would include purchasing, physical plant, personnel, auxiliary services, and financial records. The following seven speeches from the proceedings are presented: Evolution of Responsibility in the…

77 FR 11109 - Reactive Power Resources; Notice of Technical Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... options for and cost of installing reactive power equipment at the time of interconnection as well as... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD12-10-000] Reactive Power... the need for reactive power capability among newly interconnecting asynchronous generators and raises...

77 FR 37898 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... Activities; Submission to OMB for Review and Approval; Comment Request; Hazardous Remediation Waste....regulations.gov . Title: Hazardous Remediation Waste Management Requirements (HWIR- Media) (Renewal). ICR... program), EPA regulates newly generated hazardous wastes, as well as hazardous remediation wastes (i.e...

Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.

PubMed

Pemberton, Travis A; Chen, Mengbin; Harris, Golda G; Chou, Wayne K W; Duan, Lian; Köksal, Mustafa; Genshaft, Alex S; Cane, David E; Christianson, David W

2017-04-11

Terpenoid synthases catalyze isoprenoid cyclization reactions underlying the generation of more than 80,000 natural products. Such dramatic chemodiversity belies the fact that these enzymes generally consist of only three domain folds designated as α, β, and γ. Catalysis by class I terpenoid synthases occurs exclusively in the α domain, which is found with α, αα, αβ, and αβγ domain architectures. Here, we explore the influence of domain architecture on catalysis by taxadiene synthase from Taxus brevifolia (TbTS, αβγ), fusicoccadiene synthase from Phomopsis amygdali (PaFS, (αα) 6 ), and ophiobolin F synthase from Aspergillus clavatus (AcOS, αα). We show that the cyclization fidelity and catalytic efficiency of the α domain of TbTS are severely compromised by deletion of the βγ domains; however, retention of the β domain preserves significant cyclization fidelity. In PaFS, we previously demonstrated that one α domain similarly influences catalysis by the other α domain [ Chen , M. , Chou , W. K. W. , Toyomasu , T. , Cane , D. E. , and Christianson , D. W. ( 2016 ) ACS Chem. Biol. 11 , 889 - 899 ]. Here, we show that the hexameric quaternary structure of PaFS enables cluster channeling. We also show that the α domains of PaFS and AcOS can be swapped so as to make functional chimeric αα synthases. Notably, both cyclization fidelity and catalytic efficiency are altered in all chimeric synthases. Twelve newly formed and uncharacterized C 20 diterpene products and three C 25 sesterterpene products are generated by these chimeras. Thus, engineered αβγ and αα terpenoid cyclases promise to generate chemodiversity in the greater family of terpenoid natural products.

Recombinant SINEs are formed at high frequency during induced retrotransposition in vivo.

PubMed

Yadav, Vijay Pal; Mandal, Prabhat Kumar; Bhattacharya, Alok; Bhattacharya, Sudha

2012-05-22

Non-long terminal repeat Retrotransposons are referred to as long interspersed nuclear elements (LINEs) and their non-autonomous partners are short interspersed nuclear elements (SINEs). It is believed that an active SINE copy, upon retrotransposition, generates near identical copies of itself, which subsequently accumulate mutations resulting in sequence polymorphism. Here we show that when a retrotransposition-competent cell line of the parasitic protist Entamoeba histolytica, transfected with a marked SINE copy, is induced to retrotranspose, >20% of the newly retrotransposed copies are neither identical to the marked SINE nor to the mobilized resident SINEs. Rather they are recombinants of resident SINEs and the marked SINE. They are a consequence of retrotransposition and not DNA recombination, as they are absent in cells not expressing the retrotransposition functions. This high-frequency recombination provides a new explanation for the existence of mosaic SINEs, which may impact on genetic analysis of SINE lineages, and measurement of phylogenetic distances.

N-Acetylglucosamine: Production and Applications

PubMed Central

Chen, Jeen-Kuan; Shen, Chia-Rui; Liu, Chao-Lin

2010-01-01

N-Acetylglucosamine (GlcNAc) is a monosaccharide that usually polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin, the second most abundant carbohydrate after cellulose. In addition to serving as a component of this homogeneous polysaccharide, GlcNAc is also a basic component of hyaluronic acid and keratin sulfate on the cell surface. In this review, we discuss the industrial production of GlcNAc, using chitin as a substrate, by chemical, enzymatic and biotransformation methods. Also, newly developed methods to obtain GlcNAc using glucose as a substrate in genetically modified microorganisms are introduced. Moreover, GlcNAc has generated interest not only as an underutilized resource but also as a new functional material with high potential in various fields. Here we also take a closer look at the current applications of GlcNAc, and several new and cutting edge approaches in this fascinating area are thoroughly discussed. PMID:20948902

Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

PubMed

Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

2014-09-29

Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles

PubMed Central

Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo

2014-01-01

Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells. PMID:25246616

Redox-Dependent Inflammation in Islet Transplantation Rejection

PubMed Central

Barra, Jessie M.; Tse, Hubert M.

2018-01-01

Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS) by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation. PMID:29740396

Bioinformatics and molecular modeling in glycobiology

PubMed Central

Schloissnig, Siegfried

2010-01-01

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed. PMID:20364395

The pressure is all in your head: A cilia-driven high-pressure pump in the head of a deep-sea animal

NASA Astrophysics Data System (ADS)

Nawroth, Janna; Katija, Kakani; Shelley, Michael; Kanso, Eva

2017-11-01

Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. In many ciliated systems found in nature, such as the mammalian airways and marine sponges, the organization and collective behavior of the cilia favors the pumping of fluids at low pressures and high volumes. We recently discovered an alternate design located in the head of a deep-sea animal called Larvacean. Here, cilia morphology, kinematics and flow indicate a role in maintaining the hydrostatic skeleton of the animal by generating a high-pressure flow. We describe our empirical and computational approaches toward understanding the design principles and dynamic range of this newly discovered pumping mechanism. In ongoing work, we further explore the fluid dynamic constraints on the morphological diversity of cilia and the resulting categories of fluid transport functions.

The Effects of Orbital Spaceflight on Human Osteoblastic Cell Physiology and Gene Expression

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

The purpose of the proposed study is to establish whether changes in gravitational loading have a direct effect on osteoblasts to regulate TGF-6 expression. The effects of spaceflight and reloading on TGF-B MRNA and peptide levels will be studied in a newly developed line of immortalized human fetal osteoblasts (HFOB) transfected with an SV-40 temperature dependent mutant to generate proliferating, undifferentiated hFOB cells at 33-34 C and a non-proliferating, differentiated HFOB cells at 37-39'C. Unlike previous cell culture models, HFOB cells have unlimited proliferative capacity yet can be precisely regulated to differentiate into mature cells which express mature osteoblast function. If isolated osteoblasts respond to changes in mechanical loading in a manner similar to their response in animals, the cell system could provide a powerful model to investigate the signal transduction pathway for gravitational loading.

Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence

PubMed Central

Cunningham, Cameron R.; Champhekar, Ameya; Tullius, Michael V.; Dillon, Barbara Jane; Zhen, Anjie; de la Fuente, Justin Rafael; Herskovitz, Jonathan; Elsaesser, Heidi; Snell, Laura M.; Wilson, Elizabeth B.; de la Torre, Juan Carlos; Kitchen, Scott G.; Horwitz, Marcus A.; Bensinger, Steven J.; Smale, Stephen T.; Brooks, David G.

2016-01-01

Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. PMID:26808628

The Prediction of Broadband Shock-Associated Noise Including Propagation Effects

NASA Technical Reports Server (NTRS)

Miller, Steven; Morris, Philip J.

2011-01-01

An acoustic analogy is developed based on the Euler equations for broadband shock- associated noise (BBSAN) that directly incorporates the vector Green's function of the linearized Euler equations and a steady Reynolds-Averaged Navier-Stokes solution (SRANS) as the mean flow. The vector Green's function allows the BBSAN propagation through the jet shear layer to be determined. The large-scale coherent turbulence is modeled by two-point second order velocity cross-correlations. Turbulent length and time scales are related to the turbulent kinetic energy and dissipation. An adjoint vector Green's function solver is implemented to determine the vector Green's function based on a locally parallel mean flow at streamwise locations of the SRANS solution. However, the developed acoustic analogy could easily be based on any adjoint vector Green's function solver, such as one that makes no assumptions about the mean flow. The newly developed acoustic analogy can be simplified to one that uses the Green's function associated with the Helmholtz equation, which is consistent with the formulation of Morris and Miller (AIAAJ 2010). A large number of predictions are generated using three different nozzles over a wide range of fully expanded Mach numbers and jet stagnation temperatures. These predictions are compared with experimental data from multiple jet noise labs. In addition, two models for the so-called 'fine-scale' mixing noise are included in the comparisons. Improved BBSAN predictions are obtained relative to other models that do not include the propagation effects, especially in the upstream direction of the jet.

Estimating methane emissions from landfills based on rainfall, ambient temperature, and waste composition: The CLEEN model.

PubMed

Karanjekar, Richa V; Bhatt, Arpita; Altouqui, Said; Jangikhatoonabad, Neda; Durai, Vennila; Sattler, Melanie L; Hossain, M D Sahadat; Chen, Victoria

2015-12-01

Accurately estimating landfill methane emissions is important for quantifying a landfill's greenhouse gas emissions and power generation potential. Current models, including LandGEM and IPCC, often greatly simplify treatment of factors like rainfall and ambient temperature, which can substantially impact gas production. The newly developed Capturing Landfill Emissions for Energy Needs (CLEEN) model aims to improve landfill methane generation estimates, but still require inputs that are fairly easy to obtain: waste composition, annual rainfall, and ambient temperature. To develop the model, methane generation was measured from 27 laboratory scale landfill reactors, with varying waste compositions (ranging from 0% to 100%); average rainfall rates of 2, 6, and 12 mm/day; and temperatures of 20, 30, and 37°C, according to a statistical experimental design. Refuse components considered were the major biodegradable wastes, food, paper, yard/wood, and textile, as well as inert inorganic waste. Based on the data collected, a multiple linear regression equation (R(2)=0.75) was developed to predict first-order methane generation rate constant values k as functions of waste composition, annual rainfall, and temperature. Because, laboratory methane generation rates exceed field rates, a second scale-up regression equation for k was developed using actual gas-recovery data from 11 landfills in high-income countries with conventional operation. The Capturing Landfill Emissions for Energy Needs (CLEEN) model was developed by incorporating both regression equations into the first-order decay based model for estimating methane generation rates from landfills. CLEEN model values were compared to actual field data from 6 US landfills, and to estimates from LandGEM and IPCC. For 4 of the 6 cases, CLEEN model estimates were the closest to actual. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional SNP associated with birth weight in independent populations identified with a permutation step added to GBLUP-GWAS

USDA-ARS?s Scientific Manuscript database

This study was conducted as an initial assessment of a newly available genotyping assay containing about 34,000 common SNP included on previous SNP chips, and 199,000 sequence variants predicted to affect gene function. Objectives were to identify functional variants associated with birth weight in...

Vulnerable elders survey and socioeconomic status predict functional decline and death among older women with newly diagnosed nonmetastatic breast cancer.

PubMed

Owusu, Cynthia; Margevicius, Seunghee; Schluchter, Mark; Koroukian, Siran M; Schmitz, Kathryn H; Berger, Nathan A

2016-08-15

The purpose of this study was to determine the ability of the Vulnerable Elders Survey (VES-13) to predict the composite outcome of functional decline and death within 12 months of breast cancer treatment among women 65 years old or older with newly diagnosed stage I to III breast cancer. Two hundred and six participants were recruited from ambulatory oncology clinics at an academic center between April 2008 and April 2013. Participants competed the VES-13 at baseline just before neoadjuvant/adjuvant treatment. The primary outcome, functional decline/death, was defined as either a decrease of at least 1 point on the Activities of Daily Living scale and/or the Instrumental Activities of Daily Living scale or death between baseline and 12 months (yes or no). One hundred and eighty four participants (89%) completed 12 months of follow-up. Twenty-two percent functionally declined (n = 34) or died (n = 7). Univariately, with increasing VES-13 scores, the estimated risk of functional decline/death rose from 23% for participants with a VES-13 score of 3 to 76% for participants with a VES-13 score of 10. In multivariate logistic regression analysis, VES-13 scores (adjusted odds ratio, 1.37; 95% confidence interval, 1.18-1.57) and having a high school education or less (adjusted odds ratio, 2.47; 95% confidence interval, 1.08-5.65) were independent predictors of functional decline/death (area under the receiver operator curve, 0.79). Among older women with newly diagnosed nonmetastatic breast cancer, approximately 1 in 5 functionally declined and/or died within 12 months of breast cancer treatment initiation. Women with high school education or less were disproportionately affected. The VES-13 is a useful instrument for the early identification of those at risk for functional decline and/or death. Cancer 2016;122:2579-86. © 2016 American Cancer Society. © 2016 American Cancer Society.

Nanoindentation measurements of biomechanical properties in mature and newly formed bone tissue surrounding an implant.

PubMed

Vayron, Romain; Barthel, Etienne; Mathieu, Vincent; Soffer, Emmanuel; Anagnostou, Fani; Haiat, Guillaume

2012-02-01

The characterization of the biomechanical properties of newly formed bone tissue around implants is important to understand the osseointegration process. The objective of this study is to investigate the evolution of the hardness and indentation modulus of newly formed bone tissue as a function of healing time. To do so, a nanoindentation device is employed following a multimodality approach using histological analysis. Coin-shaped implants were placed in vivo at a distance of 200 μm from the cortical bone surface, leading to an initially empty cavity of 200 μm * 4.4 mm. Three New Zealand White rabbits were sacrificed after 4, 7, and 13 weeks of healing time. The bone samples were embedded and analyzed using histological analyses, allowing to distinguish mature and newly formed bone tissue. The bone mechanical properties were then measured in mature and newly formed bone tissue. The results are within the range of hardness and apparent Young's modulus values reported in previous literature. One-way ANOVA test revealed a significant effect of healing time on the indentation modulus (p < 0.001, F = 111.24) and hardness (p < 0.02, F = 3.47) of bone tissue. A Tukey-Kramer analysis revealed that the biomechanical properties of newly formed bone tissue (4 weeks) were significantly different from those of mature bone tissue. The comparison with the results obtained in Mathieu et al. (2011, "Micro-Brillouin Scattering Measurements in Mature and Newly Formed Bone Tissue Surrounding an Implant," J. Biomech. Eng., 133, 021006). shows that bone mass density increases by approximately 13.5% between newly formed bone (7 weeks) and mature bone tissue.

SVM-Prot 2016: A Web-Server for Machine Learning Prediction of Protein Functional Families from Sequence Irrespective of Similarity.

PubMed

Li, Ying Hong; Xu, Jing Yu; Tao, Lin; Li, Xiao Feng; Li, Shuang; Zeng, Xian; Chen, Shang Ying; Zhang, Peng; Qin, Chu; Zhang, Cheng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

2016-01-01

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

Results from the Solar Hidden Photon Search (SHIPS)

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

Schwarz, Matthias; Schneide, Magnus; Susol, Jaroslaw

We present the results of a search for transversely polarised hidden photons (HPs) with ∼ 3 eV energies emitted from the Sun. These hypothetical particles, known also as paraphotons or dark sector photons, are theoretically well motivated for example by string theory inspired extensions of the Standard Model. Solar HPs of sub-eV mass can convert into photons of the same energy (photon ↔ HP oscillations are similar to neutrino flavour oscillations). At SHIPS this would take place inside a long light-tight high-vacuum tube, which tracks the Sun. The generated photons would then be focused into a low-noise photomultiplier at the far end ofmore » the tube. Our analysis of 330 h of data (and 330 h of background characterisation) reveals no signal of photons from solar hidden photon conversion. We estimate the rate of newly generated photons due to this conversion to be smaller than 25 mHz/m{sup 2} at the 95% C.L . Using this and a recent model of solar HP emission, we set stringent constraints on χ, the coupling constant between HPs and photons, as a function of the HP mass.« less

Results from the Solar Hidden Photon Search (SHIPS)

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

Schwarz, Matthias; Knabbe, Ernst-Axel; Lindner, Axel

We present the results of a search for transversely polarised hidden photons (HPs) with ∼3 eV energies emitted from the Sun. These hypothetical particles, known also as paraphotons or dark sector photons, are theoretically well motivated for example by string theory inspired extensions of the Standard Model. Solar HPs of sub-eV mass can convert into photons of the same energy (photon ↔ HP oscillations are similar to neutrino flavour oscillations). At SHIPS this would take place inside a long light-tight high-vacuum tube, which tracks the Sun. The generated photons would then be focused into a low-noise photomultiplier at the farmore » end of the tube. Our analysis of 330 h of data (and 330 h of background characterisation) reveals no signal of photons from solar hidden photon conversion. We estimate the rate of newly generated photons due to this conversion to be smaller than 25 mHz/m{sup 2} at the 95% C.L. Using this and a recent model of solar HP emission, we set stringent constraints on χ, the coupling constant between HPs and photons, as a function of the HP mass.« less

A probabilistic drought forecasting framework: A combined dynamical and statistical approach

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

Yan, Hongxiang; Moradkhani, Hamid; Zarekarizi, Mahkameh

In order to improve drought forecasting skill, this study develops a probabilistic drought forecasting framework comprised of dynamical and statistical modeling components. The novelty of this study is to seek the use of data assimilation to quantify initial condition uncertainty with the Monte Carlo ensemble members, rather than relying entirely on the hydrologic model or land surface model to generate a single deterministic initial condition, as currently implemented in the operational drought forecasting systems. Next, the initial condition uncertainty is quantified through data assimilation and coupled with a newly developed probabilistic drought forecasting model using a copula function. The initialmore » condition at each forecast start date are sampled from the data assimilation ensembles for forecast initialization. Finally, seasonal drought forecasting products are generated with the updated initial conditions. This study introduces the theory behind the proposed drought forecasting system, with an application in Columbia River Basin, Pacific Northwest, United States. Results from both synthetic and real case studies suggest that the proposed drought forecasting system significantly improves the seasonal drought forecasting skills and can facilitate the state drought preparation and declaration, at least three months before the official state drought declaration.« less

A probabilistic neural network based approach for predicting the output power of wind turbines

NASA Astrophysics Data System (ADS)

Tabatabaei, Sajad

2017-03-01

Finding the authentic predicting tools of eliminating the uncertainty of wind speed forecasts is highly required while wind power sources are strongly penetrating. Recently, traditional predicting models of generating point forecasts have no longer been trustee. Thus, the present paper aims at utilising the concept of prediction intervals (PIs) to assess the uncertainty of wind power generation in power systems. Besides, this paper uses a newly introduced non-parametric approach called lower upper bound estimation (LUBE) to build the PIs since the forecasting errors are unable to be modelled properly by applying distribution probability functions. In the present proposed LUBE method, a PI combination-based fuzzy framework is used to overcome the performance instability of neutral networks (NNs) used in LUBE. In comparison to other methods, this formulation more suitably has satisfied the PI coverage and PI normalised average width (PINAW). Since this non-linear problem has a high complexity, a new heuristic-based optimisation algorithm comprising a novel modification is introduced to solve the aforesaid problems. Based on data sets taken from a wind farm in Australia, the feasibility and satisfying performance of the suggested method have been investigated.

Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in Biological Systems.

PubMed

Girotti, Albert W; Korytowski, Witold

2017-12-01

Cholesterol is like other unsaturated lipids in being susceptible to peroxidative degradation upon exposure to strong oxidants like hydroxyl radical or peroxynitrite generated under conditions of oxidative stress. In the eukaryotic cell plasma membrane, where most of the cellular cholesterol resides, peroxidation leads to membrane structural and functional damage from which pathological states may arise. In low density lipoprotein, cholesterol and phospholipid peroxidation have long been associated with atherogenesis. Among the many intermediates/products of cholesterol oxidation, hydroperoxide species (ChOOHs) have a number of different fates and deserve special attention. These fates include (a) damage-enhancement via iron-catalyzed one-electron reduction, (b) damage containment via two-electron reduction, and (c) inter-membrane, inter-lipoprotein, and membrane-lipoprotein translocation, which allows dissemination of one-electron damage or off-site suppression thereof depending on antioxidant location and capacity. In addition, ChOOHs can serve as reliable and conveniently detected mechanistic reporters of free radical-mediated reactions vs. non-radical (e.g., singlet oxygen)-mediated reactions. Iron-stimulated peroxidation of cholesterol and other lipids underlies a newly discovered form of regulated cell death called ferroptosis. These and other deleterious consequences of radical-mediated lipid peroxidation will be discussed in this review.

Thermodynamical properties of liquid lanthanides-A variational approach

NASA Astrophysics Data System (ADS)

Patel, H. P.; Thakor, P. B.; Sonvane, Y. A.

2015-06-01

Thermodynamical properties like Entropy (S), Internal energy (E) and Helmholtz free energy (F) of liquid lanthanides using a variation principle based on the Gibbs-Bogoliubuv (GB) inequality with Percus Yevick hard sphere reference system have been reported in the present investigation. To describe electron-ion interaction we have used our newly constructed parameter free model potential along with Sarkar et al. local field correction function. Lastly, we conclude that our newly constructed model potential is capable to explain the thermodynamical properties of liquid lanthanides.

Thermodynamical properties of liquid lanthanides-A variational approach

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

Patel, H. P.; Department of Applied Physics, S. V. National Institute of Technology, Surat 395 007, Gujarat; Thakor, P. B., E-mail: pbthakor@rediffmail.com

2015-06-24

Thermodynamical properties like Entropy (S), Internal energy (E) and Helmholtz free energy (F) of liquid lanthanides using a variation principle based on the Gibbs-Bogoliubuv (GB) inequality with Percus Yevick hard sphere reference system have been reported in the present investigation. To describe electron-ion interaction we have used our newly constructed parameter free model potential along with Sarkar et al. local field correction function. Lastly, we conclude that our newly constructed model potential is capable to explain the thermodynamical properties of liquid lanthanides.

Motor run-up system. [power lines

NASA Technical Reports Server (NTRS)

Daeges, J. J. (Inventor)

1975-01-01

A starting system is described for bringing a large synchronous motor up to speed to prevent large power line disturbances at the moment the motor is connected to the power line. The system includes (1) a digital counter which generates a count determined by the difference in frequency between the power line and a small current generated by the synchronous motor; (2) a latch which stores the count; and (3) a comparator which compares the stored count with a newly generated count to determine whether the synchronous motor is accelerating or decelerating. Signals generated by the counter and comparator control the current to a clutch that couples a starting motor to the large synchronous motor.

COMPARATIVE EMBRYONIC AND LARVAL DEVELOPMENTAL RESPONSES OF THE ESTUARINE GRASS SHRIMP (PALAEMONETES PUGIO) TO THE JUVENILE HORMONE AGONIST FENOXYCARB

EPA Science Inventory

This work was undertaken in order to develop a sensitive bioassay which indicates adverse effects of estuarine-applied insecticides on nontarget species. Newly developed 'third generation' insecticides are designed to act as hormone agonists and bind to endogenous insect hormone...

Retrotransposon- and microsatellite sequence-associated genomic changes in early 2 generations of a newly synthesized allotetraploid cucumis × hytivus Chen & Kirkbride

USDA-ARS?s Scientific Manuscript database

Allopolyploidization is considered an essential evolutionary process in plants that could trigger genomic shock in allopolyploid genome through activation of transcription of retrotransposons, which may be important in plant evolution. Two retrotransposon-based markers, inter-retrotransposon amplifi...

Supporting Newly Hired Science Teachers

ERIC Educational Resources Information Center

Luft, Julie A.; Nixon, Ryan S.; Dubois, Shannon L.; Campbell, Benjamin K.

2014-01-01

New teachers are common in the teaching workforce (Ingersoll and Merrill 2012). All new teachers will learn about the school curriculum and school policies in their first years. New science teachers, however, need to attend to the "Next Generation of Science Standards" (NGSS Lead States 2013) as they build their instruction and knowledge…

Retention of Idioms Following One-Time Exposure

ERIC Educational Resources Information Center

Reuterskiold, Christina; Van Lancker Sidtis, Diana

2013-01-01

This study explored retention of idioms and novel (i.e. newly created or grammatically generated) expressions in English-speaking girls following exposure only once during a conversation. Our hypothesis was that idioms, because of their inherent holistic, nonliteral and social characteristics, are acquired differently and more rapidly than novel…

Development and Validation of a Depression Scale for Asian Adolescents

ERIC Educational Resources Information Center

Woo, Bernardine S. C.; Chang, W. C.; Fung, Daniel S. S.; Koh, Jessie B. K.; Leong, Joyce S. F.; Kee, Carolyn H. Y.; Seah, Cheryl K. F.

2004-01-01

Items covering both core and culture-specific facets of depression were generated based on literature review and clinical experience. They were modified following focus group discussions with depressed adolescents and adolescents in the community. The newly constructed Asian Adolescent Depression Scale (AADS) was administered to a clinical and a…

A conceptual framework to support exposure science research and complete the source-to-outcome continuum for risk assessment

EPA Science Inventory

While knowledge of exposure is fundamental to assessing and mitigating risks, exposure information has been costly and difficult to generate. Driven by major scientific advances in analytical methods, biomonitoring, computational tools, and a newly articulated vision for a great...

Mirror Worlds: Examining the Affordances of a Next Generation Immersive Learning Environment

ERIC Educational Resources Information Center

Gautam, Aakash; Williams, Daron; Terry, Krista; Robinson, Kelly; Newbill, Phyllis

2018-01-01

As technologies continue to develop and evolve, it is imperative that instructional technologists, learning scientists, and educators involved with examining learning affordances of emerging technologies investigate the potential of innovative environments to promote and facilitate learning. This paper, as such, will describe a newly developed…

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

ERIC Educational Resources Information Center

Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

PubMed Central

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis. PMID:29051707

Newly discovered geological features and their potential impact on Darlington and Pickering. Report No. INFO-0342

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

Wallach, J.L.

1990-01-01

The design basis seismic ground motion for the nuclear generating stations at Darlington and at Pickering were determined solely through the assessment of previous earthquakes with no geological, or any other geophysical, input. Since then geophysical maps, showing a north-northwest oriented linear feature with some possible associated seismic activity, were examined. This report discusses the impact of these new discoveries on the Darlington and Pickering nuclear generating stations and on the already known geophysical features of the area.

Comparison of Electrostatic Fins with Piezoelectric Impact Hammer Techniques to Extend Impulse Calibration Range of a Torsional Thrust Stand (Preprint)

DTIC Science & Technology

2011-03-23

prac- tical max impulse to 1mNs. The newly developed Piezo - electric Impact Hammer (PIH) calibration system over- comes geometric limits of ESC...the fins to behave as part of an LRC circuit which results in voltage oscillations. By adding a resistor in series between the pulse generator and...series resistor as well as the effects of no loading on the pulse generator. III. PIEZOELECTRIC IMPACT HAMMER SYSTEM The second calibration method tested

How Fo-ATPase generates rotary torque.

PubMed

Oster, G; Wang, H; Grabe, M

2000-04-29

The F-ATPases synthesize ATP using a transmembrane ionmotive force (IMF) established by the electron transport chain. This transduction involves first converting the IMF to a rotary torque in the transmembrane Fo portion. This torque is communicated from Fo to the F1 portion where the energy is used to release the newly synthesized ATP from the catalytic sites according to Boyer's binding change mechanism. Here we explain the principle by which an IMF generates this rotary torque in the Fo ion engine.

Millisecond newly born pulsars as efficient accelerators of electrons

NASA Astrophysics Data System (ADS)

Osmanov, Zaza; Mahajan, Swadesh; Machabeli, George; Chkheidze, Nino

2015-09-01

The newly born millisecond pulsars are investigated as possible energy sources for creating ultra-high energy electrons. The transfer of energy from the star rotation to high energy electrons takes place through the Landau damping of centrifugally driven (via a two stream instability) electrostatic Langmuir waves. Generated in the bulk magnetosphere plasma, such waves grow to high amplitudes, and then damp, very effectively, on relativistic electrons driving them to even higher energies. We show that the rate of transfer of energy is so efficient that no energy losses might affect the mechanism of particle acceleration; the electrons might achieve energies of the order of 1018 eV for parameters characteristic of a young star.

Adult neurogenesis and neuronal regeneration in the central nervous system of teleost fish.

PubMed

Zupanc, Günther K H; Sîrbulescu, Ruxandra F

2011-09-01

Teleost fish are distinguished by their ability to constitutively generate new neurons in the adult central nervous system ('adult neurogenesis'), and to regenerate whole neurons after injury ('neuronal regeneration'). In the brain, new neurons are produced in large numbers in several dozens of proliferation zones. In the spinal cord, proliferating cells are present in the ependymal layer and throughout the parenchyma. In the retina, new cells arise from the ciliary marginal zone and from Müller glia. Experimental evidence has suggested that both radial glia and non-glial cells can function as adult stem cells. The proliferative activity of these cells can be regulated by molecular factors, such as fibroblast growth factor and Notch, as well as by social and behavioral experience. The young cells may either reside near the respective proliferation zone, or migrate to specific target areas. Approximately half of the newly generated cells persist for the rest of the fish's life, and many of them differentiate into neurons. After injury, a massive surge of apoptotic cell death occurs at the lesion site within a few hours. Apoptosis is followed by a marked increase in cell proliferation and neurogenesis, leading to repair of the tissue. The structural regeneration is paralleled by partial or complete recovery of function. Recent investigations have led to the identification of several dozens of molecular factors that are potentially involved in the process of regeneration. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Regionalizing nonparametric models of precipitation amounts on different temporal scales

NASA Astrophysics Data System (ADS)

Mosthaf, Tobias; Bárdossy, András

2017-05-01

Parametric distribution functions are commonly used to model precipitation amounts corresponding to different durations. The precipitation amounts themselves are crucial for stochastic rainfall generators and weather generators. Nonparametric kernel density estimates (KDEs) offer a more flexible way to model precipitation amounts. As already stated in their name, these models do not exhibit parameters that can be easily regionalized to run rainfall generators at ungauged locations as well as at gauged locations. To overcome this deficiency, we present a new interpolation scheme for nonparametric models and evaluate it for different temporal resolutions ranging from hourly to monthly. During the evaluation, the nonparametric methods are compared to commonly used parametric models like the two-parameter gamma and the mixed-exponential distribution. As water volume is considered to be an essential parameter for applications like flood modeling, a Lorenz-curve-based criterion is also introduced. To add value to the estimation of data at sub-daily resolutions, we incorporated the plentiful daily measurements in the interpolation scheme, and this idea was evaluated. The study region is the federal state of Baden-Württemberg in the southwest of Germany with more than 500 rain gauges. The validation results show that the newly proposed nonparametric interpolation scheme provides reasonable results and that the incorporation of daily values in the regionalization of sub-daily models is very beneficial.

Qualification of local advanced cryogenic cleaning technology for 14nm photomask fabrication

NASA Astrophysics Data System (ADS)

Taumer, Ralf; Krome, Thorsten; Bowers, Chuck; Varghese, Ivin; Hopkins, Tyler; White, Roy; Brunner, Martin; Yi, Daniel

2014-10-01

The march toward tighter design rules, and thus smaller defects, implies stronger surface adhesion between defects and the photomask surface compared to past generations, thereby resulting in increased difficulty in photomask cleaning. Current state-of-the-art wet clean technologies utilize functional water and various energies in an attempt to produce similar yield to the acid cleans of previous generations, but without some of the negative side effects. Still, wet cleans have continued to be plagued with issues such as persistent particles and contaminations, SRAF and feature damages, leaving contaminants behind that accelerate photo-induced defect growth, and others. This paper details work done through a design of experiments (DOE) utilized to qualify an improved cryogenic cleaning technology for production in the Advanced Mask Technology Center (AMTC) advanced production lines for 20 and 14 nm processing. All work was conducted at the AMTC facility in Dresden, Germany utilizing technology developed by Eco-Snow Systems and RAVE LLC for their cryogenic local cleaning VC1200F platform. This system uses a newly designed nozzle, improved gaseous CO2 delivery, extensive filtration to remove hydrocarbons and minimize particle adders, and other process improvements to overcome the limitations of the previous generation local cleaning tool. AMTC has successfully qualified this cryogenic cleaning technology and is currently using it regularly to enhance production yields even at the most challenging technology nodes.

Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion

PubMed Central

Osman, Christof; Noriega, Thomas R.; Okreglak, Voytek; Fung, Jennifer C.; Walter, Peter

2015-01-01

Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. We developed a LacO-LacI system to noninvasively image mtDNA dynamics in living cells. Using this system, we found that nucleoids are nonrandomly spaced within the mitochondrial network and observed the spatiotemporal events involved in mtDNA inheritance. Surprisingly, cells deficient in mitochondrial fusion and fission distributed and inherited mtDNA normally, pointing to alternative pathways involved in these processes. We identified such a mechanism, where we observed fission-independent, but F-actin–dependent, tip generation that was linked to the positioning of mtDNA to the newly generated tip. Although mitochondrial fusion and fission were dispensable for mtDNA distribution and inheritance, we show through a combination of genetics and next-generation sequencing that their absence leads to an accumulation of mitochondrial genomes harboring deleterious structural variations that cluster at the origins of mtDNA replication, thus revealing crucial roles for mitochondrial fusion and fission in maintaining the integrity of the mitochondrial genome. PMID:25730886

Identification of a functionally distinct truncated BDNF mRNA splice variant and protein in Trachemys scripta elegans.

PubMed

Ambigapathy, Ganesh; Zheng, Zhaoqing; Li, Wei; Keifer, Joyce

2013-01-01

Brain-derived neurotrophic factor (BDNF) has a diverse functional role and complex pattern of gene expression. Alternative splicing of mRNA transcripts leads to further diversity of mRNAs and protein isoforms. Here, we describe the regulation of BDNF mRNA transcripts in an in vitro model of eyeblink classical conditioning and a unique transcript that forms a functionally distinct truncated BDNF protein isoform. Nine different mRNA transcripts from the BDNF gene of the pond turtle Trachemys scripta elegans (tBDNF) are selectively regulated during classical conditioning: exon I mRNA transcripts show no change, exon II transcripts are downregulated, while exon III transcripts are upregulated. One unique transcript that codes from exon II, tBDNF2a, contains a 40 base pair deletion in the protein coding exon that generates a truncated tBDNF protein. The truncated transcript and protein are expressed in the naïve untrained state and are fully repressed during conditioning when full-length mature tBDNF is expressed, thereby having an alternate pattern of expression in conditioning. Truncated BDNF is not restricted to turtles as a truncated mRNA splice variant has been described for the human BDNF gene. Further studies are required to determine the ubiquity of truncated BDNF alternative splice variants across species and the mechanisms of regulation and function of this newly recognized BDNF protein.

Identification of a Functionally Distinct Truncated BDNF mRNA Splice Variant and Protein in Trachemys scripta elegans

PubMed Central

Ambigapathy, Ganesh; Zheng, Zhaoqing; Li, Wei; Keifer, Joyce

2013-01-01

Brain-derived neurotrophic factor (BDNF) has a diverse functional role and complex pattern of gene expression. Alternative splicing of mRNA transcripts leads to further diversity of mRNAs and protein isoforms. Here, we describe the regulation of BDNF mRNA transcripts in an in vitro model of eyeblink classical conditioning and a unique transcript that forms a functionally distinct truncated BDNF protein isoform. Nine different mRNA transcripts from the BDNF gene of the pond turtle Trachemys scripta elegans (tBDNF) are selectively regulated during classical conditioning: exon I mRNA transcripts show no change, exon II transcripts are downregulated, while exon III transcripts are upregulated. One unique transcript that codes from exon II, tBDNF2a, contains a 40 base pair deletion in the protein coding exon that generates a truncated tBDNF protein. The truncated transcript and protein are expressed in the naïve untrained state and are fully repressed during conditioning when full-length mature tBDNF is expressed, thereby having an alternate pattern of expression in conditioning. Truncated BDNF is not restricted to turtles as a truncated mRNA splice variant has been described for the human BDNF gene. Further studies are required to determine the ubiquity of truncated BDNF alternative splice variants across species and the mechanisms of regulation and function of this newly recognized BDNF protein. PMID:23825634

Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

PubMed

Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

2016-05-01

Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

The Application of the Rome IV Criteria to Functional Esophagogastroduodenal Disorders in Asia

PubMed Central

Suzuki, Hidekazu

2017-01-01

The Rome criteria were amended as Rome IV. For functional esophageal disorders, the exclusion criteria have been more specifically revised based on further understanding of other esophageal disorders, including eosinophilic esophagitis and spastic and hypercontractile motor disorders. Another revised point is the more restrictive definition of gastroesophageal reflux disease, indicating that sensitivity to a physiological reflux burden may be placed more firmly within the functional group. For functional dyspepsia (FD), only minor changes were introduced, mainly to improve specificity. Among the major symptoms of FD, not only postprandial fullness, but also epigastric pain, epigastric burning, and early satiation should be “bothersome.” Investigation on the effect of meal ingestion on symptom generation has indicated that not only postprandial fullness and early satiety, but also epigastric pain, epigastric burning sensation and nausea (not vomiting) may increase after meals. Helicobacter pylori infection is considered a possible cause of dyspepsia if successful eradication leads to sustained resolution of symptoms for more than 6 months, and such status can be termed as “H. pylori–associated dyspepsia.” Prompt esophagogastroduodenoscopy and H. pylori testing and treatment would be more beneficial, especially in Asia, which has a high prevalence of gastric cancer. Acotiamide, tandospirone, and rikkunshito are the newly listed as treatment options for FD. For further therapeutic development, clinical studies based on the strict Rome IV criteria should be performed. PMID:28672431

Specialization along the left superior temporal sulcus for auditory categorization.

PubMed

Liebenthal, Einat; Desai, Rutvik; Ellingson, Michael M; Ramachandran, Brinda; Desai, Anjali; Binder, Jeffrey R

2010-12-01

The affinity and temporal course of functional fields in middle and posterior superior temporal cortex for the categorization of complex sounds was examined using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) recorded simultaneously. Data were compared before and after subjects were trained to categorize a continuum of unfamiliar nonphonemic auditory patterns with speech-like properties (NP) and a continuum of familiar phonemic patterns (P). fMRI activation for NP increased after training in left posterior superior temporal sulcus (pSTS). The ERP P2 response to NP also increased with training, and its scalp topography was consistent with left posterior superior temporal generators. In contrast, the left middle superior temporal sulcus (mSTS) showed fMRI activation only for P, and this response was not affected by training. The P2 response to P was also independent of training, and its estimated source was more anterior in left superior temporal cortex. Results are consistent with a role for left pSTS in short-term representation of relevant sound features that provide the basis for identifying newly acquired sound categories. Categorization of highly familiar phonemic patterns is mediated by long-term representations in left mSTS. Results provide new insight regarding the function of ventral and dorsal auditory streams.

PMEL: A PIGMENT CELL-SPECIFIC MODEL FOR FUNCTIONAL AMYLOID FORMATION

PubMed Central

Watt, Brenda; van Niel, Guillaume; Raposo, Graça; Marks, Michael S.

2013-01-01

PMEL is a pigment cell-specific protein responsible for the formation of fibrillar sheets within the pigment organelle, the melanosome. The fibrillar sheets serve as a template upon which melanins polymerize as they are synthesized. The PMEL fibrils are required for optimal pigment cell function, as animals that either lack PMEL expression or express mutant PMEL variants show varying degrees of hypopigmentation and pigment cell inviability. The PMEL fibrils have biophysical properties of amyloid, a protein fold that is frequently associated with neurodegenerative and other diseases. However, PMEL is one of a growing number of non-pathogenic amyloid proteins that contribute to the function of the cell and/or organism that produces them. Understanding how PMEL generates amyloid in a non-pathogenic manner might provide insights into how to avoid toxicity due to pathological amyloid formation. In this review we summarize and reconcile data concerning the fate of PMEL from its site of synthesis in the endoplasmic reticulum to newly formed melanosomes and the role of distinct PMEL subdomains in trafficking and amyloid fibril formation. We then discuss how its progression through the secretory pathway into the endosomal system might allow for the regulated and non-toxic conversion of PMEL to an ordered amyloid polymer. PMID:23350640

Glial kon/NG2 gene network for central nervous system repair.

PubMed

Losada-Perez, Maria; Harrison, Neale; Hidalgo, Alicia

2017-01-01

The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response. A gene network involving Notch and prospero (pros) controls the balance between glial proliferation and differentiation in flies and mice, and promotes CNS repair at least in fruit-flies. A key missing link had been how to relate the function of NG2 to this gene network. Recent findings by Losada-Perez et al., published in JCB, demonstrated that the Drosophila NG2 homologue kon-tiki (kon) is functionally linked to Notch and pros in glia. By engaging in two feedback loops with Notch and Pros, in response to injury, Kon can regulate both glial cell number and glial shape homeostasis, essential for repair. Drosophila offers powerful genetics to unravel the control of stem and progenitor cells for regeneration and repair.

Regulation of hTERT Expression and Function in Newly Immortalized p53(+) Human Mammary Epithelial Cell Lines

DTIC Science & Technology

2008-06-01

proteins during embryogene- sis, neurodevelopment and cancer. Part of their function is through the repression of CKIs, including p16. Some functions...protein 2 Other AUTS2 autism susceptibility candidate 2 C1orf24 chromosome 1 open reading frame 24 C20orf97 chromosome 20 open reading frame 97

Regulation of hTERT Expression and Function in Newly Immortalized p53(+) Human Mammary Epithelial Cell Lines

DTIC Science & Technology

2007-06-01

embryogene- sis, neurodevelopment and cancer. Part of their function is through the repression of CKIs, including p16. Some functions have been attributed to...AUTS2 autism susceptibility candidate 2 C1orf24 chromosome 1 open reading frame 24 C20orf97 chromosome 20 open reading frame 97 DKFZP566B183

A Quasi-Parametric Method for Fitting Flexible Item Response Functions

ERIC Educational Resources Information Center

Liang, Longjuan; Browne, Michael W.

2015-01-01

If standard two-parameter item response functions are employed in the analysis of a test with some newly constructed items, it can be expected that, for some items, the item response function (IRF) will not fit the data well. This lack of fit can also occur when standard IRFs are fitted to personality or psychopathology items. When investigating…

Two Approaches to Estimating the Effect of Parenting on the Development of Executive Function in Early Childhood

ERIC Educational Resources Information Center

Blair, Clancy; Raver, C. Cybele; Berry, Daniel J.

2014-01-01

In the current article, we contrast 2 analytical approaches to estimate the relation of parenting to executive function development in a sample of 1,292 children assessed longitudinally between the ages of 36 and 60 months of age. Children were administered a newly developed and validated battery of 6 executive function tasks tapping inhibitory…

Systemic regulation of leaf anatomical structure, photosynthetic performance, and high-light tolerance in sorghum.

PubMed

Jiang, Chuang-Dao; Wang, Xin; Gao, Hui-Yuan; Shi, Lei; Chow, Wah Soon

2011-03-01

Leaf anatomy of C3 plants is mainly regulated by a systemic irradiance signal. Since the anatomical features of C4 plants are different from that of C3 plants, we investigated whether the systemic irradiance signal regulates leaf anatomical structure and photosynthetic performance in sorghum (Sorghum bicolor), a C4 plant. Compared with growth under ambient conditions (A), no significant changes in anatomical structure were observed in newly developed leaves by shading young leaves alone (YS). Shading mature leaves (MS) or whole plants (S), on the other hand, caused shade-leaf anatomy in newly developed leaves. By contrast, chloroplast ultrastructure in developing leaves depended only on their local light conditions. Functionally, shading young leaves alone had little effect on their net photosynthetic capacity and stomatal conductance, but shading mature leaves or whole plants significantly decreased these two parameters in newly developed leaves. Specifically, the net photosynthetic rate in newly developed leaves exhibited a positive linear correlation with that of mature leaves, as did stomatal conductance. In MS and S treatments, newly developed leaves exhibited severe photoinhibition under high light. By contrast, newly developed leaves in A and YS treatments were more resistant to high light relative to those in MS- and S-treated seedlings. We suggest that (1) leaf anatomical structure, photosynthetic capacity, and high-light tolerance in newly developed sorghum leaves were regulated by a systemic irradiance signal from mature leaves; and (2) chloroplast ultrastructure only weakly influenced the development of photosynthetic capacity and high-light tolerance. The potential significance of the regulation by a systemic irradiance signal is discussed.

GO-FAANG meeting: A gathering on functional annotation of animal genomes

USDA-ARS?s Scientific Manuscript database

The FAANG (Functional Annotation of Animal Genomes) Consortium recently held a Gathering On FAANG (GO-FAANG) Workshop in Washington, DC on October 7-8, 2015. This consortium is a grass-roots organization formed to advance the annotation of newly assembled genomes of non-model organisms (www.faang.or...

77 FR 13613 - Statement of Organization, Functions and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... Development (RM4); and (5) transfer the research function from the newly named Division of Maternal and Child... Maternal and Child Health Workforce Development (RM4); (6) Division of Healthy Start and Perinatal Services... childbearing age, infants, children, adolescents and their families, children with special health needs, and...

Highly robust thin-film composite pressure retarded osmosis (PRO) hollow fiber membranes with high power densities for renewable salinity-gradient energy generation.

PubMed

Han, Gang; Wang, Peng; Chung, Tai-Shung

2013-07-16

The practical application of pressure retarded osmosis (PRO) technology for renewable blue energy (i.e., osmotic power generation) from salinity gradient is being hindered by the absence of effective membranes. Compared to flat-sheet membranes, membranes with a hollow fiber configuration are of great interest due to their high packing density and spacer-free module fabrication. However, the development of PRO hollow fiber membranes is still in its infancy. This study aims to open up new perspectives and design strategies to molecularly construct highly robust thin film composite (TFC) PRO hollow fiber membranes with high power densities. The newly developed TFC PRO membranes consist of a selective polyamide skin formed on the lumen side of well-constructed Matrimid hollow fiber supports via interfacial polymerization. For the first time, laboratory PRO power generation tests demonstrate that the newly developed PRO hollow fiber membranes can withstand trans-membrane pressures up to 16 bar and exhibit a peak power density as high as 14 W/m(2) using seawater brine (1.0 M NaCl) as the draw solution and deionized water as the feed. We believe that the developed TFC PRO hollow fiber membranes have great potential for osmotic power harvesting.

On the formation of noise-like pulses in fiber ring cavity configurations

NASA Astrophysics Data System (ADS)

Jeong, Yoonchan; Vazquez-Zuniga, Luis Alonso; Lee, Seungjong; Kwon, Youngchul

2014-12-01

We give an overview of the current status of fiber-based noise-like pulse (NLP) research conducted over the past decade, together with presenting the newly conducted, systematic study on their temporal, spectral, and coherence characteristics in nonlinear polarization rotation (NPR)-based erbium-doped fiber ring cavity configurations. Firstly, our study includes experimental investigations on the characteristic features of NLPs both in the net anomalous dispersion regime and in the net normal dispersion regime, in comparison with coherent optical pulses that can alternatively be obtained from the same cavity configurations, i.e., with the conventional and dissipative solitons. Secondly, our study includes numerical simulations on the formation of NLPs, utilizing a simplified, scalar-field model based on the characteristic transfer function of the NPR mechanism in conjunction with the split-step Fourier algorithm, which offer a great help in exploring the interrelationship between the NLP formation and various cavity parameters, and eventually present good agreement with the experimental results. We stress that if the cavity operates with excessively high gain, i.e., higher than the levels just required for generating coherent mode-locked pulses, i.e., conventional solitons and dissipative solitons, it may trigger NLPs, depending on the characteristic transfer function of the NPR mechanism induced in the cavity. In particular, the NPR transfer function is characterized by the critical saturation power and the linear loss ratio. Finally, we also report on the applications of the fiber-based NLP sources, including supercontinuum generation in a master-oscillator power amplifier configuration seeded by a fiber-based NLP source, as one typical example. We expect that the NLP-related research area will continue to expand, and that NLP-based sources will also find more applications in the future.

Evaluation and integration of functional annotation pipelines for newly sequenced organisms: the potato genome as a test case.

PubMed

Amar, David; Frades, Itziar; Danek, Agnieszka; Goldberg, Tatyana; Sharma, Sanjeev K; Hedley, Pete E; Proux-Wera, Estelle; Andreasson, Erik; Shamir, Ron; Tzfadia, Oren; Alexandersson, Erik

2014-12-05

For most organisms, even if their genome sequence is available, little functional information about individual genes or proteins exists. Several annotation pipelines have been developed for functional analysis based on sequence, 'omics', and literature data. However, researchers encounter little guidance on how well they perform. Here, we used the recently sequenced potato genome as a case study. The potato genome was selected since its genome is newly sequenced and it is a non-model plant even if there is relatively ample information on individual potato genes, and multiple gene expression profiles are available. We show that the automatic gene annotations of potato have low accuracy when compared to a "gold standard" based on experimentally validated potato genes. Furthermore, we evaluate six state-of-the-art annotation pipelines and show that their predictions are markedly dissimilar (Jaccard similarity coefficient of 0.27 between pipelines on average). To overcome this discrepancy, we introduce a simple GO structure-based algorithm that reconciles the predictions of the different pipelines. We show that the integrated annotation covers more genes, increases by over 50% the number of highly co-expressed GO processes, and obtains much higher agreement with the gold standard. We find that different annotation pipelines produce different results, and show how to integrate them into a unified annotation that is of higher quality than each single pipeline. We offer an improved functional annotation of both PGSC and ITAG potato gene models, as well as tools that can be applied to additional pipelines and improve annotation in other organisms. This will greatly aid future functional analysis of '-omics' datasets from potato and other organisms with newly sequenced genomes. The new potato annotations are available with this paper.

Relationship of Soluble RAGE with Insulin Resistance and Beta Cell Function during Development of Type 2 Diabetes Mellitus

PubMed Central

Biswas, Subrata Kumar; Mohtarin, Sabreena; Mudi, Sonchita Rani; Anwar, Taznuva; Banu, Laila Anjuman; Alam, Sheikh Md. Khorshed; Fariduddin, Md.; Arslan, M. Iqbal

2015-01-01

This study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed T2DM. The control subjects (n = 40) and people with prediabetes (n = 52) and diabetes (n = 66) were similar in terms of age, sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found significantly higher in people with diabetes than control subjects (p < 0.001) and people with prediabetes (p = 0.005); and HOMA-%B was found significantly deteriorated in people with diabetes (p < 0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did not show any significant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate analyses did not identify any significant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM. PMID:26078977

Relationship of Soluble RAGE with Insulin Resistance and Beta Cell Function during Development of Type 2 Diabetes Mellitus.

PubMed

Biswas, Subrata Kumar; Mohtarin, Sabreena; Mudi, Sonchita Rani; Anwar, Taznuva; Banu, Laila Anjuman; Alam, Sheikh Md Khorshed; Fariduddin, Md; Arslan, M Iqbal

2015-01-01

This study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed T2DM. The control subjects (n = 40) and people with prediabetes (n = 52) and diabetes (n = 66) were similar in terms of age, sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found significantly higher in people with diabetes than control subjects (p < 0.001) and people with prediabetes (p = 0.005); and HOMA-%B was found significantly deteriorated in people with diabetes (p < 0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did not show any significant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate analyses did not identify any significant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM.

Scale Refinement and Initial Evaluation of a Behavioral Health Function Measurement Tool for Work Disability Evaluation

PubMed Central

Marfeo, Elizabeth E.; Ni, Pengsheng; Bogusz, Kara; Meterko, Mark; McDonough, Christine M.; Chan, Leighton; Rasch, Elizabeth K.; Brandt, Diane E.; Jette, Alan M.

2014-01-01

Objectives To use item response theory (IRT) data simulations to construct and perform initial psychometric testing of a newly developed instrument, the Social Security Administration Behavioral Health Function (SSA-BH) instrument, that aims to assess behavioral health functioning relevant to the context of work. Design Cross-sectional survey followed by item response theory (IRT) calibration data simulations Setting Community Participants A sample of individuals applying for SSA disability benefits, claimants (N=1015), and a normative comparative sample of US adults (N=1000) Interventions None. Main Outcome Measure Social Security Administration Behavioral Health Function (SSA-BH) measurement instrument Results Item response theory analyses supported the unidimensionality of four SSA-BH scales: Mood and Emotions (35 items), Self-Efficacy (23 items), Social Interactions (6 items), and Behavioral Control (15 items). All SSA-BH scales demonstrated strong psychometric properties including reliability, accuracy, and breadth of coverage. High correlations of the simulated 5- or 10- item CATs with the full item bank indicated robust ability of the CAT approach to comprehensively characterize behavioral health function along four distinct dimensions. Conclusions Initial testing and evaluation of the SSA-BH instrument demonstrated good accuracy, reliability, and content coverage along all four scales. Behavioral function profiles of SSA claimants were generated and compared to age and sex matched norms along four scales: Mood and Emotions, Behavioral Control, Social Interactions, and Self-Efficacy. Utilizing the CAT based approach offers the ability to collect standardized, comprehensive functional information about claimants in an efficient way, which may prove useful in the context of the SSA’s work disability programs. PMID:23542404

Applications of functional carbon nanomaterials from hydrogen storage to drug delivery

NASA Astrophysics Data System (ADS)

Leonard, Ashley Dawn

This dissertation describes the modification and functionalization of single-walled carbon nanotubes (SWCNTs). These SWCNTs were then investigated for their use in medical applications and for the storage of hydrogen. A technique was developed that leads to highly customized, individually suspended aqueous solutions of SWCNTs. These newly generated water-soluble SWCNTs were then functionalized further in water, thereby permitting the second functionalization addends to be chemically sensitive functional groups, for example drugs, that would not withstand the strongly acidic conditions of the first functionalization. The radical scavenging properties of nanovectors derived from SWCNTs were investigated and it was found that even the poorest SWCNT nanovector studied was nearly 40 times more effective at scavenging radicals than dendrite-fullerene DF-1, which has been shown to be a radioprotective to zebrafish via an antioxidant niechanism. This was used as the base to investigate using SWCNTs as protectors and mitigators of radiation exposure. SWCNTs were then explored for their use as drug delivery agents, in particular, the water insoluble chemotherapy drug, paclitaxel. SWCNTs showed promising in vivo and in vitro efficacy in the delivery of paclitaxel. Toxicity and biodistribution studies of the SWCNTs as drug delivery agents were performed in vivo using SWCNTs functionalized with radiolabeled indium. It was found that SWCNTs could be used for hydrogen storage by chemically crosslinking 3-dimensional frameworks of SWCNT fibers. These frameworks were shown to physisorb twice as much hydrogen, at low pressures, with respect to their surface areas, than typical macroporous carbon materials. This makes these SWCNT frameworks attractive materials for the development of a hydrogen vehicle fuel tank.

PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4

PubMed Central

Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A.; Alfaro, Iván E.; Imhof, Axel; Almouzni, Geneviève

2017-01-01

Abstract Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. PMID:28977641

PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.

PubMed

Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A; Alfaro, Iván E; Imhof, Axel; Almouzni, Geneviève; Loyola, Alejandra

2017-11-16

Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Generating global network structures by triad types

PubMed Central

Ferligoj, Anuška; Žiberna, Aleš

2018-01-01

This paper addresses the question of whether one can generate networks with a given global structure (defined by selected blockmodels, i.e., cohesive, core-periphery, hierarchical, and transitivity), considering only different types of triads. Two methods are used to generate networks: (i) the newly proposed method of relocating links; and (ii) the Monte Carlo Multi Chain algorithm implemented in the ergm package in R. Most of the selected blockmodel types can be generated by considering all types of triads. The selection of only a subset of triads can improve the generated networks’ blockmodel structure. Yet, in the case of a hierarchical blockmodel without complete blocks on the diagonal, additional local structures are needed to achieve the desired global structure of generated networks. This shows that blockmodels can emerge based only on local processes that do not take attributes into account. PMID:29847563

The legacy of disadvantage: multigenerational neighborhood effects on cognitive ability.

PubMed

Sharkey, Patrick; Elwert, Felix

2011-05-01

This study examines how the neighborhood environments experienced over multiple generations of a family influence children's cognitive ability. Building on recent research showing strong continuity in neighborhood environments across generations of family members, the authors argue for a revised perspective on "neighborhood effects" that considers the ways in which the neighborhood environment in one generation may have a lingering impact on the next generation. To analyze multigenerational effects, the authors use newly developed methods designed to estimate unbiased treatment effects when treatments and confounders vary over time. The results confirm a powerful link between neighborhoods and cognitive ability that extends across generations. A family's exposure to neighborhood poverty across two consecutive generations reduces child cognitive ability by more than half a standard deviation. A formal sensitivity analysis suggests that results are robust to unobserved selection bias.

Integrating support vector machines and random forests to classify crops in time series of Worldview-2 images

NASA Astrophysics Data System (ADS)

Zafari, A.; Zurita-Milla, R.; Izquierdo-Verdiguier, E.

2017-10-01

Crop maps are essential inputs for the agricultural planning done at various governmental and agribusinesses agencies. Remote sensing offers timely and costs efficient technologies to identify and map crop types over large areas. Among the plethora of classification methods, Support Vector Machine (SVM) and Random Forest (RF) are widely used because of their proven performance. In this work, we study the synergic use of both methods by introducing a random forest kernel (RFK) in an SVM classifier. A time series of multispectral WorldView-2 images acquired over Mali (West Africa) in 2014 was used to develop our case study. Ground truth containing five common crop classes (cotton, maize, millet, peanut, and sorghum) were collected at 45 farms and used to train and test the classifiers. An SVM with the standard Radial Basis Function (RBF) kernel, a RF, and an SVM-RFK were trained and tested over 10 random training and test subsets generated from the ground data. Results show that the newly proposed SVM-RFK classifier can compete with both RF and SVM-RBF. The overall accuracies based on the spectral bands only are of 83, 82 and 83% respectively. Adding vegetation indices to the analysis result in the classification accuracy of 82, 81 and 84% for SVM-RFK, RF, and SVM-RBF respectively. Overall, it can be observed that the newly tested RFK can compete with SVM-RBF and RF classifiers in terms of classification accuracy.

Understanding high endothelial venules: Lessons for cancer immunology

PubMed Central

Ager, Ann; May, Michael J

2015-01-01

High endothelial venules (HEVs) are blood vessels especially adapted for lymphocyte trafficking which are normally found in secondary lymphoid organs such as lymph nodes (LN) and Peyer's patches. It has long been known that HEVs develop in non-lymphoid organs during chronic inflammation driven by autoimmunity, infection or allografts. More recently, HEVs have been observed in solid, vascularized tumors and their presence correlated with reduced tumor size and improved patient outcome. It is proposed that newly formed HEV promote antitumor immunity by recruiting naive lymphocytes into the tumor, thus allowing the local generation of cancerous tissue-destroying lymphocytes. Understanding how HEVs develop and function are therefore important to unravel their role in human cancers. In LN, HEVs develop during embryonic and early post-natal life and are actively maintained by the LN microenvironment. Systemic blockade of lymphotoxin-β receptor leads to HEV de-differentiation, but the LN components that induce HEV differentiation have remained elusive. Recent elegant studies using gene-targeted mice have demonstrated clearly that triggering the lymphotoxin-β receptor in endothelial cells (EC) induces the differentiation of HEV and that CD11c+ dendritic cells play a crucial role in this process. It will be important to determine whether lymphotoxin-β receptor-dependent signaling in EC drives the development of HEV during tumorigenesis and which cells have HEV-inducer properties. This may reveal therapeutic approaches to promote HEV neogenesis and determine the impact of newly formed HEV on tumor immunity. PMID:26155419

[Quantity and function of T follicular helper cells in the bone marrow of patients with immune thrombocytopenia].

PubMed

Zhang, Yang; Qu, Wen; Ruan, Er-Bao; Fu, Rong; Wang, Guo-Jin; Liu, Hong; Wang, Xiao-Ming; Wu, Yu-Hong; Song, Jia; Xing, Li-Min; Guan, Jing; Li, Li-Juan; Wang, Hua-Quan; Shao, Zong-Hong

2014-06-01

This study was purposed to detect the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of patients with immune thrombocytopenia, and to explore the role of Tfh cells in the pathogenesis of ITP. Twenty-one newly diagnosed ITP patients, twenty ITP patients in recovery stage and eighteen normal controls were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 in BM were detected by flow cytometry (FCM), and the mRNA expression of BCL-6 in BMMNC was determined by semi-quantitive RT-PCR. Correlation of Tfh cell level with the disease severity of ITP patients was analysed. The results showed that the ratio of CD4(+)CXCR5(+)/CD4(+) cells in newly diagnosed ITP patients [(5.532 ± 2.599)%] was significantly higher than that in ITP patients with recovery stage [(4.064 ± 2.026)%] and controls [(4.048 ± 1.413)%] (P < 0.05). The ratio of CD4(+)CXCR5(+)ICOS(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(14.586 ± 8.561)%] was higher than that in recovery stage ITP patients [(12.884 ± 10.161)%] and controls [(7.487 ± 5.176)%]. The differences be-tween newly diagnosed ITP patients and controls were statistically significant (P < 0.05). The ratio of CD4(+)CXCR5(+) CD40L(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(15.309 ± 10.756)%] and in ITP patients with recovery stage [(18.242 ± 12.243)%] were significantly higher than that in controls [(8.618 ± 5.719) %] (P < 0.05). The ratio of intracytoplasm CD4(+) CXCR5(+) IL-21(+)/CD4(+)CXCR5(+) cells in newly diagnosed ITP patients [(58.560 ± 26.285)%] and in ITP patients with recovery stage [(57.035 ± 30.936)%] were significantly higher than that in controls [(36.289 ± 24.868)%] (P < 0.05). The relative expression levels of BCL-6 mRNA in BMMNC of three groups were (1.407 ± 0.264), (1.149 ± 0.217) and (0.846 ± 0.157), respectively. The differences between 3 groups were significant(P < 0.05). It is concluded that the quantity and function of Tfh cells in ITP patients increase, which may play an important role in the pathogenesis of ITP.

Snapshot of photovoltaics - February 2018

NASA Astrophysics Data System (ADS)

Jäger-Waldau, Arnulf

2018-05-01

Solar photovoltaic electricity generation is the fastest growing power generation source world-wide. The significant cost reduction of solar PV over the last decade, and the zero fuel cost volatility have increased the attractiveness. In 2017, the newly installed solar PV power of over 90 GW was more than all the world-wide cumulative installed PV capacity until the mid of 2012. China was again the main driver behind this strong growth with more than 50 GW of annual installations in 2017. Apart from the electricity sector, renewable energy sources for the generation of heat and environmental friendly synthetic-fuels for the transport sector will become more and more important in the future.

Generation of helical Ince-Gaussian beams: beam-shaping with a liquid crystal display

NASA Astrophysics Data System (ADS)

Davis, Jeffrey A.; Bentley, Joel B.; Bandres, Miguel A.; Gutiérrez-Vega, Julio C.

2006-08-01

We review the three types of laser beams - Hermite-Gaussian (HG), Laguerre-Gaussian (LG) and the newly discovered Ince-Gaussian (IG) beams. We discuss the helical forms of the LG and IG beams that consist of linear combinations of the even and odd solutions and form a number of vortices that are useful for optical trapping applications. We discuss how to generate these beams by encoding the desired amplitude and phase onto a single parallel-aligned liquid crystal display (LCD). We introduce a novel interference technique where we generate both the object and reference beams using a single LCD and show the vortex interference patterns.

Newly synthesized bis-benzimidazole compound 8 induces apoptosis, autophagy and reactive oxygen species generation in HeLa cells.

PubMed

Chu, Naying; Yao, Guodong; Liu, Yuan; Cheng, Maosheng; Ikejima, Takashi

2016-09-01

Compound 8 (C8) is a newly synthesized bis-benzimidazole derivative and exerts significant anti-tumor activity in vitro. Previous studies demonstrated that C8 induced apoptosis and autophagy in human promyelocytic leukemia HL60 cells. However, cytotoxicity study on human peripheral blood mononuclear cells (hPBMC) showed that C8 exhibited less toxicity in normal cells. In this study, the molecular mechanism of C8 on human cervical carcinoma HeLa cells was investigated. The results showed that C8 inhibited the growth of HeLa cells and triggered both apoptotic and autophagic cell death. Subsequent experiment also indicated that reactive oxygen species (ROS) generation was induced in C8-treated HeLa cells. Since ROS scavenger decreased the ratio of apoptotic and autophagic cells, ROS generation contributed to C8-induced apoptosis and autophagy. Furthermore, inhibitors of apoptosis and autophagy also reduced ROS generation, respectively. Autophagy inhibition increased cell growth compared to C8-treated group and attenuated apoptotic cell death, indicating that C8-induced autophagy promoted apoptosis for cell death. However, the percentage of autophagic cells was enhanced when limiting apoptosis process. Taken together, C8 induced ROS-mediated apoptosis and autophagy in HeLa cells, autophagy promoted apoptosis but the former was antagonized by the latter. The data also gave us a new perspective on the anti-tumor effect of C8. Copyright © 2016 Elsevier Ltd. All rights reserved.

Goblet Cells of the Conjunctiva: A Review of Recent Findings

PubMed Central

Gipson, Ilene K

2016-01-01

Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed. PMID:27091323

Deep FIFO Surge Buffer

NASA Technical Reports Server (NTRS)

Temple, Gerald; Siegel, Marc; Amitai, Zwie

1991-01-01

First-in/first-out (FIFO) temporarily stores short surges of data generated by data-acquisition system at excessively high rate and releases data at lower rate suitable for processing by computer. Size and complexity reduced while capacity enhanced by use of newly developed, sophisticated integrated circuits and by "byte-folding" scheme doubling effective depth and data rate.

ONR (Office of Naval Research) Far East Scientific Bulletin. Volume 10, Number 1, January to March 1985.

DTIC Science & Technology

1985-03-01

they are brazing silicon nitride to tungsten using a newly patented 80% copper- chromium -cobalt amorphous alloy. Welding Mechanics Professor K. Satoh...45. Millimeter Energy Beam Generator 46. Fusion Welders (ESW, EGW, SAW, GMAW, GTAW , PAW, etc.) ONRFE SCI BUL 10 (1) 85 26

Designing the Next-Generation Chemistry Journal: The Internet Journal of Chemistry.

ERIC Educational Resources Information Center

Bachrach, Steven M.; Burleigh, Darin C.; Krassivine, Anatoli

1998-01-01

Discusses how the journal "Internet Journal of Chemistry" is designed to take advantage of newly available technologies. Describes the development of the concept of an electronic journal, decision-making on the scope and coverage of the journal, financial logistics, and how the journal will be implemented. Includes perspectives on how this new…

Trends in emerging and high risk activities

Treesearch

Robert C. White; Richard Schreyer; Kent Downing

1980-01-01

Newly emerging and high risk activities have increased markedly in the last generation, yet little is known about trends in participation. Factors such as technological innovation and creative experimentation with traditional activities appear to play a major role in the development of new activities. Christy's criteria for mass demand in recreation are used to...

[Structure of newly formed capillaries of the rabbit cornea (electron microscopic study)].

PubMed

Gurina, O Iu; Karaganov, Ia L

1984-08-01

Owing to a complex application of topical analysis and tracer technique, it is possible to carry out a light optic and electron microscopic investigation of newly formed capillaries growing in the rabbit cornea after its chemical burn. The ultrastructural analysis demonstrates certain polymorphism of morphological organization of endotheliocyte in the newly formed capillaries. There is a rather elevated amount of free ribosomes, mitochondria, microtubules and microfilaments in cytoplasm. The granular endoplasmic reticulum and Golgi complex are hypertrophied. Weibel--Palade bodies appear. Taking into account certain morpho-functional peculiarities of endothelial cells along the course of the growing capillaries, on the 8th day of growth three zone are distinguished: 1--area of nondifferentiated endothelium (apex of the capillary), 2--transitional zone, 3--zone of relatively differentiated endothelium situating in the place where the capillary gets off the parental vessel. According to the zones distinguished, the ways of trans-endothelial transport of molecules are investigated. In formation of the capillary barrier-transport function an important role belongs to polymorphism of the endothelial cells along the course of the growing capillary which is determined by differentiation degree of these cells depending on their participation in permeability.

Study of Physical and Mental Health of Older Patients With Newly Diagnosed Cancer

ClinicalTrials.gov

2015-10-01

Cognitive/Functional Effects; Depression; Hematopoietic/Lymphoid Cancer; Malnutrition; Pain; Psychosocial Effects of Cancer and Its Treatment; Unspecified Adult Solid Tumor, Protocol Specific; Weight Changes

Preceptors' perceptions of the elements of a successful and an unsuccessful orientation period for newly graduated nurses.

PubMed

Lindfors, Kirsi; Meretoja, Riitta; Kaunonen, Marja; Paavilainen, Eija

2018-04-01

To identify existing orientation patterns and to find elements that may enhance or impede successful orientation of newly graduated nurses. Preceptors have first-hand information concerning orientation and their opinions should not be forgotten when organisations develop their orientation processes. An open-ended questionnaire was undertaken to collect data from preceptors (n = 172) about the current orientation patterns. Data were analysed by using deductive content analysis and by quantifying the phrases. Communal commitment to the orientation process, strong professional orientation know-how and supportive leadership were the enhancing elements of successful orientation. Complex interpersonal relationship problems during orientation, inadequate orientation resources and the organisation's structural and functional problems were the impeding elements of successful orientation. With the elements of successful orientation we ensure a supportive transition to practice for newly graduate nurses and possibilities to focus on good orientation practices for preceptors. Nurse leaders play an important part in ensuring newly graduated nurses have a safe nursing career starting point and, for preceptors, opportunities to provide orientation that is as good as possible. Supportive leadership, sufficient resources and good interpersonal relationships should be the leading principles during newly graduated nurses' orientation period. © 2017 John Wiley & Sons Ltd.

Thermophysical properties of liquid rare earth metals

NASA Astrophysics Data System (ADS)

Thakor, P. B.; Sonvane, Y. A.; Patel, H. P.; Jani, A. R.

2013-06-01

The thermodynamical properties like long wavelength limit S(0), iso-thermal compressibility (χT), thermal expansion coefficient (αV), thermal pressure coefficient (γV), specific heat at constant volume (CV) and specific heat at constant pressure (CP) are calculated for liquid rare earth metals. Our newly constructed parameter free model potential is used to describe the electron ion interaction due to Sarkar et al (S) local field correction function. Lastly, we conclude that our newly constructed model potential is capable to explain the thermophysical properties of liquid rare earth metals.

Executive Function in Early Childhood: Longitudinal Measurement Invariance and Developmental Change

ERIC Educational Resources Information Center

Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

2012-01-01

This study tested the longitudinal measurement invariance and developmental changes of a newly developed battery of executive function (EF) tasks for use in early childhood. The battery was administered in the Family Life Project--a prospective longitudinal study (N = 1,292) of families who were oversampled from low-income and African American…

Emerging pharmacological therapy for functional dyspepsia.

PubMed

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

2013-10-01

Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

Preparing for adulthood: thousands upon thousands of new cells are born in the hippocampus during puberty, and most survive with effortful learning

PubMed Central

Curlik, Daniel M.; DiFeo, Gina; Shors, Tracey J.

2014-01-01

The dentate gyrus of the hippocampal formation generates new granule neurons throughout life. The number of neurons produced each day is inversely related to age, with thousands more produced during puberty than during adulthood, and many fewer produced during senescence. In adulthood, approximately half of these cells undergo apoptosis shortly after they are generated. Most of these cells can be rescued from death by effortful and successful learning experiences (Gould et al., 1999; Waddell and Shors, 2008; Curlik and Shors, 2011). Once rescued, the newly-generated cells differentiate into neurons, and remain in the hippocampus for at least several months (Leuner et al., 2004). Here, we report that many new hippocampal cells also undergo cell death during puberty. Because the juvenile brain is more plastic than during adulthood, and because many experiences are new, we hypothesized that a great number of cells would be rescued by learning during puberty. Indeed, adolescent rats that successfully acquired the trace eyeblink response retained thousands more cells than animals that were not trained, and those that failed to learn. Because the hippocampus generates thousands more cells during puberty than during adulthood, these results support the idea that the adolescent brain is especially responsive to learning. This enhanced response can have significant consequences for the functional integrity of the hippocampus. Such a massive increase in cell proliferation is likely an adaptive response as the young animal must emerge from the care of its mother to face the dangers, challenges, and opportunities of adulthood. PMID:24795549

A novel far-red fluorescent xenograft model of ovarian carcinoma for preclinical evaluation of HER2-targeted immunotoxins

PubMed Central

Zdobnova, Tatiana; Sokolova, Evgeniya; Stremovskiy, Oleg; Karpenko, Dmitry; Telford, William; Turchin, Ilya; Balalaeva, Irina; Deyev, Sergey

2015-01-01

We have created a novel fluorescent model of a human ovarian carcinoma xenograft overexpressing receptor HER2, a promising molecular target of solid tumors. The model is based on a newly generated SKOV-kat cell line stably expressing far-red fluorescent protein Katushka. Katushka is most suitable for the in vivo imaging due to an optimal combination of high brightness and emission in the “window of tissue transparency”. The relevance of the fluorescent model for the in vivo monitoring of tumor growth and response to treatment was demonstrated using a newly created HER2-targeted recombinant immunotoxin based on the 4D5scFv antibody and a fragment of the Pseudomonas exotoxin A. PMID:26436696

Priming in Episodic and Semantic Memory.

ERIC Educational Resources Information Center

McKoon, Gail; Ratcliff, Roger

1979-01-01

Four experiments examined priming between newly learned paired associates through two procedures, lexical decision and item recognition. Results argue against a functional separation of the semantic and episodic memory systems. (Author/AM)

Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

PubMed

Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

2017-08-01

Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to anti-epileptic effects of aspirin.

Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

PubMed Central

Wei, Lu; Yu, Yong; Shen, Yihui; Wang, Meng C.; Min, Wei

2013-01-01

Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial–temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon–deuterium bonds (C–D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo. PMID:23798434

Growth Type and Functional Trajectories: An Empirical Study of Urban Expansion in Nanjing, China

PubMed Central

Yuan, Feng

2016-01-01

Drawing upon the Landsat satellite images of Nanjing from 1985, 1995, 2001, 2007, and 2013, this paper integrates the convex hull analysis and common edge analysis at double scales, and develops a comprehensive matrix analysis to distinguish the different types of urban land expansion. The results show that Nanjing experienced rapid urban expansion, dominated by a mix of residential and manufacturing land from 1985 to 2013, which in turn has promoted Nanjing’s shift from a compact mononuclear city to a polycentric one. Spatial patterns of three specific types of growth, namely infilling, extension, and enclave were quite different in four consecutive periods. These patterns result primarily from the existing topographic constraints, as well as government-oriented urban planning and policies. By intersecting the function maps, we also reveal the functional evolution of newly-developed urban land. Moreover, both self-enhancing and mutual promotion of the newly developed functions are surveyed over the last decade. Our study confirms that the integration of a multi-scale method and multi-perspective analysis, such as the spatiotemporal patterns and functional evolution, helps us to better understand the rapid urban growth in China. PMID:26845155

O-mannosylation and N-glycosylation: two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer

PubMed Central

Bartels, Markus F.; Miyoshi, Eiji; Pierce, Michael; Taniguchi, Naoyuki; Carneiro, Fátima; Seruca, Raquel; Reis, Celso A.; Strahl, Sabine; Pinho, Salomé S.

2016-01-01

Dysregulation of tumor suppressor protein E-cadherin is an early molecular event in cancer. O-mannosylation profile of E-cadherin is a newly-described post-translational modification crucial for its adhesive functions in homeostasis. However, the role of O-mannosyl glycans in E-cadherin-mediated cell adhesion in cancer and their interplay with N-glycans remains largely unknown. We herein demonstrated that human gastric carcinomas exhibiting a non-functional E-cadherin display a reduced expression of O-mannosyl glycans concomitantly with increased modification with branched complex N-glycans. Accordingly, overexpression of MGAT5-mediated branched N-glycans both in gastric cancer cells and transgenic mice models led to a significant decrease of O-mannosyl glycans attached to E-cadherin that was associated with impairment of its tumour suppressive functions. Importantly, overexpression of protein O-mannosyltransferase 2 (POMT2) induced a reduced expression of branched N-glycans which led to a protective effect of E-cadherin biological functions. Overall, our results reveal a newly identified mechanism of (dys)regulation of E-cadherin that occur through the interplay between O-mannosylation and N-glycosylation pathway. PMID:27533452

Feasibility of Rehabilitation Training With a Newly Developed, Portable, Gait Assistive Robot for Balance Function in Hemiplegic Patients

PubMed Central

2017-01-01

Objective To investigate the clinical feasibility of a newly developed, portable, gait assistive robot (WA-H, ‘walking assist for hemiplegia’) for improving the balance function of patients with stroke-induced hemiplegia. Methods Thirteen patients underwent 12 weeks of gait training on the treadmill while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery (SPPB) before and after 6 and 12 weeks of training. Results There were no serious complications or clinical difficulties during gait training with WA-H. In three categories of BBS, TUGT, and the balance scale of SPPB, there was a statistically significant improvement at the 6th week and 12th week of gait training with WA-H. In the subscale of balance function of FMAS, there was statistically significant improvement only at the 12th week. Conclusion Gait training using WA-H demonstrated a beneficial effect on balance function in patients with hemiplegia without a safety issue. PMID:28503449

Monolayer Transition Metal Dichalcogenides as Light Sources.

PubMed

Pu, Jiang; Takenobu, Taishi

2018-06-13

Reducing the dimensions of materials is one of the key approaches to discovering novel optical phenomena. The recent emergence of 2D transition metal dichalcogenides (TMDCs) has provided a promising platform for exploring new optoelectronic device applications, with their tunable electronic properties, structural controllability, and unique spin valley-coupled systems. This progress report provides an overview of recent advances in TMDC-based light-emitting devices discussed from several aspects in terms of device concepts, material designs, device fabrication, and their diverse functionalities. First, the advantages of TMDCs used in light-emitting devices and their possible functionalities are presented. Second, conventional approaches for fabricating TMDC light-emitting devices are emphasized, followed by introducing a newly established, versatile method for generating light emission in TMDCs. Third, current growing technologies for heterostructure fabrication, in which distinct TMDCs are vertically stacked or laterally stitched, are explained as a possible means for designing high-performance light-emitting devices. Finally, utilizing the topological features of TMDCs, the challenges for controlling circularly polarized light emission and its device applications are discussed from both theoretical and experimental points of view. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biochemical and Structural Characterization of the Human TL1A Ectodomain†¶

PubMed Central

Zhan, Chenyang; Yan, Qingrong; Patskovsky, Yury; Li, Zhenhong; Toro, Rafael; Meyer, Amanda; Cheng, Huiyong; Brenowitz, Michael; Nathenson, Stanley G; Almo, Steven C

2009-01-01

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 Å, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors. PMID:19522538

Restoration of vision after transplantation of photoreceptors.

PubMed

Pearson, R A; Barber, A C; Rizzi, M; Hippert, C; Xue, T; West, E L; Duran, Y; Smith, A J; Chuang, J Z; Azam, S A; Luhmann, U F O; Benucci, A; Sung, C H; Bainbridge, J W; Carandini, M; Yau, K-W; Sowden, J C; Ali, R R

2012-05-03

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms.

PubMed

Mion, S; Corti, C; Neki, A; Shigemoto, R; Corsi, M; Fumagalli, G; Ferraguti, F

2001-06-01

Alternative splicing in the mGluR5 gene generates two different receptor isoforms, of which expression is developmentally regulated. However, little is known about the functional significance of mGluR5 splice variants. We have examined the functional coupling, subcellular targeting, and effect on neuronal differentiation of epitope-tagged mGluR5 isoforms by expression in neuroblastoma NG108-15 cells. We found that both mGluR5 splice variants give rise to comparable [Ca2+]i transients and have similar pharmacological profile. Tagged receptors were shown by immunofluorescence to be inserted in the plasma membrane. In undifferentiated cells the subcellular localization of the two mGluR5 isoforms was partially segregated, whereas in differentiated cells the labeling largely redistributed to the newly formed neurites. Interestingly, we demonstrate that mGluR5 splice variants dramatically influence the formation and maturation of neurites; mGluR5a hinders the acquisition of mature neuronal traits and mGluR5b fosters the elaboration and extension of neurites. These effects are partly inhibited by MPEP. Copyright 2001 Academic Press.

GMars-T Enabling Multimodal Subdiffraction Structural and Functional Fluorescence Imaging in Live Cells.

PubMed

Wang, Sheng; Chen, Xuanze; Chang, Lei; Ding, Miao; Xue, Ruiying; Duan, Haifeng; Sun, Yujie

2018-06-05

Fluorescent probes with multimodal and multilevel imaging capabilities are highly valuable as imaging with such probes not only can obtain new layers of information but also enable cross-validation of results under different experimental conditions. In recent years, the development of genetically encoded reversibly photoswitchable fluorescent proteins (RSFPs) has greatly promoted the application of various kinds of live-cell nanoscopy approaches, including reversible saturable optical fluorescence transitions (RESOLFT) and stochastic optical fluctuation imaging (SOFI). However, these two classes of live-cell nanoscopy approaches require different optical characteristics of specific RSFPs. In this work, we developed GMars-T, a monomeric bright green RSFP which can satisfy both RESOLFT and photochromic SOFI (pcSOFI) imaging in live cells. We further generated biosensor based on bimolecular fluorescence complementation (BiFC) of GMars-T which offers high specificity and sensitivity in detecting and visualizing various protein-protein interactions (PPIs) in different subcellular compartments under physiological conditions (e.g., 37 °C) in live mammalian cells. Thus, the newly developed GMars-T can serve as both structural imaging probe with multimodal super-resolution imaging capability and functional imaging probe for reporting PPIs with high specificity and sensitivity based on its derived biosensor.

Addressing Facts and Gaps in the Phenolics Chemistry of Winery By-Products.

PubMed

Machado, Nelson F L; Domínguez-Perles, Raúl

2017-02-14

Grape and wine phenolics display a noticeable structural diversity, encompassing distinct compounds ranging from simple molecules to oligomers, as well as polymers usually designated as tannins. Since these compounds contribute critically to the organoleptic properties of wines, their analysis and quantification are of primordial importance for winery industry operators. Besides, the occurrence of these compounds has been also extensively described in winery residues, which have been pointed as a valuable source of bioactive phytochemicals presenting potential for the development of new added value products that could fit the current market demands. Therefore, the cumulative knowledge generated during the last decades has allowed the identification of the most promising compounds displaying interesting biological functions, as well as the chemical features responsible for the observed bioactivities. In this regard, the present review explores the scope of the existing knowledge, concerning the compounds found in these winery by-products, as well as the chemical features presumably responsible for the biological functions already identified. Moreover, the present work will hopefully pave the way for further actions to develop new powerful applications to these materials, thus, contributing to more sustainable valorization procedures and the development of newly obtained compounds with enhanced biological properties.

Biochemical and Structural Characterization of the Human TL1A Ectodomain

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

Zhan, C.; Yan, Q; Patskovsky, Y

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 {angstrom}, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3more » differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.« less

The cross-functional role of frontoparietal regions in cognition: internal attention as the overarching mechanism.

PubMed

Lückmann, Helen C; Jacobs, Heidi I L; Sack, Alexander T

2014-05-01

Neuroimaging studies have repeatedly reported findings of activation in frontoparietal regions that largely overlap across various cognitive functions. Part of this frontoparietal activation has been interpreted as reflecting attentional mechanisms that can adaptively be directed towards external stimulation as well as internal representations (internal attention), thereby generating the experience of distinct cognitive functions. Nevertheless, findings of material- and task-specific activation in frontal and parietal regions challenge this internal attention hypothesis and have been used to support more modular hypotheses of cognitive function. The aim of this review is twofold: First, it discusses evidence in support of the concept of internal attention and the so-called dorsal attention network (DAN) as its neural source with respect to three cognitive functions (working memory, episodic retrieval, and mental imagery). While DAN activation in all three functions has been separately linked to internal attention, a comprehensive and integrative review has so far been lacking. Second, the review examines findings of material- and process-specific activation within frontoparietal regions, arguing that these results are well compatible with the internal attention account of frontoparietal activation. A new model of cognition is presented, proposing that supposedly different cognitive concepts actually rely on similar attentional network dynamics to maintain, reactivate and newly create internal representations of stimuli in various modalities. Attentional as well as representational mechanisms are assigned to frontal and parietal regions, positing that some regions are implicated in the allocation of attentional resources to perceptual or internal representations, but others are involved in the representational processes themselves. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hard-Diet Feeding Recovers Neurogenesis in the Subventricular Zone and Olfactory Functions of Mice Impaired by Soft-Diet Feeding

PubMed Central

Utsugi, Chizuru; Miyazono, Sadaharu; Osada, Kazumi; Sasajima, Hitoshi; Noguchi, Tomohiro; Matsuda, Mitsuyoshi; Kashiwayanagi, Makoto

2014-01-01

The subventricular zone (SVZ) generates an immense number of neurons even during adulthood. These neurons migrate to the olfactory bulb (OB) and differentiate into granule cells and periglomerular cells. The information broadcast by general odorants is received by the olfactory sensory neurons and transmitted to the OB. Recent studies have shown that a reduction of mastication impairs both neurogenesis in the hippocampus and brain functions. To examine these effects, we first measured the difference in Fos-immunoreactivity (Fos-ir) at the principal sensory trigeminal nucleus (Pr5), which receives intraoral touch information via the trigeminal nerve, when female adult mice ingested a hard or soft diet to explore whether soft-diet feeding could mimic impaired mastication. Ingestion of a hard diet induced greater expression of Fos-ir cells at the Pr5 than did a soft diet or no diet. Bromodeoxyuridine-immunoreactive (BrdU-ir) structures in sagittal sections of the SVZ and in the OB of mice fed a soft or hard diet were studied to explore the effects of changes in mastication on newly generated neurons. After 1 month, the density of BrdU-ir cells in the SVZ and OB was lower in the soft-diet-fed mice than in the hard-diet-fed mice. The odor preferences of individual female mice to butyric acid were tested in a Y-maze apparatus. Avoidance of butyric acid was reduced by the soft-diet feeding. We then explored the effects of the hard-diet feeding on olfactory functions and neurogenesis in the SVZ of mice impaired by soft-diet feeding. At 3 months of hard-diet feeding, avoidance of butyric acid was reversed and responses to odors and neurogenesis were recovered in the SVZ. The present results suggest that feeding with a hard diet improves neurogenesis in the SVZ, which in turn enhances olfactory function at the OB. PMID:24817277

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

PubMed

Droogsma, E; van Asselt, D Z B; Schölzel-Dorenbos, C J M; van Steijn, J H M; van Walderveen, P E; van der Hooft, C S

2013-07-01

To determine the prevalence of malnutrition and its relation to various factors in community-dwelling elderly with newly diagnosed Alzheimer's disease (AD). Retrospective cross-sectional study. Memory clinic in a rural part of the Netherlands. 312 Community-dwelling AD patients, aged 65 years or older, were included. At the time the diagnosis AD was made, socio-demographic characteristics and data on nutritional status (Mini Nutritional Assessment (MNA)), cognitive function (Mini Mental State Examination (MMSE), Cambridge Cognitive Examination (Camcog)), functional status (Interview for Deterioration in Daily Living Activities in Dementia (IDDD), Barthel Index (BI)) and behaviour (Revised Memory and Behaviour Problems Checklist (RMBPC)) were assessed. Characteristics of well-nourished patients (MNA score >23.5) were compared to characteristics of patients at risk of malnutrition (MNA score 17-23.5). Linear regression analysis was performed to assess the effect of various factors on nutritional status. The prevalence of malnutrition was 0% and 14.1% was at risk of malnutrition. AD patients at risk of malnutrition were more impaired in basic and complex daily functioning than well-nourished AD patients (median IDDD score 41.5 [25th -75th percentile 38.8-48.0] versus median IDDD score 40.0 [25th -75th percentile 37.0-43.0], p = 0.028). The degree of impairment in basic and complex daily functioning (IDDD) was independently related to nutritional status (MNA) (p = 0.001, B = -0.062). One in seven community-dwelling elderly with newly diagnosed AD is at risk of malnutrition. The degree of impairment in daily functioning is independently related to nutritional status. Therefore, assessment of the nutritional status should be included in the comprehensive assessment of AD patients. The relation between daily functioning, nutritional status and AD warrants further investigation.

Regulators of Lysosome Function and Dynamics in Caenorhabditis elegans

PubMed Central

Gee, Kevin; Zamora, Danniel; Horm, Teresa; George, Laeth; Upchurch, Cameron; Randall, Justin; Weaver, Colby; Sanford, Caitlin; Miller, Austin; Hernandez, Sebastian; Dang, Hope; Fares, Hanna

2017-01-01

Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. After fusing with late endosomes, lysosomes are reformed from the resulting hybrid organelles through a process that involves budding of a nascent lysosome, extension of the nascent lysosome from the hybrid organelle, while remaining connected by a membrane bridge, and scission of the membrane bridge to release the newly formed lysosome. The newly formed lysosomes undergo cycles of homotypic fusion and fission reactions to form mature lysosomes. In this study, we used a forward genetic screen in Caenorhabditis elegans to identify six regulators of lysosome biology. We show that these proteins function in different steps of lysosome biology, regulating lysosome formation, lysosome fusion, and lysosome degradation. PMID:28122949

Vortex algebra by multiply cascaded four-wave mixing of femtosecond optical beams.

PubMed

Hansinger, Peter; Maleshkov, Georgi; Garanovich, Ivan L; Skryabin, Dmitry V; Neshev, Dragomir N; Dreischuh, Alexander; Paulus, Gerhard G

2014-05-05

Experiments performed with different vortex pump beams show for the first time the algebra of the vortex topological charge cascade, that evolves in the process of nonlinear wave mixing of optical vortex beams in Kerr media due to competition of four-wave mixing with self-and cross-phase modulation. This leads to the coherent generation of complex singular beams within a spectral bandwidth larger than 200nm. Our experimental results are in good agreement with frequency-domain numerical calculations that describe the newly generated spectral satellites.

Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge

PubMed Central

Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

2013-01-01

We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925

Biosynthesis of fibronectin by rabbit aorta.

PubMed

Takasaki, I; Chobanian, A V; Brecher, P

1991-09-15

The in vitro interactions between vascular cells and fibronectin have been shown to influence phenotypic expression of both cultured endothelial and smooth muscle cells. To more effectively assess the potential functional role of fibronectin in vivo in modulating vascular phenotypes, we have established methodology for studying fibronectin biosynthesis in the rabbit aorta using aortic rings that are morphologically and functionally intact and metabolically active. Aortic rings were incubated with 35S-labeled methionine in a supplemented physiological salt solution. The tissue was fractionated, and quantitative immunoprecipitation was performed using a polyclonal antibody directed against human plasma fibronectin. Newly synthesized fibronectin was most abundant in the fraction solubilized using 4% sodium dodecyl sulfate and in the incubation medium. In all fractions studied, fibronectin was present predominantly as a dimer with no detectable aggregates of fibronectin. Pulse-chase experiments showed that a substantial amount of newly synthesized fibronectin was found in the 4% sodium dodecyl sulfate extract after only 1 h, suggesting that fibronectin was rapidly incorporated into the extracellular matrix. The more soluble forms of newly synthesized fibronectin appeared to be the precursors for secreted fibronectin, and no precursor-product relationship between soluble and insoluble fibronectin was found. Dissection of aortic rings following incubation with labeled methionine showed that newly synthesized fibronectin was uniformally distributed in both intima-media and media-adventitia segments. Endothelial cell denudation caused only a 20% decrease of fibronectin biosynthesis concomitant with similar changes in total protein biosynthesis, consistent with the medial smooth muscle cell as the major source of newly synthesized fibronectin. Biosynthesis of fibronectin was increased following a 24-h preincubation of the aortic rings, and concomitant increases in steady state mRNA for fibronectin were found. These in vitro studies documented the utility of aortic rings for the general purpose of studying protein synthesis in vascular cells and provide new information on the characteristics of fibronectin biosynthesis by aortic tissue.

Time-series-based hybrid mathematical modelling method adapted to forecast automotive and medical waste generation: Case study of Lithuania.

PubMed

Karpušenkaitė, Aistė; Ruzgas, Tomas; Denafas, Gintaras

2018-05-01

The aim of the study was to create a hybrid forecasting method that could produce higher accuracy forecasts than previously used 'pure' time series methods. Mentioned methods were already tested with total automotive waste, hazardous automotive waste, and total medical waste generation, but demonstrated at least a 6% error rate in different cases and efforts were made to decrease it even more. Newly developed hybrid models used a random start generation method to incorporate different time-series advantages and it helped to increase the accuracy of forecasts by 3%-4% in hazardous automotive waste and total medical waste generation cases; the new model did not increase the accuracy of total automotive waste generation forecasts. Developed models' abilities to forecast short- and mid-term forecasts were tested using prediction horizon.

Development of chronic allergic responses by dampening Bcl6-mediated suppressor activity in memory T helper 2 cells

PubMed Central

Ogasawara, Takashi; Hatano, Masahiko; Satake, Hisae; Ikari, Jun; Taniguchi, Toshibumi; Tsuruoka, Nobuhide; Watanabe-Takano, Haruko; Fujimura, Lisa; Sakamoto, Akemi; Hirata, Hirokuni; Sugiyama, Kumiya; Fukushima, Yasutsugu; Nakae, Susumu; Matsumoto, Kenji; Saito, Hirohisa; Fukuda, Takeshi; Kurasawa, Kazuhiro; Tatsumi, Koichiro; Tokuhisa, Takeshi

2017-01-01

Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells. Bcl6 suppressed cytokine production epigenetically in mTH2 cells to negatively tune histone acetylation at TH2 cytokine gene loci, including Il4 loci. In addition, IL-33, a pro-TH2 cytokine, diminished Bcl6’s association with loci to which GATA3 recruitment was inversely augmented, resulting in altered IL-4, but not IL-5 and IL-13, production in mTH2 cells but no altered production in newly differentiated TH2 cells. Use of a murine asthma model that generates high levels of pro-TH2 cytokines, such as IL-33, suggested that the suppressive function of Bcl6 in mTH2 cells is abolished in severe asthma. These findings indicate a role of the interaction between TH2-promoting factors and Bcl6 in promoting appropriate IL-4 production in mTH2 cells and suggest that chronic allergic diseases involve the TH2-promoting factor-mediated functional breakdown of Bcl6, resulting in allergy exacerbation. PMID:28096407

HOW CAN NEWLY BORN RAPIDLY ROTATING NEUTRON STARS BECOME MAGNETARS?

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

Cheng, Quan; Yu, Yun-Wei, E-mail: yuyw@mail.ccnu.edu.cn

2014-05-10

In a newly born (high-temperature and Keplerian rotating) neutron star, r-mode instability can lead to stellar differential rotation, which winds the seed poloidal magnetic field (∼10{sup 11} G) to generate an ultra-high (∼10{sup 17} G) toroidal field component. Subsequently, by succumbing to the Tayler instability, the toroidal field could be partially transformed into a new poloidal field. Through such dynamo processes, the newly born neutron star with sufficiently rapid rotation could become a magnetar on a timescale of ∼10{sup 2} {sup –} {sup 3} s, with a surface dipolar magnetic field of ∼10{sup 15} G. Accompanying the field amplification, the star could spinmore » down to a period of ∼5 ms through gravitational wave radiation due to the r-mode instability and, in particular, the non-axisymmetric stellar deformation caused by the toroidal field. This scenario provides a possible explanation for why the remnant neutron stars formed in gamma-ray bursts and superluminous supernovae could be millisecond magnetars.« less

Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer

ClinicalTrials.gov

2017-11-21

Breast Cancer; Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Fatigue; Long-term Effects Secondary to Cancer Therapy in Adults; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment

Spread of Chikungunya Virus East/Central/South African Genotype in Northeast Brazil.

PubMed

Charlys da Costa, Antonio; Thézé, Julien; Komninakis, Shirley Cavalcante Vasconcelos; Sanz-Duro, Rodrigo Lopes; Felinto, Marta Rejane Lemos; Moura, Lúcia Cristina Corrêa; Barroso, Ivoneide Moreira de Oliveira; Santos, Lucineide Eliziario Correia; Nunes, Mardjane Alves de Lemos; Moura, Adriana Avila; Lourenço, José; Deng, Xutao; Delwart, Eric L; Guimarães, Maria Raquel Dos Anjos Silva; Pybus, Oliver G; Sabino, Ester C; Faria, Nuno R

2017-10-01

We investigated an outbreak of exanthematous illness in Maceió by using molecular surveillance; 76% of samples tested positive for chikungunya virus. Genetic analysis of 23 newly generated genomes identified the East/Central/South African genotype, suggesting that this lineage has persisted since mid-2014 in Brazil and may spread in the Americas and beyond.

Characterization of apple replant disease-associated microbial communities over multiple growth periods using next-generation sequencing

USDA-ARS?s Scientific Manuscript database

Replant disease in apple occurs as a result of incompletely understood and variable complexes of soil-borne pathogens that can build up over time in orchard soil. This disease limits economic viability of newly established orchards on replant sites and results in reduced productivity for the life of...

Plant Breeding: Surprisingly, Less Sex Is Better.

PubMed

van Dijk, Peter J; Rigola, Diana; Schauer, Stephen E

2016-02-08

Introduction of apomixis, asexual reproduction through seeds, into crop species has the potential to dramatically transform plant breeding. A new study demonstrates that traits can be stably transferred between generations in newly produced apomictic lines, and heralds a breeding revolution needed to increase food production for the growing planet. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a Computerized Cognitive Assessment System for Persons with Stroke: A Pilot Study

ERIC Educational Resources Information Center

Yip, Chi Kwong; Man, David W. K.

2009-01-01

This study investigates the validity of a newly developed computerized cognitive assessment system (CCAS) that is equipped with rich multimedia to generate simulated testing situations and considers both test item difficulty and the test taker's ability. It is also hypothesized that better predictive validity of the CCAS in self-care of persons…

The Determination of ’In Situ’ Anisotropic Elastic Moduli from Laboratory Ultrasonic and Field Seismic Measurements.

DTIC Science & Technology

feet of the uppermost Kayenta sandstone unit at the Mixed Company site, for which the in situ elastic moduli are determined to be as follows: C11...and plastic anisotropic properties of Kayenta sandstone from the Mixed Company site are in poor agreement with newly generated data. (Author)

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.

PubMed

Ross, Stuart A; Caballero, A Enrique; Del Prato, Stefano; Gallwitz, Baptist; Lewis-D'Agostino, Diane; Bailes, Zelie; Thiemann, Sandra; Patel, Sanjay; Woerle, Hans-Juergen; von Eynatten, Maximilian

2016-11-01

Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. www.clinicaltrials.gov identifier is NCT01512979.

The Commercialization and Functional Rationalization of College Football: Its Origins

ERIC Educational Resources Information Center

Westby, David L.; Sack, Allen

1976-01-01

The process of introducing commercialization and functional rationalization into a game originally played for fun and controlled by the participants is shown to have occurred at Yale as that institution was brought under the control of representatives of the newly rich class of bankers and industrialists coming to power in the nineteenth century.…

Contributions of Modern Measurement Theory to Measuring Executive Function in Early Childhood: An Empirical Demonstration

ERIC Educational Resources Information Center

Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

2011-01-01

This study demonstrates the merits of evaluating a newly developed battery of executive function tasks, designed for use in early childhood, from the perspective of item response theory (IRT). The battery was included in the 48-month assessment of the Family Life Project, a prospective longitudinal study of 1292 children oversampled from…

A model for mentoring newly-appointed nurse educators in nursing education institutions in South Africa.

PubMed

Seekoe, Eunice

2014-04-24

South Africa transformed higher education through the enactment of the Higher Education Act (No. 101 of 1997). The researcher identified the need to develop a model for the mentoring of newly-appointed nurse educators in nursing education institutions in South Africa.  To develop and describe the model for mentoring newly-appointed nurse educators in nursing education institutions in South Africa.  A qualitative and theory-generating design was used (following empirical findings regarding needs analysis) in order to develop the model. The conceptualisation of the framework focused on the context, content, process and the theoretical domains that influenced the model. Ideas from different theories were borrowed from and integrated with the literature and deductive and inductive strategies were applied.  The structure of the model is multidimensional and complex in nature (macro, mesoand micro) based on the philosophy of reflective practice, competency-based practice andcritical learning theories. The assumptions are in relation to stakeholders, context, mentoring, outcome, process and dynamic. The stakeholders are the mentor and mentee within an interactive participatory relationship. The mentoring takes place within the process with a sequence of activities such as relationship building, development, engagement, reflective process and assessment. Capacity building and empowerment are outcomes of mentoring driven by motivation.  The implication for nurse managers is that the model can be used to develop mentoring programmes for newly-appointed nurse educators.

A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.

PubMed

Kudo, Shinpei; Nagasaki, Yukio

2015-11-10

In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

[Analysis of the population structure of the Black Forest Draught Horse].

PubMed

Aberle, Kerstin; Wrede, Jörn; Distl, Ottmar

2003-01-01

Gene contributions of foreign populations as well as coefficients of inbreeding and relationship were evaluated in 699 Black Forest Draught horses of Baden-Württemberg actually registered in the year 2002. Based on nearly complete 5-generation-pedigrees and after taking into account the remaining incompleteness, the mean coefficient of inbreeding for the total population was 6.5%. The recently by incrossing with different breeds newly established lines of stallions showed significantly lower mean coefficients of inbreeding. High rates of inbreeding of about 1.6% in the last five generations could also be faced by incrossing stallions of foreign coldblooded populations what resulted in a decrease of inbreeding in the last generation. In the total population the mean degree of relationship was 16%. The mean degree of relationships within lines of stallions was between 18.3 and 26.8%. The coefficients of relationships between lines of stallions varied between 5.1 and 16.6%. Especially, the newly established lines of stallions showed a lower mean degree of relationships to the other different lines of stallions. The proportion of purebred Black Forest Draught horses in the total population was nearly 70%. Assuming that most animals of unknown origin were purebred, the proportion of purebred Black Forest Draught horses reached about 90%. Austrian Noric, Swiss Freiberg and South German Coldblood stallions were the most important contributors to the Black Forest Draught horse population.

Towards a Global MAP Data Base

NASA Technical Reports Server (NTRS)

Hartmann, G. K.

1985-01-01

Scientific and ecological needs call for the generation of a global data base of measured data from the Earth's atmosphere, similar but complementary to the data of the meteorological service. Right now there is a large gap between these needs and the available financial means. If this prevails, it might be prohibitive for the generation of such a data base. There must be a compromise between the needs and the means. Priorities must be set. Thus, discussions should be started on which data can be or should be stored. Newly generated data for storage in such a data base is recommended to be handled by the World Data Centers (WDCs). This brief report should help to stimulate discussions and ubsequent actions.

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

Bakosi, Jozsef; Christon, Mark A.; Francois, Marianne M.

Progress is reported on computational capabilities for the grid-to-rod-fretting (GTRF) problem of pressurized water reactors. Numeca's Hexpress/Hybrid mesh generator is demonstrated as an excellent alternative to generating computational meshes for complex flow geometries, such as in GTRF. Mesh assessment is carried out using standard industrial computational fluid dynamics practices. Hydra-TH, a simulation code developed at LANL for reactor thermal-hydraulics, is demonstrated on hybrid meshes, containing different element types. A series of new Hydra-TH calculations has been carried out collecting turbulence statistics. Preliminary results on the newly generated meshes are discussed; full analysis will be documented in the L3 milestone, THM.CFD.P5.05,more » Sept. 2012.« less

Health-related quality of life, cognitive screening, and functional status in a randomized phase III trial (EF-14) of tumor treating fields with temozolomide compared to temozolomide alone in newly diagnosed glioblastoma.

PubMed

Zhu, Jay-Jiguang; Demireva, Petya; Kanner, Andrew A; Pannullo, Susan; Mehdorn, Maximilian; Avgeropoulos, Nicholas; Salmaggi, Andrea; Silvani, Antonio; Goldlust, Samuel; David, Carlos; Benouaich-Amiel, Alexandra

2017-12-01

We characterized health-related quality of life (HRQoL), cognitive, and functional status in newly diagnosed glioblastoma (GBM) patients receiving Tumor treating fields (TTFields) with temozolomide (TMZ) versus TMZ alone in a planned interim analysis of a randomized phase III trial [NCT00916409], which showed significant improvement in progression-free and overall survival with TTFields/TMZ. After radiotherapy with concomitant TMZ, newly diagnosed GBM patients were randomized (2:1) to TTFields/TMZ (n = 210) or TMZ (n = 105). Interim analysis was performed in 315 patients with ≥18 months of follow-up. HRQoL, a secondary endpoint, was evaluated in per-protocol patient population and expressed as change from baseline (CFB) at 3, 6, and 9 months for each subscale in the EORTC QLQ-C30/BN20. Karnofsky performance scores (KPS) and Mini-Mental State Examination scores (MMSE) were assessed. CFB in HRQoL was balanced in treatment groups at the 12-month time point. Initially, HRQoL improved in patients treated with TTFields/TMZ (CFB3: 24% and CFB6: 13%) versus TMZ (CFB3: -7% and CFB6: -17%), though this difference was no longer evident at the 9-month point. General scales, including physical and social functioning, showed no difference at 9 and 12 months. TTFields/TMZ group reported higher concerns of "itchy skin". KPS over 12 months was just below 90 in both groups. Cognitive status (MMSE) was stable over time. HRQoL, KPS, and MMSE were balanced in both groups over time. There was no preliminary evidence that HRQoL, cognitive, and functional status is adversely affected by the continuous use of TTFields.

Slower EEG alpha generation, synchronization and "flow"-possible biomarkers of cognitive impairment and neuropathology of minor stroke.

PubMed

Petrovic, Jelena; Milosevic, Vuk; Zivkovic, Miroslava; Stojanov, Dragan; Milojkovic, Olga; Kalauzi, Aleksandar; Saponjic, Jasna

2017-01-01

We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-Whitney U two-tailed test, and Spearman's correlation. We demonstrated transient cognitive impairment alongside a slower alpha frequency ( α AVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter-hemispheric interactions. Although the stroke induced slower alpha was a transient phenomenon, the increased alpha intra-hemispheric synchronization, overlying the ipsi-lesional hemisphere, the increased alpha F3-F4 inter-hemispheric synchronization, the delayed alpha waves, and the newly established inter-hemispheric "alpha flow" within the frontal cortex, remained as a permanent consequence of the minor stroke. This newly established frontal inter-hemispheric "alpha flow" represented a permanent consequence of the "hidden" stroke neuropathology, despite the fact that cognitive impairment has been returned to the control values. All the detected permanent changes at the EEG level with no cognitive impairment after a minor stroke could be a way for the brain to compensate for the lesion and restore the lost function. Our study indicates slower EEG alpha generation, synchronization and "flow" as potential biomarkers of cognitive impairment onset and/or compensatory post-stroke re-organizational processes.

Synthesis of MoS2 and MoO2 for their applications in H2 generation and lithium ion batteries: a review.

PubMed

Zhao, Yufei; Zhang, Yuxia; Yang, Zhiyu; Yan, Yiming; Sun, Kening

2013-08-01

Scientists increasingly witness the applications of MoS 2 and MoO 2 in the field of energy conversion and energy storage. On the one hand, MoS 2 and MoO 2 have been widely utilized as promising catalysts for electrocatalytic or photocatalytic hydrogen evolution in aqueous solution. On the other hand, MoS 2 and MoO 2 have also been verified as efficient electrode material for lithium ion batteries. In this review, the synthesis, structure and properties of MoS 2 and MoO 2 are briefly summarized according to their applications for H 2 generation and lithium ion batteries. Firstly, we overview the recent advancements in the morphology control of MoS 2 and MoO 2 and their applications as electrocatalysts for hydrogen evolution reactions. Secondly, we focus on the photo-induced water splitting for H 2 generation, in which MoS 2 acts as an important co-catalyst when combined with other semiconductor catalysts. The newly reported research results of the significant functions of MoS 2 nanocomposites in photo-induced water splitting are presented. Thirdly, we introduce the advantages of MoS 2 and MoO 2 for their enhanced cyclic performance and high capacity as electrode materials of lithium ion batteries. Recent key achievements in MoS 2 - and MoO 2 -based lithium ion batteries are highlighted. Finally, we discuss the future scope and the important challenges emerging from these fascinating materials.

A Transient Expression of Prospero Promotes Cell Cycle Exit of Drosophila Postembryonic Neurons through the Regulation of Dacapo

PubMed Central

Colonques, Jordi; Ceron, Julian; Reichert, Heinrich; Tejedor, Francisco J.

2011-01-01

Cell proliferation, specification and terminal differentiation must be precisely coordinated during brain development to ensure the correct production of different neuronal populations. Most Drosophila neuroblasts (NBs) divide asymmetrically to generate a new NB and an intermediate progenitor called ganglion mother cell (GMC) which divides only once to generate two postmitotic cells called ganglion cells (GCs) that subsequently differentiate into neurons. During the asymmetric division of NBs, the homeodomain transcription factor PROSPERO is segregated into the GMC where it plays a key role as cell fate determinant. Previous work on embryonic neurogenesis has shown that PROSPERO is not expressed in postmitotic neuronal progeny. Thus, PROSPERO is thought to function in the GMC by repressing genes required for cell-cycle progression and activating genes involved in terminal differentiation. Here we focus on postembryonic neurogenesis and show that the expression of PROSPERO is transiently upregulated in the newly born neuronal progeny generated by most of the larval NBs of the OL and CB. Moreover, we provide evidence that this expression of PROSPERO in GCs inhibits their cell cycle progression by activating the expression of the cyclin-dependent kinase inhibitor (CKI) DACAPO. These findings imply that PROSPERO, in addition to its known role as cell fate determinant in GMCs, provides a transient signal to ensure a precise timing for cell cycle exit of prospective neurons, and hence may link the mechanisms that regulate neurogenesis and those that control cell cycle progression in postembryonic brain development. PMID:21552484

Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.

PubMed

Yoo, Chae Hwa; Na, Hee-Jun; Lee, Dong-Seol; Heo, Soon Chul; An, Yuri; Cha, Junghwa; Choi, Chulhee; Kim, Jae Ho; Park, Joo-Cheol; Cho, Yee Sook

2013-11-01

Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34(+) EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

4D inversion of time-lapse magnetotelluric data sets for monitoring geothermal reservoir

NASA Astrophysics Data System (ADS)

Nam, Myung Jin; Song, Yoonho; Jang, Hannuree; Kim, Bitnarae

2017-06-01

The productivity of a geothermal reservoir, which is a function of the pore-space and fluid-flow path of the reservoir, varies since the properties of the reservoir changes with geothermal reservoir production. Because the variation in the reservoir properties causes changes in electrical resistivity, time-lapse (TL) three-dimensional (3D) magnetotelluric (MT) methods can be applied to monitor the productivity variation of a geothermal reservoir thanks to not only its sensitivity to the electrical resistivity but also its deep depth of survey penetration. For an accurate interpretation of TL MT-data sets, a four-dimensional (4D) MT inversion algorithm has been developed to simultaneously invert all vintage data considering time-coupling between vintages. However, the changes in electrical resistivity of deep geothermal reservoirs are usually small generating minimum variation in TL MT responses. Maximizing the sensitivity of inversion to the changes in resistivity is critical in the success of 4D MT inversion. Thus, we further developed a focused 4D MT inversion method by considering not only the location of a reservoir but also the distribution of newly-generated fractures during the production. For the evaluation of the 4D MT algorithm, we tested our 4D inversion algorithms using synthetic TL MT-data sets.

Clustered regulatory interspaced short palindromic repeats (CRISPR)-mediated mutagenesis and phenotype rescue by piggyBac transgenesis in a nonmodel Drosophila species.

PubMed

Tanaka, R; Murakami, H; Ote, M; Yamamoto, D

2016-08-01

How behavioural diversity emerged in evolution is an unexplored subject in biology. To tackle this problem, genes and circuits for a behaviour need to be determined in different species for phylogenetic comparisons. The recently developed clustered regulatory interspaced short palindromic repeats/CRISPR associated protein9 (CRISPR/Cas9) system made such a challenge possible by providing the means to induce mutations in a gene of interest in any organism. Aiming at elucidating diversification in genetic and neural networks for courtship behaviour, we attempted to generate a genetic tool kit in Drosophila subobscura, a nonmodel species distantly related to the genetic model Drosophila melanogaster. Here we report the generation of yellow (y) and white mutations with the aid of the CRISPR/Cas9 system, and the rescue of the y mutant phenotype by germline transformation of the newly established y mutant fly line with a y(+) -marked piggyBac vector. This successful mutagenesis and transformation in D. subobscura open up an avenue for comprehensive genetic analyses of higher functions in this and other nonmodel Drosophila species, representing a key step toward systematic comparisons of genes and circuitries underlying behaviour amongst species. © 2016 The Royal Entomological Society.

A screen to identify Drosophila genes required for integrin-mediated adhesion.

PubMed Central

Walsh, E P; Brown, N H

1998-01-01

Drosophila integrins have essential adhesive roles during development, including adhesion between the two wing surfaces. Most position-specific integrin mutations cause lethality, and clones of homozygous mutant cells in the wing do not adhere to the apposing surface, causing blisters. We have used FLP-FRT induced mitotic recombination to generate clones of randomly induced mutations in the F1 generation and screened for mutations that cause wing blisters. This phenotype is highly selective, since only 14 lethal complementation groups were identified in screens of the five major chromosome arms. Of the loci identified, 3 are PS integrin genes, 2 are blistered and bloated, and the remaining 9 appear to be newly characterized loci. All 11 nonintegrin loci are required on both sides of the wing, in contrast to integrin alpha subunit genes. Mutations in 8 loci only disrupt adhesion in the wing, similar to integrin mutations, while mutations in the 3 other loci cause additional wing defects. Mutations in 4 loci, like the strongest integrin mutations, cause a "tail-up" embryonic lethal phenotype, and mutant alleles of 1 of these loci strongly enhance an integrin mutation. Thus several of these loci are good candidates for genes encoding cytoplasmic proteins required for integrin function. PMID:9755209

Router Agent Technology for Policy-Based Network Management

NASA Technical Reports Server (NTRS)

Chow, Edward T.; Sudhir, Gurusham; Chang, Hsin-Ping; James, Mark; Liu, Yih-Chiao J.; Chiang, Winston

2011-01-01

This innovation can be run as a standalone network application on any computer in a networked environment. This design can be configured to control one or more routers (one instance per router), and can also be configured to listen to a policy server over the network to receive new policies based on the policy- based network management technology. The Router Agent Technology transforms the received policies into suitable Access Control List syntax for the routers it is configured to control. It commits the newly generated access control lists to the routers and provides feedback regarding any errors that were faced. The innovation also automatically generates a time-stamped log file regarding all updates to the router it is configured to control. This technology, once installed on a local network computer and started, is autonomous because it has the capability to keep listening to new policies from the policy server, transforming those policies to router-compliant access lists, and committing those access lists to a specified interface on the specified router on the network with any error feedback regarding commitment process. The stand-alone application is named RouterAgent and is currently realized as a fully functional (version 1) implementation for the Windows operating system and for CISCO routers.

Novel brewing yeast hybrids: creation and application.

PubMed

Krogerus, Kristoffer; Magalhães, Frederico; Vidgren, Virve; Gibson, Brian

2017-01-01

The natural interspecies Saccharomyces cerevisiae × Saccharomyces eubayanus hybrid yeast is responsible for global lager beer production and is one of the most important industrial microorganisms. Its success in the lager brewing environment is due to a combination of traits not commonly found in pure yeast species, principally low-temperature tolerance, and maltotriose utilization. Parental transgression is typical of hybrid organisms and has been exploited previously for, e.g., the production of wine yeast with beneficial properties. The parental strain S. eubayanus has only been discovered recently and newly created lager yeast strains have not yet been applied industrially. A number of reports attest to the feasibility of this approach and artificially created hybrids are likely to have a significant impact on the future of lager brewing. De novo S. cerevisiae × S. eubayanus hybrids outperform their parent strains in a number of respects, including, but not restricted to, fermentation rate, sugar utilization, stress tolerance, and aroma formation. Hybrid genome function and stability, as well as different techniques for generating hybrids and their relative merits are discussed. Hybridization not only offers the possibility of generating novel non-GM brewing yeast strains with unique properties, but is expected to aid in unraveling the complex evolutionary history of industrial lager yeast.

Sequencing, annotation and comparative analysis of nine BACs of giant panda (Ailuropoda melanoleuca).

PubMed

Zheng, Yang; Cai, Jing; Li, JianWen; Li, Bo; Lin, Runmao; Tian, Feng; Wang, XiaoLing; Wang, Jun

2010-01-01

A 10-fold BAC library for giant panda was constructed and nine BACs were selected to generate finish sequences. These BACs could be used as a validation resource for the de novo assembly accuracy of the whole genome shotgun sequencing reads of giant panda newly generated by the Illumina GA sequencing technology. Complete sanger sequencing, assembly, annotation and comparative analysis were carried out on the selected BACs of a joint length 878 kb. Homologue search and de novo prediction methods were used to annotate genes and repeats. Twelve protein coding genes were predicted, seven of which could be functionally annotated. The seven genes have an average gene size of about 41 kb, an average coding size of about 1.2 kb and an average exon number of 6 per gene. Besides, seven tRNA genes were found. About 27 percent of the BAC sequence is composed of repeats. A phylogenetic tree was constructed using neighbor-join algorithm across five species, including giant panda, human, dog, cat and mouse, which reconfirms dog as the most related species to giant panda. Our results provide detailed sequence and structure information for new genes and repeats of giant panda, which will be helpful for further studies on the giant panda.

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

PubMed

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Comparison of in vivo polyethylene wear particles between mobile- and fixed-bearing TKA in the same patients.

PubMed

Minoda, Yukihide; Hata, Kanako; Ikebuchi, Mitsuhiko; Mizokawa, Shigekazu; Ohta, Yoichi; Nakamura, Hiroaki

2017-09-01

Polyethylene wear particle generation is one of the most important factors that affects the mid- to long-term results of total knee arthroplasties (TKA). Mobile-bearing total knee prostheses were developed to reduce polyethylene wear generation. However, whether mobile-bearing prostheses actually generate fewer polyethylene wear particles than fixed-bearing prostheses remains controversial. The aim of this study was to compare, within individual patients, the in vivo polyethylene wear particles created by a newly introduced mobile-bearing prosthesis in one knee and a conventional fixed-bearing prosthesis in other knee. Eighteen patients receiving bilateral TKAs to treat osteoarthritis were included. The synovial fluid was obtained from 36 knees at an average of 3.5 years after the operation. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined using a scanning electron microscope and an image analyser. The size and shape of the polyethylene wear particles from the mobile-bearing prostheses were similar to those from the conventional fixed-bearing prostheses. Although the number of wear particles from the mobile-bearing prosthesis (1.63 × 10 7  counts/knee) appeared smaller than that from the fixed-bearing prosthesis (2.16 × 10 7  counts/knee), the difference was not statistically significant. The current in vivo study shows that no statistically significant differences were found between the polyethylene wear particles generated by a newly introduced mobile-bearing PS prosthesis and a conventional fixed-bearing PS prosthesis during the early clinical stage after implantation. Therapeutic study, Level III.

Application-oriented computational studies on a series of D-π-A structured porphyrin sensitizers with different electron-donor groups.

PubMed

Fan, Chencheng; Zhang, Bao; Li, Yuanchao; Liang, Yuxia; Xue, Xiaodong; Feng, Yaqing

2015-11-11

A series of D-π-A zinc porphyrin sensitizers bearing a substituted iminodibenzyl group at the porphyrin meso position, which is expected to have different electron-donating abilities, were designed. Theoretical studies were performed to examine the photovoltaic properties of these molecules in dye-sensitized solar cells (DSSCs). In particular, the important concepts, the Fukui function and the extended condensed Fukui function, are employed to describe the electron-donating abilities accurately at the quantitative level. Tangui Le Bahers model was adopted to analyze charge transfer (CT) during electron transition. A correlation between the electron donating abilities of the derived iminodibenzyl group and CT was built to evaluate the cell performance based on sensitizers . The theoretical studies showed that porphyrins bearing an extremely strong electron-donating group (EDG) would fail in the generation of photocurrent in the closed circuit when applied in DSSCs due to the higher level of the HOMO energy than the redox potential of the redox couple (I(-)/I3(-)). The one with a weaker EDG () is expected to show better photovoltaic performance than porphyrin with an unsubstituted iminodibenzyl group. This study demonstrates a reliable method involving the employment of the Fukui function, the extended condensed Fukui function and the Tangui Le Bahers model for the evaluation of newly designed D-π-A type porphyrin sensitizers for use in DSSCs, and as guidance for future molecular design.

Estimation and Simulation of Inter-station Green's Functions in the Beppu-Bay Area, Oita Prefecture, Southwest Japan: the Effect of Sedimentary Basin

NASA Astrophysics Data System (ADS)

Hayashida, T.; Yoshimi, M.; Komatsu, M.; Takenaka, H.

2017-12-01

Continuous long-term observations of ambient noise (microseisms) were performed from August 2014 to February 2017 in the Beppu-Bay area, Oita prefecture, to investigate S-wave velocity structure of deep sedimentary basin (Hayashida et al., 2015SSJ; Yoshimi and Hayashida, 2017WCEE). The observation array consists of 12 broadband stations with an average spacing of 12 km. We applied the seismic interferometry technique to the ambient noise data and derived nine-component ambient noise cross-correlation functions (Z-R, Z-T, Z-Z, R-R, R-T, R-Z, T-R, T-T, and T-Z components) between 66 pairs of stations (distance of 6.4 km to 65.2 km). We assumed the stacked cross-correlation functions as "observed Green's functions" between two stations and estimated group velocities of Rayleigh and Love waves in the frequency between 0.2 and 0.5 Hz (Hayashida et al., 2017AGU-JpGU). Theoretical Green's functions for all stations pairs were also calculated using the finite difference method (HOT-FDM, Nakamura et al., 2012BSSA), with an existing three-dimensional basin structure model (J-SHIS V2) with land and seafloor topography and a seawater layer (Okunaka et al., 2016JpGU) and a newly constructed basin structure model of the target area (Yoshimi et al., 2017AGU). The comparisons between observed and simulated Green's functions generally show good agreements in the frequency range between 0.2 and 0.5 Hz. On the other hand, both observed and simulated Green's functions for some station pairs whose traverse lines run across the deeper part of the sedimentary basin (> 2000 m) show prominent later phases that might be generated and propagated inside the basin. This indicates that the understanding of the phase generation and propagation processes can be a key factor to validate the basin structure model and we investigated the characteristics of the later phases, such as its particle motions and arrival times, using observed and simulated Green's functions in detail. Acknowledgements: This work is supported by the Comprehensive Research on the Beppu-Haneyama Fault Zone funded by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan.

Embedding Task-Based Neural Models into a Connectome-Based Model of the Cerebral Cortex.

PubMed

Ulloa, Antonio; Horwitz, Barry

2016-01-01

A number of recent efforts have used large-scale, biologically realistic, neural models to help understand the neural basis for the patterns of activity observed in both resting state and task-related functional neural imaging data. An example of the former is The Virtual Brain (TVB) software platform, which allows one to apply large-scale neural modeling in a whole brain framework. TVB provides a set of structural connectomes of the human cerebral cortex, a collection of neural processing units for each connectome node, and various forward models that can convert simulated neural activity into a variety of functional brain imaging signals. In this paper, we demonstrate how to embed a previously or newly constructed task-based large-scale neural model into the TVB platform. We tested our method on a previously constructed large-scale neural model (LSNM) of visual object processing that consisted of interconnected neural populations that represent, primary and secondary visual, inferotemporal, and prefrontal cortex. Some neural elements in the original model were "non-task-specific" (NS) neurons that served as noise generators to "task-specific" neurons that processed shapes during a delayed match-to-sample (DMS) task. We replaced the NS neurons with an anatomical TVB connectome model of the cerebral cortex comprising 998 regions of interest interconnected by white matter fiber tract weights. We embedded our LSNM of visual object processing into corresponding nodes within the TVB connectome. Reciprocal connections between TVB nodes and our task-based modules were included in this framework. We ran visual object processing simulations and showed that the TVB simulator successfully replaced the noise generation originally provided by NS neurons; i.e., the DMS tasks performed with the hybrid LSNM/TVB simulator generated equivalent neural and fMRI activity to that of the original task-based models. Additionally, we found partial agreement between the functional connectivities using the hybrid LSNM/TVB model and the original LSNM. Our framework thus presents a way to embed task-based neural models into the TVB platform, enabling a better comparison between empirical and computational data, which in turn can lead to a better understanding of how interacting neural populations give rise to human cognitive behaviors.

Adaptive evolution and functional innovation of Populus-specific recently evolved microRNAs.

PubMed

Xie, Jianbo; Yang, Xiaohui; Song, Yuepeng; Du, Qingzhang; Li, Ying; Chen, Jinhui; Zhang, Deqiang

2017-01-01

Lineage-specific microRNAs (miRNAs) undergo rapid turnover during evolution; however, their origin and functional importance have remained controversial. Here, we examine the origin, evolution, and potential roles in local adaptation of Populus-specific miRNAs, which originated after the recent salicoid-specific, whole-genome duplication. RNA sequencing was used to generate extensive, comparable miRNA and gene expression data for six tissues. A natural population of Populus trichocarpa and closely related species were used to study the divergence rates, evolution, and adaptive variation of miRNAs. MiRNAs that originated in 5' untranslated regions had higher expression levels and their expression showed high correlation with their host genes. Compared with conserved miRNAs, a significantly higher proportion of Populus-specific miRNAs appear to target genes that were duplicated in salicoids. Examination of single nucleotide polymorphisms in Populus-specific miRNA precursors showed high amounts of population differentiation. We also characterized the newly emerged MIR6445 family, which could trigger the production of phased small interfering RNAs from NAC mRNAs, which encode a transcription factor with primary roles in a variety of plant developmental processes. Together, these observations provide evolutionary insights into the birth and potential roles of Populus-specific miRNAs in genome maintenance, local adaptation, and functional innovation. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Dry rotary swaging with structured and coated tools

NASA Astrophysics Data System (ADS)

Herrmann, Marius; Schenck, Christian; Kuhfuss, Bernd

2018-05-01

Rotary swaging is a cold bulk forming process for manufacturing of complex bar and tube profiles like axles and gear shafts in the automotive industry. Conventional rotary swaging is carried out under intense use of lubricant usually based on mineral oil. Besides lubrication the lubricant fulfills necessary functions like lubrication, flushing and cooling, but generates costs for recycling, replacement and cleaning of the workpieces. Hence, the development of a dry process design is highly desirable, both under economic and ecological points of view. Therefore, it is necessary to substitute the functions of the lubricant. This was realized by the combination of newly developed a-C:H:W coating systems on the tools to minimize the friction and to avoid adhesion effects. With the application of a deterministic structure in the forging zone of the tools the friction conditions are modified to control the axial process forces. In this study infeed rotary swaging with functionalized tools was experimentally investigated. Therefore, steel and aluminum tubes were formed with and without lubricant. Different structures which were coated and uncoated were implemented in the reduction zone of the tools. The antagonistic effects of coating and structuring were characterized by measuring the axial process force and the produced workpiece quality in terms of roundness and surface roughness. Thus, the presented results allow for further developments towards a dry rotary swaging process.

Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels

PubMed Central

Schneider, Elke; Machavoine, François; Pléau, Jean-Marie; Bertron, Anne-France; Thurmond, Robin L.; Ohtsu, Hiroshi; Watanabe, Takehiko; Schinkel, Alfred H.; Dy, Michel

2005-01-01

In this study, we identify the bidirectional organic cation transporter 3 (OCT3/Slc22a3) as the molecule responsible for histamine uptake by murine basophils. We demonstrate that OCT3 participates in the control of basophil functions because exogenous histamine can inhibit its own synthesis—and that of interleukin (IL)-4, IL-6, and IL-13—through this means of transport. Furthermore, ligands of H3/H4 histamine receptors or OCT3 inhibit histamine uptake, and outward transport of newly synthesized histamine. By doing so, they increase the histamine content of basophils, which explains why they mimic the effect of exogenous histamine. These drugs were no longer effective in histamine-free histidine decarboxylase (HDC)-deficient mice, in contrast with histamine itself. Histamine was not taken up and lost its inhibitory effect in mice deficient for OCT3, which proved its specific involvement. Intracellular histamine levels were increased strongly in IL-3–induced OCT3 −/− bone marrow basophils, and explained why they generated fewer cytokines than their wild-type counterpart. Their production was enhanced when histamine synthesis was blocked by the specific HDC inhibitor α-fluoro-methyl histidine, and underscored the determinant role of histamine in the inhibitory effect. We postulate that pharmacologic modulation of histamine transport might become instrumental in the control of basophil functions during allergic diseases. PMID:16061728

The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment

NASA Astrophysics Data System (ADS)

Hasan, Mahadi; Tarashima, Noriko; Fujikawa, Koki; Ohgita, Takashi; Hama, Susumu; Tanaka, Tamotsu; Saito, Hiroyuki; Minakawa, Noriaki; Kogure, Kentaro

2016-01-01

An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices.

Functional analysis of PGRP-LA in Drosophila immunity.

PubMed

Gendrin, Mathilde; Zaidman-Rémy, Anna; Broderick, Nichole A; Paredes, Juan; Poidevin, Mickaël; Roussel, Alain; Lemaitre, Bruno

2013-01-01

PeptidoGlycan Recognition Proteins (PGRPs) are key regulators of the insect innate antibacterial response. Even if they have been intensively studied, some of them have yet unknown functions. Here, we present a functional analysis of PGRP-LA, an as yet uncharacterized Drosophila PGRP. The PGRP-LA gene is located in cluster with PGRP-LC and PGRP-LF, which encode a receptor and a negative regulator of the Imd pathway, respectively. Structure predictions indicate that PGRP-LA would not bind to peptidoglycan, pointing to a regulatory role of this PGRP. PGRP-LA expression was enriched in barrier epithelia, but low in the fat body. Use of a newly generated PGRP-LA deficient mutant indicates that PGRP-LA is not required for the production of antimicrobial peptides by the fat body in response to a systemic infection. Focusing on the respiratory tract, where PGRP-LA is strongly expressed, we conducted a genome-wide microarray analysis of the tracheal immune response of wild-type, Relish, and PGRP-LA mutant larvae. Comparing our data to previous microarray studies, we report that a majority of genes regulated in the trachea upon infection differ from those induced in the gut or the fat body. Importantly, antimicrobial peptide gene expression was reduced in the tracheae of larvae and in the adult gut of PGRP-LA-deficient Drosophila upon oral bacterial infection. Together, our results suggest that PGRP-LA positively regulates the Imd pathway in barrier epithelia.

Generating Stock Trading Rules Using Genetic Network Programming with Flag Nodes and Adjustment of Importance Indexes

NASA Astrophysics Data System (ADS)

Mabu, Shingo; Chen, Yan; Hirasawa, Kotaro

Genetic Network Programming (GNP) is an evolutionary algorithm which represents its solutions using graph structures. Since GNP can create quite compact programs and has an implicit memory function, GNP works well especially in dynamic environments. In addition, a study on creating trading rules on stock markets using GNP with Importance Index (GNP-IMX) has been done. IMX is one of the criterions for decision making. However, the values of IMXs must be deteminined by our experience/knowledge. Therefore in this paper, IMXs are adjusted appropriately during the stock trading in order to predict the rise and fall of the stocks. Moreover, newly defined flag nodes are introduced to GNP, which can appropriately judge the current situation of the stock prices, and also contributes to the use of many kinds of nodes in GNP program. In the simulation, programs are evolved using the stock prices of 20 companies. Then the generalization ability is tested and compared with GNP without flag nodes, GNP without IMX adjustment and Buy&Hold.

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species.

PubMed

Perumal, Deepak; Lim, Chu Sing; Chow, Vincent T K; Sakharkar, Kishore R; Sakharkar, Meena K

2008-09-10

Comparative genomic analysis has revolutionized our ability to predict the metabolic subsystems that occur in newly sequenced genomes, and to explore the functional roles of the set of genes within each subsystem. These computational predictions can considerably reduce the volume of experimental studies required to assess basic metabolic properties of multiple bacterial species. However, experimental validations are still required to resolve the apparent inconsistencies in the predictions by multiple resources. Here, we present combined computational-experimental analyses on eight completely sequenced Pseudomonas species. Comparative pathway analyses reveal that several pathways within the Pseudomonas species show high plasticity and versatility. Potential bypasses in 11 metabolic pathways were identified. We further confirmed the presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P. syringae pv. tomato that revealed inconsistent annotations in KEGG and in the recently published SYSTOMONAS database. These analyses connect and integrate systematic data generation, computational data interpretation, and experimental validation and represent a synergistic and powerful means for conducting biological research.

Catalytic nanomotors for environmental monitoring and water remediation.

PubMed

Soler, Lluís; Sánchez, Samuel

2014-07-07

Self-propelled nanomotors hold considerable promise for developing innovative environmental applications. This review highlights the recent progress in the use of self-propelled nanomotors for water remediation and environmental monitoring applications, as well as the effect of the environmental conditions on the dynamics of nanomotors. Artificial nanomotors can sense different analytes-and therefore pollutants, or "chemical threats"-can be used for testing the quality of water, selective removal of oil, and alteration of their speeds, depending on the presence of some substances in the solution in which they swim. Newly introduced micromotors with double functionality to mix liquids at the microscale and enhance chemical reactions for the degradation of organic pollutants greatly broadens the range of applications to that of environmental. These "self-powered remediation systems" could be seen as a new generation of "smart devices" for cleaning water in small pipes or cavities difficult to reach with traditional methods. With constant improvement and considering the key challenges, we expect that artificial nanomachines could play an important role in environmental applications in the near future.

Catalytic nanomotors for environmental monitoring and water remediation

NASA Astrophysics Data System (ADS)

Soler, Lluís; Sánchez, Samuel

2014-06-01

Self-propelled nanomotors hold considerable promise for developing innovative environmental applications. This review highlights the recent progress in the use of self-propelled nanomotors for water remediation and environmental monitoring applications, as well as the effect of the environmental conditions on the dynamics of nanomotors. Artificial nanomotors can sense different analytes--and therefore pollutants, or ``chemical threats''--can be used for testing the quality of water, selective removal of oil, and alteration of their speeds, depending on the presence of some substances in the solution in which they swim. Newly introduced micromotors with double functionality to mix liquids at the microscale and enhance chemical reactions for the degradation of organic pollutants greatly broadens the range of applications to that of environmental. These ``self-powered remediation systems'' could be seen as a new generation of ``smart devices'' for cleaning water in small pipes or cavities difficult to reach with traditional methods. With constant improvement and considering the key challenges, we expect that artificial nanomachines could play an important role in environmental applications in the near future.

Magnetohydrodynamic three-dimensional flow of viscoelastic nanofluid in the presence of nonlinear thermal radiation

NASA Astrophysics Data System (ADS)

Hayat, T.; Muhammad, Taseer; Alsaedi, A.; Alhuthali, M. S.

2015-07-01

Magnetohydrodynamic (MHD) three-dimensional flow of couple stress nanofluid in the presence of thermophoresis and Brownian motion effects is analyzed. Energy equation subject to nonlinear thermal radiation is taken into account. The flow is generated by a bidirectional stretching surface. Fluid is electrically conducting in the presence of a constant applied magnetic field. The induced magnetic field is neglected for a small magnetic Reynolds number. Mathematical formulation is performed using boundary layer analysis. Newly proposed boundary condition requiring zero nanoparticle mass flux is employed. The governing nonlinear mathematical problems are first converted into dimensionless expressions and then solved for the series solutions of velocities, temperature and nanoparticles concentration. Convergence of the constructed solutions is verified. Effects of emerging parameters on the temperature and nanoparticles concentration are plotted and discussed. Skin friction coefficients and Nusselt number are also computed and analyzed. It is found that the thermal boundary layer thickness is an increasing function of radiative effect.

GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

PubMed Central

Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

2009-01-01

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

Polymerizable Supramolecular Approach to Highly Conductive PEDOT:PSS Patterns.

PubMed

Kim, Tae Geun; Ha, Su Ryong; Choi, Hyosung; Uh, Kyungchan; Kundapur, Umesha; Park, Sumin; Lee, Chan Woo; Lee, Sang-Hwa; Kim, Jaeyong; Kim, Jong-Man

2017-06-07

Owing to its high conductivity, solution processability, mechanical flexibility, and transparency, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been extensively explored for use in functional devices including solar cells, sensors, light-emitting diodes, and supercapacitors. The ability to fabricate patterned PEDOT:PSS on a solid substrate is of significant importance to develop practical applications of this conducting polymer. Herein, we describe a new approach to obtain PEDOT:PSS patterns that are based on a polymerizable supramolecular concept. Specifically, we found that UV irradiation of a photopolymerizable diacetylene containing PEDOT:PSS film followed by development in deionized water and subsequent treatment with sulfuric acid (glass and silicon wafer) or formic acid (PET) produces micron-sized PEDOT:PSS patterns on solid substrates. The newly designed photolithographic method, which can be employed to generate highly conductive (>1000 S/cm) PEDOT:PSS patterns, has many advantages including the use of aqueous process conditions, a reduced number of process steps, and no requirement for plasma etching procedures.

Computational Design of Self-Assembling Cyclic Protein Homo-oligomers

PubMed Central

Fallas, Jorge A.; Ueda, George; Sheffler, William; Nguyen, Vanessa; McNamara, Dan E.; Sankaran, Banumathi; Pereira, Jose Henrique; Parmeggiani, Fabio; Brunette, TJ; Cascio, Duilio; Yeates, Todd R.; Zwart, Peter; Baker, David

2016-01-01

Self-assembling cyclic protein homo-oligomers play important roles in biology and the ability to generate custom homo-oligomeric structures could enable new approaches to probe biological function. Here we report a general approach to design cyclic homo-oligomers that employs a new residue pair transform method for assessing the design ability of a protein-protein interface. This method is sufficiently rapid to enable systematic enumeration of cyclically docked arrangements of a monomer followed by sequence design of the newly formed interfaces. We use this method to design interfaces onto idealized repeat proteins that direct their assembly into complexes that possess cyclic symmetry. Of 96 designs that were experimentally characterized, 21 were found to form stable monodisperse homo-oligomers in solution, and 15 (4 homodimers, 6 homotrimers, 6 homotetramers and 1 homopentamer) had solution small angle X-ray scattering data consistent with the design models. X-ray crystal structures were obtained for five of the designs and each of these were shown to be very close to their design model. PMID:28338692

Spin-dependent post-Newtonian parameters from EMRI computation in Kerr background

NASA Astrophysics Data System (ADS)

Friedman, John; Le Tiec, Alexandre; Shah, Abhay

2013-04-01

Because the extreme mass-ratio inspiral (EMRI) approximation is accurate to all orders in v/c, it can be used to find high order post-Newtonian parameters that are not yet analytically accessible. We report here on progress in computing spin-dependent, conservative, post-Newtonian parameters from a radiation-gauge computation for a particle in circular orbit in a family of Kerr geometries. For a particle with 4-velocity u^α= U k^α, with k^α the helical Killing vector of the perturbed spacetime, the renormalized perturbation δU, when written as a function of the particle's angular velocity, is invariant under gauge transformations generated by helically symmetric vectors. The EMRI computations are done in a modified radiation gauge. Extracted parameters are compared to previously known and newly computed spin-dependent post-Newtonian terms. This work is modeled on earlier computations by Blanchet, Detweiler, Le Tiec and Whiting of spin-independent terms for a particle in circular orbit in a Schwarzschild geometry.

tRNAscan-SE On-line: integrating search and context for analysis of transfer RNA genes.

PubMed

Lowe, Todd M; Chan, Patricia P

2016-07-08

High-throughput genome sequencing continues to grow the need for rapid, accurate genome annotation and tRNA genes constitute the largest family of essential, ever-present non-coding RNA genes. Newly developed tRNAscan-SE 2.0 has advanced the state-of-the-art methodology in tRNA gene detection and functional prediction, captured by rich new content of the companion Genomic tRNA Database. Previously, web-server tRNA detection was isolated from knowledge of existing tRNAs and their annotation. In this update of the tRNAscan-SE On-line resource, we tie together improvements in tRNA classification with greatly enhanced biological context via dynamically generated links between web server search results, the most relevant genes in the GtRNAdb and interactive, rich genome context provided by UCSC genome browsers. The tRNAscan-SE On-line web server can be accessed at http://trna.ucsc.edu/tRNAscan-SE/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Numerical modelling of the Madison Dynamo Experiment.

NASA Astrophysics Data System (ADS)

Bayliss, R. A.; Wright, J. C.; Forest, C. B.; O'Connell, R.; Truitt, J. L.

2000-10-01

Growth, saturation and turbulent evolution of the Madison dynamo experiment is investigated numerically using a newly developed 3-D pseudo-spectral simulation of the MHD equations; results of the simulations will be compared to the experimental results obtained from the experiment. The code, Dynamo, is in Fortran90 and allows for full evolution of the magnetic and velocity fields. The induction equation governing B and the Navier-Stokes equation governing V are solved. The code uses a spectral representation via spherical harmonic basis functions of the vector fields in longitude and latitude, and finite differences in the radial direction. The magnetic field evolution has been benchmarked against the laminar kinematic dynamo predicted by M.L. Dudley and R.W. James (M.L. Dudley and R.W. James, Time-dependant kinematic dynamos with stationary flows, Proc. R. Soc. Lond. A 425, p. 407 (1989)). Initial results on magnetic field saturation, generated by the simultaneous evolution of magnetic and velocity fields be presented using a variety of mechanical forcing terms.

Effects of delays on 6-year-old children’s self-generation and retention of knowledge through integration

PubMed Central

Varga, Nicole L.; Bauer, Patricia J.

2013-01-01

The present research was an investigation of the effect of delay on self-generation and retention of knowledge derived through integration by 6-year-old children. Children were presented with novel facts from passages read aloud to them (stem facts) and tested for self-generation of new knowledge through integration of the facts. In Experiment 1, children integrated the stem facts at Session 1 and retained the self-generated memory traces over 1 week. In Experiment 2, 1-week delays were imposed either between the to-be-integrated facts (between-stem delay) or after the stem facts but before the test (before-test delay). Integration performance was diminished in both conditions. Moreover, memory for individual stem facts was lower in Experiment 2 than in Experiment 1, suggesting that self-generation through integration promoted memory for explicitly taught information. The results indicate the importance of tests for promoting self-generation through integration as well as for retaining newly self-generated and explicitly taught information. PMID:23563162

Traction force dynamics predict gap formation in activated endothelium

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

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneousmore » distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.« less

VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse

PubMed Central

Huang, Lin; Lange, Miles D.; Zhang, Zhixin

2014-01-01

VH replacement occurs through RAG-mediated secondary recombination between a rearranged VH gene and an upstream unrearranged VH gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3′ end of VH gene coding region, a short stretch of nucleotides from the previous rearranged VH gene can be retained in the newly formed VH–DH junction as a “footprint” of VH replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through VH replacement. To explore the contribution of VH replacement products to the antibody repertoire, we developed a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it searches for VH replacement footprint motifs within the VH–DH junction (N1) regions of IgH gene sequences to identify potential VH replacement products; it can also analyze the frequencies of VH replacement products in correlation with publications, keywords, or VH, DH, and JH gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified VH replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of VH replacement products in human and mouse. PMID:24575092

Local Luminosity Function at 15 micro m and Galaxy Evolution Seen by ISOCAM 15 micro m Surveys

NASA Technical Reports Server (NTRS)

Xu, C.

2000-01-01

A local luminosity function at 15 micro m is derived using the bivariate (15 micro m vs. 60 micro m luminosities) method, based on the newly published ISOCAM LW3-band (15 micro m) survey of the very deep IRAS 60 micro m sample in the north ecliptic pole region (NEPR).

Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes

USDA-ARS?s Scientific Manuscript database

The objective of our study was to examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children. Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other n...

Patients with haematological malignancies show a restricted body image focusing on function and emotion.

PubMed

Weber, C S; Fliege, H; Arck, P C; Kreuzer, K-A; Rose, M; Klapp, B F

2005-05-01

The diagnosis of cancer threatens the psychological and bodily integrity. Based on this assumption, we aimed to explore how newly diagnosed patients cope with special regard to the body image (BI). In total, 40 patients (32 haematological malignancies) were assessed by questionnaires on mood, complaints, self-regulation and quality of life (QOL). The BI was assessed by the 'Body Grid' which reveals the constructs patients choose to characterize the body. The constructs were categorized using a model of six predefined categories comprising: emotion, control, activity, strength, function and appearance. Tinnitus sufferers and medical students served as comparison groups. Cancer patients showed significantly more anxious depression and a significantly lower QOL than controls. Their BI was restricted, focusing the functional status of body organs (e.g. opposing healthy vs. ill organs) as well as emotional aspects (e.g. trust vs. fear). The data convey fundamental psychological distress in newly diagnosed cancer patients. Restriction of BI and use of functional constructs may help to buffer the threat to body integrity. The emotional constructs reflect the existential impact. The data give a clear indication for the need for early psychosocial support which should aim at stabilizing the psychological and bodily integrity of the patient.

Exploratory factor analysis of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale in people newly diagnosed with advanced cancer.

PubMed

Bai, Mei; Dixon, Jane K

2014-01-01

The purpose of this study was to reexamine the factor pattern of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp-12) using exploratory factor analysis in people newly diagnosed with advanced cancer. Principal components analysis (PCA) and 3 common factor analysis methods were used to explore the factor pattern of the FACIT-Sp-12. Factorial validity was assessed in association with quality of life (QOL). Principal factor analysis (PFA), iterative PFA, and maximum likelihood suggested retrieving 3 factors: Peace, Meaning, and Faith. Both Peace and Meaning positively related to QOL, whereas only Peace uniquely contributed to QOL. This study supported the 3-factor model of the FACIT-Sp-12. Suggestions for revision of items and further validation of the identified factor pattern were provided.

Exploring the mental health effects of political trauma with newly arrived refugees.

PubMed

Shannon, Patricia J; Wieling, Elizabeth; McCleary, Jennifer Simmelink; Becher, Emily

2015-04-01

We explored the mental health effects of war trauma and torture as described by 111 refugees newly arrived in the United States. We used ethnocultural methodologies to inform 13 culture-specific focus groups with refugees from Bhutan (34), Burma (23), Ethiopia (27), and Somalia (27). Contrary to the belief that stigma prevents refugees from discussing mental health distress, participants readily described complex conceptualizations of degrees of mental health distress informed by political context, observation of symptoms, cultural idioms, and functional impairment. Recommendations for health care providers include assessment processes that inquire about symptoms in their political context, the degree of distress as it is culturally conceptualized, and its effect on functioning. Findings confirm the cross-cultural recognition of symptoms associated with posttraumatic stress disorder; however, refugees described significant cultural variation in expressions of distress, indicating the need for more research on culture-bound disorders and idioms of distress. © The Author(s) 2014.

Simulations of Turbulent Momentum and Scalar Transport in Non-Reacting Confined Swirling Coaxial Jets

NASA Technical Reports Server (NTRS)

Shih, Tsan-Hsing; Liu, Nan-Suey; Moder, Jeffrey P.

2015-01-01

This paper presents the numerical simulations of confined three-dimensional coaxial water jets. The objectives are to validate the newly proposed nonlinear turbulence models of momentum and scalar transport, and to evaluate the newly introduced scalar APDF and DWFDF equation along with its Eulerian implementation in the National Combustion Code (NCC). Simulations conducted include the steady RANS, the unsteady RANS (URANS), and the time-filtered Navier-Stokes (TFNS); both without and with invoking the APDF or DWFDF equation. When the APDF (ensemble averaged probability density function) or DWFDF (density weighted filtered density function) equation is invoked, the simulations are of a hybrid nature, i.e., the transport equations of energy and species are replaced by the APDF or DWFDF equation. Results of simulations are compared with the available experimental data. Some positive impacts of the nonlinear turbulence models and the Eulerian scalar APDF and DWFDF approach are observed.

Implementing a rational and consistent nomenclature for serine/arginine-rich protein splicing factors (SR proteins) in plants.

PubMed

Barta, Andrea; Kalyna, Maria; Reddy, Anireddy S N

2010-09-01

Growing interest in alternative splicing in plants and the extensive sequencing of new plant genomes necessitate more precise definition and classification of genes coding for splicing factors. SR proteins are a family of RNA binding proteins, which function as essential factors for constitutive and alternative splicing. We propose a unified nomenclature for plant SR proteins, taking into account the newly revised nomenclature of the mammalian SR proteins and a number of plant-specific properties of the plant proteins. We identify six subfamilies of SR proteins in Arabidopsis thaliana and rice (Oryza sativa), three of which are plant specific. The proposed subdivision of plant SR proteins into different subfamilies will allow grouping of paralogous proteins and simple assignment of newly discovered SR orthologs from other plant species and will promote functional comparisons in diverse plant species.

Decoding sORF translation - from small proteins to gene regulation.

PubMed

Cabrera-Quio, Luis Enrique; Herberg, Sarah; Pauli, Andrea

2016-11-01

Translation is best known as the fundamental mechanism by which the ribosome converts a sequence of nucleotides into a string of amino acids. Extensive research over many years has elucidated the key principles of translation, and the majority of translated regions were thought to be known. The recent discovery of wide-spread translation outside of annotated protein-coding open reading frames (ORFs) came therefore as a surprise, raising the intriguing possibility that these newly discovered translated regions might have unrecognized protein-coding or gene-regulatory functions. Here, we highlight recent findings that provide evidence that some of these newly discovered translated short ORFs (sORFs) encode functional, previously missed small proteins, while others have regulatory roles. Based on known examples we will also speculate about putative additional roles and the potentially much wider impact that these translated regions might have on cellular homeostasis and gene regulation.

Fungal Evolution: Mucor and Phycomyces See Double.

PubMed

Stajich, Jason E

2016-08-22

Newly available genome sequences of two Mucoralean fungi, Phycomyces blakesleeanus and Mucor circinelloides, provide evidence for an ancient whole-genome duplication that contributed to the generation of expanded gene families. These fungi have robust responses to light that can be correlated with the expansion of gene networks involved in light sensing and signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Teaching a Child with ASD to Approach Communication Partners and Use a Speech-Generating Device across Settings: Clinic, School, and Home

ERIC Educational Resources Information Center

Waddington, Hannah; van der Meer, Larah; Carnett, Amarie; Sigafoos, Jeff

2017-01-01

Individuals with autism spectrum disorder (ASD) often have difficulty generalizing newly acquired communication skills to different contexts. In this study, a multiple baseline across settings (clinic, school, and home) design was used to determine whether an 8-year-old boy with ASD could learn to approach communication partners to request…

Campus-Based Tensions in the Structural Development of a Newly Merged University: The Case of the University of Eastern Finland

ERIC Educational Resources Information Center

Vartiainen, Perttu

2017-01-01

This paper analyzes the campus-based tensions which are emerging in the multi-campus university during a critical period of structural development. A multi-campus system easily generates intrinsic tensions between "localist" campus-based interests and system-level interests, in which the interests of external stakeholders often play a…

Middlesex Community College Geothermal Project

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

Klein, Jessie; Spaziani, Gina

The purpose of the project was to install a geothermal system in the trustees house on the Bedford campus of Middlesex Community College. In partnership with the environmental science faculty, learning activities for environmental science courses were developed to explain geothermal energy and more specifically the newly installed system to Middlesex students. A real-time monitoring system highlights the energy use and generation.

U.S. Department of Defense Official Website - World War II Memorial

Science.gov Websites

- The newly opened World War II Memorial on the National Mall in Washington, D.C., was dedicated May 29 . It honors the 16 million who served in the armed forces of the United States during World War II, the ;greatest generation." Defense Department photo illustration by Navy Lt. Cmdr. Jane Campbell World War

Transfer of Training: The Role of Feedback in Supportive Social Networks

ERIC Educational Resources Information Center

Van den Bossche, Piet; Segers, Mien; Jansen, Niekie

2010-01-01

The transfer of training to the workplace often fails to occur. The authors argue that feedback generated within the work environment about the application of newly learned skills in the workplace helps to close the gap between the current performance and the desired goal of full application of what is learned during training. This study takes a…

Propulsion and service power for New Orleans sternwheelers

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

Clevenger, M.

1995-11-01

The spurt in designing and building casino and show boats for the U. S. inland waterways over the last few years opened up an opportunity for naval architects and marine engineers to work with a variety of imaginative boats. For example, on the newly built Grand Palais and Crescent City Queen, six 1200 r/min generator sets based on Caterpillar 3516TA engines and 1090 kW, 600-V Kato generators provide power to operate paddlewheels, Z-drives, and a complex of equipment. This paper describes the design, layout and electrical equipment and propulsion of the ships.

Second and third order nonlinear optical properties of conjugated molecules and polymers

NASA Technical Reports Server (NTRS)

Perry, Joseph W.; Stiegman, Albert E.; Marder, Seth R.; Coulter, Daniel R.; Beratan, David N.; Brinza, David E.

1988-01-01

Second- and third-order nonlinear optical properties of some newly synthesized organic molecules and polymers are reported. Powder second-harmonic-generation efficiencies of up to 200 times urea have been realized for asymmetric donor-acceptor acetylenes. Third harmonic generation chi(3)s have been determined for a series of small conjugated molecules in solution. THG chi(3)s have also been determined for a series of soluble conjugated copolymers prepared using ring-opening metathesis polymerization. The results are discussed in terms of relevant molecular and/or macroscopic structural features of these conjugated organic materials.

3D augmented reality with integral imaging display

NASA Astrophysics Data System (ADS)

Shen, Xin; Hua, Hong; Javidi, Bahram

2016-06-01

In this paper, a three-dimensional (3D) integral imaging display for augmented reality is presented. By implementing the pseudoscopic-to-orthoscopic conversion method, elemental image arrays with different capturing parameters can be transferred into the identical format for 3D display. With the proposed merging algorithm, a new set of elemental images for augmented reality display is generated. The newly generated elemental images contain both the virtual objects and real world scene with desired depth information and transparency parameters. The experimental results indicate the feasibility of the proposed 3D augmented reality with integral imaging.

THE LEGACY OF DISADVANTAGE: MULTIGENERATIONAL NEIGHBORHOOD EFFECTS ON COGNITIVE ABILITY1

PubMed Central

Sharkey, Patrick; Elwert, Felix

2012-01-01

This study examines how the neighborhood environments experienced over multiple generations of a family influence children’s cognitive ability. Building on recent research showing strong continuity in neighborhood environments across generations of family members, we argue for a revised perspective on “neighborhood effects” that considers the ways in which the neighborhood environment in one generation may have a lingering impact on the next generation. To specify such multigenerational effects is not simply a theoretical problem, but poses considerable methodological challenges. Instead of traditional regression techniques that may obscure multigenerational effects of neighborhood disadvantage, we utilize newly developed methods designed to generate unbiased treatment effects when treatments and confounders vary over time. The results confirm a powerful link between neighborhoods and cognitive ability that extends across generations. Being raised in a high-poverty neighborhood in one generation has a substantial negative effect on child cognitive ability in the next generation. A family’s exposure to neighborhood poverty across two consecutive generations reduces child cognitive ability by more than half a standard deviation. A formal sensitivity analysis suggests that results are robust to unobserved selection bias. PMID:21932471

Ultrastructural study on dynamics of plastids and mitochondria during microgametogenesis in watermelon.

PubMed

Liu, Lin

2012-02-01

Dynamics of plastids and mitochondria during microgametogenesis in watermelon were examined by means of transmission electron microscopy. Plastids are present as proplastids in the microspore and as amyloplasts in the vegetative cell of the bicellular pollen grain, whereas the generative cell is completely devoid of plastids, suggesting that microspore plastids are excluded from the generative cell during the microspore mitotic division. Therefore, watermelon is classified as Lycopersicon type, where plastids exclusion from the generative cell leads to purely maternal plastid inheritance. Mitochondria in the generative cell show noticeable alterations in size and cristae during microgametogenesis. The diameter of mitochondria is about 0.5 μm in the newly born generative cell, while only about 0.16 μm in the spindle-shaped generative cell. Numerous cristae are present in mitochondria in the spherical generative cell, but, in contrast, mere two or three cristae retain in the spindle-shaped generative cell in the mature pollen grain. In conclusion, the size and cristae number of mitochondria in the generative cell are reduced significantly during microgametogenesis in watermelon. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multimodal Kelvin Probe Force Microscopy Investigations of a Photovoltaic WSe2/MoS2 Type-II Interface.

PubMed

Almadori, Yann; Bendiab, Nedjma; Grévin, Benjamin

2018-01-10

Atomically thin transition-metal dichalcogenides (TMDC) have become a new platform for the development of next-generation optoelectronic and light-harvesting devices. Here, we report a Kelvin probe force microscopy (KPFM) investigation carried out on a type-II photovoltaic heterojunction based on WSe 2 monolayer flakes and a bilayer MoS 2 film stacked in vertical configuration on a Si/SiO 2 substrate. Band offset characterized by a significant interfacial dipole is pointed out at the WSe 2 /MoS 2 vertical junction. The photocarrier generation process and phototransport are studied by applying a differential technique allowing to map directly two-dimensional images of the surface photovoltage (SPV) over the vertical heterojunctions (vHJ) and in its immediate vicinity. Differential SPV reveals the impact of chemical defects on the photocarrier generation and that negative charges diffuse in the MoS 2 a few hundreds of nanometers away from the vHJ. The analysis of the SPV data confirms unambiguously that light absorption results in the generation of free charge carriers that do not remain coulomb-bound at the type-II interface. A truly quantitative determination of the electron-hole (e-h) quasi-Fermi levels splitting (i.e., the open-circuit voltage) is achieved by measuring the differential vacuum-level shift over the WSe 2 flakes and the MoS 2 layer. The dependence of the energy-level splitting as a function of the optical power reveals that Shockley-Read-Hall processes significantly contribute to the interlayer recombination dynamics. Finally, a newly developed time-resolved mode of the KPFM is applied to map the SPV decay time constants. The time-resolved SPV images reveal the dynamics of delayed recombination processes originating from photocarriers trapping at the SiO 2 /TMDC interfaces.

WONOEP appraisal: new genetic approaches to study epilepsy

PubMed Central

Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

2014-01-01

Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non-coding RNAs involved in modifying gene expression following seizures. In addition, genetically-based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient iPS cells and genetically-modified zebrafish have become high-throughput means to investigate disease mechanisms and potential new therapies. Significance Genetics has considerably changed the field of epilepsy research and is paving the way for better diagnosis and therapies for patients with epilepsy. PMID:24965021

Scale refinement and initial evaluation of a behavioral health function measurement tool for work disability evaluation.

PubMed

Marfeo, Elizabeth E; Ni, Pengsheng; Haley, Stephen M; Bogusz, Kara; Meterko, Mark; McDonough, Christine M; Chan, Leighton; Rasch, Elizabeth K; Brandt, Diane E; Jette, Alan M

2013-09-01

To use item response theory (IRT) data simulations to construct and perform initial psychometric testing of a newly developed instrument, the Social Security Administration Behavioral Health Function (SSA-BH) instrument, that aims to assess behavioral health functioning relevant to the context of work. Cross-sectional survey followed by IRT calibration data simulations. Community. Sample of individuals applying for Social Security Administration disability benefits: claimants (n=1015) and a normative comparative sample of U.S. adults (n=1000). None. SSA-BH measurement instrument. IRT analyses supported the unidimensionality of 4 SSA-BH scales: mood and emotions (35 items), self-efficacy (23 items), social interactions (6 items), and behavioral control (15 items). All SSA-BH scales demonstrated strong psychometric properties including reliability, accuracy, and breadth of coverage. High correlations of the simulated 5- or 10-item computer adaptive tests with the full item bank indicated robust ability of the computer adaptive testing approach to comprehensively characterize behavioral health function along 4 distinct dimensions. Initial testing and evaluation of the SSA-BH instrument demonstrated good accuracy, reliability, and content coverage along all 4 scales. Behavioral function profiles of Social Security Administration claimants were generated and compared with age- and sex-matched norms along 4 scales: mood and emotions, behavioral control, social interactions, and self-efficacy. Using the computer adaptive test-based approach offers the ability to collect standardized, comprehensive functional information about claimants in an efficient way, which may prove useful in the context of the Social Security Administration's work disability programs. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse.

PubMed

Romand, Raymond; Ripp, Raymond; Poidevin, Laetitia; Boeglin, Marcel; Geffers, Lars; Dollé, Pascal; Poch, Olivier

2015-01-01

An in situ hybridization (ISH) study was performed on 2000 murine genes representing around 10% of the protein-coding genes present in the mouse genome using data generated by the EURExpress consortium. This study was carried out in 25 tissues of late gestation embryos (E14.5), with a special emphasis on the developing ear and on five distinct developing sensory organs, including the cochlea, the vestibular receptors, the sensory retina, the olfactory organ, and the vibrissae follicles. The results obtained from an analysis of more than 11,000 micrographs have been integrated in a newly developed knowledgebase, called ImAnno. In addition to managing the multilevel micrograph annotations performed by human experts, ImAnno provides public access to various integrated databases and tools. Thus, it facilitates the analysis of complex ISH gene expression patterns, as well as functional annotation and interaction of gene sets. It also provides direct links to human pathways and diseases. Hierarchical clustering of expression patterns in the 25 tissues revealed three main branches corresponding to tissues with common functions and/or embryonic origins. To illustrate the integrative power of ImAnno, we explored the expression, function and disease traits of the sensory epithelia of the five presumptive sensory organs. The study identified 623 genes (out of 2000) concomitantly expressed in the five embryonic epithelia, among which many (∼12%) were involved in human disorders. Finally, various multilevel interaction networks were characterized, highlighting differential functional enrichments of directly or indirectly interacting genes. These analyses exemplify an under-represention of "sensory" functions in the sensory gene set suggests that E14.5 is a pivotal stage between the developmental stage and the functional phase that will be fully reached only after birth.

Multi-Octave Spectral Imaging in the Infrared - A Newly Emerging Approach

DTIC Science & Technology

2002-01-01

as a function of wavelength, that arises from an example scene, and compare this with total noise (also as a function of wavelength). The signal...0.9 emissivity, for the purpose of this estimate of baseline performance. Total noise (in rms electrons) is estimated as a function of wavelength (or...spectral pixel number following the correspondence in Figure 2) from photon noise arising from both scene and optics emission, dark current noise , and

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

PubMed

Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.

PubMed

Kozlov, Anatoly; Jaumouillé, Edouard; Machado Almeida, Pedro; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C; Nagoshi, Emi

2017-07-12

Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled ( unf ) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period ( per ) (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837 , which we termed R and B ( Rnb ), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit. SIGNIFICANCE STATEMENT Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics distinguishing the s-LNvs, the master pacemaker of the locomotor rhythms, from other clock neuron subtypes. We demonstrated that a newly identified gene Rnb is an s-LNv-specific regulator of the molecular clock and essential for the generation of circadian locomotor behavior. Our results provide additional evidence to the emerging view that the differential regulation of the molecular clocks underlies the functional differences among the pacemaker neuron subgroups. Copyright © 2017 the authors 0270-6474/17/376673-13$15.00/0.

The experience of learning to speak up: a narrative inquiry on newly graduated registered nurses.

PubMed

Law, Bernice Yee-Shui; Chan, Engle Angela

2015-07-01

To explore the process of learning to speak up in practice among newly graduated registered nurses. Speaking up is an important aspect of communication to ensure patient safety within a healthcare team. However, nurses have reported being hesitant about speaking up or being unable to be heard, despite adopting various safety tools. A power differential could be a factor in their hesitation to speak up. While a large number of new graduates are employed in the lower rungs of the hospital hierarchy to resolve local and global nursing shortages, the process of their learning to speak up remains under-explored. The narrative concept of experience is addressed through the three-dimensional space of a narrative inquiry. Eighteen new graduates were recruited. Stories of experiences of speaking up emerged naturally during repeated unstructured interviews and ongoing email conversations with three participants. The complex process of learning to speak up is schematically represented. Three interrelated narrative threads were identified: (1) learning to speak up requires more than one-off training and safety tools, (2) mentoring speaking up in the midst of educative and miseducative experiences and (3) making public spaces safe for telling secret stories. Speaking up requires ongoing mentoring to see new possibilities for sustaining professional identities in the midst of miseducative experiences under the potential shaping of the Chinese culture and generational differences. Appreciative inquiry might be a new approach that can be used to promote positive cultural changes to encourage newly graduated registered nurses to learn to speak up to ensure patient safety. Cultivating a safe and open culture of communication and mentoring new graduates to speak up will benefit patient safety now and in the future by helping to retain committed patient advocates who could mentor future generations. © 2015 John Wiley & Sons Ltd.

Development of Electric Power Units Driven by Waste Heat

NASA Astrophysics Data System (ADS)

Inoue, Naoyuki; Takeuchi, Takao; Kaneko, Atsushi; Uchimura, Tomoyuki; Irie, Kiichi; Watanabe, Hiroyoshi

For the development of a simple and compact power generator driven by waste heat, working fluids and an expander were studied, then a practical electric power unit was put to test. Many working fluids were calculated with the low temperature power cycle (evaporated at 77°C, condensed at 42°C),and TFE,R123,R245fa were selected to be suitable for the cycle. TFE(Trifluoroethanol CF3CH2OH) was adopted to the actual power generator which was tested. A radial turbine was adopted as an expander, and was newly designed and manufactured for working fluid TFE. The equipment was driven by hot water as heat source and cooling water as cooling source, and generated power was connected with electric utility. Characteristics of the power generating cycle and characteristics of the turbine were obtained experimentally.

DNA Photolithography with Cinnamate Crosslinkers

NASA Technical Reports Server (NTRS)

Feng, Lang (Inventor); Chaikin, Paul Michael (Inventor)

2016-01-01

The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

Evaluation of new binders using newly developed fracture energy test : [summary].

DOT National Transportation Integrated Search

2013-07-01

The flexibility and cohesion that give asphalt concrete its performance characteristics largely derive from the properties of binders. The durability of binders affects the function and lifetime of paving, and considering how extensive Floridas ro...

A lower baseline glomerular filtration rate predicts high mortality and newly cerebrovascular accidents in acute ischemic stroke patients.

PubMed

Dong, Kai; Huang, Xiaoqin; Zhang, Qian; Yu, Zhipeng; Ding, Jianping; Song, Haiqing

2017-02-01

Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population.Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients' outcomes.Of all patients, 130 patients (13.4%) had reduced eGFR (<60 mL/min/1.73 m), and 556 patients had a normal eGFR (≥90 mL/min/1.73 m). A total of 694 patients suffered from cerebral artery stenosis, in which 293 patients only had intracranial artery stenosis (ICAS), 110 only with extracranial carotid atherosclerotic stenosis (ECAS), and 301 with both ICAS and ECAS. The patients with eGFR <60 mL/min/1.73m had a higher proportion of death and newly ischemic events compared with those with a relatively normal eGFR. Multivariate analysis revealed that a baseline eGFR <60 mL/min/1.73 m increased the risk of mortality by 3.089-fold and newly ischemic events by 4.067-fold. In further analysis, a reduced eGFR was associated with increased rates of mortality and newly events both in ICAS patients and ECAS patients. However, only an increased risk of newly events was found as the degree of renal function deteriorated in ICAS patients (odds ratio = 8.169, 95% confidence interval = 2.445-14.127).A low baseline eGFR predicted a high mortality and newly ischemic events at 3 months in ischemic stroke patients. A low baseline eGFR was also a strong independent predictor for newly ischemic events in ICAS patients.

Depth-Variable Settlement Patterns and Predation Influence on Newly Settled Reef Fishes (Haemulon spp., Haemulidae)

PubMed Central

Jordan, Lance K. B.; Lindeman, Kenyon C.; Spieler, Richard E.

2012-01-01

During early demersal ontogeny, many marine fishes display complex habitat-use patterns. Grunts of the speciose genus Haemulon are among the most abundant fishes on western North Atlantic coral reefs, with most species settling to shallow habitats (≤12 m). To gain understanding into cross-shelf distributional patterns exhibited by newly settled stages of grunts (<2 cm total length), we examined: 1) depth-specific distributions of congeners at settlement among sites at 8 m, 12 m, and 21 m, and 2) depth-variable predation pressure on newly settled individuals (species pooled). Of the six species identified from collections of newly settled specimens (n = 2125), Haemulon aurolineatum (tomtate), H. flavolineatum (French grunt), and H. striatum (striped grunt) comprised 98% of the total abundance; with the first two species present at all sites. Prevalence of H. aurolineatum and H. flavolineatum decreased substantially from the 8-m site to the two deeper sites. In contrast, H. striatum was absent from the 8-m site and exhibited its highest frequency at the 21-m site. Comparison of newly settled grunt delta density for all species on caged (predator exclusion) and control artificial reefs at the shallowest site (8-m) revealed no difference, while the 12-m and 21-m sites exhibited significantly greater delta densities on the caged treatment. This result, along with significantly higher abundances of co-occurring piscivorous fishes at the deeper sites, indicated lower predation pressure at the 8-m site. This study suggests habitat-use patterns of newly settled stages of some coral reef fishes that undergo ontogenetic shifts are a function of depth-variable predation pressure while, for at least one deeper-water species, proximity to adult habitat appears to be an important factor affecting settlement distribution. PMID:23272077

Leaf area and photosynthesis of newly emerged trifoliolate leaves are regulated by mature leaves in soybean.

PubMed

Wu, Yushan; Gong, Wanzhuo; Wang, Yangmei; Yong, Taiwen; Yang, Feng; Liu, Weigui; Wu, Xiaoling; Du, Junbo; Shu, Kai; Liu, Jiang; Liu, Chunyan; Yang, Wenyu

2018-03-29

Leaf anatomy and the stomatal development of developing leaves of plants have been shown to be regulated by the same light environment as that of mature leaves, but no report has yet been written on whether such a long-distance signal from mature leaves regulates the total leaf area of newly emerged leaves. To explore this question, we created an investigation in which we collected data on the leaf area, leaf mass per area (LMA), leaf anatomy, cell size, cell number, gas exchange and soluble sugar content of leaves from three soybean varieties grown under full sunlight (NS), shaded mature leaves (MS) or whole plants grown in shade (WS). Our results show that MS or WS cause a marked decline both in leaf area and LMA in newly developing leaves. Leaf anatomy also showed characteristics of shade leaves with decreased leaf thickness, palisade tissue thickness, sponge tissue thickness, cell size and cell numbers. In addition, in the MS and WS treatments, newly developed leaves exhibited lower net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (E), but higher carbon dioxide (CO 2 ) concentration in the intercellular space (Ci) than plants grown in full sunlight. Moreover, soluble sugar content was significantly decreased in newly developed leaves in MS and WS treatments. These results clearly indicate that (1) leaf area, leaf anatomical structure, and photosynthetic function of newly developing leaves are regulated by a systemic irradiance signal from mature leaves; (2) decreased cell size and cell number are the major cause of smaller and thinner leaves in shade; and (3) sugars could possibly act as candidate signal substances to regulate leaf area systemically.

Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

PubMed

Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

2014-08-01

Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

Piezoelectric power generation using friction-induced vibration

NASA Astrophysics Data System (ADS)

Tadokoro, Chiharu; Matsumoto, Aya; Nagamine, Takuo; Sasaki, Shinya

2017-06-01

In order to examine the feasibility of power generation by using friction-induced vibration with a piezoelectric element, we performed experiments and numerical analysis. In the experiments, the generated power in the piezoelectric element and the displacement of an oscillator were measured by a newly developed apparatus that embodied a single-degree-of-freedom (1-DOF) system with friction. In the numerical analysis, an analytical model of a 1-DOF system with friction and piezoelectric element was proposed to simulate the experiments. The experimental results demonstrated that the power of a few microwatts was generated by sliding between a steel ball and a steel plate lubricated with glycerol. In this study, a maximum power of approximately 10 μW was generated at a driving velocity of 40 mm s-1 and a normal load of 15 N. The numerical results demonstrated good qualitative agreement with the experimental results. This implies that this analytical model can be applied to optimize the oscillator design in piezoelectric power generation using friction-induced vibration.

Flagstaff Robotic Survey Telescope (FRoST): Rapid Response for NEOs

NASA Astrophysics Data System (ADS)

Avner, Louis Daniel; Trilling, David E.; Dunham, Edward W.

2016-10-01

The Flagstaff Robotic Survey Telescope (FRoST) is a robotic 0.6m Schmidt telescope that will be used for instant follow-up observations of newly discovered Near Earth Objects (NEOs). Here, we present the progress being made on FRoST as well as the remaining tasks until the telescope is fully operational. With more than one thousand NEOs being found yearly, more telescopes are needed to carry out follow-up observations. Most NEOs are found at their peak brightness, meaning that these observations need to happen quickly before they fade. By using the Catalina Sky Survey Queue Manager, FRoST will be able to accept interruptions during the night and prioritize observations automatically, allowing instant follow-up observations. FRoST will help refine the orbit of these newly discovered objects while providing optical colors. We will ingest information from the NEOCP and JPL's Scout program at five minute intervals and observe newly discovered targets robotically, process the data automatically, and autonomously generate astrometry and colors. We estimate that will we provide essentially 100% recovery of objects brighter than V~20. This work was supported by the NSF MRI program as well as by NAU and Lowell Observatory.

The Measurement of Executive Function at Age 3 Years: Psychometric Properties and Criterion Validity of a New Battery of Tasks

ERIC Educational Resources Information Center

Willoughby, Michael T.; Blair, Clancy B.; Wirth, R. J.; Greenberg, Mark

2010-01-01

In this study, the authors examined the psychometric properties and criterion validity of a newly developed battery of tasks that were designed to assess executive function (EF) abilities in early childhood. The battery was included in the 36-month assessment of the Family Life Project (FLP), a prospective longitudinal study of 1,292 children…

Considerations in prophylaxis for tumor-associated epilepsy: prevention of status epilepticus and tolerability of newer generation AEDs.

PubMed

Wychowski, Thomas; Wang, Hongyue; Buniak, Liana; Henry, J Craig; Mohile, Nimish

2013-11-01

To identify risk factors for the development of tumor-associated epilepsy (TAE) and potential benefit of newer generation AEDs in seizure prevention. We performed an IRB approved retrospective study of newly diagnosed GBM patients at the University of Rochester between 1/1/05 and 5/13/11. Records were reviewed to describe demographics, seizure incidence, occurrence of status epilepticus, and AED use and toxicity. 172 patients with newly diagnosed GBM were included in the study. 53.4% developed TAE. 31.4% had seizure prior to diagnosis. 118 patients were seizure-free at diagnosis: 32.2% developed post-diagnosis TIE (PostTAE) and 60.2% remained seizure-free. 70 seizure-free patients received an AED peri-operatively. 36 were weaned off AEDs and 31 were continued. Incidence of PostTAE and time to first seizure were comparable in AED-treated and untreated patients. 4 PostTAE patients presented with status epilepticus (SE), all were not AED treated. AEDs were withdrawn in 10 patients due to toxicity: 9 from phenytoin and 1 from levetiracetam. There is a high incidence of PostTAE in GBM. Prophylactic AED therapy did not reduce PostTAE but may have prevented SE. Minimal toxicity was observed on 2nd generation AEDs. The high burden of epilepsy in this population and tolerability of newer AEDS suggest that AAN guidelines should be revisited. Copyright © 2013 Elsevier B.V. All rights reserved.

Pharmacological modulation of lipopolysaccharide-induced pleural eosinophilia in the rat; a role for a newly generated protein.

PubMed

Bozza, P T; Castro-Faria-Neto, H C; Martins, M A; Larangeira, A P; Perales, J E; e Silva, P M; Cordeiro, R S

1993-06-01

Intrathoracic injection of endotoxin lipopolysaccharide, LPS into rats induced a dose-dependent increase in the number of eosinophils recovered from the pleural cavity. The pleural eosinophil accumulation peaked within 24-48 h, and returned to basal levels within 120 h. This phenomenon was accompanied by mononuclear cell infiltration, and preceded by massive neutrophil accumulation. Pretreatment with indomethacin, BW 755C (a dual cyclo/lipoxygenase inhibitor), BW A4C (a specific lipoxygenase inhibitor) or the platelet activating factor (PAF) antagonists WEB 2086 and PCA 4248 failed to inhibit the endotoxin-induced pleural eosinophilia, whilst dexamethasone (5-10 micrograms/cavity) or cycloheximide (14-28 micrograms/cavity) abolished this phenomenon. Transfer of the cell-free pleural washing from LPS-treated donor rats to normal recipient rats led to a two-fold increase in the eosinophil counts. Treatment of donors, but not recipients, with cycloheximide or dexamethasone inhibited the eosinophil accumulation induced by the pleural washings, indicating that the generation of the eosinophilotactic activity, but not its effects, depends on protein synthesis. This eosinophilotactic activity was maintained after lyophilization and heating (100 degrees C for 30 min), but was destroyed by trypsin. This substance has a molecular weight ranging between 10 and 50 kDa. The available data suggest that the late eosinophil accumulation induced by LPS is independent of arachidonic acid metabolites and PAF, and probably depends on a newly generated heat-stable soluble protein.

A New Method for Incremental Testing of Finite State Machines

NASA Technical Reports Server (NTRS)

Pedrosa, Lehilton Lelis Chaves; Moura, Arnaldo Vieira

2010-01-01

The automatic generation of test cases is an important issue for conformance testing of several critical systems. We present a new method for the derivation of test suites when the specification is modeled as a combined Finite State Machine (FSM). A combined FSM is obtained conjoining previously tested submachines with newly added states. This new concept is used to describe a fault model suitable for incremental testing of new systems, or for retesting modified implementations. For this fault model, only the newly added or modified states need to be tested, thereby considerably reducing the size of the test suites. The new method is a generalization of the well-known W-method and the G-method, but is scalable, and so it can be used to test FSMs with an arbitrarily large number of states.

Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances neurogenesis in the subgranular zone of dentate gyrus after transient global cerebral ischemia in rats.

PubMed

Lei, Shan; Zhang, Pengbo; Li, Weisong; Gao, Ming; He, Xijing; Zheng, Juan; Li, Xu; Wang, Xiao; Wang, Ning; Zhang, Junfeng; Qi, Cunfang; Lu, Haixia; Chen, Xinlin; Liu, Yong

2014-01-01

Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment with edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pre- and Posttreatment With Edaravone Protects CA1 Hippocampus and Enhances Neurogenesis in the Subgranular Zone of Dentate Gyrus After Transient Global Cerebral Ischemia in Rats

PubMed Central

Lei, Shan; Li, Weisong; Gao, Ming; He, Xijing; Zheng, Juan; Li, Xu; Wang, Xiao; Wang, Ning; Zhang, Junfeng; Qi, Cunfang; Lu, Haixia; Chen, Xinlin; Liu, Yong

2014-01-01

Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment with edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia. PMID:25388889

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells[S

PubMed Central

Nguyen, Su Duy; Öörni, Katariina; Lee-Rueckert, Miriam; Pihlajamaa, Tero; Metso, Jari; Jauhiainen, Matti; Kovanen, Petri T.

2012-01-01

HDL particles may enter atherosclerotic lesions having an acidic intimal fluid. Therefore, we investigated whether acidic pH would affect their structural and functional properties. For this purpose, HDL2 and HDL3 subfractions were incubated for various periods of time at different pH values ranging from 5.5 to 7.5, after which their protein and lipid compositions, size, structure, and cholesterol efflux capacity were analyzed. Incubation of either subfraction at acidic pH induced unfolding of apolipoproteins, which was followed by release of lipid-poor apoA-I and ensuing fusion of the HDL particles. The acidic pH-modified HDL particles exhibited an enhanced ability to promote cholesterol efflux from cholesterol-laden primary human macrophages. Importantly, treatment of the acidic pH-modified HDL with the mast cell-derived protease chymase completely depleted the newly generated lipid-poor apoA-I, and prevented the acidic pH-dependent increase in cholesterol efflux. The above-found pH-dependent structural and functional changes were stronger in HDL3 than in HDL2. Spontaneous acidic pH-induced remodeling of mature spherical HDL particles increases HDL-induced cholesterol efflux from macrophage foam cells, and therefore may have atheroprotective effects. PMID:22855736

Conceptualizing adverse outcome pathways for ...

EPA Pesticide Factsheets

Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions (e.g., reproduction). This study utilized newly generated high content (transcriptomic and metabolomic) empirical data in combination with existing high throughput (ACTOR, epa.gov) toxicity data to facilitate development of adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. We examined effects of a waterborne, 96h exposure to three COX inhibitors (indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on the liver metabolome and ovarian gene expression (using oligonucleotide microarray 4 x15K platform) in sexually mature fathead minnows (n=8). Differentially expressed genes were identified (t-test, p < 0.01), and functional analyses performed to determine enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (p < 0.05). Principal component analysis indicated that liver metabolomics profiles of IN, IB and CX were not significantly different from control or one another. When compared to control, exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. KEGG pathway analyses show that IN had extensive effects on oocyte meios

Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and Spine Density in the Adult Mouse Motor Cortex.

PubMed

Zemmar, Ajmal; Chen, Chia-Chien; Weinmann, Oliver; Kast, Brigitt; Vajda, Flora; Bozeman, James; Isaad, Noel; Zuo, Yi; Schwab, Martin E

2018-06-01

Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic branching and spine densities in layer 2/3 cortical pyramidal neurons. These effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser scanning microscopy to measure the spine turnover rate of adult mouse motor cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine remodeling after 4 days. Our results suggest relevant control functions of glial as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for more selective and targeted plasticity enhancing strategies.

AnnoLnc: a web server for systematically annotating novel human lncRNAs.

PubMed

Hou, Mei; Tang, Xing; Tian, Feng; Shi, Fangyuan; Liu, Fenglin; Gao, Ge

2016-11-16

Long noncoding RNAs (lncRNAs) have been shown to play essential roles in almost every important biological process through multiple mechanisms. Although the repertoire of human lncRNAs has rapidly expanded, their biological function and regulation remain largely elusive, calling for a systematic and integrative annotation tool. Here we present AnnoLnc ( http://annolnc.cbi.pku.edu.cn ), a one-stop portal for systematically annotating novel human lncRNAs. Based on more than 700 data sources and various tool chains, AnnoLnc enables a systematic annotation covering genomic location, secondary structure, expression patterns, transcriptional regulation, miRNA interaction, protein interaction, genetic association and evolution. An intuitive web interface is available for interactive analysis through both desktops and mobile devices, and programmers can further integrate AnnoLnc into their pipeline through standard JSON-based Web Service APIs. To the best of our knowledge, AnnoLnc is the only web server to provide on-the-fly and systematic annotation for newly identified human lncRNAs. Compared with similar tools, the annotation generated by AnnoLnc covers a much wider spectrum with intuitive visualization. Case studies demonstrate the power of AnnoLnc in not only rediscovering known functions of human lncRNAs but also inspiring novel hypotheses.

Improved mitochondrial function underlies the protective effect of pirfenidone against tubulointerstitial fibrosis in 5/6 nephrectomized rats.

PubMed

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells.

Development of an Expression Vector to Overexpress or Downregulate Genes in Curvularia protuberata.

PubMed

Liu, Chengke; Cleckler, Blake; Morsy, Mustafa

2018-05-05

Curvularia protuberata , an endophytic fungus in the Ascomycota, provides plants with thermotolerance only when it carries a mycovirus known as Curvularia thermotolerance virus (CThTV), and forms a three-way symbiotic relationship among these organisms. Under heat stress, several genes are expressed differently between virus-free C. protuberata (VF) and C. protuberata carrying CThTV (AN). We developed an expression vector, pM2Z-fun, carrying a zeocin resistance gene driven by the ToxA promoter, to study gene functions in C. protuberata to better understand this three-way symbiosis. Using this new 3.7-kb vector, five genes that are differentially expressed in C. protuberata —including genes involved in the trehalose, melanin, and catalase biosynthesis pathways—were successfully overexpressed or downregulated in VF or AN C. protuberata strains, respectively. The VF overexpression lines showed higher metabolite and enzyme activity than in the control VF strain. Furthermore, downregulation of expression of the same genes in the AN strain resulted in lower metabolite and enzyme activity than in the control AN strain. The newly generated expression vector, pM2Z-fun, has been successfully used to express target genes in C. protuberata and will be useful in further functional expression studies in other Ascomycota fungi.

Improved Mitochondrial Function Underlies the Protective Effect of Pirfenidone against Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats

PubMed Central

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells. PMID:24349535

A conserved loop-wedge motif moderates reaction site search and recognition by FEN1.

PubMed

Thompson, Mark J; Gotham, Victoria J B; Ciani, Barbara; Grasby, Jane A

2018-06-07

DNA replication and repair frequently involve intermediate two-way junction structures with overhangs, or flaps, that must be promptly removed; a task performed by the essential enzyme flap endonuclease 1 (FEN1). We demonstrate a functional relationship between two intrinsically disordered regions of the FEN1 protein, which recognize opposing sides of the junction and order in response to the requisite substrate. Our results inform a model in which short-range translocation of FEN1 on DNA facilitates search for the annealed 3'-terminus of a primer strand, which is recognized by breaking the terminal base pair to generate a substrate with a single nucleotide 3'-flap. This recognition event allosterically signals hydrolytic removal of the 5'-flap through reaction in the opposing junction duplex, by controlling access of the scissile phosphate diester to the active site. The recognition process relies on a highly-conserved 'wedge' residue located on a mobile loop that orders to bind the newly-unpaired base. The unanticipated 'loop-wedge' mechanism exerts control over substrate selection, rate of reaction and reaction site precision, and shares features with other enzymes that recognize irregular DNA structures. These new findings reveal how FEN1 precisely couples 3'-flap verification to function.

A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.

PubMed

Tamura, Kazuhiro; Naraba, Hiroaki; Hara, Takahiko; Nakamura, Kota; Yoshie, Mikihiro; Kogo, Hiroshi; Tachikawa, Eiichi

2016-03-01

Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs. Copyright © 2016 Elsevier Inc. All rights reserved.

Penguins reduced olfactory receptor genes common to other waterbirds

PubMed Central

Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

2016-01-01

The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins. PMID:27527385

BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

PubMed

Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

2015-10-01

Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

A versatile microsatellite instability reporter system in human cells.

PubMed

Koole, Wouter; Schäfer, Henning S; Agami, Reuven; van Haaften, Gijs; Tijsterman, Marcel

2013-09-01

Here, we report the investigation of microsatellite instability (MSI) in human cells with a newly developed reporter system based on fluorescence. We composed a vector into which microsatellites of different lengths and nucleotide composition can be introduced between a functional copy of the fluorescent protein mCherry and an out-of-frame copy of EGFP; in vivo frameshifting will lead to EGFP expression, which can be quantified by fluorescence activated cell sorting (FACS). Via targeted recombineering, single copy reporters were introduced in HEK293 and MCF-7 cells. We found predominantly -1 and +1 base pair frameshifts, the levels of which are kept in tune by mismatch repair. We show that tract length and composition greatly influences MSI. In contrast, a tracts' potential to form a G-quadruplex structure, its strand orientation or its transcriptional status is not affecting MSI. We further validated the functionality of the reporter system for screening microsatellite mutagenicity of compounds and for identifying modifiers of MSI: using a retroviral miRNA expression library, we identified miR-21, which targets MSH2, as a miRNA that induces MSI when overexpressed. Our data also provide proof of principle for the strategy of combining fluorescent reporters with next-generation sequencing technology to identify genetic factors in specific pathways.

Evaluting the Validity of Technology-Enhanced Educational Assessment Items and Tasks: An Emprical Approach to Studying Item Features and Scoring Rubrics

ERIC Educational Resources Information Center

Thomas, Ally

2016-01-01

With the advent of the newly developed Common Core State Standards and the Next Generation Science Standards, innovative assessments, including technology-enhanced items and tasks, will be needed to meet the challenges of developing valid and reliable assessments in a world of computer-based testing. In a recent critique of the next generation…

Revisiting the phylogeny of Ocellularieae, the second largest tribe within Graphidaceae (lichenized Ascomycota: Ostropales)

Treesearch

Ekaphan Kraichak; Sittiporn Parnmen; Robert Lücking; Eimy Rivas Plata; Andre Aptroot; Marcela E.S. Caceres; Damien Ertz; Armin Mangold; Joel A. Mercado-Diaz; Khwanruan Papong; Dries Van der Broeck; Gothamie Weerakoon; H. Thorsten Lumbsch; NO-VALUE

2014-01-01

We present an updated 3-locus molecular phylogeny of tribe Ocellularieae, the second largest tribe within subfamily Graphidoideae in the Graphidaceae. Adding 165 newly generated sequences from the mitochondrial small subunit rDNA (mtSSU), the nuclear large subunit rDNA (nuLSU), and the second largest subunit of the DNA-directed RNA polymerase II (RPB2), we currently...

Artificial rearing of 10 species of wood-boring insects

Treesearch

Jimmy R. Galford

1969-01-01

Small numbers of 10 species of wood-boring insects were reared from newly hatched larvae to adults on artificial media with good survival. Species with life cycles of up to 2 years in nature were reared on the media in less than 1 year. Although all of the adults appeared normal physically, some were sterile. One species was reared artificially for three generations....

Investigation of Possible Electromagnetic Disturbances caused by Spacecraft-Plasma Interactions at 4 Radii

NASA Technical Reports Server (NTRS)

Okada, M.; Tsurutani, B. T.; Goldstein, G. E.; Matsumoto, H.; Brinca, A. L.; Kellogg, P. J.

1995-01-01

The proposed Small Solar Probe mission features a close approach to the sun with a perihelion of 4 radii. Carbon molecules emitted from the spacecraft's heat shield will become ionized by electron impact and photoionization. The newly created ions and electrons may generate electromagnetic and electrostatic plasma waves which are possible sources of interference with in-situ plasma measurements.

The Hybrid Aesthetic Functional (HAF) Appliance: A Less Visible Proposal for Functional Orthodontics

PubMed Central

2013-01-01

In modern orthodontics, aesthetics appear to have a decisive influence on orthodontic appliance preferences and acceptability. This paper reports the early application of a newly emerged functional device with enhanced aesthetics in a Class II treatment. Patient perspectives and technical considerations are discussed along with recommendations for further design development. It can be assumed that the use of thermoplastic material-based appliances may meet both the therapeutic and aesthetic demands of young age groups. PMID:23956884

Comparing the ISO-recommended and the cumulative data-reduction algorithms in S-on-1 laser damage test by a reverse approach method

NASA Astrophysics Data System (ADS)

Zorila, Alexandru; Stratan, Aurel; Nemes, George

2018-01-01

We compare the ISO-recommended (the standard) data-reduction algorithm used to determine the surface laser-induced damage threshold of optical materials by the S-on-1 test with two newly suggested algorithms, both named "cumulative" algorithms/methods, a regular one and a limit-case one, intended to perform in some respects better than the standard one. To avoid additional errors due to real experiments, a simulated test is performed, named the reverse approach. This approach simulates the real damage experiments, by generating artificial test-data of damaged and non-damaged sites, based on an assumed, known damage threshold fluence of the target and on a given probability distribution function to induce the damage. In this work, a database of 12 sets of test-data containing both damaged and non-damaged sites was generated by using four different reverse techniques and by assuming three specific damage probability distribution functions. The same value for the threshold fluence was assumed, and a Gaussian fluence distribution on each irradiated site was considered, as usual for the S-on-1 test. Each of the test-data was independently processed by the standard and by the two cumulative data-reduction algorithms, the resulting fitted probability distributions were compared with the initially assumed probability distribution functions, and the quantities used to compare these algorithms were determined. These quantities characterize the accuracy and the precision in determining the damage threshold and the goodness of fit of the damage probability curves. The results indicate that the accuracy in determining the absolute damage threshold is best for the ISO-recommended method, the precision is best for the limit-case of the cumulative method, and the goodness of fit estimator (adjusted R-squared) is almost the same for all three algorithms.

Acute Stress in Parents of Children Newly Diagnosed With Cancer

PubMed Central

Patiño-Fernández, Anna Maria; Pai, Ahna L.H.; Alderfer, Melissa; Hwang, Wei-Ting; Reilly, Anne; Kazak, Anne E.

2010-01-01

Objective Acute Stress Disorder (ASD) and subclinical symptoms of acute stress (SAS) may be a useful framework for understanding the psychological reactions of mothers and fathers of children newly diagnosed with a pediatric malignancy. Patients and Methods Mothers (N = 129) and fathers (N = 72) of 138 children newly diagnosed with cancer completed questionnaires assessing acute distress, anxiety, and family functioning. Demographic data were also gathered. Inclusion criteria were: a confirmed diagnosis of a pediatric malignancy in a child under the age of 18 years without prior chronic or life threatening illness and fluency in English or Spanish. Results Descriptive statistics and multiple linear regressions were used to examine predictors of SAS. Fifty-one percent (N = 66) of mothers and 40% (N = 29) of fathers met DSM-IV diagnostic criteria for ASD. The majority of the sample reported experiencing at least one SAS. General anxiety, but not family functioning, was a strong predictor of SAS in both mothers and fathers even after controlling for demographic characteristics. Conclusions Immediately following their child’s diagnosis of cancer, most mothers and fathers experience SAS, with a subsample meeting criteria for ASD. More anxious parents are at heightened risk of more intense reactions. The findings support the need for evidence-based psychosocial support at diagnosis and throughout treatment for families who are at risk for acute distress reactions. PMID:17514742

Global Regulatory Functions of the Staphylococcus aureus Endoribonuclease III in Gene Expression

PubMed Central

Lioliou, Efthimia; Sharma, Cynthia M.; Caldelari, Isabelle; Helfer, Anne-Catherine; Fechter, Pierre; Vandenesch, François; Vogel, Jörg; Romby, Pascale

2012-01-01

RNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that were co-immunoprecipitated with wild-type RNase III or two different cleavage-defective mutant variants in vivo. Several newly identified RNase III targets were validated by independent experimental methods. We identified various classes of structured RNAs as RNase III substrates and demonstrated that this enzyme is involved in the maturation of rRNAs and tRNAs, regulates the turnover of mRNAs and non-coding RNAs, and autoregulates its synthesis by cleaving within the coding region of its own mRNA. Moreover, we identified a positive effect of RNase III on protein synthesis based on novel mechanisms. RNase III–mediated cleavage in the 5′ untranslated region (5′UTR) enhanced the stability and translation of cspA mRNA, which encodes the major cold-shock protein. Furthermore, RNase III cleaved overlapping 5′UTRs of divergently transcribed genes to generate leaderless mRNAs, which constitutes a novel way to co-regulate neighboring genes. In agreement with recent findings, low abundance antisense RNAs covering 44% of the annotated genes were captured by co-immunoprecipitation with RNase III mutant proteins. Thus, in addition to gene regulation, RNase III is associated with RNA quality control of pervasive transcription. Overall, this study illustrates the complexity of post-transcriptional regulation mediated by RNase III. PMID:22761586

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

PubMed Central

Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.

2016-01-01

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649

PREVAIL TRANSAPICAL: multicentre trial of transcatheter aortic valve implantation using the newly designed bioprosthesis (SAPIEN-XT) and delivery system (ASCENDRA-II).

PubMed

Walther, Thomas; Thielmann, Matthias; Kempfert, Joerg; Schroefel, Holger; Wimmer-Greinecker, Gerhard; Treede, Hendrik; Wahlers, Thorsten; Wendler, Olaf

2012-08-01

Transapical (TA) aortic valve implantation (AVI) has evolved as an alternative procedure for high-risk patients. We evaluated the second-generation SAPIEN XT™ prosthesis in a prospective multicentre clinical trial. A total of 150 patients (age: 81.6 ± 5.8 years; 40.7% female) were included. Prosthetic valves (diameter: 23 mm (n = 36), 26 mm (n = 57) and 29 mm (n = 57)) were implanted. The ASCENDRA-II™ modified delivery system was used in the smaller sizes. Mean logistic EuroSCORE was 24.3 ± 7.0%, and mean STS score 7.5 ± 4.4%. All patients gave written informed consent. Off-pump AVI was performed using femoral arterial and venous access wires as a safety net. All but two patients received TA-AVI, as planned. The 29-mm valve showed similar function as the values of two other diameters did. Three patients (2%) required temporary cardiopulmonary bypass support. Postoperative complications included renal failure requiring long-term dialysis in four, bleeding requiring rethoracotomy in four, respiratory complication requiring reintubation in eight and sepsis in four patients, respectively. Thirty-day mortality was 13 (8.7%) for the total cohort and 2/57 (3.5%) for patients receiving the 29-mm valve, respectively. Echocardiography at discharge showed none or trivial aortic incompetence (AI) in 71% and mild-AI in 22% of the patients. Post-implantation AI was predominantly paravalvular and ≥ 2+ in 7% of patients. One patient required reoperation for AI within 30 days. The PREVAIL TA multicentre trial demonstrates good functionality and good outcomes for TA-AVI, using the SAPIEN XT™ prosthesis and its second-generation ASCENDRA-II™ delivery system, as well successful introduction of the 29-mm SAPIEN XT™ valve for the benefit of high-risk elderly patients.

Modulated regeneration of acid-etched human tooth enamel by a functionalized dendrimer that is an analog of amelogenin.

PubMed

Chen, Mei; Yang, Jiaojiao; Li, Jiyao; Liang, Kunneng; He, Libang; Lin, Zaifu; Chen, Xingyu; Ren, Xiaokang; Li, Jianshu

2014-10-01

In the bioinspired repair process of tooth enamel, it is important to simultaneously mimic the organic-matrix-induced biomineralization and increase the binding strength at the remineralization interface. In this work, a fourth-generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to obtain phosphate-terminated dendrimer (PAMAM-PO3H2) since it has a similar dimensional scale and peripheral functionalities to that of amelogenin, which plays important role in the natural development process of enamel. Its phosphate group has stronger affinity for calcium ion than carboxyl group and can simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT assay demonstrates the low cytotoxicity of PAMAM-PO3H2. Adsorption tests indicate that PAMAM-PO3H2 can be tightly adsorbed on the human tooth enamel. Scanning electron microscopy and X-ray diffraction are used to analyze the remineralization process. After being incubated in artificial saliva for 3weeks, there is a newly generated HA layer of 11.23μm thickness on the acid-etched tooth enamel treated by PAMAM-PO3H2, while the thickness for the carboxyl-terminated one (PAMAM-COOH) is only 6.02μm. PAMAM-PO3H2 can regulate the remineralization process to form ordered new crystals oriented along the Z-axis and produce an enamel prism-like structure that is similar to that of natural tooth enamel. The animal experiment also demonstrates that PAMAM-PO3H2 can induce significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO3H2 shows great potential as a biomimetic restorative material for human tooth enamel. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

PubMed

Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

2016-05-04

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

STARTUP REACTIVITY ACCOUNTABILITY ATTRIBUTED TO ISOTOPIC TRANSMUTATIONS IN THE IRRADIATED BERYLLIUM REFLECTOR OF THE HIGH FLUX ISTOTOPE REACTOR

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

Chandler, David; Maldonado, G Ivan; Primm, Trent

2010-01-01

The objective of this study is to develop a methodology to predict the reactivity impact as a function of outage time between cycles of 3He, 6Li, and other poisons in the High Flux Isotope Reactor s (HFIR) beryllium reflector. The reactivity worth at startup of the HFIR has been incorrectly predicted in the past after the reactor has been shut-down for long periods of time. The incorrect prediction was postulated to be due to the erroneous calculation of 3He buildup in the beryllium reflector. It is necessary to develop a better estimate of the start-of-cycle symmetric critical control element positionsmore » since if the estimated and actual symmetrical critical control element positions differ by more than $1.55 in reactivity (approximately one-half inch in control element startup position), HFIR is to be shutdown and a technical evaluation is performed to resolve the discrepancy prior to restart. 3He is generated and depleted during operation, but during an outage, the depletion of 3He ceases because it is a stable isotope. 3He is born from the radioactive decay of tritium, and thus the concentration of 3He increases during shutdown. The computer program SCALE, specifically the TRITON and CSAS5 control modules including the KENO V.A, COUPLE, and ORIGEN functional modules were utilized in this study. An equation relating the down time (td) to the change in symmetric control element position was generated and validated against measurements for approximately 40 HFIR operating cycles. The newly-derived correlation was shown to improve accuracy of predictions for long periods of down time.« less

A NGS approach to the encrusting Mediterranean sponge Crella elegans (Porifera, Demospongiae, Poecilosclerida): transcriptome sequencing, characterization and overview of the gene expression along three life cycle stages.

PubMed

Pérez-Porro, A R; Navarro-Gómez, D; Uriz, M J; Giribet, G

2013-05-01

Sponges can be dominant organisms in many marine and freshwater habitats where they play essential ecological roles. They also represent a key group to address important questions in early metazoan evolution. Recent approaches for improving knowledge on sponge biological and ecological functions as well as on animal evolution have focused on the genetic toolkits involved in ecological responses to environmental changes (biotic and abiotic), development and reproduction. These approaches are possible thanks to newly available, massive sequencing technologies-such as the Illumina platform, which facilitate genome and transcriptome sequencing in a cost-effective manner. Here we present the first NGS (next-generation sequencing) approach to understanding the life cycle of an encrusting marine sponge. For this we sequenced libraries of three different life cycle stages of the Mediterranean sponge Crella elegans and generated de novo transcriptome assemblies. Three assemblies were based on sponge tissue of a particular life cycle stage, including non-reproductive tissue, tissue with sperm cysts and tissue with larvae. The fourth assembly pooled the data from all three stages. By aggregating data from all the different life cycle stages we obtained a higher total number of contigs, contigs with blast hit and annotated contigs than from one stage-based assemblies. In that multi-stage assembly we obtained a larger number of the developmental regulatory genes known for metazoans than in any other assembly. We also advance the differential expression of selected genes in the three life cycle stages to explore the potential of RNA-seq for improving knowledge on functional processes along the sponge life cycle. © 2013 Blackwell Publishing Ltd.

Reactivity Accountability Attributed to Reflector Poisons in the High Flux Isotope Reactor

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

Chandler, David; Maldonado, G Ivan; Primm, Trent

2009-12-01

The objective of this study is to develop a methodology to predict the reactivity impact as a function of outage time between cycles of 3He, 6Li, and other poisons in the High Flux Isotope Reactor s (HFIR) beryllium reflector. The reactivity worth at startup of the HFIR has been incorrectly predicted in the past after the reactor has been shut-down for long periods of time. The incorrect prediction was postulated to be due to the erroneous calculation of 3He buildup in the beryllium reflector. It is necessary to develop a better estimate of the start-of-cycle symmetric critical control element positionsmore » since if the estimated and actual symmetrical critical control element positions differ by more than $1.55 in reactivity (approximately one-half inch in control element startup position), HFIR is to be shutdown and a technical evaluation is performed to resolve the discrepancy prior to restart. 3He is generated and depleted during operation, but during an outage, the depletion of 3He ceases because it is a stable isotope. 3He is born from the radioactive decay of tritium, and thus the concentration of 3He increases during shutdown. SCALE, specifically the TRITON and CSAS5 control modules including the KENO V.A, COUPLE, and ORIGEN functional modules were utilized in this study. An equation relating the down time (td) to the change in symmetric control element position was generated and validated against measurements for approximately 40 HFIR operating cycles. The newly-derived correlation was shown to improve accuracy of predictions for long periods of down time.« less

Depressive symptoms and their impact on health-seeking behaviors in newly-diagnosed HIV-infected patients in Durban, South Africa.

PubMed

Ramirez-Avila, Lynn; Regan, Susan; Giddy, Janet; Chetty, Senica; Ross, Douglas; Katz, Jeffrey N; Freedberg, Kenneth A; Walensky, Rochelle P; Losina, Elena; Bassett, Ingrid V

2012-11-01

We evaluated the prevalence and correlates of depressive symptoms prior to HIV diagnosis and determined the effect of these symptoms on seeking HIV care at an urban and rural clinic in Durban, South Africa. Adults were administered a questionnaire which included the 5-item Mental Health Index (MHI-5) before HIV testing. We determined the depressive symptoms among HIV-infected subjects. Of 1,545 newly-diagnosed HIV-infected subjects, 55% had depressive symptoms by MHI-5 score. Enrolling at the urban clinic and decreasing functional activity score were associated with depressive symptoms. Subjects with depressive symptoms who were referred for HIV testing by a healthcare provider were less likely to obtain a CD4 count than those without depressive symptoms who self-referred for testing. Depressive symptoms were common among newly-diagnosed HIV-infected participants and impacted CD4 uptake. Depression screening at the time of HIV diagnosis is critical for improving linkage to mental health and HIV services in South Africa.

High-Throughput Screening based Identification of Small Molecule Antagonists of Integrin CD11b/CD18 Ligand Binding

PubMed Central

Faridi, Mohd Hafeez; Maiguel, Dony; Brown, Brock T.; Suyama, Eigo; Barth, Constantinos J.; Hedrick, Michael; Vasile, Stefan; Sergienko, Eduard; Schürer, Stephan; Gupta, Vineet

2010-01-01

Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique. PMID:20188705

Health-related quality of life of children with newly diagnosed specific learning disability.

PubMed

Karande, Sunil; Bhosrekar, Kirankumar; Kulkarni, Madhuri; Thakker, Arpita

2009-06-01

The objective of this study was to measure health-related quality of life (HRQL) of children with newly diagnosed specific learning disability (SpLD) using the Child Health Questionnaire-Parent Form 50. We detected clinically significant deficits (effect size > or = -0.5) in 9 out of 12 domains: limitations in family activities, emotional impact on parents, social limitations as a result of emotional-behavioral problems, time impact on parents, general behavior, physical functioning, social limitations as a result of physical health, general health perceptions and mental health; and in both summary scores (psychosocial > physical). Multivariate analysis revealed having > or = 1 non-academic problem(s) (p < 0.0001), attention-deficit hyperactivity disorder (p = 0.005) or first-born status (p = 0.009) predicted a poor psychosocial summary score; and having > or =1 non-academic problem(s) (p = 0.006) or first-born status (p = 0.035) predicted a poor physical summary score. HRQL is significantly compromised in children having newly diagnosed SpLD.

Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition

PubMed Central

2014-01-01

Background Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the “rewiring” of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury. PMID:24618249

MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution

PubMed Central

Luo, Junjie; Wang, Yirong; Yuan, Jian

2018-01-01

The repertoire of miRNAs has considerably expanded during metazoan evolution, and duplication is an important mechanism for generating new functional miRNAs. However, relatively little is known about the functional divergence between paralogous miRNAs and the possible coevolution between duplicated miRNAs and the genomic contexts. By systematically examining small RNA expression profiles across various human tissues and interrogating the publicly available miRNA:mRNA pairing chimeras, we found that changes in expression patterns and targeting preferences are widespread for duplicated miRNAs in vertebrates. Both the empirical interactions and target predictions suggest that evolutionarily conserved homo-seed duplicated miRNAs pair with significantly higher numbers of target sites compared to the single-copy miRNAs. Our birth-and-death evolutionary analysis revealed that the new target sites of miRNAs experienced frequent gains and losses during function development. Our results suggest that a newly emerged target site has a higher probability to be functional and maintained by natural selection if it is paired to a seed shared by multiple paralogous miRNAs rather than being paired to a single-copy miRNA. We experimentally verified the divergence in target repression between two paralogous miRNAs by transfecting let-7a and let-7b mimics into kidney-derived cell lines of four mammalian species and measuring the resulting transcriptome alterations by extensive high-throughput sequencing. Our results also suggest that the gains and losses of let-7 target sites might be associated with the evolution of repressiveness of let-7 across mammalian species. PMID:29511046

How to build a molecular shock absorber.

PubMed

McGough, A

1999-12-02

Newly determined structures of the alpha-helical repeats that make up the key 'rod' domains of spectrin and alpha-actinin - which serve as spacers between their actin-binding domains - have provided important insights into how these proteins function as molecular shock absorbers in cells.

26 CFR 601.106 - Appeals functions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Director, Foreign Operations District, the Appeals office may waive jurisdiction to the director who issued... to having the case returned to the district director for reconsideration. Where newly discovered... the Assistant Commissioner (Technical), and will usually be attended by a person who has authority to...

26 CFR 601.106 - Appeals functions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Director, Foreign Operations District, the Appeals office may waive jurisdiction to the director who issued... to having the case returned to the district director for reconsideration. Where newly discovered... the Assistant Commissioner (Technical), and will usually be attended by a person who has authority to...

26 CFR 601.106 - Appeals functions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Director, Foreign Operations District, the Appeals office may waive jurisdiction to the director who issued... to having the case returned to the district director for reconsideration. Where newly discovered... the Assistant Commissioner (Technical), and will usually be attended by a person who has authority to...

Project of Near-Real-Time Generation of ShakeMaps and a New Hazard Map in Austria

NASA Astrophysics Data System (ADS)

Jia, Yan; Weginger, Stefan; Horn, Nikolaus; Hausmann, Helmut; Lenhardt, Wolfgang

2016-04-01

Target-orientated prevention and effective crisis management can reduce or avoid damage and save lives in case of a strong earthquake. To achieve this goal, a project for automatic generated ShakeMaps (maps of ground motion and shaking intensity) and updating the Austrian hazard map was started at ZAMG (Zentralanstalt für Meteorologie und Geodynamik) in 2015. The first goal of the project is set for a near-real-time generation of ShakeMaps following strong earthquakes in Austria to provide rapid, accurate and official information to support the governmental crisis management. Using newly developed methods and software by SHARE (Seismic Hazard Harmonization in Europe) and GEM (Global Earthquake Model), which allows a transnational analysis at European level, a new generation of Austrian hazard maps will be ultimately calculated. More information and a status of our project will be given by this presentation.

Monte Carlo generators for hadron physics: updates on PHOKHARA and EKHARA generators

NASA Astrophysics Data System (ADS)

Czyż, Henryk; Kisza, Patrycja; Tracz, Szymon

2017-04-01

A short review of current upgrades of the PHOKHARA and EKHARA generators is presented together with a report on the work in progress. The upgrades are based on a newly constructed model of the χci - γ* - γ* and χci - J/ψ* - γ* form factors. Within this model predictions were made for the electronic widths of χc1 and χc2 and, based on the event generators results, cross sections e+e- → χc1 (→ J/ψ(→ μ+μ-)γ), e+e-→ e+e-χc1 and e+e-→ e+e-χc1 (→ J/ψ(→ μ+μ-)γ). Work supported in part by the Polish National Science Centre, grant number DEC-2012/07/B/ST2/03867 and German Research Foundation DFG under Contract No. Collaborative Research Center CRC-1044.

Method of making compost and spawned compost, mushroom spawn and generating methane gas

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

Stoller, B.B.

1981-04-28

Newly designed ribbon-type mixers provide an improved method for making composts, aerating composts, growing mushroom spawn, generating methane gas, and filling conveyors in the mushroom-growing industry. The mixers may be the double-ribbon type for purely mixing operations or the single-ribbon type for moving the material from one place to another. Both types can operate under pressure. In preparing compost for mushroom growing, operators can first use the airtight mixers for a preliminary anaerobic fermentation to produce methane, then by changing the atmosphere to an oxidizing one, complete the compost preparation under the necessary aerobic conditions.

Uncaging a catalytic hydrogen peroxide generator through the photo-induced release of nitric oxide from a {MnNO}(6) complex.

PubMed

Iwamoto, Yuji; Kodera, Masahito; Hitomi, Yutaka

2015-06-11

The photo-initiated cytotoxicity of a newly developed manganese nitrosyl {MnNO}(6) complex (UG1NO) to HeLa cells is described. The complex was found to be strongly cytotoxic after being exposed to light with a wavelength of 650 nm. Cell death was caused by a manganese(II) complex, UG1, generated from UG1NO through the photo-dissociation of NO, rather than by NO directly. Mechanistic studies revealed that UG1 consumes O2 only in the presence of a reducing agent to catalytically produce H2O2.

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

PubMed

Le, Van So; Do, Zoe Phuc-Hien; Le, Minh Khoi; Le, Vicki; Le, Natalie Nha-Truc

2014-06-10

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

The local matrix distribution and the functional development of tissue engineered cartilage, a finite element study.

PubMed

Sengers, B G; Van Donkelaar, C C; Oomens, C W J; Baaijens, F P T

2004-12-01

Assessment of the functionality of tissue engineered cartilage constructs is hampered by the lack of correlation between global measurements of extra cellular matrix constituents and the global mechanical properties. Based on patterns of matrix deposition around individual cells, it has been hypothesized previously, that mechanical functionality arises when contact occurs between zones of matrix associated with individual cells. The objective of this study is to determine whether the local distribution of newly synthesized extracellular matrix components contributes to the evolution of the mechanical properties of tissue engineered cartilage constructs. A computational homogenization approach was adopted, based on the concept of a periodic representative volume element. Local transport and immobilization of newly synthesized matrix components were described. Mechanical properties were taken dependent on the local matrix concentration and subsequently the global aggregate modulus and hydraulic permeability were derived. The transport parameters were varied to assess the effect of the evolving matrix distribution during culture. The results indicate that the overall stiffness and permeability are to a large extent insensitive to differences in local matrix distribution. This emphasizes the need for caution in the visual interpretation of tissue functionality from histology and underlines the importance of complementary measurements of the matrix's intrinsic molecular organization.

Modification and identification of a vector for making a large phage antibody library.

PubMed

Zhang, Guo-min; Chen, Yü-ping; Guan, Yuan-zhi; Wang, Yan; An, Yun-qing

2007-11-20

The large phage antibody library is used to obtain high-affinity human antibody, and the Loxp/cre site-specific recombination system is a potential method for constructing a large phage antibody library. In the present study, a phage antibody library vector pDF was reconstructed to construct diabody more quickly and conveniently without injury to homologous recombination and the expression function of the vector and thus to integrate construction of the large phage antibody library with the preparation of diabodies. scFv was obtained by overlap polymerase chain reaction (PCR) amplification with the newly designed VL and VH extension primers. loxp511 was flanked by VL and VH and the endonuclease ACC III encoding sequences were introduced on both sides of loxp511. scFv was cloned into the vector pDF to obtain the vector pDscFv. The vector expression function was identified and the feasibility of diabody preparation was evaluated. A large phage antibody library was constructed in pDscFv. Several antigens were used to screen the antibody library and the quality of the antibody library was evaluated. The phage antibody library expression vector pDscFv was successfully constructed and confirmed to express functional scFv. The large phage antibody library constructed using this vector was of high diversity. Screening of the library on 6 antigens confirmed the generation of specific antibodies to these antigens. Two antibodies were subjected to enzymatic digestion and were prepared into diabody with functional expression. The reconstructed vector pDscFv retains its recombination capability and expression function and can be used to construct large phage antibody libraries. It can be used as a convenient and quick method for preparing diabodies after simple enzymatic digestion, which facilitates clinical trials and application of antibody therapy.

Viewing-zone control of integral imaging display using a directional projection and elemental image resizing method.

PubMed

Alam, Md Ashraful; Piao, Mei-Lan; Bang, Le Thanh; Kim, Nam

2013-10-01

Viewing-zone control of integral imaging (II) displays using a directional projection and elemental image (EI) resizing method is proposed. Directional projection of EIs with the same size of microlens pitch causes an EI mismatch at the EI plane. In this method, EIs are generated computationally using a newly introduced algorithm: the directional elemental image generation and resizing algorithm considering the directional projection geometry of each pixel as well as an EI resizing method to prevent the EI mismatch. Generated EIs are projected as a collimated projection beam with a predefined directional angle, either horizontally or vertically. The proposed II display system allows reconstruction of a 3D image within a predefined viewing zone that is determined by the directional projection angle.

Protein Function Prediction: Problems and Pitfalls.

PubMed

Pearson, William R

2015-09-03

The characterization of new genomes based on their protein sets has been revolutionized by new sequencing technologies, but biologists seeking to exploit new sequence information are often frustrated by the challenges associated with accurately assigning biological functions to newly identified proteins. Here, we highlight some of the challenges in functional inference from sequence similarity. Investigators can improve the accuracy of function prediction by (1) being conservative about the evolutionary distance to a protein of known function; (2) considering the ambiguous meaning of "functional similarity," and (3) being aware of the limitations of annotations in functional databases. Protein function prediction does not offer "one-size-fits-all" solutions. Prediction strategies work better when the idiosyncrasies of function and functional annotation are better understood. Copyright © 2015 John Wiley & Sons, Inc.

New concept of the contraction-extension property of the left ventricular myocardium.

PubMed

Tanaka, Motonao; Sakamoto, Tsuguya; Sugawara, Shigeo; Katahira, Yoshiaki; Tabuchi, Haruna; Nakajima, Hiroyuki; Kurokawa, Takafumi; Kanai, Hiroshi; Hasegawa, Hideyuki; Ohtsuki, Shigeo

2014-04-01

Using newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction-extension (C-E) property, which has an important relationship to LV function. Strain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821μm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30-50 years). The time course of the SR distribution disclosed the characteristic C-E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function. The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions. The newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C-E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

PubMed

Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

2007-12-01

To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures. A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence. Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

Vortex and half-vortex dynamics in a nonlinear spinor quantum fluid

PubMed Central

Dominici, Lorenzo; Dagvadorj, Galbadrakh; Fellows, Jonathan M.; Ballarini, Dario; De Giorgi, Milena; Marchetti, Francesca M.; Piccirillo, Bruno; Marrucci, Lorenzo; Bramati, Alberto; Gigli, Giuseppe; Szymańska, Marzena H.; Sanvitto, Daniele

2015-01-01

Vortices are archetypal objects that recur in the universe across the scale of complexity, from subatomic particles to galaxies and black holes. Their appearance is connected with spontaneous symmetry breaking and phase transitions. In Bose-Einstein condensates and superfluids, vortices are both point-like and quantized quasiparticles. We use a two-dimensional (2D) fluid of polaritons, bosonic particles constituted by hybrid photonic and electronic oscillations, to study quantum vortex dynamics. Polaritons benefit from easiness of wave function phase detection, a spinor nature sustaining half-integer vorticity, strong nonlinearity, and tuning of the background disorder. We can directly generate by resonant pulsed excitations a polariton condensate carrying either a full or half-integer vortex as initial condition and follow their coherent evolution using ultrafast imaging on the picosecond scale. The observations highlight a rich phenomenology, such as the spiraling of the half-vortex and the joint path of the twin charges of a full vortex, until the moment of their splitting. Furthermore, we observe the ordered branching into newly generated secondary couples, associated with the breaking of radial and azimuthal symmetries. This allows us to devise the interplay of nonlinearity and sample disorder in shaping the fluid and driving the vortex dynamics. In addition, our observations suggest that phase singularities may be seen as fundamental particles whose quantized events span from pair creation and recombination to 2D+t topological vortex strings. PMID:26665174

New progress of ranging technology at Wuhan Satellite Laser Ranging Station

NASA Technical Reports Server (NTRS)

Xia, Zhiz-Hong; Ye, Wen-Wei; Cai, Qing-Fu

1993-01-01

A satellite laser ranging system with an accuracy of the level of centimeter has been successfully developed at the Institute of Seismology, State Seismological Bureau with the cooperation of the Institute of Geodesy and Geophysics, Chinese Academy of Science. With significant improvements on the base of the second generation SLR system developed in 1985, ranging accuracy of the new system has been upgraded from 15 cm to 3-4 cm. Measuring range has also been expanded, so that the ETALON satellite with an orbit height of 20,000 km launched by the former U.S.S.R. can now be tracked. Compared with the 2nd generation SLR system, the newly developed system has the following improvements. A Q modulated laser is replaced by a mode-locked YAG laser. The new device has a pulse width of 150 ps and a repetition rate of 1-4 pps. A quick response photomultiplier has been adopted as the receiver for echo; for example, the adoption of the MCP tube has obviously reduced the jitter error of the transit time and has improved the ranging accuracy. The whole system is controlled by an IBM PC/XT Computer to guide automatic tracking and measurement. It can carry out these functions for satellite orbit calculation, real-time tracking and adjusting, data acquisition and the preprocessed of observing data, etc. The automatization level and reliability of the observation have obviously improved.

An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

PubMed

Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

2016-06-01

The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

Expression, purification and characterization of inactive and active forms of ERK2 from insect expression system.

PubMed

Yan, Kelly; Merritt, Hanne; Crawford, Kenneth; Pardee, Gwynn; Cheng, Jan Marie; Widger, Stephania; Hekmat-Nejad, Mohammad; Zaror, Isabel; Sim, Janet

2015-06-01

Extracellular signal-regulated kinase 2 (ERK2) is a serine/threonine protein kinase involved in many cellular programs, such as cell proliferation, differentiation, motility and programed cell-death. It is therefore considered an important target in the treatment of cancer. In an effort to support biochemical screening and small molecule drug discovery, we established a robust system to generate both inactive and active forms of ERK2 using insect expression system. We report here, for the first time, that inactive ERK2 can be expressed and purified with 100% homogeneity in the unphosphorylated form using insect system. This resulted in a significant 20-fold yield improvement compared to that previously reported using bacterial expression system. We also report a newly developed system to generate active ERK2 in insect cells through in vivo co-expression with a constitutively active MEK1 (S218D S222D). Isolated active ERK2 was confirmed to be doubly phosphorylated at the correct sites, T185 and Y187, in the activation loop of ERK2. Both ERK2 forms, inactive and active, were well characterized by biochemical activity assay for their kinase function. Inactive and active ERK2 were the two key reagents that enabled successful high through-put biochemical assay screen and structural drug discovery studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

Vortex and half-vortex dynamics in a nonlinear spinor quantum fluid.

PubMed

Dominici, Lorenzo; Dagvadorj, Galbadrakh; Fellows, Jonathan M; Ballarini, Dario; De Giorgi, Milena; Marchetti, Francesca M; Piccirillo, Bruno; Marrucci, Lorenzo; Bramati, Alberto; Gigli, Giuseppe; Szymańska, Marzena H; Sanvitto, Daniele

2015-12-01

Vortices are archetypal objects that recur in the universe across the scale of complexity, from subatomic particles to galaxies and black holes. Their appearance is connected with spontaneous symmetry breaking and phase transitions. In Bose-Einstein condensates and superfluids, vortices are both point-like and quantized quasiparticles. We use a two-dimensional (2D) fluid of polaritons, bosonic particles constituted by hybrid photonic and electronic oscillations, to study quantum vortex dynamics. Polaritons benefit from easiness of wave function phase detection, a spinor nature sustaining half-integer vorticity, strong nonlinearity, and tuning of the background disorder. We can directly generate by resonant pulsed excitations a polariton condensate carrying either a full or half-integer vortex as initial condition and follow their coherent evolution using ultrafast imaging on the picosecond scale. The observations highlight a rich phenomenology, such as the spiraling of the half-vortex and the joint path of the twin charges of a full vortex, until the moment of their splitting. Furthermore, we observe the ordered branching into newly generated secondary couples, associated with the breaking of radial and azimuthal symmetries. This allows us to devise the interplay of nonlinearity and sample disorder in shaping the fluid and driving the vortex dynamics. In addition, our observations suggest that phase singularities may be seen as fundamental particles whose quantized events span from pair creation and recombination to 2D+t topological vortex strings.

A Modified Normalization Technique for Frequency-Domain Full Waveform Inversion

NASA Astrophysics Data System (ADS)

Hwang, J.; Jeong, G.; Min, D. J.; KIM, S.; Heo, J. Y.

2016-12-01

Full waveform inversion (FWI) is a technique to estimate subsurface material properties minimizing the misfit function built with residuals between field and modeled data. To achieve computational efficiency, FWI has been performed in the frequency domain by carrying out modeling in the frequency domain, whereas observed data (time-series data) are Fourier-transformed.One of the main drawbacks of seismic FWI is that it easily gets stuck in local minima because of lacking of low-frequency data. To compensate for this limitation, damped wavefields are used, as in the Laplace-domain waveform inversion. Using damped wavefield in FWI plays a role in generating low-frequency components and help recover long-wavelength structures. With these newly generated low-frequency components, we propose a modified frequency-normalization technique, which has an effect of boosting contribution of low-frequency components to model parameter update.In this study, we introduce the modified frequency-normalization technique which effectively amplifies low-frequency components of damped wavefields. Our method is demonstrated for synthetic data for the SEG/EAGE salt model. AcknowledgementsThis work was supported by the Korea Institute of Energy Technology Evaluation and Planning(KETEP) and the Ministry of Trade, Industry & Energy(MOTIE) of the Republic of Korea (No. 20168510030830) and by the Dual Use Technology Program, granted financial resource from the Ministry of Trade, Industry & Energy, Republic of Korea.

Colloquium: Mechanical formalisms for tissue dynamics.

PubMed

Tlili, Sham; Gay, Cyprien; Graner, François; Marcq, Philippe; Molino, François; Saramito, Pierre

2015-05-01

The understanding of morphogenesis in living organisms has been renewed by tremendous progress in experimental techniques that provide access to cell scale, quantitative information both on the shapes of cells within tissues and on the genes being expressed. This information suggests that our understanding of the respective contributions of gene expression and mechanics, and of their crucial entanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assist the design and interpretation of experiments, point out the main ingredients and assumptions, and ultimately lead to predictions. The newly accessible local information thus calls for a reflection on how to select suitable classes of mechanical models. We review both mechanical ingredients suggested by the current knowledge of tissue behaviour, and modelling methods that can help generate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell") and tissue scale ("inter-cell") contributions. We recall the mathematical framework developed for continuum materials and explain how to transform a constitutive equation into a set of partial differential equations amenable to numerical resolution. We show that when plastic behaviour is relevant, the dissipation function formalism appears appropriate to generate constitutive equations; its variational nature facilitates numerical implementation, and we discuss adaptations needed in the case of large deformations. The present article gathers theoretical methods that can readily enhance the significance of the data to be extracted from recent or future high throughput biomechanical experiments.

Launching the chaotic realm of iso-fractals: A short remark

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

O'Schmidt, Nathan; Katebi, Reza; Corda, Christian

In this brief note, we introduce the new, emerging sub-discipline of iso-fractals by highlighting and discussing the preliminary results of recent works. First, we note the abundance of fractal, chaotic, non-linear, and self-similar structures in nature while emphasizing the importance of studying such systems because fractal geometry is the language of chaos. Second, we outline the iso-fractal generalization of the Mandelbrot set to exemplify the newly generated Mandelbrot iso-sets. Third, we present the cutting-edge notion of dynamic iso-spaces and explain how a mathematical space can be iso-topically lifted with iso-unit functions that (continuously or discretely) change; in the discrete casemore » examples, we mention that iteratively generated sequences like Fibonacci’s numbers and (the complex moduli of) Mandelbrot’s numbers can supply a deterministic chain of iso-units to construct an ordered series of (magnified and/or de-magnified) iso-spaces that are locally iso-morphic. Fourth, we consider the initiation of iso-fractals with Inopin’s holographic ring (IHR) topology and fractional statistics for 2D and 3D iso-spaces. In total, the reviewed iso-fractal results are a significant improvement over traditional fractals because the application of Santilli’s iso-mathematics arms us an extra degree of freedom for attacking problems in chaos. Finally, we conclude by proposing some questions and ideas for future research work.« less

The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

PubMed Central

Pujol, Josep M.; Eisenberg, Joseph E.; Haas, Charles N.; Koopman, James S.

2009-01-01

Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens. PMID:19503605

The mammalian ovary from genesis to revelation.

PubMed

Edson, Mark A; Nagaraja, Ankur K; Matzuk, Martin M

2009-10-01

Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

PubMed

Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

2016-02-16

Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

PubMed Central

Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

2016-01-01

Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

PubMed

Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

2018-04-25

Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data

PubMed Central

2010-01-01

Background Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. Results A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. Conclusions MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses. PMID:20650010

The Mammalian Ovary from Genesis to Revelation

PubMed Central

Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

2009-01-01

Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209