Aspetti deontologici e giuridici della Responsabilità professionale del chirurgo in Italia. Evoluzione storica a partire dal '900.

PubMed

Picardi, Nicola

2018-01-01

È pleonastico ricordare che ogni individuo raziocinante delle essere responsabile delle sue azioni: deve agire con la coscienza degli scopi che si propone evitando possibili conseguenze negative dei suoi atti. In ambito medico questo tipo di responsabilità è codificata con le norme della "deontologia". Per secoli l'arte terapeutica è stata praticata da individui dotati di una particolare vocazione ed una particolare cultura acquisita da Maestri dell'arte ancor prima che dalla propria esperienza, con nozioni di erboristeria e di elementari conoscenze anatomiche e di fisiologia, circondati da un'aura sacerdotale e da un rispetto derivante dal timore e dall'ammirazione per il coraggio e auspicabilmente dai successi, e facendo riferimento nell'occidente mediterraneo alle regole operative fissate nel Giuramento di Ippocrate, di significato tra il sacro ed il deontologico. Lo sviluppo delle tecniche anestesiologiche a partire dalla seconda metà dell'800 ha determinato l'ampliamento delle iniziative chirurgiche di tipo elettivo, a fianco con gli storici interventi in emergenza per la cura di lesioni traumatiche, ancor prima delle acquisizioni riguardanti le infezioni. Con l'espansione del campo di azione della chirurgia, le possibili complicanze ed i possibili insuccessi hanno fatto da contrappeso ai sentimenti di rispetto e di fiducia nei confronti dei chirurghi, giungendo a far assimilare in tali casi la loro opera quale causa all'origine di danni, provocati rientrando quindi nella categoria dei reati sottoposti alla Legge penale. Così, al termine deontologico di "responsabilità" valido per ogni iniziativa ed ogni professione, per i medici è venuto ad associarsi la qualifica di "professionale", con un significato di presunta colpevolezza. Da una parte le regole deontologiche si sono ampliate, ed hanno coinvolto direttamente il paziente nella fase decisionale delle terapie chirurgiche, formalizzate programmaticamente in moderni codici deontologici ed operativamente nel documento del "consenso informato". Per altro verso le leggi innovative del Codice Civile definito nel 1942, che al posto delle pene del codice penale introduceva il criterio della risarcibilità economica del danno in caso di riconosciuta "responsabilità professionale", ha determinato il coinvolgimento di altre figura professionali, e cioè di avvocati e di medici legali, oltre che delle organizzazioni assicurative, con detrimento alla serenità nell'espletamento delle professioni sanitarie e con l'insorgenza per reazione della cosidetta "medicina difensiva". La concretezza di queste problematiche hanno richiesto l'interessamento attivo della Giurisprudenza con una serie di sentenze, ed una formulazione di decreti e nuove leggi parlamentari, ancora in pieno assestamento nel corso del 2017, lasciano in qualche modo ancora irrisolti alcuni nodi.

Central radio galaxies in groups: cavities, bubbles and the history of AGN heating

NASA Astrophysics Data System (ADS)

Giacintucci, S.; Venturi, T.; Raychaudhury, S.; Vrtilek, J.

2008-10-01

E' noto che le regioni centrali degli ammassi e gruppi di galassie costituiscono un ambiente in cui gas caldo e plasma radioemittente proveniente dalle galassie dominanti interagiscono tra loro. In particolare, si pensa che la radioemissione dell'AGN centrale ed i suoi possibili cicli di attivita', siano strettamente legati alla presenza di cavita' e "bubbles" nel gas intergalattico. Si presentera' lo status di un progetto osservativo effettuato con il Giant Metrewave Radio Telescope (GMRT, India) su di un campione di 18 gruppi di galassie, osservati a tre frequenze radio (235 MHz, 325 MHz e 610 MHz). Lo studio della morfologia radio degli AGN centrali e la relativa analisi spettrale permettono di ottenere stime sull'eta' di questi oggetti, e sulla loro energia totale, che a loro volta sono in relazione con le proprieta' X dei gruppi stessi. Per tutti gli oggetti del campione sono disponibili osservazioni Chandra di proprieta'. Per due oggetti del campione, 4C+24.36 (al centro di AWM04) e NGC741 (al centro di RSOG17) verra' presentato uno studio dettagliato.

[Trattamento della dipendenza da alcol. Alcol e giovani: punto di vista sociale].

PubMed

Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Lombardo, Giuseppe; De Rosa, Francesca; Messina, Marisa Patrizia; Vitali, Mario; Pisciotta, Fabiola; Nanut, Miriana; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Gli adolescenti rappresentano la fascia di età più vulnerabile ai danni causati dall'abuso di alcol, in quanto iniziare a bere in giovane età è associato a un aumento del rischio di dipendenza da alcolici in età adulta. I giovani tendono a bere grandi quantità di alcolici al fine di ricercare forti emozioni e nel tentativo di raggiungere il divertimento a ogni costo, tramite le proprietà psicotrope degli alcolici. Le cause che li inducono ad assumere questi comportamenti sono da ricercare nella non conoscenza degli effetti dannosi dell'alcol, nel rito di convivialità sociale (evenienza per la quale si attribuisce all'alcol la funzione di facilitatore dell'aggregazione tra giovani), nella mancanza di interessi personali, nella scarsità dei controlli e nelle abitudini familiari. Le azioni da intraprendere per limitare o arrestare il consumo nocivo di alcol nei giovani si devono basare su interventi finalizzati a ritardare l'età del primo contatto con le bevande alcoliche, mediante la realizzazione di campagne educazionali rivolte ai giovani stessi, ai loro familiari e alla società intera.

Toluidine blue-O is a Nissl bright-field counterstain for lipophilic fluorescent tracers Di-ASP, DiI and DiO.

PubMed

Chelvanayagam, D K; Beazley, L D

1997-03-01

The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.

Enzymatic Production of c-di-GMP Using a Thermophilic Diguanylate Cyclase.

PubMed

Venkataramani, Prabhadevi; Liang, Zhao-Xun

2017-01-01

C-di-GMP has emerged as a prevalent bacterial messenger that controls a multitude of bacterial behaviors. Having access to milligram or gram quantities of c-di-GMP is essential for the biochemical and structural characterization of enzymes and effectors involved in c-di-GMP signaling. Although c-di-GMP can be synthesized using chemical methods, diguanylate cyclases (DGC)-based enzymatic synthesis is the most efficient method of preparing c-di-GMP today. Many DGCs are not suitable for c-di-GMP production because of poor protein stability and the presence of a c-di-GMP-binding inhibitory site (I-site) in most DGCs. We have identified and engineered a thermophilic DGC for efficient production of c-di-GMP for characterizing c-di-GMP signaling proteins and riboswitches. Importantly, residue replacement in the inhibitory I-site of the thermophilic DGC drastically relieved product inhibition to enable the production of hundreds of milligrams of c-di-GMP using 5-10 mg of this robust biocatalyst.

40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

Acute myeloid leukemia and diabetes insipidus with monosomy 7.

PubMed

Harb, Antoine; Tan, Wei; Wilding, Gregory E; Battiwalla, Minoo; Sait, Sheila N J; Wang, Eunice S; Wetzler, Meir

2009-04-15

The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

IL TRAPIANTO ORTOTOPICO DEL FEGATO

PubMed Central

STARZL, THOMAS E.

2010-01-01

E’ormai noto che esiste la possibilità rivoluzionaria di utilizzare il fegato per il trattamento della stadio terminale delle epatopatie. Nel gennaio 1980 si celebra il decimo anna di sopravvivenza con fegato trapiantato (la più lunga della letteratura) di un paziente da noi trattato. Si tratta di uno dei 12 malati sottoposti a trapianto e seguiti per più di 5 anni. La nota positiva di questa tipo di trattamento è rappresentata dall’eccellente tenore di vita che i pazienti conducono e dalla riabilitazione sociale e professionale. La nota negativa è data, invece, dal fatto che i buoni risultati non vengono raggiunti con regolarità e non possono essere previsti con esattezza. In questa breve rassegna considereremo la esperienza da noi fatta presso l’Università di Denver nel Colorado, mettendo in risalto le cause dell’elevata mortalità precoce e le prospettive future di questa mezzo terapeutico. PMID:21572898

Trasforiiazioni Termoelastiche Finite di Solidi Incomprimibili

NASA Astrophysics Data System (ADS)

Signorini, A.

Queste lezlioni hanno come direttiva una sintesi di quanto si trova sistematicamente sviluppato in una mia Memoria sulle trasformazioni termoelastiche finite di solidi incomprimibili, in corso di stampa negli Annali di Matematica pura e applicata t. XXXIX ( 1955) pp. 147-201 , Verranno anche esposti, come necessaria premessa, alcuni d ei risultati di due precedenti Memorie degli stessi Annali. Invece, per motivo di brevità, non potrò dare neppure un cenno delle ulteriori ricerche svilup pate dal prof. T. Manacorda in tre recentissimi suoi lavori:

Elaborazione dei dati sperimentali

NASA Astrophysics Data System (ADS)

Dapor, M.; Ropele, M.

L'analisi statistica dei dati sperimentali, la loro elaborazione ed una corretta stima degli errori sono conoscenze necessarie agli studenti di fisica, biologia, chimica, ingegneria e dei corsi di specializzazione tecnico-scientifici in cui a di laboratorio. Chi si occupa di problemi tecnici e di misure, per studio o per lavoro, deve possedere gli strumenti matematici di calcolo e di analisi necessari ad una corretta interpretazione dei dati sperimentali. Il testo fornisce in modo sintetico, chiaro ed esaustivo, tutte le nozioni e le conoscenze utili allo scopo.

c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

PubMed Central

Fahmi, Tazin; Port, Gary C.

2017-01-01

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096

Il ruolo svolto dall’attività lavorativa sull’ipertensione arteriosa

PubMed Central

Barbini, N.; Gorini, G.; Ferrucci, L.; Biggeri, A.

2009-01-01

RIASSUNTO Introduzione I parametri di pressione arteriosa, sistolica (PAS) o diastolica (PAD) hanno costituito I’oggetto di numerosi studi, alcuni dei quali stabiliscono un’associazione tra I’aumnto di tali parametri e la mortalità, in particolare alle età medie. I fattori di rischio di ipertensione più frequentemente studiati sono il consumo di alcol, il fumo e I’origine etnica in riferimento sia alle differenze genetiche che nella condotta alimentare, mentre i fattori di origine professionale sono stati presi in considerazione più raramente e in maniera poco approfondita, inoltre sono state riferite notevoli differenze nelle pressioni arteriose medie di individui che svolgono professioni diverse. Sembra infatti che i “colletti blu” siano più a rischio dei “colletti bianchi”. Obiettivi Il nostro scopo è valutare se determinati rischi o vincoli connessi con l’attività professionale o determinati stili di vita rappresentano un fattore di rischio per l’ipertensione arteriosa in considerazioni dell’aumentare dell’età. Elementi specifici che rendano conto di questa relazione non sono stati ancora completamente chiariti e soprattutto i dati sulla popolazione italiana sono molto limitati. Metodi La metodologia di ricerca utilizzata è stata quella dell’indagine francese ESTEV (Derriennic, Touranchet, Volkoff) - VISAT (Marquie, Janson), studio epidemiologico longitudinale su oltre 23000 lavoratori attivata in Francia nel 1990 al fine di indagare gli effetti a lungo termine delle condizioni di lavoro, riferite all’intera vita professionale, sia sull’invecchiamento sia sulla salute dei lavoratori. Analoga indagine è stata avviata in Italia, nel 2000, in 6 Regioni, prendendo in esame i lavoratori dipendenti di diversi settori produttivi appartenenti a 5 coorti di età: da 32 a 52 anni con intervallo di 5 anni. Le rilevazioni sono state effettuate dai medici del lavoro di azienda attraverso 3 questionari: 1. sulle condizioni professionali (esposizione a determinati rischi o vincoli); 2. sugli stili di vita e la salute percepita secondo il Nottingham Health Profile; 3. sulle condizioni oggettive di salute. Per il presente lavoro saranno considerati solo alcuni parametri utili all’approfondimento epidemiologico nel settore cardiocircolatorio. Essi riguarderanno: 1) le condizioni di lavoro, 2) la valutazione soggettiva del lavoro, 3) costrizioni specifiche del lavoro vissute come più gravose con l’avanzare dell’età. Relativamente all’ipertensione, sono stati considerati ipertesi i soggetti che presentavano una PAS ≥160 mm/Hg e/o una PAD ≥90 mm/Hg nonché coloro in cura antipertensiva. Risultati I risultati si riferiscono a 1104 lavoratori, di cui 76% uomini e 24% donne. La prevalenza di ipertensione si è dimostrata più elevata nei maschi (33% Vs 22%). Le stime del rischio hanno evidenziato una associazione statisticamente significativa con alcuni fattori lavorativi come mantenere posture difficili (O.R. 1.71), lavorare in presenza di calore (O.R. 1.43), a contatto con agenti chimici (O.R, 1.31). stare a lungo seduti (O.R. 1.48), fare più cose contemporaneamente (O.R. 1.41), essere interrotti nel proprio lavoro (O.R. 1,35). non poter distogilere gli occhi dal lavoro (O.R.1.61). Conclusioni Noi abbiamo osservato che alcune caratteristiche fisiche del lavoro, ma soprattutto quelle di tipo organizzativo sono fortemente associate all’ipertensione arteriosa. Un elemento importante è sembrata la valutazione soggettiva del valore che i lavoratori danno del proprio lavoro: tale elemento è fortemente connesso con I’organizzazione del lavoro, pertanto è un possibile target di prevenzione (fattore di rischio modificabile). PMID:17886759

[Atmospheric non-methane hydrocarbons near plants of crude oil first treatment].

PubMed

Bustaffa, Elisa; De Marinis Loiotile, Annamaria; Farella, Genoveffa; Petraccone, Stefania; De Gennaro, Gianluigi; Bianchi, Fabrizio

2016-01-01

La continua espansione delle attività di perforazione ai fini dell'estrazione petrolifera in prossimità di aree abitate ha fatto sì che negli ultimi anni l'attenzione si focalizzasse sull'impatto di questo processo fortemente industrializzato sulla salute pubblica. Le comunità che vivono nei dintorni di impianti di questo tipo devono, infatti, fronteggiare diversi problemi, quali l'inquinamento atmosferico e acustico, la contaminazione del suolo e delle acque sotterranee, il traffico dei camion da e verso il sito, incidenti e malfunzionamenti all'interno dell'impianto. In questo contesto, la valutazione del rischio per la salute è ostacolata dal fatto che l'esposizione alle sostanze chimiche presenti non può essere valutata in via definitiva, poiché non sempre si è a conoscenza di tutti i composti immessi nell'ambiente né delle loro concentrazioni, per non parlare del problema delle coesposizioni ad altri inquinanti. Nonostante l'oramai conclamato e vasto interesse generato da questo argomento, ad oggi esistono pochi studi basati su popolazioni riguardanti gli effetti sulla salute delle comunità che vivono in prossimità dei siti di perforazione ed estrazione; ciò genera la necessità di condurre campagne di monitoraggio mirate e studi epidemiologici che verifichino l'eventuale esistenza e natura di pattern di malattie associati a tali attività. La presente rassegna bibliografica individua, quindi, i principali inquinanti atmosferici presenti in prossimità di un impianto di primo trattamento del greggio e cerca di fornire un quadro generale delle loro potenziali sorgenti e caratteristiche.

[Cyberstalking among Italian nurses: a large multicentric study].

PubMed

Comparcini, Dania; Simonetti, Valentina; Lupo, Roberto; Galli, Francesco; Bocij, Paul; Cicolini, Giancarlo

2016-01-01

Determinare la prevalenza di cyberstalking tra gli infermieri italiani e valutare il livello di ansia e depressione nelle vittime. Da aprile a settembre 2014 è stato condotto uno studio multicentrico trasversale in un campione di infermieri italiani (n=997) utilizzando il questionario "Cyberstalking" per analizzare il fenomeno del cyberstalking. Ai partecipanti, che si sono autodefinite vittime di cyberstalking, è stato chiesto anche di compilare gli strumenti "Beck Depression Inventory" e "State-Trait Anxiety Inventory" per valutare, rispettivamente, i livelli di depressione ed ansia. La prevalenza di cyberstalking tra gli infermieri italiani è risultata pari al 23.3%. Il 42.7% ha dovuto cambiare il proprio stile di vita e lavorativo. Il cyberstalker era prevalentemente di sesso maschile (52%) e, nel 49% dei casi, era un paziente. Le vittime hanno riferito moderati livelli di ansia (media=28.4, SD=23.2) e depressione (media=92.7, SD=18.3); i risultati hanno mostrato un aumento dei livelli di depressione negli infermieri esperti nell'utilizzo del computer, gestori di siti web o blog, e una correlazione negativa tra il livello di ansia e gli infermieri esperti (r = -0.264). Il cyberstalking è un fenomeno che si riscontra frequentemente tra gli infermieri. Il rapporto infermiere - paziente gioca un ruolo centrale nello sviluppo del fenomeno e le vittime hanno riferito disordini correlati allo stress che influenzano la vita lavorativa. Questi risultati preliminari potrebbero sensibilizzare, i dirigenti ospedalieri, la politica e i centri antiviolenza al fine di sviluppare strategie risolutiv.

Numerical Optimization.

DTIC Science & Technology

1988-01-01

TASK AREA & WORK UNIT NUMBERS Dipartimento di Matematica -G.--iattelnuoz .’ Universita di Roma "La Sapienze" rlnlRr% Pnmaq (Tt-al’g) I$. CONTROLLING...guaranteed. 3. Adminisrtrative actions The following investigators are working on the contract: (i) Francesco Zirilli Dipartimento di Matematica "G...Castelnuovo" Universiti di Roma "La Sapienza" 00185 Romna (Italy) (ii) Filippo Aluffi-Pentini Dipartimento di Matematica Universiti di Barn 80125 Bari (Italy

Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms

PubMed Central

2015-01-01

ABSTRACT Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms. PMID:26055114

[Mortality from respiratory diseases in the provinces of Apulia Region (Southern Italy) from 1933 to 2010].

PubMed

Montinari, Maria Rosa; Gianicolo, Emilio Antonio Luca; Vigotti, Maria Angela

2016-01-01

OBIETTIVI: valutare l'andamento temporale della mortalità per patologie respiratorie nelle province pugliesi utilizzando dati omogenei per fonte e metodologia di calcolo. DISEGNO: analisi ecologica storica degli andamenti temporali di mortalità per tumori e patologie dell'apparato respiratorio nelle province pugliesi, in Puglia e nelle ripartizioni geografiche italiane dal 1933 al 2010. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate tutte le cause di decesso, il tumore della laringe, il tumore del polmone, l'insieme dei tumori respiratori, la bronchite, la polmonite e la broncopolmonite considerate congiuntamente, e l'insieme delle patologie respiratorie. Le analisi sono disaggregate per sesso dal 1969. PRINCIPALI MISURE DI OUTCOME: rapporti standardizzati di mortalità (SMR%) in riferimento all'Italia, con intervalli di confidenza al 95%, e tassi di mortalità standardizzati col metodo diretto (TSD ) in riferimento alla popolazione standard europea. RISULTATI: dal 1933 al 2010, i TSD per tumori respiratori e per bronchiti diminuiscono in tutte le aree analizzate. Tuttavia, nelle province di Taranto, Brindisi e Lecce, l'SMR% per tumori respiratori, inferiore al riferimento nazionale fino agli anni Sessanta, si allinea (a Brindisi) e supera (a Lecce e Taranto) il riferimento negli anni successivi. Nelle province di Foggia e Bari il numero dei decessi per tumore del polmone è costantemente inferiore all'atteso. CONCLUSIONI: la ricostruzione storica e l'analisi dei trend temporali di mortalità dal 1933 al 2010 mostrano alcune criticità sanitarie in periodi specifici. L'elaborazione dei dati di mortalità per un arco temporale di circa 80 anni ha messo in evidenza la maggiore rilevanza di queste criticità con l'avvio dello sviluppo industriale.

Structural Basis of Ligand Binding by a C-di-GMP Riboswitch

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

Smith, K.; Lipchock, S; Ames, T

2009-01-01

The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structuralmore » data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.« less

[Un processo che può gettare luce sulla cosiddetta 'paura di sé' nel disturbo ossessivo-compulsivo: l'Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni].

PubMed

Mannino, Gherardo; Guerini, Rossella

2018-01-01

RIASSUNTO. Al fine di comprendere meglio la psicopatologia del disturbo ossessivo-compulsivo (DOC), in anni recenti è stata prestata una crescente attenzione alla cosiddetta "paura di sé" (fear of self), vale a dire la paura che le persone con DOC nutrono di ospitare dentro di sé aspetti inaccettabili. Tuttavia, l'esatta dinamica di questo fenomeno ancora non è chiara: di conseguenza, allo scopo di delucidarla meglio, sarà qui descritto uno specifico processo psicologico denominato Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni (IRMI). Quando un paziente con DOC valuta in qualche modo come inaccettabile una propria esperienza interna (pensieri, emozioni, immagini mentali, ecc.) o un proprio comportamento, identificherà retrospettivamente le presunte motivazioni/inclinazioni negative che sarebbero state all'origine di quell'esperienza o comportamento. L'IRMI non solo aiuta a comprendere meglio il fenomeno della "paura di sé", ma possiede anche importanti implicazioni per la terapia.

Control and Estimation of Distributed Parameter Systems. Volume 126, International Conference in Vorau (Austria)

DTIC Science & Technology

1998-01-01

Parabolic Boundary Control Problem ARIELA BRIANI AND MAURIZIO FALCONE Dipartimento di Matematica Universitä di Pisa Dipartimento di Matematica ...Ministry for University and Scientific Research (MURST Project "Analisi Numerica e Matematica Computazionale"). 50 A Priori Estimates for the...Briani Dipartimento di Matematica Universitä di Pisa Via Buonarroti 2 1-56126 Pisa e-mail:briani@dm.unipi.it Maurizio Falcone Dipartimento di

X-ray Observations of the Sun: Solar Flares and their Impact on the Geophysical Space

DTIC Science & Technology

2012-07-01

Michele Piana Universita’ di Genova Dipartimento Di Matematica Via Dodecaneso 35 Genova, Italy 16146 EOARD Grant 09-3050 Report...ORGANIZATION NAME(S) AND ADDRESS(ES) Universita’ di Genova Dipartimento Di Matematica Via Dodecaneso 35 Genova, Italy 16146 8. PERFORMING...Piana, DIpartimento di Matematica , Universita’ di Genova Scientific Report The aim of the present project was to apply computational tools based on

Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein–protein interaction

PubMed Central

Steiner, Samuel; Lori, Christian; Boehm, Alex; Jenal, Urs

2013-01-01

In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein–protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria. PMID:23202856

Waveform Diversity and Design for Interoperating Radar Systems

DTIC Science & Technology

2013-01-01

University Di Pisa Department Di Ingegneria Dell Informazione Elettronica, Informatica , Telecomunicazioni Via Girolamo Caruso 16 Pisa, Italy 56122...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) University Di Pisa Department Di Ingegneria Dell Informazione Elettronica, Informatica ...DIPARTIMENTO DI INGEGNERIA DELL’INFORMAZIONE ELETTRONICA, INFORMATICA , TELECOMUNICAZIONI WAVEFORM DIVERSITY AND DESIGN FOR INTEROPERATING

The Italian Army’s Role in Homeland Security

DTIC Science & Technology

2003-04-07

Operazione “Vespri Siciliani”. Ciclo delle lezioni apprese (Civitavecchia: Scuola di Guerra, Maggio 1998) and Operazione “Forza Paris”. Ciclo delle lezioni...di un Esercito di qualita`.” Rivista Militare 6 (Novembre-Dicembre 2002): II. 61 Scuola di Guerra, Operazione “Vespri Siciliani”. Ciclo delle lezioni...A/2. 64 Scuola di Guerra, Operazione “Vespri Siciliani”. Ciclo delle lezioni apprese, C-13. 65 Scuola di Guerra, Operazione “Forza Paris”. Ciclo

[Assessment of a project for integrated management of care given to patients with type-2 diabetes in the Local Health Authority 21 of Legnago (Veneto Region, Northern Italy) in the period 2010-2012].

PubMed

Marcon, Alessandro; Vaona, Alberto; Rigon, Giulio; Carazzolo, Marco; Del Zotti, Franco; Girotto, Sandro; Marafetti, Claudio

2016-01-01

OBIETTIVI: descrivere, nella ASL 21 di Legnago (VR), l'andamento di alcuni indicatori sanitari tra il 2009, anno precedente all'avvio di un progetto triennale per la gestione integrata dell'assistenza al paziente con diabete mellito di tipo 2, e il 2012, ultimo anno del progetto. DISEGNO: studio longitudinale trasversale ripetuto. SETTING E PARTECIPANTI: tutti i pazienti diabetici di tipo 2 della ASL 21, identificati nei database aziendali (in base a esenzioni per patologia, accessi al servizio diabetologico, consumo di farmaci antidiabetici e strisce per la determinazione della glicemia) e nelle cartelle cliniche dei medici di famiglia. PRINCIPALI MISURE DI OUTCOME: numero di test diagnostici e di follow-up erogati, consumo di farmaci, prestazioni specialistiche, accessi al pronto soccorso, ricoveri e mortalità. RISULTATI: nonostante un calo generalizzato (-3,1%) nei test erogati dalla ASL 21 ai suoi assistititi nel periodo 2009-2012, l'analisi ha documentato un marcato aumento per gli esami previsti nella gestione del diabete, quali curve da carico glicemico (+104,3%), emoglobina glicata (+19,0%) e microalbuminuria (+296,1%). I soggetti identificati come diabetici sono aumentati da 8.084 nel 2009 (5,2%) a 9.221 nel 2012 (5,9%). Sono stati osservati aumenti nella prevalenza di pazienti visitati presso un servizio diabetologico (dal 22,6% al 39,0%), nonché negli utilizzatori di metformina (dal 28,0% al 37,5%), insuline (dal 13,5% al 18,3%) e incretine (dall'1,4% al 9,0%). Il consumo di sulfaniluree è, invece, calato (dal 49,9% al 40,8%), come anche l'erogazione di alcune prestazioni specialistiche, gli accessi al pronto soccorso e i ricoveri, mentre il tasso di mortalità è rimasto stabile (29,6 decessi x1.000/anno). CONCLUSIONE: durante il periodo di implementazione del progetto sembra essersi verificato un aumento della sensibilità diagnostica e una maggiore presa in carico del paziente diabetico. Anche se la natura osservazionale dello studio non consente di dimostrare una relazione causa-effetto, i risultati sembrano supportare l'ipotesi che la gestione integrata della patologia migliori l'appropriatezza dell'assistenza.

Sviluppi di Ricevitori E di Componentistica Per Banda 3 mm Ad INAF-OA Cagliari

NASA Astrophysics Data System (ADS)

Navarrini, Alessandro

2017-11-01

L'INAF-OA Cagliari (OACa) sta sviluppando un ricevitore criogenico a basso rumore basato su un mixer SSB (Single Side Band) a superconduttore SIS (Superconductor-Insulator-Superconductor) per la banda 3 mm. Il ricevitore, acquistato da IRAM, è stato fortemente modificato per essere adattato al fuoco Gregoriano di SRT (Sardinia Radio Telescope). Lo strumento è caratterizzato da una nuova criogenia a ciclo chiuso 4 K (per evitare l'uso di elio liquido in antenna), da un nuovo oscillatore locale (di tipo ALMA Banda 3) e da un nuovo sistema di controllo e di monitoraggio basato su schede Raspberry ed Arduino sviluppato ad OACa. Verranno presentati i recenti sviluppi sul ricevitore, inclusi i risultati preliminari della misura della temperatura di rumore, che raggiunge un valore pari a Trec=66 K alla frequenza di 86 GHz, nonostante la criogenia non sia ancora ottimizzata. L'INAF-OACa è coinvolto nel progetto AETHRA (Advanced European Technologies for Heterodyne Receivers for Astronomy) nel quadro del programma Radionet/Horizon2020 per il quale sta contribuendo al WP1 (Work Package 1). Lo scopo del WP1 è di sviluppare e costruire un dimostratore di un array di ricevitori a doppia polarizzazione per la banda 3 mm basato su amplificatori criogenici a basso rumore (LNA) in tecnologia a semiconduttore MMIC. Nell'ambito del WP1 l'OACa ha in carico il progetto di un OrthomodeTransducer (OMT) in guida d'onda o in tecnologia planare per la banda 72-116 GHz che sia integrabile con amplificatori MMICs ed adatto all'integrazione in un array da installare nel piano focale di un radiotelescopio. Verranno presentati i design preliminari degli OMT per AETHRA, che sono basati su prototipi sviluppati in passato da OACa.

RATE CONSTANTS FOR THE REACTIONS OF OH RADICALS AND CL ATOMS WITH DI-N-PROPYL ETHER AND DI-N-BUTYL ETHER AND THEIR DEUTERATED ANALOGS. (R825252)

EPA Science Inventory

Using relative rate methods, rate constants for the gas-phase reactions of OH radicals and Cl atoms with di-n-propyl ether, di-n-propyl ether-d₁₄, di-n-butyl ether and di-n-butyl ether-d₁₈ have been measured at 296 ? 2 K and atmos...

Worldwide Report, Telecommunications Policy, Research and Development, No. 258

DTIC Science & Technology

1983-01-28

3379, December 1979. [20] F. Vatalaro: Caratteristiche di un filtro digitale dpplicato al sistema DME di precisione per MLS, F.U.B., Relazione 43...Spring 1980. [8] F. Chiarini, M. Gori: Possibilitä di miglioramento della precisione di un DME in banda L öfferta da u’n sistema di antenne a...Vecchio, G. Pedrini, F. Vatalaro: Rapporto sul programma per la determinazione delta forma d’onda impulsiva ottima per un sistema DME di precisione in

An experiment of formation of charmoni states in annihilation P-Pbarra. Un esperimento di formazione di stati del charmonio in annichilazione P-Pbarra (in Italian)

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

Pallavicini, Marco

1995-01-01

Oggetto di questa tesi e la misura di alcune caratteristiche fisiche (massa, larghezza, e larghezza parziale in p -more » $$\\bar{p}$$) degli stati 3P 1 e 3P 2 del charmonio, -ovvero del sistema legato di un quark "charm" e del suo antiquark-, nell'amito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab.« less

Misura della sezione d'urto totale e Dello scattering elastico all'energia Nel centro di massa di $$\\sqrt{s}=1.8$$ TeV (in Italian)

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

Paoletti, Riccardo

La produzione di eventi elastici è stata misurata al Collider Tevatron del Fermi National Accelerator Laboratory (Batavia. 11.~ U .S.A.) alla energia nel centro di massa. di √s = 1800 GeV, nell'intervallo 0.06 < I t I< 0.24. Sono forniti dettagli sull'esperimento CDF che ha compiuto la misura e sui criteri di selezione degli eventi.

A Simple Algorithm for Obtaining Nearly Optimal Quadrature Rules for NURBS-based Isogeometric Analysis

DTIC Science & Technology

2012-01-05

Università degli Studi di Pavia bIstituto di Matematica Applicata e Tecnologie Informatiche “E. Magenes” del CNR, Pavia cDAEIMI, Università degli Studi di...Cassino d Institute for Computational Engineering and Sciences, University of Texas at Austin eDipartimento di Matematica , Università degli Studi di

INFEZIONI VIRALI CONGENITE, PERINATALI E NEONATALI VIRAL INFECTIONS OF THE FETUS AND NEWBORN INFANT

PubMed Central

Tremolada, Sara; Delbue, Serena; Ferrante, Pasquale

2009-01-01

Riassunto Alcuni virus possono essere trasmessi verticalmente da madre a figlio in seguito allo sviluppo, da parte della madre, di un’infezione primaria, ricorrente o cronica. La trasmissione materno-fetale dei virus, che può avvenire in utero (infezione congenita), durante il travaglio del parto (infezione perinatale), oppure attraverso l’allattamento (infezione postnatale), può causare aborto spontaneo, morte fetale, ritardo di crescita intrauterino, anomalie congenite e patologie neonatali o postnatali di diversa entità. Alcuni fattori di rischio sembrano influenzare l’incidenza di trasmissione materno-fetale dei virus, come ad esempio la presenza di altre infezioni virali, la carica virale materna, il tipo di infezione (primaria o ricorrente), la durata della rottura delle membrane, la modalità con cui avviene il parto, le condizioni socio-economiche e l’allattamento. Oggi è possibile prevenire la trasmissione materno-fetale di molti virus grazie all’utilizzo di vaccini, immunizzazione passiva e farmaci antivirali. Il rischio di trasmissione delle infezioni perinatali e postnatali, inoltre, può essere diminuito evitando l’allattamento o ricorrendo ad un parto cesareo. PMID:19216201

Donor insemination: Israel as a representative case of a competitive market examining the possibility of policy reform.

PubMed

Gonen, Limor D

2017-03-01

To measure the private and social benefits of donor insemination (DI). An empirical model investigates the general public and DI clients' willingness to pay (WTP) for DI, and the willingness of potential donors to become altruistic or paid sperm donors. The general public and DI clients value DI and have a positive WTP for it, whereas willingness to donate, altruistically or for payment, is either low or very low. The general public's and DI clients' WTP for DI is in average above actual cost, so the government should consider funding or subsidizing DI. The government should encourage altruistic gamete donation through information and education of all parties involved directly and indirectly in the process of donation whose ultimate goal is the birth of a child.

Preference and Frequency of Mobile Phone App Use for Drug Information Among Student Pharmacists

PubMed Central

Park, Sharon K.; Purnell, Miriam C.; Freeman, Maisha Kelly; Reese, Racquel V.; Varga, Stefan

2017-01-01

Background: Health care professionals commonly use mobile devices to retrieve drug information (DI) in clinical practice. The preference and frequency of such use by student pharmacists are not well understood. Objective: To investigate the preference and frequency of mobile phone application (app) use for retrieving DI among student pharmacists. Methods: DI specialists from 3 pharmacy schools generated a 13-question survey relating to students’ preference and frequency of DI app use via their mobile phone. The survey was tested and electronically disseminated to all current P1 through P4 students from all 3 schools. Data were collected for student demographics, availability of mobile phone and DI apps, frequency of using DI apps, and whether DI apps were purchased. Data were analyzed descriptively and statistically. Results: About 74% (n = 221) of students reported using their mobile phone apps for retrieving DI. About 95% of the students used 1 to 3 apps for DI purposes and more than 85% used them a few times a week or more. About 17.6% of the students reported purchasing apps for the purpose of finding DI and that purchased apps are more accurate (27.6%), more comprehensive (36.2%), and more current (26.2%), compared with free apps. Conclusions: Student pharmacists used 1 to 3 mobile apps, at least a few times a week for DI. Some students purchased apps for DI use in addition to free subscriptions from their school. Students perceived purchased DI apps being more accurate, more comprehensive, and more up to date than the free apps.

Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy.

PubMed

Afzal, Samina; Wherrett, Diane; Bartels, Ute; Tabori, Uri; Huang, Annie; Stephens, Derek; Bouffet, Eric

2010-05-01

Patients with intracranial germ cell tumor (IGCT) often present with pituitary dysfunction, including diabetes insipidus (DI). Recent protocols have used pre-radiation chemotherapy with combinations of etoposide, carboplatin and/or cisplatin, and ifosfamide. Management of DI in these patients requires monitoring of electrolytes and fluids during chemotherapy and hyperhydration. All consecutive patients treated with chemotherapy for an IGCT during the period 1990-2007 at the Hospital for Sick Children, Toronto were reviewed. Out of 32 patients who received chemotherapy, 21 had DI. Only cycles containing cisplatin and/or ifosfamide and hyperhydration were considered. DI and non-DI patients were compared for each cycle of chemotherapy. Patients were studied for number of days in hospital per chemotherapy course, daily fluid input and output, changes in dose, schedule and route of administration of desmopressin (DDAVP) during chemotherapy, daily variations in sodium level, electrolyte monitoring requirements per day, and complications related to fluid and electrolyte disturbances. Fifty-four cycles of chemotherapy in DI patients were compared to 25 cycles in non DI patients. All 21 patients with DI required daily change in dosage and schedule of DDAVP. Marked variations in daily sodium level were observed in the DI group. Seventeen courses required prolonged admission in the DI group (one in non DI patients) and 6 patients experienced serious complications. In conclusion, DI is a risk factor for complications when cisplatin and/or ifosfamide based protocols are used. The role of these agents in the management of ICGT should be carefully evaluated and guidelines for management of DI established.

Calibrazioni a terra e prestazioni in volo di spettrometri ad immagine nel visibile e nel vicino infrarosso per l'esplorazione planetaria

NASA Astrophysics Data System (ADS)

Filacchione, Gianrico

2006-10-01

Nel corso dell’ultimo decennio l’esplorazione planetaria ha potuto beneficiare dei dati prodotti dagli spettrometri ad immagine: grazie a questa nuova classe di strumenti, realizzati per l’osservazione in remoto di superfici ed atmosfere planetarie, è possibile acquisire dati iperspettrali con elevati poteri risolutivi spaziali e spettrali. Il principale vantaggio offerto dagli spettrometri ad immagine, rispetto alle camere ed agli spettrometri puntuali, è rappresentato dalla capacità di misurare, identificare e mappare le unità composizionali delle superfici planetarie; queste informazioni permettono di investigare sia l’evoluzione geochimica delle superfici sia la dinamica e la composizione delle atmosfere. Sebbene i primi spettrometri ad immagine siano stati francesi (Phobos/ISM, Imaging Spectrometer for Mars) e statunitensi (Galileo/NIMS, Near Infrared Mapping Spectrometer), il nostro paese nel corso degli ultimi anni è stato in grado di proporre alla com unità spaziale internazionale degli strumenti dalle elevate prestazioni che sono stati infatti accettati come payload scientifici su diverse missioni interplanetarie: dai canali visibili di VIMS (Visual and Infrared Mapping Spectrometer) su Cassini (Nasa, JPL, ESA, ASI) e di OMEGA (Observatoire pour la Minéralogie, l’Eau, les Glacies et l’Activitè de Mars) su MarsExpress (ESA) ai due VIRTIS (Visible and Infrared Thermal Imaging Spectrometer) su Rosetta (ESA) e VenusExpress (ESA) fino a VIR-MS (Visible and Infrared Mapping Spectrometer) su Dawn (Nasa). In questo momento inoltre altri due spettrometri sono in avanzata fase di studio: JIRAM (Jovian InfraRed Auroral Mapper) su Juno (missione New Discovery Nasa) e VIHI (Visible and Infrared Hyperspectral Imager) integrato nel payload italiano di remote sensing SIMBIO-SYS di BepiColombo (missione cornerstone ESA). La realizzazione di uno spettrometro ad immagini da utilizzare su una missione interplanetaria richiede un’accurata analisi in fase progettuale e realizzativa dei parametri e de lle prestazioni strumentali; in generale infatti non solo sarà necessario mantenere le dimensioni, il peso, i consumi elettrici ed il data-volume entro i requisiti disponibili del satellite ma anche ottimizzare i disegni ottici, meccanici ed elettronici al fine di ottenere le massime prestazioni possibili in funzione della natura del target osservato e dei parametri orbitali della missione. Questa tesi descrive i metodi utilizzati per caratterizzare il funzionamento di spettrometri ad immagine per l’esplorazione planetaria. L’attività svolta ha riguardato sia la misura in laboratorio dei parametri strumentali fondamentali sia l’analisi dei dati in volo su cui verificarne ed eventualmente correggerne la risposta. Il funzionamento degli strumenti e la metodologia di calibrazione vengono descritti nelle due parti principali e nelle appendici di questa tesi per gli esperimenti Cassini-VIMS-V e Rosetta-VIRTIS-M. La prima parte è dedicata all’esperimento VIMS-V sul satellite Cassini, il cui disegno ottico, originariamente proposto da Francis Reininger, verrà successivamente riutilizzato e perfezionato su VIRTIS-M (Reininger et al., 1994; Miller et al., 1996). Il capitolo 1 contiene una descrizione dei parametri ottici, strutturali, termici ed elettronici di VIMS-V mettendone in risalto gli aspetti più innovativi del progetto. Vengono inoltre descritti la collocazione dell’esperimento sul satellite Cassini, il coallineamento con gli altri strumenti di remote sensing, i possibili modi operativi ed il formato dei dati scientifici. Il capitolo 2 riguarda il processo di calibrazione ed analisi dei dati in volo di VIMS-V. La procedura eseguita per calibrare radiometricamente lo strumento utilizzando i dati della superficie della Luna e per stimare il flat-field mediante i dati dell’atmosfera di Venere viene dettagliatamente descritta assieme agli algoritmi utilizzati per la rimozione di diversi effetti strumentali (read-out noise e tilt spettrale); alcuni di questi effetti sono stati caratterizzati e dettagliamente misurati in laboratorio utilizzando il modello spare (flight) di VIMS-V. Parte del capitolo è dedicata alla verifica della procedura di calibrazione su diversi target aventi caratteristiche spettroradiometriche note. Questi algoritmi di processamento sono correntemente utilizzati dal team scientifico di VIMS per calibrare i dati del canale -VIS rilasciati ufficialmente alla comunità scientifica internazionale attraverso il Planetary Data System (PDS) della Nasa. La seconda parte riguarda l’esperimento VIRTIS-M sul satellite Rosetta. Il capitolo 3 contiene la descrizione dello strumento mettendo in risalto l’evoluzione dal precedente progetto VIMS-V ed i problemi tecnologici e costruttivi da questo derivanti. I diversi modi operativi, la sequenza di acquisizione e di processamento dei dati nell’elettronica principale sono ampiament e discussi. Viene inoltre evidenziata la collocazione dello spettrometro sul satellite Rosetta. Nel capitolo 4 viene descritta l’attività di calibrazione effettuata in Galileo Avionica (Campi Bisenzio, FI, Italia) ed allo IAS (Orsay, Francia) subito dopo l’integrazione di VIRTIS ed il conseguente processamento dei dati necessario per ricavare i principali parametri di funzionamento (calibrazioni spettrali e geometriche, flat-field, funzioni di trasferimento, lampade di calibrazione interne). Nel capitolo 5 l’accuratezza di queste grandezze è stata verificata su i primi dati in volo ottenuti da VIRTIS-M durante la fase di commissioning e di cruise del satellite (Terra, Luna e Saturno); queste osservazioni sono inoltre state utilizzate per migliorare e verificare alcuni aspetti della procedura di calibrazione che non erano stati sufficientemente definiti durante i test a terra. L’appendice A riguarda il formato PDS (Planetary Data System) utilizzato per l’archiviazione dei dati e degli housekeepings ingegnerisitici e scientifici delle osservazioni; nell’appendice B è contenuta la descrizione del modello radiometrico teorico di VIRTIS-M utilizzato per stimare il rapporto segnale/rumore; nelle appendici C e D sono infine contenute diverse Tabelle non incluse nel testo delle parti principali a causa della loro lunghezza.

Identification of Synthetic Fluids Utilizing Pyrolysis Gas Liquid Chromatographic Techniques

DTIC Science & Technology

1981-09-01

Base Stock No. 6327 Di-isodecyl Azelate II 7 Synthetic Base Stock No. 6318 Di-2-ethylhexyl Azelate I 8 Synthetic Base Stock No. 6323 l)i-2-ethylhexyl...Adipatc 13 9 Synthetic Base Stock No. 6321 Di-2-cthylhexyl Sebacattk 14 10 Synthetic Base Stock No. 6326 Di-tridecyl Azelate 15 11 Synthetic Base...Stock No. 6319 Di-tridecyl Adipate 16 12 Synthetic Base Stock No. 6320 Di-iso-octyl Azelate 17 13 Synthetic Base Stock No. 6516 TMP Triheptanoate 18 14

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

Duality and Unified Analysis of Discrete Approximations in Structural Dynamics and Wave Propagation: Comparison of rho-method Finite Elements with kappa-method NURBS (Preprint)

DTIC Science & Technology

2007-10-10

Dipartimento di Meccanica Strutturale, Università degli Studi di Pavia cDipartimento di Matematica , Università degli Studi di Pavia dEuropean Centre...for Training and Research in Earthquake Engineering, Pavia eIstituto di Matematica Applicata e Tecnologie Informatiche del CNR, Pavia “Comparisons

Meningococco B: controllo di due focolai epidemici mediante vaccinazione

PubMed Central

2014-01-01

Riassunto La problematica di un efficace approccio vaccinale nei confronti del Meningococco B (MenB) è stata superata identificando con la metodica della "reverse vaccinology" alcuni antigeni capaci di indurre una risposta verso la maggior parte dei ceppi di MenB circolanti nel mondo. Il nuovo vaccino MenB a 4 componenti (4CMenB) è stato autorizzato in Europa, Australia e Canada, ed è entrato nei calendari di immunizzazione pediatrica internazionali: Australia, Canada, UK. In Italia, le prime regioni che hanno raccomandato la vaccinazione contro il MenB sono state Basilicata e Puglia. La gestione di epidemie/focolai epidemici richiede la messa in atto di una risposta rapida da parte delle autorità sanitarie nei confronti di una emergenza sanitaria ad elevato impatto, anche emotivo, sulla popolazione, come recentemente dimostrato in due università americane. Alla dichiarazione di focolaio epidemico in atto, in entrambi i contesti si è attivata una procedura per l'uso del vaccino 4CMenB non ancora autorizzato negli USA. È stato così possibile organizzare gli interventi di profilassi attiva nei due campus universitari, adottando il primo impiego su larga scala del nuovo vaccino 4CMenB e conseguendo, in tempi relativamente brevi, elevati tassi di copertura vaccinale. A fronte di circa 14000 studenti immunizzati con almeno una dose, non è stata segnalata alcuna problematica di eventi avversi conseguenti all'immunizzazione; ad oggi non si sono verificati casi nei soggetti che hanno ricevuto il vaccino. Come conseguenza dei due focolai descritti, è oggi in corso la valutazione da parte dell'FDA per l'estensione dell'uso del vaccino 4CMenB negli Stati Uniti negli adolescenti e giovani adulti. PMID:25916017

Clinical Predictors of Diabetes Insipidus After Transcranial Surgery for Pituitary Adenoma.

PubMed

Wang, Songquan; Li, Deling; Ni, Ming; Jia, Wang; Zhang, Qing; He, Jue; Jia, Guijun

2017-05-01

Diabetes insipidus (DI) is a well-known complication of transsphenoidal pituitary adenoma surgery. However, the risk factors for DI after transcranial surgery have not been clarified. In this study, the clinical parameters for predicting DI after transcranial surgery were investigated. The perioperative records of 90 patients who underwent transcranial (TC) surgery at the authors' institution between November 2011 and March 2013 were chosen from 1657 patients with pituitary adenoma and retrospectively analyzed. The degree of deformation of the third ventricle and hypothalamus were assessed by preoperative magnetic resonance imaging. Immediate postoperative DI was found in 30 patients (33.3%). Persistent DI was noted in 11 patients (12.6%). Compared with patients in the nonpostoperative DI group, those with postoperative DI had a higher degree of deformation of the third ventricle and hypothalamus (P < 0.001). In a binary logistic regression analysis, the degree of deformation of the third ventricle and hypothalamus (odds ratio [OR], 3.079; 95% confidence interval [CI], 1.600-5.925; P = 0.001) had a significant positive correlation with immediate postoperative DI, as well as postoperative hemorrhage (OR, 6.235, 95% CI, 1.457-26.689; P = 0.014). Postoperative hemorrhage (OR, 4.363; 95% CI, 1.021-18.647; P = 0.047) showed a positive correlation with permanent DI, as well as the degree of deformation of the third ventricle and hypothalamus (OR, 2.336; 95% CI, 1.005-5.427; P = 0.049). The degree of deformation of the third ventricle and hypothalamus assessed by preoperative magnetic resonance imaging may help to predict postoperative DI. Postoperative hemorrhage might increase the incidence of postoperative DI, whether it is immediate postoperative DI or permanent DI. Copyright © 2017 Elsevier Inc. All rights reserved.

Delayed Occurrence of Diabetes Insipidus After Transsphenoidal Surgery with Radiologic Evaluation of the Pituitary Stalk on Magnetic Resonance Imaging.

PubMed

Hayashi, Yasuhiko; Aida, Yasuhiro; Sasagawa, Yasuo; Oishi, Masahiro; Kita, Daisuke; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi

2018-02-01

Diabetes insipidus (DI) is a major complication of transsphenoidal surgery (TSS). DI usually occurs within a couple of days after TSS. Delayed occurrence of postoperative DI is rarely observed and its developing mechanisms remain unknown. Six patients were identified as having postoperative delayed DI, which was defined as DI that first occurred 2 or more weeks after TSS. They consisted of 1 male and 5 females, and their mean age was 38.3 years (range, 10-76 years). Five patients were histologically diagnosed with Rathke cleft cyst (RCC), and one had RCC coexisting with prolactin-secreting adenoma. Sequential T1-weighted magnetic resonance imaging was evaluated for hyperintensity (HI) in the pituitary stalk and the posterior lobe, indicating the location of antidiuretic hormone. No patients had any DI before TSS. Delayed DI occurred 2 weeks to 3 months after TSS and persisted for 2 weeks to 5 months. T1-weighted magnetic resonance imaging showed that the HI in the posterior lobe became faint but did not disappear after DI occurrence, and their intensities increased with recovery from DI. In contrast, the HI in the pituitary stalk was found faintly preoperatively and turned clear postoperatively and decreased with recovery from DI. The morphologic patterns were dependent on DI duration. In the delayed occurrence of DI, it was suggested that preoperative antidiuretic hormone transport was mildly congested yet not completely blocked when DI manifested postoperatively. Gradual spreading of inflammation to the infundibulum after RCC removal was considered as 1 possible mechanism of this delayed DI development. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and evaluation of a computerized intervention for low distress tolerance and its effect on performance on a neutralization task.

PubMed

Macatee, Richard J; Cougle, Jesse R

2015-09-01

A growing body of research has linked high distress intolerance (DI) to obsessions, but not other OCD symptom domains. However, existing research is correlational. Experimental studies are needed, but brief methods for reducing DI are lacking. To address these gaps in the literature, a brief, computerized intervention aimed at reducing DI was developed to determine if changing DI affected obsessional phenomena. Individuals reporting high DI were randomized to a treatment or waitlist control group (N = 53). Individuals in the treatment group received the DI treatment (i.e., a 2 h computerized intervention) over two weeks, and then underwent a post-assessment in which DI and obsession-relevant phenomena were measured. Individuals in the control group only received the post-assessment. Analyses revealed a greater reduction in self-reported DI on one measure and smaller decreases in behavioral DI in the intervention condition relative to the waitlist condition, as well as lower in-vivo urges to neutralize an intrusive thought; however, anxious reactivity to the intrusion and neutralization behavior were not affected. Further, bootstrapping analyses revealed that reductions in DI mediated the effect of the intervention on neutralization urges. A clinical sample and placebo control condition were not used. These results provide experimental evidence for the role of DI in obsessional phenomena, specifically in affecting urges to neutralize intrusions, findings consistent with negative reinforcement models of DI. Further, results revealed that DI can be reduced with a brief, computerized intervention, which has important implications for future experimental research and treatment development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Introduction to Kinetic Model Equations

DTIC Science & Technology

2011-01-01

application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 ∗Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano

[Ecological study on the mortality of residents in Manfredonia (Apulia Region, Southern Italy) from 1970 to 2013].

PubMed

Gianicolo, Emilio Antonio Luca; Mangia, Cristina; Cervino, Marco; Bruni, Antonella; De Marchi, Bruna; Biggeri, Annibale; Porcu, Rosa; Vigotti, Maria Angela

2016-01-01

OBIETTIVI: valutare lo stato di salute della popolazione residente nel comune di Manfredonia dal 1970 al 2013. DISEGNO: analisi descrittiva dell'andamento temporale della mortalità generale, per gruppi di cause, dal 1970 al 2013. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate 55 cause di decesso. Le analisi sono disaggregate per sesso e periodo. PRINCIPALI MISURE DI OUTCOME: sono stati elaborati i rapporti standardizzati di mortalità (SMR%), con i rispettivi intervalli di confidenza al 90% (IC90%), e i tassi di mortalità standardizzati col metodo diretto (TSD ). RISULTATI: lo stato di salute misurato dal tasso di mortalità per tutte le cause migliora nel tempo: i TSD passano da 92 x10.000 negli anni 1970-1974 a 52 x10.000 nel biennio 2012-2013 negli uomini, da 70 x10.000 a 39 x10.000 nelle donne. Tuttavia, rispetto alla media regionale Manfredonia perde progressivamente il suo vantaggio, passando da -20% a -10% negli uomini, e da -20% a +1,5% nelle donne. Questo andamento è molto evidente per il complesso delle cause cardiovascolari, mentre i tumori maligni sono in generale nella media regionale. Nell'ultimo periodo disponibile per causa di decesso (2006-2011), la mortalità per infarto miocardico è stata più alta della media regionale (uomini: +35%; donne: +54%). I rapporti standardizzati di mortalità (SMR) mostrano tra gli uomini valori in crescita, in particolar modo rispetto al riferimento provinciale, con un eccesso a cominciare dal periodo 2006-2011 (22 decessi/anno e 19 attesi; SMR%: 117,2; IC90% 101,1-135,2; riferimento: provincia di Foggia). Anche tra le donne gli SMR% superano i riferimenti provinciali negli ultimi periodi esaminati (nel 2012-2013: 7 decessi/ anno e 4,2 attesi; SMR%: 116,4; IC90% 97,0-260,7; riferimento: provincia di Foggia). CONCLUSIONI: la mortalità a Manfredonia è diminuita in misura minore rispetto a quella osservata nei riferimenti provinciali e regionali. Il vantaggio che si osservava negli anni Sessanta si è, infatti, ridotto nel tempo, fino ad annullarsi negli ultimi anni. Dal 1970, Manfredonia ha progressivamente perso il vantaggio che aveva. Dagli anni Duemila, la mortalità per infarto del miocardio è in eccesso sulla media regionale e provinciale. Da casi documentati in letteratura si osserva che le popolazioni che sperimentano catastrofi di origine naturale o antropica possono fronteggiare un aumento di patologie cardiovascolari. La mortalità per tumore polmonare mostra un eccesso sulla media regionale, in particolare provinciale, a cominciare dal 2000, coerentemente con i tempi di latenza legati all'esposizione ad arsenico negli anni Settanta.

Diabetes insipidus during pregnancy.

PubMed

Ananthakrishnan, Sonia

2016-03-01

Diabetes insipidus (DI) in pregnancy is a heterogeneous syndrome, most classically presenting with polyuria and polydipsia that can complicate approximately 1 in 30,000 pregnancies. The presentation can involve exacerbation of central or nephrogenic DI during pregnancy, which may have been either overt or subclinical prior to pregnancy. Women without preexisting DI can also be affected by the actions of placental vasopressinase which increases in activity between the 4th and 38th weeks of gestation, leading to accelerated metabolism of AVP and causing a transient form of DI of pregnancy. This type of DI may be associated with certain complications during pregnancy and delivery, such as preeclampsia. Management of DI of pregnancy depends on the pathophysiology of the disease; forms of DI that lack AVP can be treated with desmopressin (DDAVP), while forms of DI that involve resistance to AVP require evaluation of the underlying causes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fourth International Congress on Industrial and Applied Mathematics. Book of Abstracts

DTIC Science & Technology

1999-01-01

Dipartimento di Matematica , Universita’ di Pavia, Italy) Logarithmic Sobolev inequalities for kinetic semiconductor equations In this paper we analyze the...terms of Whitney forms. FERNANDES, Paolo (Istituto per la Matematica Applicata del Consiglio Nazionale delle Ricerche, Italy) Dealing with realistic... Matematica dell Universita di Pavia, Italy. PERUGIA, Ilaria (Diaprtimento di Matematica , Universita’ di Pavia - Italy) An adaptive field-based method

TU-FG-209-08: Distribution of the Deviation Index (DI) in Digital Radiography Practices Across the United States

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

Jones, A; Shepard, S; Dave, J

Purpose: To characterize the distribution of the deviation index (DI) in digital radiography practices across the United States. Methods: DI data was obtained from 10 collaborating institutions in the United States between 2012 and 2015. Each institution complied with the requirements of the Institutional Review Board at their site. DI data from radiographs of the body parts chest, abdomen, pelvis and extremity were analyzed for anteroposterior, posteroanterior, lateral, and decubitus views. The DI data was analyzed both in aggregate and stratified by exposure control method, image receptor technology, patient age, and participating site for each body part and view. Themore » number of exposures with DI falling within previously published control limits for DI and descriptive statistics were calculated. Results: DI data from 505,930 radiographic exposures was analyzed. The number of exposures with DI falling within published control limits for DI varied from 10 to 20% for adult patients and 10 to 23% for pediatric patients for different body parts and views. Mean DI values averaged over other parameters for radiographs of the abdomen, chest, pelvis, and extremities ranged from 0.3 to 1.0, −0.6 to 0.5, 0.8, and −0.9 to 0.5 for the different adult views and ranged from −1.6 to −0.1, −0.3 to 0.5, −0.1, −0.2 to 1.4 for the different pediatric views, respectively (DI data was solicited only for anteroposterior view of pelvis). Standard deviation values of DI from individual sites ranged from 1.3 to 3.6 and 1.3 to 3.0 for the different adult and pediatric views, respectively. Also of interest was that target exposure indicators varied by up to a factor of 6 between sites for certain body parts and views. Conclusion: Previously published DI control limits do not reflect the state of clinical practice in digital radiography. Mean DI and target exposure indicators are targets for quality improvement efforts in radiography.« less

[Health expenditure for prevention in Italy (2006-2013): descriptive analysis, regional trends and international comparisons].

PubMed

Signorelli, Carlo; Odone, Anna; Bianco, Daniela; Di Vivo, Natalia; Bevere, Francesco

2016-01-01

Il dato dell'Organizzazione per la cooperazione e lo sviluppo economico (OCSE) del 2012, che indicava l'Italia come il Paese con la più bassa spesa in prevenzione sanitaria, ha dato lo spunto per una raccolta sistematica e un'analisi critica dei flussi disponibili sulla spesa per le attività di prevenzione in Italia. Le statistiche correnti di spesa sanitaria sono raccolte centralmente dall'Agenzia nazionale per i servizi sanitari regionali (Agenas) attraverso i modelli di rilevazione dei costi dei livelli essenziali di assistenza (LEA) delle aziende USL. Le tre macroaree dei LEA sono: assistenza distrettuale, assistenza ospedaliera e assistenza sanitaria collettiva in ambiente di vita e di lavoro. Le spese per la prevenzione rientrano in quest'ultima e sono ripartite nelle seguenti voci: attività di prevenzione rivolte alle persone, igiene degli alimenti e della nutrizione, igiene e sanità pubblica, prevenzione e sicurezza negli ambienti di lavoro, sanità pubblica veterinaria, attività medico-legale per finalità pubblica. Tra il 2006 e il 2013, ultimo dato disponibile, la spesa per le attività di prevenzione del Servizio sanitario nazionale (SSN) è rimasta costante in rapporto alla spesa sanitaria totale (4,2%), pari a 4,9 miliardi nel 2013. Nel periodo di studio considerato (2006-2013) appaiono in aumento le spese per le attività rivolte alle persone (+8,7%), attribuibili soprattutto a vaccinazioni e screening, e in diminuzione le attività di igiene pubblica (-5,7%) e quelle della sanità pubblica veterinaria (-3,8%). I confronti internazionali indicano una spesa per la prevenzione del 2,9% rispetto alla spesa sanitaria totale, costante negli anni e nella media dei Paesi OCSE. Per la prevenzione, l'Italia spende tanto quanto i Paesi che non possiedono un servizio sanitario pubblico; il dato risulta inferiore del 5% rispetto alla programmazione nazionale, con poche eccezioni e molta variabilità regionale all'interno delle componenti delle voci di spesa. In questo contesto si sottolinea l'importanza di investire maggiori risorse nella pianificazione e nell'implementazione di interventi preventivi di provata efficacia e costo-efficacia.

Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

PubMed Central

Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

2013-01-01

ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

Surface Circulation in the Northeastern Mediterranean (NEMED)

DTIC Science & Technology

2011-09-30

NEMED) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy, 8. PERFORMING ORGANIZATION

Circulation in the Southeastern Mediterranean Sea (EGITTO-NICOP)

DTIC Science & Technology

2007-09-30

Circulation in the Southeastern Mediterranean Sea (EGITTO-NICOP) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica ...Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy, , 8. PERFORMING ORGANIZATION REPORT NUMBER

Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

PubMed

O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

2017-09-15

Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. Copyright © 2017 American Society for Microbiology.

Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense

PubMed Central

O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark

2017-01-01

ABSTRACT Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense, c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. PMID:28264994

Coastal Ocean Circulation Experiment off Senegal (COCES)

DTIC Science & Technology

2011-09-30

Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste

Coastal Ocean Circulation Experiment off Senegal (COCES)

DTIC Science & Technology

2009-01-01

Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c

Efficacy of the Direct Instruction Language for Learning (DI-LL) Program to Promote Expressive and Receptive Language in Children with Autism Spectrum Disorder

DTIC Science & Technology

2017-07-01

spectrum disorder. However, DI-LL has not yet been carefully studied in children with ASD. As in ABA, the DI-LL curriculum incorporates immediate... study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of DI-LL in a six-month randomized trial in...fading. To date, there is only one small study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of

[Analysis of factors predicting early unplanned readmissions].

PubMed

Di Domenico, Gabriella; Tersigni, Ivan; Federico, Bruno; Leuter, Cinzia

2016-01-01

OBIETTIVI: determinare i fattori associati ai ricoveri ripetuti per identificare i pazienti a rischio di riospedalizzazione entro i 30 giorni dalla dimissione. DISEGNO: analisi retrospettiva delle dimissioni nell'anno 2013 attraverso le schede di dimissione ospedaliera (SDO). 3.900 pazienti ricoverati presso il presidio ospedaliero "Fabrizio Spaziani" di Frosinone. PRINCIPALI MISURE DI OUTCOME: analisi bivariata per l'analisi dell'associazione tra variabili. La regressione logistica è stata utilizzata per identificare i fattori di rischio associati al ricovero ripetuto. RISULTATI: tra i 3.900 pazienti considerati, il 12,8% ha avuto una riammissione non programmata entro un mese dalla dimissione precedente per le stesse categorie diagnostiche principali (MCD). Sono state rilevate differenze statisticamente significative tra i pazienti con e senza ricovero ripetuto per età, durata della degenza, titolo di studio, condizione occupazionale e diagnosi. I fattori che aumentano la probabilità di una riospedalizzazione sono il vivere da solo, la condizione di pensionato o casalinga, una degenza più lunga e alcune diagnosi, fra cui malattie dell'apparato respiratorio, del sistema nervoso e dell'apparato urinario. CONCLUSIONE: alcune caratteristiche sociodemografiche e la diagnosi dei pazienti ospedalizzati sono associate al rischio di riospedalizzazione entro 30 giorni dalla dimissione. I dati disponibili nell'archivio delle SDO possono essere utilizzati per un'identificazione dei pazienti a rischio sui quali definire specifici piani di dimissione.

Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.

PubMed

Forner-Piquer, Isabel; Maradonna, Francesca; Gioacchini, Giorgia; Santangeli, Stefania; Allarà, Marco; Piscitelli, Fabiana; Habibi, Hamid R; Di Marzo, Vincenzo; Carnevali, Oliana

2017-10-01

Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. Copyright © 2017 Endocrine Society.

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.

PubMed

Berti, Valentina; Walters, Michelle; Sterling, Joanna; Quinn, Crystal G; Logue, Michelle; Andrews, Randolph; Matthews, Dawn C; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Mosconi, Lisa

2018-05-15

To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11 C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18 F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions ( p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group ( p interaction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD. © 2018 American Academy of Neurology.

Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs.

PubMed

Wong, William D; Wang, Lu; Paré, Peter D; Seow, Chun Y

2017-02-01

Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the lung are known to inhibit the broncho-motor tone and enhance vasodilatation; the former directly reduces airway resistance, and the latter facilitates removal of contractile agonists through the bronchial circulation. If the DI effect is solely mediated by factors extrinsic to the lung, the DI effect would be absent in isolated, nonperfused lungs. Here we examined the DI effect in freshly isolated, nonperfused sheep lungs. We found that imposition of DI on isolated lungs resulted in significant bronchodilation, that this DI effect was present only after the lungs were challenged with a contractile agonist (acetylcholine or histamine), and that the effect was independent of the difference in lung volume observed pre- and post-DI. We conclude that a significant portion of the bronchodilatory DI effect stems from factors internal to the lung related to the activation of ASM. Copyright © 2017 the American Physiological Society.

How changes in nutrition have influenced the development of allergic diseases in childhood

PubMed Central

2012-01-01

The increasing prevalence of allergic diseases in childhood in the last decades could be linked to concomitant dietary changes, especially with the modified and lower consumption of fruit, vegetables and minerals. The consumption of these foods by pregnant women and children in the first years of life seems to be associated with a reduced risk of asthma and related symptoms. Foods that can prevent the development of wheezing through their antioxidant effects contain vitamin C and selenium; blood levels of these elements correlate negatively with the risk of wheezing. Intake of vitamin E during pregnancy also appears to be correlated with a reduced risk of wheezing for the unborn child. Similarly, low intake of zinc and carotenoids by pregnant women is associated with an increased risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory properties and protective effects against allergic diseases such as atopic dermatitis and asthma. The consumption of fat influences the development of the airways. Populations in Western countries have increased their consumption of n-6 PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production of PGE2, which is believed to have a protective effect against inflammation of the airways. Conflicting hypotheses also concern vitamin D; both an excess and a deficiency of vitamin D, in fact, have been associated with an increased risk of asthma. Further studies on the role of these substances are necessary before any conclusions can be drawn on a clinical level. Astratto La crescente prevalenza negli ultimi decenni delle malattie allergiche in età pediatrica potrebbe essere legata a concomitanti cambiamenti nella dieta, in particolare alla minore e modificata introduzione di frutta, verdura e minerali. Il consumo di questi alimenti da parte delle donne in gravidanza e dei bambini nei primi anni di vita sembra essere associato ad un ridotto rischio di asma e di sintomi correlati. Gli alimenti che possono prevenire lo sviluppo di respiro sibilante (wheezing) attraverso i loro effetti antiossidanti contengono vitamina C e selenio; i livelli ematici di questi elementi sono correlati negativamente con il rischio di wheezing. Inoltre l'assunzione di vitamina E durante la gravidanza sembra essere correlato con un rischio ridotto di respiro sibilante per il nascituro. Allo stesso modo, basso apporto di zinco e di carotenoidi in donne in gravidanza è associata ad un aumentato rischio di wheezing e asma nell'infanzia. Anche le fibre hanno proprietà anti-infiammatorie ed effetti protettivi contro le malattie allergiche come la dermatite atopica e l’asma. Il consumo di grassi influenza lo sviluppo delle vie aeree. Le popolazioni dei paesi occidentali hanno aumentato il loro consumo di n-6 PUFA e, parallelamente, ridotto n-3 PUFA. Ciò ha portato alla diminuzione della produzione di PGE2, che si ritiene abbia un effetto protettivo contro l'infiammazione delle vie aeree. Ipotesi contrastanti riguardano la vitamina D, sia un eccesso che una carenza di vitamina D, infatti, sono stati associati ad un aumentato rischio di asma. Ulteriori studi sul ruolo di queste sostanze sono necessari prima di trarre conclusioni sul piano clinico. PMID:22651129

Surface Circulation in the Northeastern Mediterranean (NEMED)

DTIC Science & Technology

2010-09-30

NEMED) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale

Coastal Ocean Circulation Experiment off Senegal (COCES)

DTIC Science & Technology

2010-09-30

Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy

Diabetes insipidus and pregnancy.

PubMed

Chanson, Philippe; Salenave, Sylvie

2016-06-01

Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Novel naphthylstyryl-pyridium potentiometric dyes offer advantages for neural network analysis.

PubMed

Obaid, A L; Loew, L M; Wuskell, J P; Salzberg, B M

2004-04-30

The submucous plexus of the guinea pig intestine is a quasi-two-dimensional mammalian neural network that is particularly amenable to study using multiple site optical recording of transmembrane voltage (MSORTV) [Biol. Bull. 183 (1992) 344; J. Neurosci. 19 (1999) 3073]. For several years the potentiometric dye of choice for monitoring the electrical activity of its individual neurons has been di-8-ANEPPS [Neuron 9 (1992) 393], a naphthylstyryl-pyridinium dye with a propylsulfonate headgroup that provides relatively large fluorescence changes during action potentials and synaptic potentials. Limitations to the use of this dye, however, have been its phototoxicity and its low water solubility which requires the presence of DMSO and Pluronic F-127 in the staining solution. In searching for less toxic and more soluble dyes exhibiting larger fluorescence signals, we first tried the dienylstyryl-pyridinium dye RH795 [J. Neurosci. 14 (1994) 2545] which is highly soluble in water. This dye yielded relatively large signals, but it was internalized quickly by the submucosal neurons resulting in rapid degradation of the signal-to-noise ratio. We decided to synthesize a series of naphthylstyryl-pyridinium dyes (di-n-ANEPPDHQ) having the same chromophore as di-8-ANEPPS and the quaternary ammonium headgroup (DHQ) of RH795 (resulting in two positive charges versus the neutral propylsulfonate-ring nitrogen combination), and we tested the di-methyl (JPW3039), di-ethyl (JPW2081), di-propyl (JPW3031), di-butyl (JPW5029), and di-octyl (JPW5037) analogues, all of them soluble in ethanol. We found that the di-propyl (di-3-ANEPPDHQ) and the di-butyl (di-4-ANEPPDHQ) forms yielded the best combination of signal-to-noise ratio, moderate phototoxicity and absence of dye internalization.

Children with chronic renal disease undergoing dialysis or conservative treatment--differences in structural and functional echocardiographic parameters.

PubMed

Scavarda, Valeska Tavares; Pinheiro, Aurelio Carvalho; Costa, Symône Damasceno; de Andrade, Zélia Maria; Carvalhaes, João Tomás de Abreu; Campos, Orlando; Carvalho, Antonio Carlos; Moises, Valdir Ambrosio

2014-10-01

Cardiac disease frequently occurs in children with chronic kidney disease (CKD) undergoing dialysis (DI), but it is not well studied in patients undergoing conservative treatment (CT). The aim of our study was to use echocardiography to analyze and compare the cardiac involvement of children with CKD undergoing DI or CT. Seventy-one children with CKD were included; 41 undergoing DI and 30 undergoing CT. There were 33 controls. Measurements of arterial pressure and structural and functional echocardiographic variables were obtained; the children were followed up for 18 months. Tests of comparison and multiple regression were used; significant if P < 0.05. Arterial hypertension (AH) was present in 37 of 71 (52%) children with CKD: 27 (65.8%) in DI and 10 (33.3%) in CT (X2 = 8.7; P = 0.003). An abnormal left ventricular geometric pattern was present in 37/41 (90.3%) undergoing DI, 33 had left ventricular hypertrophy (LVH), and in 14/30 (46.7%) undergoing CT, 5 had LVH. Ejection fraction was normal in all groups; diastolic function alteration (DFA) occurred in 28/41 (68.3%) children on DI and in 10/30 (33.3%) on CT (X2 = 9.2; P = 0.002). For children with CKD, DI (P = 0.002) and hypertension (P = 0.04) were associated with LVH; among those on DI, only AH was associated with LVH (P = 0.02). During the follow-up, 18 (43.9%) children undergoing DI had at least one cardiovascular event. Children with CKD undergoing CT had less cardiac involvement than those undergoing DI. LVH was associated with DI and AH in all children with CKD and with AH in those on DI.

A Change Impact Analysis to Characterize Evolving Program Behaviors

NASA Technical Reports Server (NTRS)

Rungta, Neha Shyam; Person, Suzette; Branchaud, Joshua

2012-01-01

Change impact analysis techniques estimate the potential effects of changes made to software. Directed Incremental Symbolic Execution (DiSE) is an intraprocedural technique for characterizing the impact of software changes on program behaviors. DiSE first estimates the impact of the changes on the source code using program slicing techniques, and then uses the impact sets to guide symbolic execution to generate path conditions that characterize impacted program behaviors. DiSE, however, cannot reason about the flow of impact between methods and will fail to generate path conditions for certain impacted program behaviors. In this work, we present iDiSE, an extension to DiSE that performs an interprocedural analysis. iDiSE combines static and dynamic calling context information to efficiently generate impacted program behaviors across calling contexts. Information about impacted program behaviors is useful for testing, verification, and debugging of evolving programs. We present a case-study of our implementation of the iDiSE algorithm to demonstrate its efficiency at computing impacted program behaviors. Traditional notions of coverage are insufficient for characterizing the testing efforts used to validate evolving program behaviors because they do not take into account the impact of changes to the code. In this work we present novel definitions of impacted coverage metrics that are useful for evaluating the testing effort required to test evolving programs. We then describe how the notions of impacted coverage can be used to configure techniques such as DiSE and iDiSE in order to support regression testing related tasks. We also discuss how DiSE and iDiSE can be configured for debugging finding the root cause of errors introduced by changes made to the code. In our empirical evaluation we demonstrate that the configurations of DiSE and iDiSE can be used to support various software maintenance tasks

The electrical and dielectrical behavior of n-conducting perylene tetracarboxylic diimide derivatives

NASA Astrophysics Data System (ADS)

Lehmann, Daniel; Zahn, Dietrich R. T.

2009-04-01

A comparison of the electrical characteristics of organic field-effect transistors (OFETs) based on derivatives of the electron-conductor perylene tetracarboxylic diimide (PTCDI) in top-contact configuration is presented. The derivatives used are N,N'-dimethyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiMe-PTCDI), N,N'-diphenyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiPhenyl-PTCDI), N,N'-dimethoxyethyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiMethoxyethyl-PTCDI), N,N'-di(3-pentyl)-3,4,9,10-perylene-tetracarboxylic-diimide (Di3Pentyl-PTCDI), and N,N'-diheptyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiHeptyl-PTCDI). Current/voltage measurements were first performed in situ and later ex situ. Additionally, the effect of annealing and bias stress was probed in situ. A strong influence of the different side groups on the order of magnitude of the electron mobility is revealed, ranging from 4×10-6 cm2/V s for DiMethoxyethyl-PTCDI to 5×10-2 cm2/V s for DiHeptyl-PTCDI. While none of the devices was stable in air after exposition to air, only the DiMe-PTCDI one resumed its functionality after restoring vacuum conditions. The dielectric functions of the derivatives was derived, additionally revealing optical isotropy for all films and varying surface roughness. While DiHeptyl-PTCDI and Di3Pentyl-PTCDI, yielding also the highest electron mobilities, form smooth layers with negligible surface roughness, strong island formation was be observed for DiPhenyl-PTCDI and DiMethoxyethyl-PTCDI, yielding low mobilities. This island growth was also confirmed by atomic force microscopy measurements. Ageing of the samples for several months under ambient conditions leads to increased roughness for the very rough samples. Layers with smooth surface, on the other hand, showed no significant change in the dielectric behavior of the sample.

Comparison of the Conventional and Electroenhanced Direct-Immersion Solid-Phase Microextraction for Sampling of Nicotine in Biological Fluids of the Human Body.

PubMed

Abdolhosseini, Sana; Ghiasvand, Ali Reza; Heidari, Nahid

2018-05-14

A stainless steel fiber was made porous and adhesive by platinization and then coated by nanostructured polypyrrole (PPy), using an appropriate electrophoretic deposition (EPD) method. The morphological surface structure and functional groups of the PPy-coated fiber were studied using SEM (Scanning electron microscope) instrument. The prepared fiber was used for comparison of direct immersion (DI) and electroenhanced direct immersion solid-phase microextraction (EE-DI-SPME) of nicotine in human plasma and urine samples followed by gas chromatography flame ionization detector (GC-FID) determination. The effects of the influential experimental parameters on the efficiency of the DI-SPME and EE-DI-SPME methods, including the pH and ionic strength of the sample solution, applied Direct current (DC) voltage, extraction temperature and time and stirring rate, were optimized. Under the optimal conditions, the calibration curves for the DI-SPME-GC-FID and EE-DI-SPME-GC-FID methods were linear over the ranges of 0.1⁻10.0 μg mL -1 and 0.001⁻10.0 μg mL -1 , respectively. The relative standard deviations (RSDs, n = 6) were found to be 6.1% and 4.6% for the DI and EE strategies, respectively. The LODs (limit of detection) of the DI-SPME-GC-FID and EE-DI-SPME-GC-FID methods were found to be 10 and 0.3 ng mL -1 , respectively. The relative recovery values (for the analysis of 1 µg mL -1 nicotine) were found to be 91⁻110% for EE-DI-SPME and 75⁻105% for DI-SPME. The enrichment factors for DI-SPME and EE-DI-SPME sampling were obtained as 38,734 and 50,597, respectively. The results indicated that EE-SPME was more efficient for quantitation of nicotine in biological fluids. The developed procedure was successfully carried out for the extraction and measurement of nicotine in real plasma and urine samples.

Improvement of porcine islet isolation by inhibition of trypsin activity during pancreas preservation and digestion using α1-antitrypsin.

PubMed

Shimoda, Masayuki; Noguchi, Hirofumi; Fujita, Yasutaka; Takita, Morihito; Ikemoto, Tetsuya; Chujo, Daisuke; Naziruddin, Bashoo; Levy, Marlon F; Kobayashi, Naoya; Grayburn, Paul A; Matsumoto, Shinichi

2012-01-01

Porcine islets are considered to be a promising resource for xenotransplantation. However, it is difficult to isolate porcine islets because of the marked fragility and rapid dissociation. Endogenous trypsin is one of the main factors to damage islets during the isolation procedure. Recent studies have suggested that trypsin inhibitors during the preservation of pancreas or the collagenase digestion can improve the result of islet isolation. In this study, we examined whether α1-antitrypsin (Aralast™), which inhibits several endogenous proteases and has immunomodulatory properties, can protect islets from the proteases and improve the results of porcine islet isolation. Twelve porcine pancreata were divided into three groups: without Aralast group (standard, n = 5), preserved with Aralast using the ductal injection (DI) method (DI, n = 3), and with Aralast using the DI method and in the collagenase solution (DI+C, n = 4). Efficacy of islet isolation was assessed by islet yields, purity, and viability. The trypsin activity of the preservation and the digestion solution during the isolation procedure was measured. During islet isolation, the trypsin activity in DI+C group was significantly inhibited compared to the standard group, whereas DI group showed less effect than DI+C group. The average of postpurification islet equivalents (IEQ) per pancreas weight in the DI+C group was significantly higher than the standard group (standard: 3516 ± 497 IEQ/g, DI: 4607 ± 1090 IEQ/g, DI+C: 7097 ± 995 IEQ/g; p = 0.017 between standard and DI+C). In the DI+C group, stimulation index was higher than in other groups, although there was no significant difference. The presence of Aralast in both DI solution and collagenase solution markedly inhibited trypsin activity during pancreas digestion procedure and improved the porcine islet isolation. Inhibition of trypsin activity by Aralast could improve porcine islet isolation.

Coastal Ocean Circulation Experiment Off Senegal (COCES - II)

DTIC Science & Technology

2012-09-30

II) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica

Near-Surface Dispersion and Circulation in the Marmara Sea (MARMARA)

DTIC Science & Technology

2009-01-01

Sea (MARMARA) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico

Surface Circulation in the Northeastern Mediterranean (NEMED)

DTIC Science & Technology

2008-09-30

Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy Phone: +39 040 2140322 Fax: +39 040...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c

URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS

EPA Science Inventory

Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...

Water homeostasis and diabetes insipidus in horses.

PubMed

Schott, Harold C

2011-04-01

Diabetes insipidus (DI) is a rare disorder of horses characterized by profound polyuria and polydipsia (PU/PD), which can be caused by loss of production of arginine vasopressin (AVP). This condition is termed neurogenic or central DI. DI may also develop with absence or loss of AVP receptors or activity on the basolateral membrane of collecting-duct epithelial cells. This condition is termed nephrogenic DI. Equine clinicians may differentiate true DI from more common causes of PU/PD by a systematic diagnostic approach. DI may not be a correctable disorder, and supportive care of affected horses requires an adequate water source. Copyright © 2011 Elsevier Inc. All rights reserved.

High-Performance Liquid Chromatography (HPLC)-Based Detection and Quantitation of Cellular c-di-GMP.

PubMed

Petrova, Olga E; Sauer, Karin

2017-01-01

The modulation of c-di-GMP levels plays a vital role in the regulation of various processes in a wide array of bacterial species. Thus, investigation of c-di-GMP regulation requires reliable methods for the assessment of c-di-GMP levels and turnover. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis has become a commonly used approach to accomplish these goals. The following describes the extraction and HPLC-based detection and quantification of c-di-GMP from Pseudomonas aeruginosa samples, a procedure that is amenable to modifications for the analysis of c-di-GMP in other bacterial species.

Lo Gnomone Clementino Astronomia Meridiana in Basilica

NASA Astrophysics Data System (ADS)

Sigismondi, Costantino

2014-05-01

Costruito per chiara volontà del papa 70 anni dopo il caso Galileo, lo Gnomone Clementino è un grande telescopio solare che non fa uso di lenti a 92 anni dall’invenzione del cannocchiale. Queste due caratteristiche basterebbero da sole a giustificare l’interesse verso questo strumento. L’astronomia meridiana è alla base dell’astrometria e dell’astrofisica moderna. Lo Gnomone Clementino sta oggi all’astronomia, come il veliero “Amerigo Vespucci” sta alla Marina Italiana. E’ possibile svolgere ogni genere di osservazione e studio su questo strumento, e dal 2002 vi tengo lezioni teorico-pratiche del corso di Storia dell’Astronomia e La Terra nel Sistema Solare della Sapienza, Università di Roma, Facoltà di Lettere e Filosofia. Questo testo aggiunge alcuni tasselli alla ricerca storica sulla meridiana, appoggiandosi, com’è naturale, sulle spalle di giganti che mi hanno preceduto in questi studi. In particolare la misura dell’azimut della meridiana, ed il suo inquadramento tra gli strumenti simili ed alcuni studi di astrometria sui dati del 1701-1703 di Bianchini, che sono apparsi fin’ora soltanto su riviste specializzate ed in Inglese vengono qui proposti in Italiano e semplificati, per valorizzare sempre più questa straordinaria opera d’arte e di scienza.

Assessment of skeletal maturation using mandibular second molar maturation stages.

PubMed

Goyal, S; Goyal, S; Gugnani, N

2014-01-01

To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.

Structural isomers of polyfluorinated di- and tri-alkylated phosphate ester surfactants present in industrial blends and in microwave popcorn bags.

PubMed

Trier, Xenia; Nielsen, Nikoline Juul; Christensen, Jan H

2011-09-01

In this study, we provide strategies for detecting and quantifying the structural isomers of polyfluorinated di- and tri-alkyl surfactants (PFAS) by mass spectrometry (MS). We specifically investigate polyfluorinated dialkylated phosphate ester surfactants (x:2/y:2 diPAPS, (F(CF(2))( x )CH(2)CH(2)O-P(O)(O)(-)-OCH(2)CH(2)(CF(2))( y )F)) and their thioether analogues (x:2/y:2 S-diPAPS, F(CF(2))( x )CH(2)CH(2)SCH(2)-C[CH(2)O)(2)P(O)(O)(-)]-CH(2)SCH(2)CH(2)(CF(2))( y )F), which are used for industrial applications, such as oil- and water-repellent coatings on paper and board. DiPAPS have been found in human blood and are metabolised to the persistent perfluoroalkyl carboxylic acids (PFCA) in rats. A microwave popcorn bag extract was analysed by ultrahigh-pressure liquid chromatography coupled to a negative electrospray ionisation-quadrupole time-of-flight MS. The extract contained S-diPAPS, diPAPS and trialkylated (triPAPS) impurities. TriPAPS were also present in industrial and synthetic diPAPS standards, and were verified with an 8:2/8:2/8:2 triPAPS standard. The eight elemental compositions (m/z's) of diPAPS in the extract represent 19 precursor ion structures, and the six S-diPAPS m/z's represent at least 13 structures. The diPAPS had [M-H](-) precursor ions of m/z 789, 889,…1,489 and the S-diPAPS of m/z 921, 1,021,…1,421, corresponding to fluorinated chains from C(6-18). Each m/z appeared as one to three chromatographic peaks of structural isomers, where, e.g. m/z 1,189 was present as 10:2/10:2, 8:2/12:2 and 6:2/14:2 diPAPS. The isomers formed different products ions, thus only half of the m/z 1,189 diPAPS concentration was measured with one precursor ion > product ion transition. In general, knowledge about structural isomers of poly-alkylated PFAS is needed for the estimation of types and amounts of perfluorinated degradation products, such as PFCA from diPAPS.

Solving Kinetic Equations on GPU’s

DTIC Science & Technology

2011-01-01

7 Acknowledgments 23 8 Appendix: CUDA pseudo-codes 27 ∗Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano, Italy 8

Systemic lupus erythematosus with Sjögren's syndrome and renal tubular acidosis presenting as nephrogenic diabetes insipidus.

PubMed

Parrey, Ashaq Hussain; Ahmad, Fayaz; Ahmad, Mushtaq; Basher, Adil

2018-01-01

Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a rare association; there is a case report of neurogenic DI in patients of SLE; however, SLE and nephrogenic DI has not been reported in literature. We present a case of SLE presenting as nephrogenic DI. We report a case who presented with DI (nephrogenic) and fulfilled criteria for SLE and Sjögren's syndrome with renal tubular acidosis.

Illustrated review of the leaf-mining Nepticulidae of the central Andes (Peru and Bolivia).

PubMed

Stonis, Jonas R; Diškus, Arūnas; Remeikis, Andrius; Karsholt, Ole; Torres, Nixon Cumbicus

2017-04-24

We review forty-five species of Nepticulidae (Lepidoptera) based on an analysis of samples collected in the central Andean region of Peru and Bolivia. Thirteen of these species are new to science, and are named and described here: Stigmella paracosma Remeikis & Stonis, sp. nov., S. expressa Remeikis & Stonis, sp. nov., S. acalyphae Diškus & Stonis, sp. nov., S. lepida Diškus & Stonis, sp. nov., S. misera Diškus & Stonis, sp. nov., S. inca Diškus & Stonis, sp. nov., S. eiffeli Diškus & Stonis, sp. nov., S. arequipica Remeikis & Stonis, sp. nov., S. coronaria Diškus & Stonis, sp. nov., S. azulella Diškus & Stonis, sp. nov., S. sparsella Diškus & Stonis, sp. nov., Manoneura forcipis Diškus & Stonis, sp. nov., and Acalyptris murex Diškus & Stonis, sp. nov. Some of the central Andean species are recorded here as leaf-miners on Euphorbiaceae (Acalypha), Fabaceae (Collaea), Rosaceae (Polylepis), Malvaceae (Sida), Calceolariaceae (Calceolaria), Lamiaceae (Clinopodium), and Asteraceae (Ageratina and Trixis). We create eleven new species groups based on morphological characters designated in Stigmella and one in Acalyptris. A pictorial key to the species groups and distribution maps are provided. All new species are illustrated with 150 photographs and drawings of the adults and genitalia, and, where known and/or available, photographs of host-plants and leaf-mines.

The Tumor Suppressor DiRas3 Forms a Complex with H-Ras and C-RAF Proteins and Regulates Localization, Dimerization, and Kinase Activity of C-RAF*

PubMed Central

Baljuls, Angela; Beck, Matthias; Oenel, Ayla; Robubi, Armin; Kroschewski, Ruth; Hekman, Mirko; Rudel, Thomas; Rapp, Ulf R.

2012-01-01

The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down-regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic effect of DiRas3 is achieved through several mechanisms, including inhibition of cell proliferation, motility, and invasion, as well as induction of apoptosis and autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling through Ras/MAPK and PI3K. Despite intensive research, the mode of interference of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of speculation. In this study, we show that DiRas3 associates with the H-Ras oncogene and that activation of H-Ras enforces this interaction. Furthermore, while associated with DiRas3, H-Ras is able to bind to its effector protein C-RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H-Ras is more stable than the two protein complexes H-Ras·C-RAF or H-Ras·DiRas3, respectively. The consequence of this complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID:22605333

Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.

PubMed

Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M

2013-05-01

The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis.

Cyclic Di-GMP Modulates the Disease Progression of Erwinia amylovora

PubMed Central

Edmunds, Adam C.; Castiblanco, Luisa F.; Sundin, George W.

2013-01-01

The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis. PMID:23475975

Molecular basis for the recognition of cyclic-di-AMP by PstA, a PII-like signal transduction protein.

PubMed

Choi, Philip H; Sureka, Kamakshi; Woodward, Joshua J; Tong, Liang

2015-06-01

Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized PII -like protein which has been identified as a c-di-AMP receptor. PstA is widely distributed and conserved among Gram-positive bacteria in the phylum Firmicutes. Here, we report the biochemical, structural, and functional characterization of PstA from Listeria monocytogenes. We have determined the crystal structures of PstA in the c-di-AMP-bound and apo forms at 1.6 and 2.9 Å resolution, respectively, which provide the molecular basis for its specific recognition of c-di-AMP. PstA forms a homotrimer structure that has overall similarity to the PII protein family which binds ATP. However, PstA is markedly different from PII proteins in the loop regions, and these structural differences mediate the specific recognition of their respective nucleotide ligand. The residues composing the c-di-AMP binding pocket are conserved, suggesting that c-di-AMP recognition by PstA is of functional importance. Disruption of pstA in L. monocytogenes affected c-di-AMP-mediated alterations in bacterial growth and lysis. Overall, we have defined the PstA family as a conserved and specific c-di-AMP receptor in bacteria. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Enhanced healing of full-thickness burn wounds using di-rhamnolipid

PubMed Central

Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

2006-01-01

The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213

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

Tzeng, W.-P.; Frey, Teryl K.

Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5' end of the capsid protein (C) gene that has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, itmore » was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5' end of the C gene and the 3' end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.« less

Nicholas DiOrio | NREL

Science.gov Websites

Engineering Intern, NREL, Golden, CO, 2013 Featured Publications N. DiOrio, A. Dobos, S. Janzou, A. Nelson and Renewable Energy Laboratory, Golden, CO. N. DiOrio, A. Dobos and S. Janzou. 2015. "Economic Analysis . C. Christensen, J. Maguire, J. Burch, N. DiOrio. "Simplified Solar Water Heater Simulation

A glossary for dissemination and implementation research in health.

PubMed

Rabin, Borsika A; Brownson, Ross C; Haire-Joshu, Debra; Kreuter, Matthew W; Weaver, Nancy L

2008-01-01

Dissemination and implementation (D&I) Research is increasingly Recognized as an important function of academia and is a growing priority for major health-related funders. Because D&I Research in the health field has emerged from Research traditions in diverse disciplines Ranging from agriculture to education, there are inconsistencies in the use and meaning of terms and main concepts. This glossary provides definitions for the key concepts and terms of D&I Research in health (in both public health and clinical settings). Definitions are organized under five major sections: (1) foundation concepts; (2) types of Research; (3) models, theories, and frameworks; (4) factors influencing the D&I processes; and (5) measurement/evaluation of the D&I process. The aim of this glossary is to aid in the development of more standardized and established terminology for D&I Research, facilitate the communication across different stakeholders, and ultimately contribute to higher-quality D&I Research.

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

PubMed

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

2018-01-01

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

Application of the diligence inventory in dental education.

PubMed

Jasinevicius, T R; Bernard, H; Schuttenberg, E M

1998-04-01

The fifty-five-item Diligence Inventory for Higher Education (DI-HE) was applied to a new subject group--190 dental students. After item and factor analysis, a fifty-item (four subscale) inventory best reflected this group. The DI-HE's split half reliability was 0.81 (p < 0.001), the reliability coefficient for the pre- and post-test was 0.68 (p < 0.01), and the correlation coefficient alpha was 0.90. The DI-HE scores were high, with no statistical differences among the four classes. Overall, significant relationships were found between grade point averages (GPAs) and DI-HE total and subscale scores, with r values as high as 0.44. While female students' DI-HE scores were significantly higher (p = 0.023) than male students' scores, no correlations between DI-HE scores and GPAs for females were found. The results suggest that DI-HE may be useful for assessment purposes in professional education.

A High-Order Test for Optimality of Bang-Bang Controls.

DTIC Science & Technology

1983-11-01

Systems * Istituto di Matematica Applicata, Universitl di Padova, ITALY. sponsored by the United States Army under Contract No. DAAG29-80-C-0041...the first order variation at the terminal point of the trajectory lim [x(T,u ) - x(TW)]/E (1.1) Istituto di Matematica Applicata, Universitl di Padova

40 CFR 721.10261 - Oxime, di-Me silane (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

40 CFR 721.10261 - Oxime, di-Me silane (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

Structural Analysis of the GGDEF-EAL Domain-Containing c-di-GMP Receptor FimX

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

Navarro, M.; De, N; Bae, N

2009-01-01

Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data andmore » crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.« less

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

PubMed

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

2018-01-01

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

c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

PubMed Central

Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

2009-01-01

Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

[Trattamento della dipendenza da alcol. Alcol e persone senza fissa dimora: punto di vista sociale].

PubMed

Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Cereatti, Federica; Gencarelli, Simona; Messina, Marisa Patrizia; Vitali, Mario; De Rosa, Francesca; Ledda, Roberta; Mancini, Serena; Attilia, Maria Luisa

2018-01-01

RIASSUNTO. Il fenomeno delle persone senza fissa dimora sta assumendo in questi anni una rilevanza sociale devastante, con una prevalenza stimata in USA e in Europa compresa tra il 5,6% e il 13,9%. Queste persone hanno una scarsa qualità di vita, una limitata o assente vita sociale, sono spesso disoccupate o lavorano solo saltuariamente. Sono a rischio di problemi con la legge, sono spesso affette da dipendenza da droghe, da patologie psichiatriche e internistiche. L'alcol spesso non rappresenta la causa della loro condizione sociale, ma solo la conseguenza, contribuendo in questo modo al loro degrado bio-psico-sociale. Nel 2009 lo US Department of Housing and Urban Development's Homelessness Assistance Programs e nel 2010 la European Consensus Conference on Homelessness hanno segnato un grande passo avanti nella riabilitazione sociale di queste persone, utilizzando il concetto del "case management". In particolare lo Standard Case Management si è dimostrato in grado di migliorare la stabilità abitativa, di ridurre l'uso di droghe e di rimuovere le barriere lavorative. L'Assertive Community Treatment si è dimostrato, invece, in grado di migliorare la stabilità abitativa e ha un rapporto costo/beneficio migliore per i pazienti affetti da doppia diagnosi.

AraC-like transcriptional activator CuxR binds c-di-GMP by a PilZ-like mechanism to regulate extracellular polysaccharide production

PubMed Central

Schäper, Simon; Steinchen, Wieland; Krol, Elizaveta; Altegoer, Florian; Skotnicka, Dorota; Bange, Gert; Becker, Anke

2017-01-01

Cyclic dimeric GMP (c-di-GMP) has emerged as a key regulatory player in the transition between planktonic and sedentary biofilm-associated bacterial lifestyles. It controls a multitude of processes including production of extracellular polysaccharides (EPSs). The PilZ domain, consisting of an N-terminal “RxxxR” motif and a β-barrel domain, represents a prototype c-di-GMP receptor. We identified a class of c-di-GMP–responsive proteins, represented by the AraC-like transcription factor CuxR in plant symbiotic α-proteobacteria. In Sinorhizobium meliloti, CuxR stimulates transcription of an EPS biosynthesis gene cluster at elevated c-di-GMP levels. CuxR consists of a Cupin domain, a helical hairpin, and bipartite helix-turn-helix motif. Although unrelated in sequence, the mode of c-di-GMP binding to CuxR is highly reminiscent to that of PilZ domains. c-di-GMP interacts with a conserved N-terminal RxxxR motif and the Cupin domain, thereby promoting CuxR dimerization and DNA binding. We unravel structure and mechanism of a previously unrecognized c-di-GMP–responsive transcription factor and provide insights into the molecular evolution of c-di-GMP binding to proteins. PMID:28559336

Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma.

PubMed

Nakamura, Takashi; Miyabe, Hiroko; Hyodo, Mamoru; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi

2015-10-28

Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC-I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated within YSK05-liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c-di-GMP/YSK05-Lip induces MHC-I non-restricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas. Copyright © 2015 Elsevier B.V. All rights reserved.

The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

PubMed

Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

2016-12-01

Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bridging the Chasm: Challenges, Opportunities, and Resources for Integrating a Dissemination and Implementation Science Curriculum into Medical Education.

PubMed

Ginossar, Tamar; Heckman, Carolyn J; Cragun, Deborah; Quintiliani, Lisa M; Proctor, Enola K; Chambers, David A; Skolarus, Ted; Brownson, Ross C

2018-01-01

Physicians are charged with implementing evidence-based medicine, yet few are trained in the science of Dissemination and Implementation (D&I). In view of the potential of evidence-based training in D&I to help close the gap between research and practice, the goal of this review is to examine the importance of D&I training in medical education, describe challenges to implementing such training, and provide strategies and resources for building D&I capacity. We conducted (1) a systematic review to identify US-based D&I training efforts and (2) a critical review of additional literature to inform our evaluation of the challenges and opportunities of integrating D&I training in medical education. Out of 269 unique articles reviewed, 11 described US-based D&I training. Although vibrant and diverse training opportunities exist, their capacity is limited, and they are not designed to meet physicians' needs. Synthesis of relevant literature using a critical review approach identified challenges inherent to changing medical education, as well as challenges related to D&I science. Finally, selected strategies and resources are available for facilitating incorporation of D&I training into medical education and overcoming existing challenges. Integrating D&I training in the medical education curriculum, and particularly in residency and fellowship training, holds promise for bridging the chasm between scientific discoveries and improved patient care and outcomes. However, unique challenges should be addressed, including the need for greater evidence.

Influence of nitrogen fertilization and defoliation frequency on nitrogen constituents and feeding value of annual ryegrass.

PubMed

Zhang, Y; Bunting, L D; Kappel, L C; Hafley, J L

1995-08-01

Two experiments were conducted to determine the seasonal effects of N fertilizer (NF) and defoliation interval (DI) on specific N fractions within annual ryegrass (AR) and overall usage of AR N by growing lambs. In Exp. 1, NF (0, 112, 224, and 336 kg of N/ha) and DI of 2, 4, or 6 wk were factorially applied to AR plots. Both decreasing DI and increasing NF increased N levels in AR in a manner that depended on harvest date (NF or DI x harvest date interaction, P < .05). The proportions of .2% NaOH soluble N or soluble protein N were not affected (P > .05) by NF or DI. Although NF had no effect (P > .05) on in situ disappearance of DM, decreasing the DI seemed to reduce the severity of the season-induced reduction in DM disappearance (DI x harvest date interaction, P = .04). In Exp. 2, NF (0 or 224 kg of N/ha) and a DI of 2 or 6 wk were factorially applied to AR plots. Fresh, frozen AR was fed in semipurified diets (48% of DM as AR) to four wether lambs (23 +/- 1.3 kg) using a 4 x 4 Latin square. Diets including AR had greater ruminal DM and plant N digestibilities when AR had a 2-wk vs a 6-wk DI with NF but had reduced digestibilities when AR had a 2-wk vs a 6-wk DI without NF.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence, predictors and early post-operative course of diabetes insipidus in paediatric craniopharygioma: a comparison with adults.

PubMed

Pratheesh, Ravindran; Swallow, Diane Margaret A; Rajaratnam, Simon; Jacob, K S; Chacko, Geeta; Joseph, Mathew; Chacko, Ari G

2013-06-01

This study aims to determine the incidence, predictors, early post-operative course of diabetes insipidus (DI) in paediatric craniopharyngiomas(CP) and compare the findings with adults. Retrospective analysis of clinical, biochemical, radiological and operative data for 102 consecutive CP surgeries (45 paediatric and 57 adult cases) was done. Bivariate and multivariate analyses were done to determine the predictors of DI. The incidence of the triphasic response and electrolyte abnormalities in the first post-operative week was compared between children and adults. Children had larger tumours and higher incidence of cystic tumours and hydrocephalus. Preoperative DI was close to 15 % in both the age groups. Radical/subtotal excision was achieved in 58 % of children and 53 % of adults. The incidence of post-operative DI was 80 % and 63 % in children and adults, respectively. Children had significantly higher incidence of permanent DI (55.6 %). Radical excision in children (p = 0.000); previous tumour surgery (p = 0.014) and new onset hypopituitarism (p = 0.019) in adults were associated with permanent DI. The triphasic response (23 %), wide intra-day serum sodium fluctuations and hyponatraemia were more common in children. Post-operative DI is a frequent and significant cause of morbidity in children undergoing surgery for CP. Children have a higher incidence of permanent DI. Radical excision is a predictor of permanent DI in children, whereas previous tumour excision and new onset hypopituitarism were predictors of permanent DI among adults. The management of post-operative DI is more difficult in children and the treating physician needs to be alert to detect the triphasic response.

Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers.

PubMed

Cooper, Peter D; Petrovsky, Nikolai

2011-05-01

We report a novel isoform of β-D-[2 → 1] poly(fructo-furanosyl) α-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.

Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.

PubMed

Winzeler, Bettina; Zweifel, Christian; Nigro, Nicole; Arici, Birsen; Bally, Martina; Schuetz, Philipp; Blum, Claudine Angela; Kelly, Christopher; Berkmann, Sven; Huber, Andreas; Gentili, Fred; Zadeh, Gelareh; Landolt, Hans; Mariani, Luigi; Müller, Beat; Christ-Crain, Mirjam

2015-06-01

Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.

Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose

PubMed Central

Zorraquino, Violeta; García, Begoña; Latasa, Cristina; Echeverz, Maite; Toledo-Arana, Alejandro; Valle, Jaione

2013-01-01

Cyclic di-GMP (c-di-GMP) is a secondary messenger that controls a variety of cellular processes, including the switch between a biofilm and a planktonic bacterial lifestyle. This nucleotide binds to cellular effectors in order to exert its regulatory functions. In Salmonella, two proteins, BcsA and YcgR, both of them containing a c-di-GMP binding PilZ domain, are the only known c-di-GMP receptors. BcsA, upon c-di-GMP binding, synthesizes cellulose, the main exopolysaccharide of the biofilm matrix. YcgR is dedicated to c-di-GMP-dependent inhibition of motility through its interaction with flagellar motor proteins. However, previous evidences indicate that in the absence of YcgR, there is still an additional element that mediates motility impairment under high c-di-GMP levels. Here we have uncovered that cellulose per se is the factor that further promotes inhibition of bacterial motility once high c-di-GMP contents drive the activation of a sessile lifestyle. Inactivation of different genes of the bcsABZC operon, mutation of the conserved residues in the RxxxR motif of the BcsA PilZ domain, or degradation of the cellulose produced by BcsA rescued the motility defect of ΔycgR strains in which high c-di-GMP levels were reached through the overexpression of diguanylate cyclases. High c-di-GMP levels provoked cellulose accumulation around cells that impeded flagellar rotation, probably by means of steric hindrance, without affecting flagellum gene expression, exportation, or assembly. Our results highlight the relevance of cellulose in Salmonella lifestyle switching as an architectural element that is both essential for biofilm development and required, in collaboration with YcgR, for complete motility inhibition. PMID:23161026

Remote Sensing Global Surface Air Pressure Using Differential Absorption BArometric Radar (DiBAR)

NASA Technical Reports Server (NTRS)

Lin, Bing; Harrah, Steven; Lawrence, Wes; Hu, Yongxiang; Min, Qilong

2016-01-01

Tropical storms and severe weathers are listed as one of core events that need improved observations and predictions in World Meteorological Organization and NASA Decadal Survey (DS) documents and have major impacts on public safety and national security. This effort tries to observe surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at the 50-55 gigahertz O2 absorption band. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 4 millibars (approximately 1 millibar under all weather conditions). With these sea level pressure measurements, the forecasts of severe weathers such as hurricanes will be significantly improved. Since the development of the DiBAR concept about a decade ago, NASA Langley DiBAR research team has made substantial progress in advancing the concept. The feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. The team has developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.

Use of ferrous iron by metallo-β-lactamases.

PubMed

Cahill, Samuel T; Tarhonskaya, Hanna; Rydzik, Anna M; Flashman, Emily; McDonough, Michael A; Schofield, Christopher J; Brem, Jürgen

2016-10-01

Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibacterials including the latest generation carbapenems and are a growing worldwide clinical problem. It is proposed that MBLs employ one or two zinc ion cofactors in vivo. Isolated MBLs are reported to use transition metal ions other than zinc, including copper, cadmium and manganese, with iron ions being a notable exception. We report kinetic and biophysical studies with the di-iron(II)-substituted metallo-β-lactamase II from Bacillus cereus (di-Fe(II) BcII) and the clinically relevant B1 subclass Verona integron-encoded metallo-β-lactamase 2 (di-Fe(II) VIM-2). The results reveal that MBLs can employ ferrous iron in catalysis, but with altered kinetic and inhibition profiles compared to the zinc enzymes. A crystal structure of di-Fe(II) BcII reveals only small overall changes in the active site compared to the di-Zn(II) enzyme including retention of the di-metal bridging water; however, the positions of the metal ions are altered in the di-Fe(II) compared to the di-Zn(II) structure. Stopped-flow analyses reveal that the mechanism of nitrocefin hydrolysis by both di-Fe(II) BcII and di-Fe(II) VIM-2 is altered compared to the di-Zn(II) enzymes. Notably, given that the MBLs are the subject of current medicinal chemistry efforts, the results raise the possibility the Fe(II)-substituted MBLs may be of clinical relevance under conditions of low zinc availability, and reveal potential variation in inhibitor activity against the differently metallated MBLs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

PubMed Central

Galperin, Michael Y.; Gomelsky, Mark

2013-01-01

SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger. PMID:23471616

Biological and pharmacological evaluation of dimethoxycurcumin: A metabolically stable curcumin analogue with a promising therapeutic potential.

PubMed

Teymouri, Manouchehr; Barati, Nastaran; Pirro, Matteo; Sahebkar, Amirhosein

2018-01-01

Dimethoxycurcumin (DiMC) is a synthetic analog of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic, and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. © 2016 Wiley Periodicals, Inc.

Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

PubMed

Schreckinger, Matthew; Walker, Blake; Knepper, Jordan; Hornyak, Mark; Hong, David; Kim, Jung-Min; Folbe, Adam; Guthikonda, Murali; Mittal, Sandeep; Szerlip, Nicholas J

2013-12-01

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Crystal structures of isomeric 3,5-di-chloro-N-(2,3-di-methyl-phen-yl)benzene-sulfonamide, 3,5-di-chloro-N-(2,6-di-methyl-phen-yl)benzene-sulfonamide and 3,5-di-chloro-N-(3,5-di-methyl-phen-yl)benzene-sulfonamide.

PubMed

Shakuntala, K; Naveen, S; Lokanath, N K; Suchetan, P A

2017-05-01

The crystal structures of three isomeric compounds of formula C 14 H 13 Cl 2 NO 2 S, namely 3,5-di-chloro- N -(2,3-di-methyl-phen-yl)-benzene-sulfonamide (I), 3,5-di-chloro- N -(2,6-di-methyl-phen-yl)benzene-sulfonamide (II) and 3,5-di-chloro- N -(3,5-di-methyl-phen-yl)benzene-sulfonamide (III) are described. The mol-ecules of all the three compounds are U-shaped with the two aromatic rings inclined at 41.3 (6)° in (I), 42.1 (2)° in (II) and 54.4 (3)° in (III). The mol-ecular conformation of (II) is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. The crystal structure of (I) features N-H⋯O hydrogen-bonded R 2 2 (8) loops inter-connected via C (7) chains of C-H⋯O inter-actions, forming a three-dimensional architecture. The structure also features π-π inter-actions [ Cg ⋯ Cg = 3.6970 (14) Å]. In (II), N-H⋯O hydrogen-bonded R 2 2 (8) loops are inter-connected via π-π inter-actions [inter-centroid distance = 3.606 (3) Å] to form a one-dimensional architecture running parallel to the a axis. In (III), adjacent C (4) chains of N-H⋯O hydrogen-bonded mol-ecules running parallel to [010] are connected via C-H⋯π inter-actions, forming sheets parallel to the ab plane. Neighbouring sheets are linked via offset π-π inter-actions [inter-centroid distance = 3.8303 (16) Å] to form a three-dimensional architecture.

Leaf-mining Nepticulidae (Lepidoptera) from record high altitudes: documenting an entire new fauna in the Andean páramo and puna.

PubMed

Stonis, Jonas R; Diškus, Arūnas; Remeikis, Andrius; Gerulaitis, Virginijus; Karsholt, Ole

2016-11-01

The monograph treats 29 species of leaf-mining pygmy moths (Insecta, Lepidoptera, Nepticulidae) discovered in the northern Andean bush and grass páramo and the central Andean puna at altitudes above 3700 m. They represent the world's highest-altitudinal Nepticulidae fauna known. The height record belongs to Stigmella nivea sp. nov. from Peru collected at an elevation of 4700 m. Except for one species, all belong to Stigmella Schrank. Twenty-two of the species recorded are new and are named and described in the current paper: Stigmella paramica Diškus & Stonis, sp. nov.; S. lachemillae Diškus & Stonis, sp. nov.; S. gynoxyphaga Diškus & Stonis, sp. nov.; S. calceolariae Diškus & Stonis, sp. nov.; S. rigida Diškus & Stonis, sp. nov.; S. altiplanica Diškus & Stonis, sp. nov.; S. robusta Remeikis & Stonis, sp. nov.; S. pseudorobusta Remeikis & Stonis, sp. nov.; S. auriargentata Remeikis & Stonis, sp. nov.; S. altimontana Remeikis & Stonis, sp. nov.; S. pandora Remeikis & Stonis, sp. nov.; S. ampla Diškus & Stonis, sp. nov.; S. evanida Diškus & Stonis, sp. nov.; S. mustelina Remeikis & Stonis, sp. nov.; S. angusta Diškus & Stonis, sp. nov.; S. alticosma Remeikis & Stonis, sp. nov.; S. nivea Remeikis & Stonis, sp. nov.; S. kristenseni Diškus & Stonis, sp. nov.; S. lobata Remeikis & Stonis, sp. nov.; S. ageratinae Diškus & Stonis, sp. nov.; S. clinopodiella Diškus & Stonis, sp. nov.; and S. calceolarifoliae Diškus & Stonis, sp. nov. Some of these species are leaf-miners on Asteraceae (Pentacalia, Baccharis, Gynoxys, and Ageratina plants), Calceolariaceae (Calceolaria), Lamiaceae (Clinopodium), and Rosaceae (Lachemilla). Twenty species are known only from adults with no data on their biology and host-plants. In addition, we present data and discuss recently discovered nepticulid taxa associated with Polylepis forests that is the natural vegetation in much of the High Andes. All High-Andean Stigmella species treated are illustrated with photographs of the adults and genitalia, distribution maps, including some with photographs of the leaf-mines and habitats.

A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer immunotherapy.

PubMed

Miyabe, Hiroko; Hyodo, Mamoru; Nakamura, Takashi; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi

2014-06-28

Cyclic dinucleotides are of importance in the field of microbiology and immunology. They function as second messengers and are thought to participate in the signal transduction of cytosolic DNA immune responses. One such dinucleotide, cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons. Therefore c-di-GMP can be thought of as a new class of adjuvant. However, because c-di-GMP contains two phosphate groups, this prevents its use as an adjuvant because it cannot pass through the cell membrane, even though the target molecule of c-di-GMP is located in the cytoplasm. Our group has been developing a series of liposomal drug delivery systems and recently investigated YSK05 which is a synthetic, pH sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN-β in Raw264.7 cells. The induction of IFN-β from c-di-GMP liposomes was inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of IFN-β caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I. The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell activity and the inhibition of tumor growth in a mouse model. These findings indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di-GMP to the cytosol and induce an innate immune system but also as a platform for investigating the mechanism of immune sensing with cyclic dinucleotides in vitro and in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

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

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that leadmore » to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL shares morphologic/mechanistic similarities with Niemann–Pick type C disease. • Di-22:6-BMP is an effective DIPL biomarker in humans via NPC patient validation.« less

A Single Amino Acid Substitution within the Paramyxovirus Sendai Virus Nucleoprotein Is a Critical Determinant for Production of Interferon-Beta-Inducing Copyback-Type Defective Interfering Genomes.

PubMed

Yoshida, Asuka; Kawabata, Ryoko; Honda, Tomoyuki; Sakai, Kouji; Ami, Yasushi; Sakaguchi, Takemasa; Irie, Takashi

2018-03-01

One of the first defenses against infecting pathogens is the innate immune system activated by cellular recognition of pathogen-associated molecular patterns (PAMPs). Although virus-derived RNA species, especially copyback (cb)-type defective interfering (DI) genomes, have been shown to serve as real PAMPs, which strongly induce interferon-beta (IFN-β) during mononegavirus infection, the mechanisms underlying DI generation remain unclear. Here, for the first time, we identified a single amino acid substitution causing production of cbDI genomes by successful isolation of two distinct types of viral clones with cbDI-producing and cbDI-nonproducing phenotypes from the stock Sendai virus (SeV) strain Cantell, which has been widely used in a number of studies on antiviral innate immunity as a representative IFN-β-inducing virus. IFN-β induction was totally dependent on the presence of a significant amount of cbDI genome-containing viral particles (DI particles) in the viral stock, but not on deficiency of the IFN-antagonistic viral accessory proteins C and V. Comparison of the isolates indicated that a single amino acid substitution found within the N protein of the cbDI-producing clone was enough to cause the emergence of DI genomes. The mutated N protein of the cbDI-producing clone resulted in a lower density of nucleocapsids than that of the DI-nonproducing clone, probably causing both production of the DI genomes and their formation of a stem-loop structure, which serves as an ideal ligand for RIG-I. These results suggested that the integrity of mononegaviral nucleocapsids might be a critical factor in avoiding the undesirable recognition of infection by host cells. IMPORTANCE The type I interferon (IFN) system is a pivotal defense against infecting RNA viruses that is activated by sensing viral RNA species. RIG-I is a major sensor for infection with most mononegaviruses, and copyback (cb)-type defective interfering (DI) genomes have been shown to serve as strong RIG-I ligands in real infections. However, the mechanism underlying production of cbDI genomes remains unclear, although DI genomes emerge as the result of an error during viral replication with high doses of viruses. Sendai virus has been extensively studied and is unique in that its interaction with innate immunity reveals opposing characteristics, such as high-level IFN-β induction and strong inhibition of type I IFN pathways. Our findings provide novel insights into the mechanism of production of mononegaviral cbDI genomes, as well as virus-host interactions during innate immunity. Copyright © 2018 American Society for Microbiology.

40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...

40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...

URINARY AND AMNIOTIC FLUID LEVELS OF PHTHALATE MONOESTERS IN RATS AFTER THE ORAL ADMINISTRATION OF DI(2-ETHYLHEXYL) PHTHALATE AND DI-N-BUTYL PHTHALATE

EPA Science Inventory

Two studies were designed to examine amniotic fluid and maternal urine concentrations of the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethylhexyl) phthalate (MEHP) and the di-n-butyl phthalate (DBP) metabolite monobutyl phthalate (MBP) after administration of DEHP and D...

Geo-database use to promote dengue infection prevention and control.

PubMed

Wongbutdee, Jaruwan; Chaikoolvatana, Anun; Saengnill, Wacharapong; Krasuaythong, Nantaya; Phuphak, Surajit

2010-07-01

Dengue infection (DI) is a major health problem in Thailand and is especially prevalent in Ubon Ratchathani Province. The objectives of the project were: (1) to develop a geo-database system for DI prevention and control, (2) to perform an Aedes aegypti larval vector survey for DI prevention and control in Ubon Ratchathani Province, (3) to study the behavior and perceptions regarding DI prevention among the target population in Ubon Ratchathani Province. Ten villages with high incidences of DI over a 3 year period from 2005 to 2007 were selected. The survey was divided into 2 periods, pre-outbreak period (February-April 2008) and outbreak period (June-August 2008). The data were collected in April and June 2008. The households in each village were purposively sampled. Water containers inside and outside of the houses were surveyed using the World Health Organization's house index (HI), container index (CI), and Breteau index (BI). The location of each household was recorded using the global positioning system (GPS). Data regarding people's perceptions and behaviors concerning DI prevention were collected during interviews of 383 families in Mach 2008. A database for DI was developed using ArcView version 9.2. The results showed during the pre-outbreak period, Non Jig, Non Sawang, and Huai Teeneu villages had the highest risk level (BI > or =50). During the outbreak period, Non Jig and Huai Teeneu village had the highest risk level (BI > or =50). Results regarding DI perceptions showed the target population had high levels of DI perceptions. DI preventive behavior was found in 50.9%.

Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway

PubMed Central

Russell, Matthew H.; Bible, Amber N.; Fang, Xin; Gooding, Jessica R.; Campagna, Shawn R.; Gomelsky, Mark; Alexandre, Gladys

2013-01-01

ABSTRACT Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors. PMID:23512960

Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B Cell Acute Lymphoblastic Leukemia.

PubMed

Noh, O Kyu; Park, Se Jin; Park, Hyeon Jin; Ju, HeeYoung; Han, Seung Hyon; Jung, Hyun Joo; Park, Jun Eun

2017-09-01

We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p =0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p <0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols. © 2017 by the Association of Clinical Scientists, Inc.

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

PubMed Central

Novak, Elizabeth A.; Sultan, Syed Z.; Motaleb, Md. A.

2014-01-01

In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease. PMID:24822172

Evaluation of skeletal maturation using mandibular third molar development in Indian adolescents.

PubMed

Mehta, Nishit; Patel, Dolly; Mehta, Falguni; Gupta, Bhaskar; Zaveri, Grishma; Shah, Unnati

2016-01-01

This study was done with the following objectives: to estimate dental maturity using the Demirjian Index (DI) for the mandibular third molar; to investigate the relationship between dental maturity and skeletal maturity among growing patients; to evaluate the use of the mandibular third molar as an adjunctive tool for adolescent growth assessment in combination with the cervical vertebrae; to evaluate the clinical value of the third molar as a growth evaluation index. Samples were derived from panoramic radiographs and lateral cephalograms of 615 subjects (300 males and 315 females) of ages ranging 9-18 years, and estimates of dental maturity (DI) and skeletal maturity [cervical vertebrae maturation indicators (CVMI)] were made. A highly significant association (r = 0.81 for males and r = 0.72 for females) was found between DI and CVMI. DI Stage B corresponded to Stage 2 of CVMI (prepeak of pubertal growth spurt) in both sexes. In males, DI stages C and D represent the peak of the pubertal growth spurt. In females, stages B and C show that the peak of the pubertal growth spurt has not been passed. DI stage E in females and DI Stage F in males correlate that the peak of the pubertal growth spurt has been passed. A highly significant association exists between DI and CVMI. Mandibular third molar DI stages are reliable adjunctive indicators of skeletal maturity.

Lista dei caratteri macroscopici per l’identificazione dei legni

Treesearch

Flavio Ruffinatto; Alan Crivellaro; Alex C. Wiedenhoeft

2016-01-01

L’identificazione dei legni costituisce il primo passo per ottenere conoscenze indispensabili in molti ambiti di studio. Ad esempio, prima di eseguire il restauro di un manufatto di interesse culturale è indispensabile conoscere il nome dei legni che lo compongono. Oppure, nel caso in cui si sospetti che un legno protetto da convenzioni internazionali sia stato...

European Conference on Visual Perception (6th).

DTIC Science & Technology

1983-11-30

Institut fuer Verhaltenswissenschaft, ETH- Zentrum, 8092 Zuerich - Switzerland W. GERBINO: Istituto di Psicologia , Universitk di Padova, Piazza Capitaniato...fuer medizinische Psychologie, Schillerstrasse 42 - 8000 Muenchen 2, West Germany L. JANEZ ESCALADA: Psicologia Matem&tica, Facultad de Psicologla...Norway P. MANCINI: Istituto di Fisiologia clinica del C.N.R., Via Bonanno Pisano - 56100 Pisa, Italy C.A. MARZI: Istituto di Psicologia . Universit

Di-n-butyl Phthalate (DNBP) and Diisobutyl Phthalate (DiBP) Metabolism in a Human Volunteer after Single Oral Doses [Journal Article

EPA Science Inventory

An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...

Diabetes insipidus following resection of pituitary tumors.

PubMed

Schreckinger, Matthew; Szerlip, Nicholas; Mittal, Sandeep

2013-02-01

Diabetes insipidus (DI) is a common complication following pituitary surgery and can be transient or permanent. Neurogenic DI occurs following injury to the magnocellular neurons in the hypothalamus that produce and transport arginine vasopressin (AVP) and form the hypothalamo-hypophyseal tract. DI is defined by a constellation of signs and symptoms resulting in dilute high-volume urine output and increasing serum osmolality. The body's inability to concentrate urine leaves the patient dehydrated and leads to metabolic abnormalities that can be life threatening if not recognized and treated in a timely manner with an exogenous AVP analog. The reported incidence of postsurgical central DI varies from 1 to 67%. This wide range likely reflects inconsistencies in the working definition of DI across the literature. Factors affecting the rate of DI include pituitary tumor size, adherence to surrounding structures, surgical approach, and histopathology of pituitary lesion. The likelihood of postoperative DI can be reduced by careful preservation of the neurovascular structures of the hypothalamus, infundibulum, and neurohypophysis. Vigilance and meticulous surgical technique are essential to minimize injury to these critical regions that can lead to postsurgical DI. Copyright © 2012 Elsevier B.V. All rights reserved.

The Effect of a Shear Flow on the Uptake of LDL and Ac-LDL by Cultured Vascular Endothelial Cells

NASA Astrophysics Data System (ADS)

Niwa, Koichi; Karino, Takeshi

The effects of a shear flow on the uptake of fluorescence-labeled low-density lipoprotein (DiI-LDL), acetylated LDL (DiI-Ac-LDL), and lucifer yellow (LY; a tracer of fluid-phase endocytosis) by cultured bovine aortic ECs were studied using a rotating-disk shearing apparatus. It was found that 2hours’ exposure of ECs to a laminar shear flow that imposed ECs an area-mean shear stress of 10dynes/cm2 caused an increase in the uptake of DiI-LDL and LY. By contrast, the uptake of DiI-Ac-LDL was decreased by exposure of the ECs to a shear flow. Addition of dextran sulfate (DS), a competitive inhibitor of scavenger receptors, reversed the effect of a shear flow on the uptake of DiI-Ac-LDL, resulting in an increase by the imposition of a shear flow, while the uptake of DiI-LDL and LY remained unaffected. It was concluded that a shear flow promotes the endocytosis of DiI-LDL and LY by ECs, but suppresses the uptake of DiI-Ac-LDL by ECs by inhibiting scavenger receptor-mediated endocytosis.

A 100J-level nanosecond pulsed DPSSL for pumping high-efficiency, high-repetition rate PW-class lasers

NASA Astrophysics Data System (ADS)

De Vido, M.; Ertel, K.; Mason, P. D.; Banerjee, S.; Phillips, P. J.; Smith, J. M.; Butcher, T. J.; Chekhlov, O.; Divoky, M.; Pilar, J.; Hooker, C.; Shaikh, W.; Lucianetti, A.; Hernandez-Gomez, C.; Mocek, T.; Edwards, C.; Collier, J. L.

2017-02-01

In this paper, we review the development, at the STFC's Central Laser Facility (CLF), of high energy, high repetition rate diode-pumped solid-state laser (DPSSL) systems based on cryogenically-cooled multi-slab ceramic Yb:YAG. Up to date, two systems have been completed, namely the DiPOLE prototype and the DiPOLE100 system. The DiPOLE prototype has demonstrated amplification of nanosecond pulses in excess of 10 J at 10 Hz repetition rate with an opticalto- optical efficiency of 22%. The larger scale DiPOLE100 system, designed to deliver 100J temporally-shaped nanosecond pulses at 10 Hz repetition rate, has been developed at the CLF for the HiLASE project in the Czech Republic. Recent experiments conducted on the DiPOLE100 system demonstrated the energy scalability of the DiPOLE concept to the 100 J pulse energy level. Furthermore, second harmonic generation experiments carried out on the DiPOLE prototype confirmed the suitability of DiPOLE-based systems for pumping high repetition rate PW-class laser systems based on Ti:sapphire or optical parametric chirped pulse amplification (OPCPA) technology.

LtmA, a novel cyclic di-GMP-responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis

PubMed Central

Li, Weihui; He, Zheng-Guo

2012-01-01

In a bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport and metabolism genes. c-di-GMP could enhance the ability of Ms6479 to bind to its target DNA. Furthermore, our results establish Ms6479 as a global activator that positively regulates the expression of diverse target genes. Overexpression of Ms6479 in M. smegmatis significantly reduced the permeability of the cell wall to crystal violet and increased mycobacterial resistance to anti-tuberculosis antibiotics. Interestingly, Ms6479 lacks the previously reported c-di-GMP binding motifs. Our findings introduce Ms6479 (here designated LtmA for lipid transport and metabolism activator) as a new c-di-GMP-responsive regulator. PMID:23047950

DI: An interactive debugging interpreter for applicative languages

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

Skedzielewski, S.K.; Yates, R.K.; Oldehoeft, R.R.

1987-03-12

The DI interpreter is both a debugger and interpreter of SISLAL programs. Its use as a program interpreter is only a small part of its role; it is designed to be a tool for studying compilation techniques for applicative languages. DI interprets dataflow graphs expressed in the IF1 and IF2 languages, and is heavily instrumented to report the activity of dynamic storage activity, reference counting, copying and updating of structured data values. It also aids the SISAL language evaluation by providing an interim execution vehicle for SISAL programs. DI provides determinate, sequential interpretation of graph nodes for sequential and parallelmore » operations in a canonical order. As a debugging aid, DI allows tracing, breakpointing, and interactive display of program data values. DI handles creation of SISAL and IF1 error values for each data type and propagates them according to a well-defined algebra. We have begun to implement IF1 optimizers and have measured the improvements with DI.« less

Extractant compositions for co-extracting cesium and strontium, a method of separating cesium and strontium from an aqueous feed, and calixarene compounds

DOEpatents

Peterman, Dean R [Idaho Falls, ID; Meikrantz, David H [Idaho Falls, ID; Law, Jack D [Pocatello, ID; Riddle, Catherine L [Idaho Falls, ID; Todd, Terry A [Firth, ID; Greenhalgh, Mitchell R [Iona, ID; Tillotson, Richard D [Moore, ID; Bartsch, Richard A [Lubbock, TX; Moyer, Bruce A [Oak Ridge, TN; Delmau, Laetitia H [Oak Ridge, TN; Bonnesen, Peter V [Knoxville, TN

2012-04-17

A mixed extractant solvent that includes at least one dialkyloxycalix[4]arenebenzocrown-6 compound, 4',4',(5')-di-(t-butyldicyclohexano)-18-crown-6, at least one modifier, and, optionally, a diluent. The dialkyloxycalix[4]arenebenzocrown-6 compound is 1,3-alternate-25,27-di(octyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(decyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(dodecyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(2-ethylhexyl-1-oxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(3,7-dimethyloctyl-1-oxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(4-butyloctyl-1-oxy)calix[4]arenebenzocrown-6, or combinations thereof. The modifier is a primary alcohol. A method of separating cesium and strontium from an aqueous feed is also disclosed, as are dialkyloxycalix[4]arenebenzocrown-6 compounds and an alcohol modifier.

Disability Benefit Generosity and Labor Force Withdrawal*

PubMed Central

Mullen, Kathleen J.; Staubli, Stefan

2016-01-01

A key component for estimating the optimal size and structure of disability insurance (DI) programs is the elasticity of DI claiming with respect to benefit generosity. Yet, in many countries, including the United States, all workers face identical benefit schedules, which are a function of one’s labor market history, making it difficult to separate the effect of the benefit level from the effect of unobserved preferences for work on individuals’ claiming decisions. To circumvent this problem, we exploit exogenous variation in DI benefits in Austria arising from several reforms to its DI and old age pension system in the 1990s and 2000s. We use comprehensive administrative social security records data on the universe of Austrian workers to compute benefit levels under six different regimes, allowing us to identify and precisely estimate the elasticity of DI claiming with respect to benefit generosity. We find that, over this time period, a one percent increase in potential DI benefits was associated with a 1.2 percent increase in DI claiming. PMID:28216797

Skeletal maturation evaluation using mandibular second molar calcification stages.

PubMed

Kumar, Sushil; Singla, Anu; Sharma, Rekha; Virdi, Mandeep S; Anupam, Anant; Mittal, Bindia

2012-05-01

To investigate (1) the relationships between the stages of mandibular second molar calcification and skeletal maturity; and (2) whether second molar calcification stages can be used as a reliable diagnostic tool to determine skeletal maturity. Samples were derived from panoramic radiographs and lateral cephalograms of 300 subjects (137 males and 163 females) with ages ranging from 9 to 18 years, and estimates of dental maturity (Demirjian Index [DI]) and skeletal maturity (cervical vertebrae maturation indicators [CVMI]) were made. A highly significant association (C*  =  0.854 for males and 0.866 for females) was found between DI and CVMI. DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). A highly significant association exists between DI and CVMI. Mandibular second molar DI stages are reliable indicators of skeletal maturity.

Delusional infestation with unusual pathogens: a report of three cases.

PubMed

Dewan, P; Miller, J; Musters, C; Taylor, R E; Bewley, A P

2011-10-01

Delusional infestation (DI) is a psychiatric disorder characterized by a fixed, false belief that the patient is infested with extracorporeal agents. It is known by several names, including the more commonly used term 'delusional parasitosis'. The psychiatric disease is responsible for the cutaneous pathology. About 90% of patients with DI seek help from dermatologists, and most reject psychiatric referral. Thus, effective management requires incorporation of psychiatric principles. We report three cases of DI with inanimate materials, and examine 'Morgellons' disease. We believe that patients with unusual presentations of DI are likely to be seen more commonly in the future. These patients appear to be a subgroup of DI, and may be even more difficult to treat than other patients with DI. © The Author(s). CED © 2011 British Association of Dermatologists.

Homologous interference mediated by defective interfering influenza virus derived from a temperature-sensitive mutant of influenza virus.

PubMed Central

Nayak, D P; Tobita, K; Janda, J M; Davis, A R; De, B K

1978-01-01

A temperature-sensitive group II mutant of influenza virus, ts-52, with a presumed defect in viral RNA synthesis, readily produced von Magnus-type defective interfering virus (DI virus) when passed serially (four times) at high multiplicity in MDBK cells. The defective virus (ts-52 DI virus) had a high hemagglutinin and a low infectivity titer, and strongly interfered with the replication of standard infectious viruses (both ts-52 and wild-type ts+) in co-infected cells. Progeny virus particles produced by co-infection of DI virus and infectious virus were also defective and also had low infectivity, high hemagglutinating activity, and a strong interfering property. Infectious viruses ts+ and ts-52 were indistinguishable from ts-52 DI viruses by sucrose velocity or density gradient analysis. Additionally, these viruses all possessed similar morphology. However, when the RNA of DI viruses was analyzed by use of polyacrylamide gels containing 6 M urea, there was a reduction in the amount of large RNA species (V1 to V4), and a number of new smaller RNA species (D1 to D6) with molecular weights ranging from 2.9 X 10(5) to 1.05 X 10(5) appeared. Since these smaller RNA species (D1 to D6) were absent in some clones of infectious viruses, but were consistently associated with DI viruses and increased during undiluted passages and during co-infection of ts-52 with DI virus, they appeared to be a characteristic of DI viruses. Additionally, the UV target size of interfering activity and infectivity of DI virus indicated that interfering activity was 40 times more resistant to UV irradiation than was infectivity, further implicating small RNA molecules in interference. Our data suggest that the loss of infectivity observed among DI viruses may be due to nonspecific loss of a viral RNA segment(s), and the interfering property of DI viruses may be due to interfering RNA segments (DIRNA, D1 to D6). ts-52 DI virus interfered with the replication of standard virus (ts+) at both permissive (34 degrees C) and nonpermissive temperatures. The infectivity of the progeny virus was reduced to 0.2% for ts+ and 0.05% for ts-52 virus without a reduction in hemagglutinin titer. Interference was dependent on the concentration of DI virus. A particle ratio of 1 between DI virus (0.001 PFU/cell) and infectious virus (1.0 PFU/cell) produced a maximal amount of interference. Infectious virus yield was reduced 99.9% without any reduction of the yield of DI viruses Interference was also dependent on the time of addition of DI virus. Interference was most effective within the first 3 h of infection by infectious virus, indicating interference with an early function during viral replication. Images PMID:702654

A minimalist biosensor: Quantitation of cyclic di-GMP using the conformational change of a riboswitch aptamer.

PubMed

Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C

2015-01-01

Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA.

How Financial Incentives Induce Disability Insurance Recipients to Return to Work.

PubMed

Kostol, Andreas Ravndal; Mogstad, Magne

2014-02-01

Using a local randomized experiment that arises from a sharp discontinuity in Disability Insurance (DI) policy in Norway, we provide transparent and credible identification of how financial incentives induce DI recipients to return to work. We find that many DI recipients have considerable capacity to work that can be effectively induced by providing financial work incentives. We further show that providing work incentives to DI recipients may both increase their disposable income and reduce program costs. Our findings also suggest that targeted policies may be the most effective in encouraging DI recipients to return to work.

Migration of cyclo-diBA from coatings into canned food: method of analysis, concentration determined in a survey and in silico hazard profiling.

PubMed

Biedermann, Sandra; Zurfluh, Michael; Grob, Koni; Vedani, Angelo; Brüschweiler, Beat J

2013-08-01

Cyclo-diBA, the cyclic product formed from bisphenol A and bisphenol A diglycidyl ether during production of epoxy resins, was measured in canned food using reversed phase HPLC with fluorescence detection. Half (9 of 17) of the samples of canned fish in oil collected in April 2010 contained cyclo-diBA with an average concentration of 1025 μg/kg and a maximum of 1980 μg/kg. In September 2012, cyclo-diBA was detectable (>25 μg/kg) in merely 13 from 44 such products; the average concentration in these was 807 μg/kg and the maximum now reached 2640 μg/kg. Fish in brine contained far less cyclo-diBA. The majority of the canned meat products contained cyclo-diBA at a mean concentration of 477 μg/kg and a maximum of 1050 μg/kg. All prepared meals, such as ravioli or soups, contained cyclo-diBA, with a mean at 287 μg/kg. In canned tomatoes, peas and other vegetables in water or fruits in syrup, no cyclo-diBA was detected (<25 μg/kg). Since no experimental toxicity data are available except for its cytotoxicity, an in silico hazard profiling was performed. Cyclo-diBA seems to be stable and of low reactivity. There is indication for considerable oral bioavailability and for the potential to accumulate in the human body. Cyclo-diBA can be metabolized into cyclic and acyclic compounds. Based on SAR assessment for cyclo-diBA and read-across from BADGE to linear cyclo-diBA metabolites, genotoxic effects are improbable. Specific binding of cyclo-diBA to nuclear receptors, such as ERβ, can be predicted, indicating a potential endocrine-disrupting potency. The limit by the EFSA guidelines of 50 μg/person/d for compounds shown not to be genotoxic as well as the TTC-based Cramer structural class III value of 90 μg/person/d could be exceeded several fold by high consumers of canned fish in oil with high brand loyalty. As a consequence, risk reduction measures were taken. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

PubMed

Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael

2014-12-04

Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

Developing educational competencies for dissemination and implementation research training programs: an exploratory analysis using card sorts.

PubMed

Padek, Margaret; Colditz, Graham; Dobbins, Maureen; Koscielniak, Nikolas; Proctor, Enola K; Sales, Anne E; Brownson, Ross C

2015-08-12

With demand increasing for dissemination and implementation (D&I) training programs in the USA and other countries, more structured, competency-based, and tested curricula are needed to guide training programs. There are many benefits to the use of competencies in practice-based education such as the establishment of rigorous standards as well as providing an additional metrics for development and growth. As the first aim of a D&I training grant, an exploratory study was conducted to establish a new set of D&I competencies to guide training in D&I research. Based upon existing D&I training literature, the leadership team compiled an initial list of competencies. The research team then engaged 16 additional colleagues in the area of D&I science to provide suggestions to the initial list. The competency list was then additionally narrowed to 43 unique competencies following feedback elicited from these D&I researchers. Three hundred additional D&I researchers were then invited via email to complete a card sort in which the list of competencies were sorted into three categories of experience levels. Participants had previous first-hand experience with D&I or knowledge translation training programs in the past. Participants reported their self-identified D&I expertise level as well as the country in which their home institution is located. A mean score was calculated for each competency based on their experience level categorization. From these mean scores, beginner-, intermediate-, and advanced-level tertiles were created for the competencies. The card sort request achieved a 41 % response rate (n = 124). The list of 43 competencies was organized into four broad domains and sorted based on their experience level score. Eleven competencies were classified into the "Beginner" category, 27 into "Intermediate," and 5 into "Advanced." Education and training developers can use this competency list to formalize future trainings in D&I research, create more evidence-informed curricula, and enable overall capacity building and accompanying metrics in the field of D&I training and research.

Adherence to a Mediterranean diet in Morocco and its correlates: cross-sectional analysis of a sample of the adult Moroccan population

PubMed Central

2012-01-01

Background Dietary habits in Morocco are changing and the causes are not well understood. This study aimed to analyse socio-demographic factors associated with adherence to the Mediterranean diet (MeDi) in a national random sample of the adult Moroccan population. Methods The data collected in this cross-sectional survey included socio-demographic factors and a food frequency questionnaire. MeDi adherence was assessed in 2214 individuals with complete dietary data. MeDi adherence was measured according to a simplified MeDi score based on the weekly frequency of intake of eight food groups (vegetables, legumes, fruits, cereal or potatoes, fish, red meat, dairy products and olive oil) with the use of the sex specific medians of the sample as cut-offs. A value of 0 or 1 was assigned to consumption of each component according to its presumed detrimental or beneficial effect on health. Logistic regression was used to estimate the association between MeDi adherence (low score 1-4 vs. high 5-8) and other factors. Results Mean age of the sample was 41.4 (standard deviation 15.3) years, 45.4% were men and 29.9% had a low MeDi adherence. Married subjects (adjusted odds ratio ORa=0.68, 95% CI 0.55-0.84) were less likely to have a low MeDi adherence compared to single, divorced or widowed persons. Persons from rural areas (ORa=1.46, 95% CI: 1.02-2.08), were more often low MeDi adherents compared to those from urban areas. Obese persons (ORa=1.56, 95% CI: 1.16-2.11) were more prone to low MeDi adherence than normal weight individuals. Conclusion MeDi is far from being a universal pattern in the Moroccan population. Intervention strategies should be implemented in target groups to maintain the traditional MeDi pattern considered as the original diet in Morocco. PMID:22578133

Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

PubMed

Miner, Kyle D; Kurtz, Donald M

2016-02-16

HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

The use of VA Disability Compensation and Social Security Disability Insurance among working-aged veterans.

PubMed

Wilmoth, Janet M; London, Andrew S; Heflin, Colleen M

2015-07-01

Although there is substantial disability among veterans, relatively little is known about working-aged veterans' uptake of Department of Veterans Affairs (VA) Disability Compensation and Social Security Disability Insurance (DI). This study identifies levels of veteran participation in VA disability and/or DI benefit programs, examines transitions into and out of VA and DI programs among veterans, and estimates the size and composition of the veteran population receiving VA and/or DI benefits over time. Data from the 1992, 1993, 1996, 2001, 2004, and 2008 Survey of Income and Program Participation (SIPP) are used to describe VA and DI program participation among veterans under the age of 65. The majority of working-aged veterans do not receive VA or DI benefits and joint participation is low, but use of these programs has increased over time. A higher percentage of veterans receive VA compensation, which ranges from 4.9% in 1992 to 13.2% in 2008, than DI compensation, which ranges from 2.9% in 1992 to 6.7% in 2008. The rate of joint participation ranges from less than 1% in 1992 to 3.6% in 2008. Veterans experience few transitions between VA and DI programs during the 36-48 months they are observed. The number of veterans receiving benefits from VA and/or DI nearly doubled between 1992 and 2008. There have been substantial shifts in the composition of veterans using these programs, as cohorts who served prior to 1964 are replaced by those who served after 1964. The findings suggest potential gaps in veterans' access to disability programs that might be addressed through improved coordination of VA and DI benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic variation and potential coinfection of Wolbachia among widespread Asian citrus psyllid (Diaphorina citri Kuwayama) populations.

PubMed

Chu, Chia-Ching; Hoffmann, Mark; Braswell, W Evan; Pelz-Stelinski, Kirsten S

2017-12-29

Wolbachia can profoundly influence the survival, reproduction, and defenses of insect hosts. These interactions could potentially be harnessed for managing pests or insect-transmitted diseases. Diaphorina citri Kuwayama is a phloem-feeding pest capable of transmitting the putative causal agent of citrus greening, Candidatus Liberibacter asiaticus (CLas). Like many insects, D. citri is also infected with Wolbachia (wDi). Recent studies indicate that the relative abundance of wDi could be associated with the abundance of CLas, and that wDi may contribute to regulating expression of phage lytic cycle genes in CLas, suggesting the need for better understanding of wDi biology in general. This study investigated the genetic diversity of wDi among D. citri in populations spanning eleven countries and two U.S. territories. Six Wolbachia genes, wsp, coxA, fbpA, ftsZ, gatB, and hcpA, were sequenced and compared across samples. Two prevalent wDi strains were identified across the samples, and screening of clone libraries revealed possible coinfection of wDi strains in specific populations. D. citri mitochondrial cytochrome oxidase subunit I gene (mtCOI) were more divergent between D. citri populations that were infected with different wDi strains or had different infection statuses (single infection vs. coinfection). While we could not eliminate the possibility that maternal transmission may contribute to such patterns, it is also possible that wDi may induce cytoplasmic incompatibility in their host. These findings should contribute to the understanding of wDi population ecology, which may facilitate manipulation of this endosymbiont for management of citrus greening disease worldwide. © 2017 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.

Primary treatment regimen and diabetes insipidus as predictors of health outcomes in adults with childhood-onset craniopharyngioma.

PubMed

Yuen, Kevin C J; Kołtowska-Häggström, Maria; Cook, David M; Fox, Janet L; Jönsson, Peter J; Geffner, Mitchell E; Abs, Roger

2014-04-01

Craniopharyngiomas are often associated with significant morbidity due to their location and treatment effects. Little is known of the effects of primary treatment regimen and diabetes insipidus (DI), a clinical surrogate of hypothalamic obesity, on health outcomes in adults with childhood-onset craniopharyngioma (COCP). The objective of the study was to examine health outcomes of adults with COCP based on primary treatment regimens and the presence of DI. This study included a retrospective KIMS (Pfizer International Metabolic Database) data analysis of 180 adults with COCP according to the primary treatment regimen [one surgery (1Surg) vs complex treatment regimen (CTrR) of more than 1Surg and/or radiotherapy] and the presence of DI. The majority of COCP patients underwent transcranial surgery (77%) without receiving radiotherapy (84%). Compared with the 1Surg group, more CTrR patients developed visual field defects and ophthalmoplegia (all P < .01). Compared with patients without DI, those with DI had higher rates of anterior pituitary hormone deficits, body mass index, and fat mass (all P < .01). By contrast, fasting glucose, hemoglobin A1c, lipid panel, and quality of life were comparable among 1Surg vs CTrR patients, and patients with vs without DI. Regardless of primary treatment received, the presence of DI in either group was associated with higher rates of anterior pituitary hormone deficits and obesity. CTrR and DI predicted health outcomes differently. CTrR predisposed to the development of visual dysfunction, whereas DI was associated with higher rates of anterior pituitary dysfunction and weight gain. Higher body mass index and fat mass in patients with DI further implicate the role of hypothalamic damage as an important causal factor of obesity in these patients.

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

Riboswitches in eubacteria sense the second messenger c-di-AMP

PubMed Central

Nelson, James W.; Sudarsan, Narasimhan; Furukawa, Kazuhiro; Weinberg, Zasha; Wang, Joy X.; Breaker, Ronald R.

2013-01-01

Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial second messenger implicated in the control of cell wall metabolism, osmotic stress responses, and sporulation. However, the mechanisms by which c-di-AMP triggers these physiological responses have remained largely unknown. Intriguingly, a candidate riboswitch class called ydaO associates with numerous genes involved in these same processes. Although a representative ydaO motif RNA recently was reported to weakly bind ATP, we report that numerous members of this noncoding RNA class selectively respond to c-di-AMP with sub-nanomolar affinity. Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP. PMID:24141192

Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.

PubMed

Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang

2017-10-13

Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

European Upper Atmosphere Server DIAS - Final Conference/ Abstract

DTIC Science & Technology

2007-01-10

PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) INGV - Istituto Nazionale di Geofisica e Vulcanologia (Nat Instit Geophysics, Volcanology) Via di Vigna...organised by the Istituto Nazionale di Geofisica e Vulcanologia (INGV), Rome, Italy. D6.8 Report on the Final Conference - 3 - In general, the DIAS...the Istituto Nazionale di Geofisica e Vulcanologia in Rome focused on the general overview of scientific and technical tools adopted by the DIAS

Misura de Massa e Larghezza degli Stati $$x_1$$ e $$x_2$$ del Charmonio Formati in Interazioni $$p - \\bar{p}$$

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

Pallavicini, Marco

1995-01-01

Oggetto di questa tesi è la misura di alcune caratteristiche fisiche ( massa, larghezza, e larghezza parziale in p - p) degli stati 3 Pi e 3 A del charmonio, - overo del sistema legato di un quark "charm" e del suo antiquark-, nell'ambito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab (U.S.A).

Broad-Spectrum Protection against Tombusviruses Elicited by Defective Interfering RNAs in Transgenic Plants

PubMed Central

Rubio, Teresa; Borja, Marisé; Scholthof, Herman B.; Feldstein, Paul A.; Morris, T. Jack; Jackson, Andrew O.

1999-01-01

We have designed a DNA cassette to transcribe defective interfering (DI) RNAs of tomato bushy stunt virus (TBSV) and have investigated their potential to protect transgenic Nicotiana benthamiana plants from tombusvirus infections. To produce RNAs with authentic 5′ and 3′ termini identical to those of the native B10 DI RNA, the DI RNA sequences were flanked by ribozymes (RzDI). When RzDI RNAs transcribed in vitro were mixed with parental TBSV transcripts and inoculated into protoplasts or plants, they became amplified, reduced the accumulation of the parental RNA, and mediated attenuation of the lethal syndrome characteristic of TBSV infections. Analysis of F1 and F2 RzDI transformants indicated that uninfected plants expressed the DI RNAs in low abundance, but these RNAs were amplified to very high levels during TBSV infection. By two weeks postinoculation with TBSV, all untransformed N. benthamiana plants and transformed negative controls died. Although infection of transgenic RzDI plants initially induced moderate to severe symptoms, these plants subsequently recovered, flowered, and set seed. Plants from the same transgenic lines also exhibited broad-spectrum protection against related tombusviruses but remained susceptible to a distantly related tombus-like virus and to unrelated viruses. PMID:10233970

The behavioural effects of a novel substance P analogue following infusion into the ventral tegmental area or substantia nigra of rat brain.

PubMed

Eison, A S; Eison, M S; Iversen, S D

1982-04-22

The behavioural response following infusion of a novel, stable substance P (SP) analogue, DiMe-C7, into the ventral tegmental area (VTA) of rats was characterized and contrasted with the response to an equal dose of the parent compound SP. DiMe-C7 produced a longer-lasting behavioural stimulation than SP as evidenced in several behaviours, including locomotor activity, wet dog shakes, rearing and grooming. DiMe-C7-induced locomotor activity and rearing were potentiated by concurrent peripheral administration of D-amphetamine and blocked by pretreatment with haloperidol. Such responses to DiMe-C7 may thus be dependent upon dopaminergic activity. When given immediately following VTA infusion of DiMe-C7, morphine decreased, while naloxone had no effect upon most behavioural measures. The effect of methysergide on DiMe-C7 or SP into the substantia nigra reticulata produced a pattern of responses similar to nature to those produced by VTA infusion but different with respect to time course. These findings suggest that DiMe-C7 is a metabolically stable analogue of substance P which manifests prolonged actions on behaviour when centrally administered. Further, a role for central dopaminergic mechanisms is implicated in DiMe-C7-induced behavioural action.

Correlation between Maxillary Canine Calcification and Skeletal Maturation.

PubMed

Kumar, Sushil; Roy, Abhishek Singha; Garg, Ankit; Hamid, Saeed Bin; Tyagi, Sumit; Kumar, Atish

2017-05-01

Skeletal maturation assessment has a great role in many health professions especially in Orthodontics & Dentofacial Orthopedics. Functional appliances have proved to be more effective when used at the peak of mandibular growth, rather than before. The aim of this study was to evaluate whether the calcification stages of permanent maxillary canine are useful to assess skeletal maturity. In this cross-sectional study, samples were derived from panoramic radiographs and lateral cephalograms of 300 subjects (137 males and 163 females) with their age ranging from 9 to 18 years. Dental maturity {Demirjian Index (DI)} and skeletal maturity {Cervical Stages (CS)} were assessed from radiographs. The Pearson chi-square test (χ 2 ) and Sakoda adjusted Pearson contingency coefficient (C*) were calculated to determine the correlation between DI and CS. A highly significant association (C* = 0.851, p <.001for males and 0.879, p <.001 for females) was found between DI and CS. DI stage E coincided with CS2 (pre-peak of pubertal growth spurt) & DI stage F coincided with CS3 (peak of pubertal growth spurt) for all the subjects. DI stage H corresponded to CS5 and CS6 (end of peak of pubertal growth spurt). A highly significant association was found between DI and CS. Maxillary canine DI stages could be useful to assess skeletal maturity.

Synergistic Effect of Carbon Nanotubes and Graphene on Diopside Scaffolds.

PubMed

Liu, Tingting; Wu, Ping; Gao, Chengde; Feng, Pei; Xiao, Tao; Deng, Youwen; Shuai, Cijun; Peng, Shuping

2016-01-01

A synergetic effect between carbon nanotubes (CNTs) and graphene on diopside (Di) scaffolds was demonstrated. 3D network architecture in the matrix was formed through the 1D CNTs inlaid among the 2D graphene platelets (GNPs). The mechanical properties of the CNTs/GNPs/Di scaffolds were significantly improved compared with the CNTs/Di scaffolds and GNPs/Di scaffolds. In addition, the scaffolds exhibited excellent apatite-forming ability, a modest degradation rate, and stable mechanical properties in simulated body fluid (SBF). Moreover, cell culturing tests indicated that the scaffolds supported the cells attachment and proliferation. Taken together, the CNTs/GNPs/Di scaffolds offered great potential for bone tissue engineering.

The oxidation of 2,6-di-tert-butyl-4-methylphenol

USGS Publications Warehouse

Yohe, G.R.; Dunbar, J.E.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.

1956-01-01

The products formed in the oxidation of 2,6-di-tert-butyl-4-methylphenol with oxygen and sodium hydroxide at about 100?? are 3,5-di-tert-butyl-4-hydroxybenzaldehyde, trimethylacetic acid, an acidic compound C14H22O3, and probably 2,6-di-tert-butylbenzoquinone (which was actually isolated in the similar oxidation of the above-named benzaldehyde), in addition to compounds previously reported. Some of the properties of C14H22O3 are given, and the oxidation of it to 2,3-di-tert-butylsuccinic anhydride is described, but assignment of structure is reserved pending the completion of more experimental work.

IRIS (Integrity and Reliability in Integrated Circuits) Test Article Generation (ITAG)

DTIC Science & Technology

2015-03-31

67 M12 edram_di_19 O 111 B9 edram_addr_9 O 24 L1 edram_do_12 I 68 N14 edram_di_18 O 112 A9 edram_addr_8 O 25 K2 edram_do_11 I 69 M13 edram_di_17 O 113... M13 edram_di_17 O 113 A8 padVDD 2.5V 26 M1 edram_do_10 I 70 L12 edram_di_16 O 114 B8 padVSS GND 27 L2 edram_do_9 I 71 M14 padVDD 2.5V 115 C8

Dissemination and Implementation Research for Occupational Safety and Health.

PubMed

Dugan, Alicia G; Punnett, Laura

2017-12-01

The translation of evidence-based health innovations into real-world practice is both incomplete and exceedingly slow. This represents a poor return on research investment dollars for the general public. U.S. funders of health sciences research (e.g., NIH, CDC, NIOSH) are increasingly calling for dissemination plans, and to a lesser extent for dissemination and implementation (D&I) research, which are studies that examine the effectiveness of D&I efforts and strategies and the predictors of D&I success. For example, rather than merely broadcasting information about a preventable hazard, D&I research in occupational safety and health (OSH) might examine how employers or practitioners are most likely to receive and act upon that information. We propose here that D&I research should be seen as a dedicated and necessary area of study within OSH, as a way to generate new knowledge that can bridge the research-to-practice gap. We present D&I concepts, frameworks, and examples that can increase the capacity of OSH professionals to conduct D&I research and accelerate the translation of research findings into meaningful everyday practice to improve worker safety and health.

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

PubMed

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

2018-01-01

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

PREFACE: Fourth Meeting on Constrained Dynamics and Quantum Gravity

NASA Astrophysics Data System (ADS)

Cadoni, Mariano; Cavaglia, Marco; Nelson, Jeanette E.

2006-04-01

The formulation of a quantum theory of gravity seems to be the unavoidable endpoint of modern theoretical physics. Yet the quantum description of the gravitational field remains elusive. The year 2005 marks the tenth anniversary of the First Meeting on Constrained Dynamics and Quantum Gravity, held in Dubna (Russia) due to the efforts of Alexandre T. Filippov (JINR, Dubna) and Vittorio de Alfaro (University of Torino, Italy). At the heart of this initiative was the desire for an international forum where the status and perspectives of research in quantum gravity could be discussed from the broader viewpoint of modern gauge field theories. Since the Dubna meeting, an increasing number of scientists has joined this quest. Progress was reported in two other conferences in this series: in Santa Margherita Ligure (Italy) in 1996 and in Villasimius (Sardinia, Italy) in 1999. After a few years of ``working silence'' the time was now mature for a new gathering. The Fourth Meeting on Constrained Dynamics and Quantum Gravity (QG05) was held in Cala Gonone (Sardinia, Italy) from Monday 12th to Friday 16th September 2005. Surrounded by beautiful scenery, 100 scientists from 23 countries working in field theory, general relativity and related areas discussed the latest developments in the quantum treatment of gravitational systems. The QG05 edition covered many of the issues that had been addressed in the previous meetings and new interesting developments in the field, such as brane world models, large extra dimensions, analogue models of gravity, non-commutative techniques etc. The format of the meeting was similar to the previous ones. The programme consisted of invited plenary talks and parallel sessions on cosmology, quantum gravity, strings and phenomenology, gauge theories and quantisation and black holes. A major goal was to bring together senior scientists and younger people at the beginning of their scientific career. We were able to give financial support to both groups. In particular, help was provided to students and scientists from non-EU countries. It is our great pleasure to thank those people and institutions whose help and support was crucial to the success of the meeting. We appreciate the enthusiastic support of our colleagues of the academic community, especially those from the Istituto Nazionale di Fisica Nucleare and the Universities of Cagliari, Pisa, Torino and Mississippi. Financial support was provided by the Istituto Nazionale di Fisica Nucleare, the Universities of Cagliari, Torino, Pisa and Mississippi. This was used largely to support participants, especially younger people. Special thanks go to Pietro Menotti (University of Pisa) and Stefano Sciuto (University of Torino) for their friendship and their universities' financial contributions. It is also a pleasure to acknowledge financial support from the Regione Autonoma della Sardegna and from Tiscali, the communications and Internet company, for providing free telephone cards. Technical support and local organisation was provided by the Sezione di Cagliari of the Istituto Nazionale di Fisica Nucleare. Warmest thanks go to our administrative and technical staff - Maria Assunta Lecca and Simona Renieri, for their untiring assistance, and to Palmasera Village and Hotel Smeraldo for their splendid hospitality. And finally, our gratitude goes to all the participants and especially the many experienced scientists. Their contributions highlighted the meeting and were largely without support. The success of the meeting is due to them and to the enthusiasm of the younger participants. The Editors January 2006 COMMITTEES Organising Committee Mariano Cadoni (Università and INFN Cagliari) Marco Cavaglià (University of Mississippi) Jeanette E. Nelson (Università and INFN Torino) Advisory Committee Orfeu Bertolami (IST Lisboa, Portugal) Luca Bombelli (Univ. Mississippi) Steve Carlip (UC Davis, USA) Alessandro D'Adda (INFN Torino, Italy) Stanley Deser (Brandeis, USA) Georgi Dvali (NYU, USA) Sergio Ferrara (CERN) Gian Francesco Giudice (CERN) Roman Jackiw (MIT, USA) Edward W. Kolb (Fermilab, USA) Luca Lusanna (INFN Firenze, Italy) Roy Maartens (Univ. Portsmouth, UK) Hermann Nicolai (AEI, Potsdam, Germany) Tullio Regge (Politecnico di Torino, Italy) Augusto Sagnotti (Univ. Roma Tor Vergata, Italy) Kellogg S. Stelle (Imperial College London, UK) Ruth Williams (DAMTP, Cambridge, UK) SPONSORS Istituto Nazionale di Fisica Nucleare Università di Cagliari Università di Torino University of Mississippi Università di Pisa Regione autonoma della Sardegna Tiscali LIST OF PARTICIPANTS Eun-Joo Ahn (University of Chicago, USA) David Alba (Università di Firenze, Italy) Stanislav Alexeyev (Lomonosov Moscow State U., Russia) Damiano Anselmi (Università di Pisa, Italy) Ignatios Antoniadis (CERN, Geneva, Switzerland) Maria Da Conceicao Bento (Instituto Superior Técnico, Lisboa, Portugal) Orfeu Bertolami (Instituto Superior Técnico, Lisboa, Portugal) Massimo Bianchi (Università di Roma Tor Vergata, Italy) Mariam Bouhmadi-Lopez (University of Portsmouth, UK) Raphael Bousso (University of California at Berkeley, USA) Mariano Cadoni (Università di Cagliari, Italy) Steven Carlip (University of California at Davis, USA) Roberto Casadio (Università di Bologna, Italy) Marco Cavaglià (University of Mississippi, USA) Demian Cho (Raman Research Institute, Bangalore, India) Theodosios Christodoulakis (University of Athens, Greece) Chryssomalis Chryssomalakos (Inst. de Ciencias Nucleares - UNAM, Mexico) Diego Julio Cirilo-Lombardo (JINR, Dubna, Russia) Denis Comelli INFN, Sezione di Ferrara, Italy ) Ruben Cordero-Elizalde (Instituto Politecnico Nacional, Mexico) Lorenzo Cornalba (Università di Roma Tor Vergata, Italy) Branislav Cvetkovic (Institute of Physics, Belgrade, Serbia ) Maro Cvitan (University of Zagreb, Croatia) Alessandro D'Adda (Università di Torino, Italy) Claudio Dappiaggi (Università di Pavia, Italy) Roberto De Leo (Università di Cagliari, Italy) Roberto De Pietri (Università di Parma, Italy) Giuseppe De Risi (Università di Bari, Italy) Hans-Thomas Elze (Univ. Federal do Rio de Janeiro, Brasil) Alessandro Fabbri (Università di Bologna, Italy) Sergey Fadeev (VNIIMS, Moscow, Russia) Serena Fagnocchi (Università di Bologna, Italy) Sara Farese (Universidad de Valencia, Spain) Alessandra Feo (Università di Parma, Italy) Dario Francia (Università di Roma Tor Vergata, Italy) Francesco Fucito (Università di Roma Tor Vergata, Italy) Dmitri Fursaev (JINR, Dubna, Russia) Daniel Galehouse (University of Akron, Ohio, USA) Remo Garattini (Università di Bergamo, Italy) Florian Girelli (Perimeter Institute, Waterloo, Canada) Luca Griguolo (Università di Parma, Italy) Daniel Grumiller (Universität Leipzig, Germany) Shinichi Horata (Hayama Center of Advanced Research, Japan) Giorgio Immirzi (Università di Perugia, Italy) Roman Jackiw (MIT, Cambridge, USA) Matyas Karadi (DAMTP, University of Cambridge, UK) Mikhail Katanaev (Steklov Mathematical Institute, Moscow, Russia) Claus Kiefer (Universität Koln, Germany) John Klauder (University of Florida, Gainesville, USA) Pavel Klepac (Masaryk University, Brno, Czech Republic) Jen-Chi Lee (National Chiao-Tung University, Taiwan) Carlos Leiva (Universidad de Tarapacá, Arica, Chile) Stefano Liberati (SISSA/ISAS, Trieste, Italy) Jorma Louko (University of Nottingham, UK) Luca Lusanna (INFN, Sezione di Firenze, Italy) Roy Maartens (University of Portsmouth, UK) Fotini Markopoulou (Perimeter Institute, Waterloo, Canada) Annalisa Marzuoli (Università di Pavia, Italy) Evangelos Melas (QMW, University of London, UK) Maurizio Melis (Università di Cagliary, Italy) Vitaly Melnikov (VNIIMS, Moscow, Russia) Guillermo A. Mena Marugan (CSIC, Madrid, Spain) Pietro Menotti (Università di Pisa, Italy) Salvatore Mignemi (Università di Cagliari, Italy) Aleksandar Mikovic (Universidade Lusófona, Lisboa, Portugal) Leonardo Modesto (Université de la Mediterranée, Marseille, France) Michael Mueller (Sardinien.com, Cagliari, Italy) Mario Nadalini (Università di Trento, Italy) José Navarro-Salas (Universidad de Valencia, Spain) Jeanette E. Nelson (Università di Torino, Italy) Alexander Nesterov (Universidad de Guadalajara, Mexico) Hermann Nicolai (Albert-Einstein-Institut, Golm, Germany) Daniele Oriti (DAMTP, University of Cambridge, UK) Marcello Ortaggio (Charles University, Prague, Czech Republic) Silvio Pallua (University of Zagreb, Croatia) Matej Pavsic (Jozef Stefan Institute, Ljubljana, Slovenia) Wlodzimierz Piechocki (Soltan Inst. for Nuclear Studies, Warsaw, Poland) Nicola Pinamonti (Università di Trento, Italy) J. Brian Pitts (University of Notre Dame, Indiana, USA) Vojtech Pravda (Academy of Sciences, Praha, Czech Rep.) Gianpaolo Procopio (DAMTP, University of Cambridge, UK) Alice Rogers (King's College London, UK) Efrain Rojas (Universidad Veracruzana, Mexico) James Ryan (DAMTP, University of Cambridge, UK) Augusto Sagnotti (Università di Roma Tor Vergata, Italy) Wenceslao Santiago-German (University of California at Davis, USA) Stefano Sciuto (Università di Torino, Italy) Domenico Seminara (Università di Firenze, Italy) Lorenzo Sindoni (Università di Udine, Italy) Kellogg S. Stelle (Imperial College, London, UK) Cosimo Stornaiolo (INFN, Sezione di Napoli, Italy) Ward Struyve (Perimeter Institute, Waterloo, Canada) Makoto Tanabe (Waseda University, Tokyo, Japan) Daniel Terno (Perimeter Institute, Waterloo, Canada) Charles Wang (Lancaster University, UK) Silke Weinfurtner (Victoria University, Wellington, New Zealand) Hans Westman (Perimeter Institute, Waterloo, Canada) Ruth Williams (DAMTP, University of Cambridge, UK) Tetsuyuki Yukawa (Graduate U. for Adv. Studies, Kanagawa, Japan) Jorge Zanelli (CECS, Santiago, Chile)

Repeated deflation-inflation events at Kilauea Volcano, Hawai'i: What's up (and down) with that?

NASA Astrophysics Data System (ADS)

Poland, M. P.; Miklius, A.; Lundgren, P.; Sutton, A. J.

2011-12-01

Cyclic deflation-inflation ("DI") events are a common occurrence at Kilauea Volcano. Most DI events begin with deflation at the summit that generally lasts 12-72 hours and accumulate ~1-5 microradians of tilt as measured on the rim of Kilauea caldera, followed by inflation that is initially rapid but wanes as the net deformation approaches pre-event levels over the course of 12-48 hours. In rare cases, the initial deflation is followed by large-magnitude (~20 microradians) inflation over a few hours followed by hours to days of deflation to pre-event levels. Such DID events have only been recorded during 2000-2004. DI events are also manifested at the Pu'u 'O'o eruptive vent on Kilauea's east rift zone, about 15 km from the summit, and lag summit deformation by about 1-2 hours. For DI events with relatively large-magnitudes (i.e., several microradians) and long-durations (i.e., several days), deformation is manifested along the east rift zone between Pu'u 'O'o and the summit, and eruptive activity at Pu'u 'O'o is impacted with long periods of deflation and inflation associated with eruptive pauses and surges, respectively. During a period of increased magma transport between the summit and Pu'u 'O'o in 2005-2007, DI events recorded at the summit were not detected at Pu'u 'O'o. Since the March 2008 start of Kilauea's ongoing summit eruption, the number of DI events per year has increased from about 5-10 to about 50-60. The level of the summit lava column (continuously visible since early 2010), has generally tracked DI deformation. Surface deformation associated with DI events is measured by tilt, GPS, and InSAR. At the summit, preliminary source models suggest a depth of 1-2 km and a sill-like geometry beneath the center of the caldera, with volume loss and subsequent recovery on the order of tens of thousands of cubic meters with each DI cycle. The localized nature of the DI signal at Pu'u 'O'o argues for a shallow source that is probably less than 1 km deep. At least two mechanisms are consistent with the occurrence of DI events at Kilauea. First, blockage and subsequent clearing of the transport pathway that feeds the shallow summit magma system and conduit to Pu'u 'O'o could cause the observed deformation. A second possibility is that DI events represent convective overturns caused by replacement of degassed magma with gas-rich magma. Such a model is consistent with the increased number of DI events following the onset of Kilauea's summit eruption, when summit gas emissions increased by a factor of about 5, but there have been no changes in degassing rates during periods of frequent (i.e., daily) or rare (i.e., monthly) DI events during 2008-2011. The source of DI events therefore remains a target of continued study.

Mathematical Models of Smart Obstacles

DTIC Science & Technology

2006-10-01

Matematica “G. Castelnuovo” Università di Roma “La Sapienza”, Piazzale Aldo Moro 2 00185 Roma Italy Ph. N. +39-06-49913282, FAX N. +39-06...Dipartimento di Matematica G. Castelnuovo Università di Roma La Sapienza, Piazzale Aldo Moro 2 00185 Roma Italy 8. PERFORMING ORGANIZATION REPORT NUMBER 9... Matematica G. Castelnuovo Università di Roma “La Sapienza” 00185 Roma, Italy 2 Smart (or active) obstacles are obstacles that when illuminated by an

c-di-GMP can form remarkably stable G-quadruplexes at physiological conditions in the presence of some planar intercalators.

PubMed

Nakayama, Shizuka; Kelsey, Ilana; Wang, Jingxin; Sintim, Herman O

2011-04-28

The ubiquitous bacterial biofilm regulator, c-di-GMP can form G-quadruplexes at physiological conditions in the presence of some aromatic compounds, such as acriflavine and proflavine. The fluorescence of these compounds is quenched upon c-di-GMP binding and some of the formed c-di-GMP G-quadruplexes are stable even at 75 °C. © The Royal Society of Chemistry 2011

A C-di-GMP-proflavine-hemin supramolecular complex has peroxidase activity--implication for a simple colorimetric detection.

PubMed

Nakayama, Shizuka; Roelofs, Kevin; Lee, Vincent T; Sintim, Herman O

2012-03-01

Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) and hence provides simple colorimetric detection of c-di-GMP at low micromolar concentrations.

Hadfield holds bubble detectors for the RaDI-N Experiment in the Columbus Module

NASA Image and Video Library

2013-01-25

ISS034-E-034506 (25 Jan. 2013) --- Canadian Space Agency astronaut Chris Hadfield, Expedition 34 flight engineer, holds bubble detectors for the RaDI-N experiment in the International Space Station?s Kibo laboratory. RaDI-N measures neutron radiation levels onboard the space station. RaDI-N uses bubble detectors as neutron monitors which have been designed to only detect neutrons and ignore all other radiation.

Data Economics in Army Information Systems

DTIC Science & Technology

1989-03-01

CONTACTED: LtCol Robert DiBona Chief, Policy Plans and Integration Division (703) 664-3986 DATE: 17 January 1989 DISCUSSION: 1. The MITRE study group called...LtCol Robert DiBona on the recommendation of Mr. James Glymph of Data Management Directorate (DMD), Information Systems Engineering Command (ISEC...LtCol DiBona is in charge of the ISEC Standard Army Management Information System (STAMIS) Modernization (STAMOD) program. 2. LtCol DiBona did not know

Vasopressin Receptor Signaling and Cycling of Water Channels in Renal Epithelia (HBC)

DTIC Science & Technology

1993-08-27

in the cellular ultrastructure that results in mucosal membrane reorganization to numerous microvilli from the normal phase of microridges ( DiBona ...a restructuring of the apical membrane microridges into numerous microvilli with an increase in membrane surface area ( DiBona , 1981; DiBona et aL...markers in freeze-fracture studies of toad urinary bladder. J. Histochem. Cytochem., 35, 1405-1414. DiBona , D.R. 1981. Vasopressin action on the

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

Lin, Chun-Han; Su, Chia-Ying; Chen, Chung-Hui

Further reduction of the efficiency droop effect and further enhancements of internal quantum efficiency (IQE) and output intensity of a surface plasmon coupled, blue-emitting light-emitting diode (LED) by inserting a dielectric interlayer (DI) of a lower refractive index between p-GaN and surface Ag nanoparticles are demonstrated. The insertion of a DI leads to a blue shift of the localized surface plasmon (LSP) resonance spectrum and increases the LSP coupling strength at the quantum well emitting wavelength in the blue range. With SiO{sub 2} as the DI, a thinner DI leads to a stronger LSP coupling effect, when compared with themore » case of a thicker DI. By using GaZnO, which is a dielectric in the optical range and a good conductor under direct-current operation, as the DI, the LSP coupling results in the highest IQE, highest LED output intensity, and weakest droop effect.« less

Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5.

PubMed

Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin

2016-05-01

The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical diagnosis. Confirmatory factor analyses found a better fit against a DSM-5 model than a DSM-IV-TR model of ASD. Exploration of the content validity of the 3Di-sv for the DSM-5 revealed some construct underrepresentation, therefore we obtained data from a panel of 3Di-trained clinicians from ASD-specialized centers to recommend items to fill these gaps. Taken together, the 3Di-sv provides a solid basis to create a similar instrument suitable for DSM-5. Concrete recommendations are provided to improve DSM-5 compatibility.

Workplace injuries and the take-up of Social Security disability benefits.

PubMed

O'Leary, Paul; Boden, Leslie I; Seabury, Seth A; Ozonoff, Al; Scherer, Ethan

2012-01-01

Workplace injuries and illnesses are an important cause of disability. State workers' compensation programs provide almost $60 billion per year in cash and medical-care benefits for those injuries and illnesses. Social Security Disability Insurance (DI) is the largest disability insurance program in the United States, with annual cash payments to disabled workers of $95 billion in 2008. Because injured workers may also receive DI benefits, it is important to understand how those two systems interact to provide benefits. This article uses matched state workers' compensation and Social Security data to study the relationship between workplace injuries and illnesses and DI benefit receipt. We find that having a lost-time injury substantially increases the probability of DI receipt, and, for people who become DI beneficiaries, those with injuries receive DI benefits at younger ages. This relationship remains robust even after we account for important personal and work characteristics.

Rigid 2',4'-difluororibonucleosides: synthesis, conformational analysis, and incorporation into nascent RNA by HCV polymerase.

PubMed

Martínez-Montero, Saúl; Deleavey, Glen F; Kulkarni, Anupriya; Martín-Pintado, Nerea; Lindovska, Petra; Thomson, Michael; González, Carlos; Götte, Matthias; Damha, Masad J

2014-06-20

We report on the synthesis and conformational properties of 2'-deoxy-2',4'-difluorouridine (2',4'-diF-rU) and cytidine (2',4'-diF-rC) nucleosides. NMR analysis and quantum mechanical calculations show that the strong stereoelectronic effects induced by the two fluorines essentially "lock" the conformation of the sugar in the North region of the pseudorotational cycle. Our studies also demonstrate that NS5B HCV RNA polymerase was able to accommodate 2',4'-diF-rU 5'-triphosphate (2',4'-diF-rUTP) and to link the monophosphate to the RNA primer strand. 2',4'-diF-rUTP inhibited RNA synthesis in dinucleotide-primed reactions, although with relatively high half-maximal inhibitory concentrations (IC50 > 50 μM). 2',4'-diF-rU/C represents rare examples of "locked" ribonucleoside mimics that lack a bicyclic ring structure.

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

Claus, Claudia; Tzeng, W.-P.; Liebert, Uwe Gerd

During serial passaging of rubella virus (RUB) in cell culture, the dominant species of defective-interfering RNA (DI) generated contains an in-frame deletion between the capsid protein (C) gene and E1 glycoprotein gene resulting in production of a C-E1 fusion protein that is necessary for the maintenance of the DI [Tzeng, W.P., Frey, T.K. (2006). C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage. Virology 356 198-207.]. A BHK cell line stably expressing the RUB structural proteins was established which was used to package DIs into virus particles following transfection with in vitro transcripts from DI infectiousmore » cDNA constructs. Packaging of a DI encoding an in-frame C-GFP-E1 reporter fusion protein corresponding to the C-E1 fusion protein expressed in a native DI was only marginally more efficient than packaging of a DI encoding GFP, indicating that the C-E1 fusion protein did not function by enhancing packaging. However, infection with the DI encoding the C-GFP-E1 fusion protein (in the absence of wt RUB helper virus) resulted in formation of clusters of GFP-positive cells and the percentage of GFP-positive cells in the culture following infection remained relatively constant. In contrast, a DI encoding GFP did not form GFP-positive clusters and the percentage of GFP-positive cells declined by roughly half from 2 to 4 days post-infection. Cluster formation and sustaining the percentage of infected (GFP-positive) cells required the C part of the fusion protein, including the downstream but not the upstream of two arginine clusters (both of which are associated with RNA binding and association with mitochondrial p32 protein) and the E1 part through the transmembrane sequence, but not the C-terminal cytoplasmic tail. Among a collection of mutant DI constructs, cluster formation and sustaining infected cell percentage correlated with maintenance during serial passage with wt RUB. We hypothesize that cluster formation and sustaining infected cell percentage increase the likelihood of co-infection by a DI and wt RUB during serial passage thus enhancing maintenance of the DI. Cluster formation and sustaining infected cell percentage were found to be due to a combination of attenuated cytopathogenicity of DIs that express the C-E1 fusion protein and cell-to-cell movement of the DI. In infected cells, the C-GFP-E1 fusion protein was localized to potentially novel vesicular structures that appear to originate from ER-Golgi transport vacuoles. This species of DI expressing a C-E1 fusion protein that exhibits attenuated cytopathogenicity and the ability to increase the number of infected cells through cell-to-cell movement could be the basis for development of an attractive vaccine vector.« less

Fate of four phthalate plasticizers under various wastewater treatment processes.

PubMed

Armstrong, Dana L; Rice, Clifford P; Ramirez, Mark; Torrents, Alba

2018-05-18

The fate of four phthalate plasticizers during wastewater treatment processes at six different wastewater treatment plants (WWTPs) was investigated. Concentrations of benzyl butyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP) were determined prior to either aerobic or anaerobic (conventional and advanced) treatment, after treatment, and in final, dewatered solids. Despite their elevated use worldwide, the fate of DiNP and DiDP during wastewater treatment have not been well characterized. DEHP was readily degraded during aerobic treatments while anaerobic digestion resulted in either no significant change in concentrations or an increase in concentration, in the case of more advanced anaerobic processes (thermal hydrolysis pretreatment and a two-phase acid/gas process). Impacts of the various treatment systems on DiNP, DiDP, and BBP concentrations were more varied - anaerobic digestion led to significant decreases, increases, or no significant change for these compounds, depending on the treatment facility, while aerobic treatment was generally effective at degrading the compounds. Additionally, thermal hydrolysis pretreatment of sludge prior to anaerobic digestion resulted in increases in DiNP, DiDP, and BBP concentrations. The predicted environmental concentrations for all four compounds in soils after a single biosolids application were calculated and the risk quotients for DEHP in soils were determined. The estimated toxicity risk for DEHP in soils treated with a single application of sludge from any of the six studied WWTPs is lower than the level of concern for acute and chronic risk, as defined by the US EPA.

Central diabetes insipidus: clinical profile and factors indicating organic etiology in children.

PubMed

Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

2008-06-01

To evaluate the profile of children with central diabetes insipidus (DI) and identify factors indicating organic etiology. Retrospective chart review. Tertiary referral hospital. Fifty-nine children with central DI (40 boys, 19 girls). Features of organic and idiopathic central DI were compared using students t test and chi square test. Odds ratio was calculated for factors indicating organic etiology. Diagnosis included post-operative central DI (13, 22%), central nervous system (CNS) malformations (5, 8.6% holoprosencephaly 4 and hydrocephalus 1), histiocytosis (11, 18.6%), CNS pathology (11, 18.6%; craniopharyngioma 3, empty sella 2, germinoma 2, neuro-tuberculosis 2, arachnoid cyst 1 and glioma 1) and idiopathic central DI (19, 32.2%). Children with organic central DI were diagnosed later (7.8+/- 3.1 years against 5.3+/-2.4 years, P=0.03) and had lower height standard deviation score (-2.7+/-1.0 versus -1.0+/- 1.0, P<0.001) compared to idiopathic group. A greater proportion of children with organic central DI had short stature (81.8% against 10.5%, P <0.001, odds ratio 38.25), neurological features (45.5% against 0%, p 0.009) and anterior pituitary hormone deficiency (81.8% against 5.3%, P<0.001, odds ratio 81) compared to idiopathic group. A combination of short stature and onset after five years of age led to discrimination of organic central DI from idiopathic group in all cases. Organic central DI should be suspected in children presenting after the age of five years with growth retardation and features of anterior pituitary deficiency.

Drug-induced lupus erythematosus.

PubMed

Marzano, A V; Tavecchio, S; Menicanti, C; Crosti, C

2014-06-01

Drug-induced lupus erythematosus (DI-LE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to drug exposure and resolves after withdrawal of the implicated drug. Similarly to idiopathic lupus, DI-LE can be divided into systemic LE, subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE) and cutaneous LE tumidus. DI-SCLE is the most frequent variant of drug-induced cutaneous LE and presents mainly with annular-polycyclic lesions; the clinical picture is often widespread, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are typically present, whereas antihistone antibodies are uncommonly found. We have recently addressed the question whether DI-SCLE differs significantly from its idiopathic counterpart by virtue of clinical features and, based on our findings, we have suggested that the frequent occurrence of malar rash and bullous, erythema multiforme-like and vasculitic manifestations can be regarded as the hallmark of DI-SCLE. In contrast, the histology is not a useful diagnostic criterion for DI-SCLE, considering that the typical pattern of lichenoid interface dermatitis is seen only in the early stage of disease and tissue eosinophilia does not represent a differentiating histopathological feature. DI-CCLE and DI-LE tumidus, albeit possibly misdiagnosed, are rarely observed and are characterized by classic discoid lesions and erythematous-oedematous plaques on sun exposed areas, respectively. Management of DI-LE is based on the discontinuation of the offending drug; topical and/or systemic corticosteroids and other immunomodulating/immunosuppressive agents should be reserved for resistant cases.

The Effect of Geometrical Isomerism of 3,5-Dicaffeoylquinic Acid on Its Binding Affinity to HIV-Integrase Enzyme: A Molecular Docking Study.

PubMed

Makola, Mpho M; Dubery, Ian A; Koorsen, Gerrit; Steenkamp, Paul A; Kabanda, Mwadham M; du Preez, Louis L; Madala, Ntakadzeni E

2016-01-01

A potent plant-derived HIV-1 inhibitor, 3,5-dicaffeoylquinic acid (diCQA), has been shown to undergo isomerisation upon UV exposure where the naturally occurring 3 trans ,5 trans -diCQA isomer gives rise to the 3 cis ,5 trans -diCQA, 3 trans ,5 cis -diCQA, and 3 cis ,5 cis -diCQA isomers. In this study, inhibition of HIV-1 INT by UV-induced isomers was investigated using molecular docking methods. Here, density functional theory (DFT) models were used for geometry optimization of the 3,5-diCQA isomers. The YASARA and Autodock VINA software packages were then used to determine the binding interactions between the HIV-1 INT catalytic domain and the 3,5-diCQA isomers and the Discovery Studio suite was used to visualise the interactions between the isomers and the protein. The geometrical isomers of 3,5-diCQA were all found to bind to the catalytic core domain of the INT enzyme. Moreover, the cis geometrical isomers were found to interact with the metal cofactor of HIV-1INT, a phenomenon which has been linked to antiviral potency. Furthermore, the 3 trans ,5 cis -diCQA isomer was also found to interact with both LYS156 and LYS159 which are important residues for viral DNA integration. The differences in binding modes of these naturally coexisting isomers may allow wider synergistic activity which may be beneficial in comparison to the activities of each individual isomer.

Prevalence of Diego blood group antigen and the antibody in three ethnic population groups in Klang valley of Malaysia.

PubMed

Wei, Cheong Tar; Al-Hassan, Faisal Muti; Naim, Norris; Knight, Aishah; Joshi, Sanmukh R

2013-01-01

Diego blood group antigen, Di(a), is very rare among Caucasians and Blacks, but relatively common among the South American Indians and Asians of Mongolian origin. The antibody to Di(a) is clinically significant to cause hemolytic disease in a new-born or hemolytic transfusion reaction. This study was designed to determine the prevalence of Di(a) antigen among the blood donors from the three major ethnic groups in Klang Valley of Malaysia as well as to find an incidence of an antibody of the Diego antigen, anti-Di(a), in a tertiary care hospital to ascertain the need to include Di(a+) red cells for an antibody screen cell panel. Serological tests were performed by column agglutination technique using commercial reagents and following instruction as per kit insert. Di(a) antigen was found with a frequency of 2.1% among the Malaysians donors in three ethnic groups viz, Malay, Chinese and Indian. It was present among 1.25% of 401 Malay, 4.01% of Chinese and 0.88% of 114 Indian origin donors. None of the 1442 patients, including 703 antenatal outpatients, had anti-Di(a) in serum. The prevalence of Di(a) antigen was found among the donors of all the three ethnic background with varying frequency. Inclusion of Di(a+) red cells in routine antibody screening program would certainly help in detection of this clinically significant antibody and to provide safe blood transfusion in the Klang Valley, though the incidence of antibody appears to be very low in the region.

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

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

Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp; Törnqvist, Margareta; Nishiyama, Naohiro

2014-03-15

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at differentmore » time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels. • diHOPrVal is considered a useful exposure and in vivo dose marker of G.« less

Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease.

PubMed

Marder, Karen; Gu, Yian; Eberly, Shirley; Tanner, Caroline M; Scarmeas, Nikolaos; Oakes, David; Shoulson, Ira

2013-11-01

Adherence to Mediterranean-type diet (MeDi) may delay onset of Alzheimer and Parkinson diseases. Whether adherence to MeDi affects time to phenoconversion in Huntington disease (HD), a highly penetrant, single-gene disorder, is unknown. To determine if MeDi modifies the time to clinical onset of HD (phenoconversion) in premanifest carriers participating in Prospective Huntington at Risk Observational Study (PHAROS), and to examine the effects of body mass index and caloric intake on time to phenoconversion. A prospective cohort study of 41 Huntington study group sites in the United States and Canada involving 1001 participants enrolled in PHAROS between July 1999 and January 2004 who were followed up every 9 months until 2010. A total of 211 participants aged 26 to 57 years had an expanded CAG repeat length (≥ 37). A semiquantitative food frequency questionnaire was administered 33 months after baseline. We calculated daily gram intake for dairy, meat, fruit, vegetables, legumes, cereals, fish, monounsaturated and saturated fatty acids, and alcohol and constructed MeDi scores (0-9); higher scores indicate higher adherence. Demographics, medical history, body mass index, and Unified Huntington's Disease Rating Scale (UHDRS) score were collected. Cox proportional hazards regression models to determine the association of MeDi and phenoconversion. RESULTS Age, sex, caloric intake, education status, and UHDRS motor scores did not differ among MeDi tertiles (0-3, 4-5, and 6-9). The highest body mass index was associated with the lowest adherence to MeDi. Thirty-one participants phenoconverted. In a model adjusted for age, CAG repeat length, and caloric intake, MeDi was not associated with phenoconversion (P for trend = 0.14 for tertile of MeDi, and P = .22 for continuous MeDi). When individual components of MeDi were analyzed, higher dairy consumption (hazard ratio, 2.36; 95% CI, 1.0-5.57; P = .05) and higher caloric intake (P = .04) were associated with risk of phenoconversion. MeDi was not associated with phenoconversion; however, higher consumption of dairy products had a 2-fold increased risk and may be a surrogate for lower urate levels (associated with faster progression in manifest HD). Studies of diet and energy expenditure in premanifest HD may provide data for interventions to modify specific components of diet that may delay the onset of HD.

Oxidation of 2,6-di-tert-butyl-4-methylphenol. The structure of C14H22O3

USGS Publications Warehouse

Yohe, G.R.; Dunbar, J.E.; Lansford, M.W.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.

1959-01-01

The acidic compound C14H22O3, previously reported without assignment of structure as an oxidation product of 2,6-di-tert-butyl-4-methylphenol, is now believed to be DL-trans-5,6-di-tert-butyl-2-hydroxy-1,4-diketo-2-cyclohexene (I). Chemical properties are described and infrared spectra are presented in support of this structure. This structure is of interest in relation to the problem of the existence of o-di-tert-alkylbenzene derivatives. The relatively easy racemization of optically active I suggests that its completely enolized form, 5,6-di-tert-butyl-1,2,4-trihydroxybenzene, is capable of transitory existence.

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome.

PubMed

Shefi, Shai; Raviv, Gil; Rienstein, Shlomit; Barkai, Gad; Aviram-Goldring, Ayala; Levron, Jacob

2009-07-01

To report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome. Case report. Academic referral center. A 32 year-old female affected by DiGeorge syndrome. History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization. Avoidance of pregnancy with embryo affected by DiGeorge syndrome. Termination of pregnancy with an affected embryo followed by fluorescence in-situ hybridization based preimplantation genetic diagnosis and delivery of healthy offspring. The combination of preimplantation genetic diagnosis with fluorescence in-situ hybridization is recommended to prevent pregnancies with DiGeorge syndrome affected embryos in properly selected patients.

Synergistic Effect of Carbon Nanotubes and Graphene on Diopside Scaffolds

PubMed Central

Liu, Tingting; Wu, Ping; Gao, Chengde; Feng, Pei; Xiao, Tao; Deng, Youwen; Shuai, Cijun; Peng, Shuping

2016-01-01

A synergetic effect between carbon nanotubes (CNTs) and graphene on diopside (Di) scaffolds was demonstrated. 3D network architecture in the matrix was formed through the 1D CNTs inlaid among the 2D graphene platelets (GNPs). The mechanical properties of the CNTs/GNPs/Di scaffolds were significantly improved compared with the CNTs/Di scaffolds and GNPs/Di scaffolds. In addition, the scaffolds exhibited excellent apatite-forming ability, a modest degradation rate, and stable mechanical properties in simulated body fluid (SBF). Moreover, cell culturing tests indicated that the scaffolds supported the cells attachment and proliferation. Taken together, the CNTs/GNPs/Di scaffolds offered great potential for bone tissue engineering. PMID:27144173

Pitfall in the Diagnosis of Diabetes Insipidus and Pregnancy

PubMed Central

Fleischer, Jessica B.; Khandji, Alexander G.; Wardlaw, Sharon L.

2017-01-01

Diabetes insipidus (DI) during pregnancy and the perinatal period is an uncommon medical problem characterized by polyuria and excessive thirst. Diagnosis of DI may be overlooked in the setting of pregnancy, a time when increased water intake and urine output are commonly reported. We report two cases: one of transient DI in a young woman during her third trimester of twin pregnancy in association with acute fatty liver and hypertension and one of postpartum DI secondary to Sheehan syndrome from rupture of a splenic artery aneurysm. These cases illustrate the spectrum with which DI related to pregnancy and delivery can present and highlight the difficulty in making the diagnosis since the symptoms are often initially overlooked. PMID:28819576

Pedestrian Validation in Infrared Images by Means of Active Contours and Neural Networks

DTIC Science & Technology

2010-01-01

Research Article Pedestrian Validation in Infrared Images byMeans of Active Contours and Neural Networks Massimo Bertozzi,1 Pietro Cerri,1 Mirko Felisa,1...Stefano Ghidoni,2 andMichael Del Rose3 1VisLab, Dipartimento di Ingegneria dell’Informazione, Università di Parma, 43124 Parma, Italy 2 IAS-Lab...Dipartimento di Ingegneria dell’Informazione, Università di Padova, 35131 Padova, Italy 3Vetronics Research Center, U. S. Army TARDEC, MI 48397, USA

40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6...-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92-343 and P-92-344) are subject to...

40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry.

PubMed

Kato, Yoji; Dozaki, Natsuko; Nakamura, Toshiyuki; Kitamoto, Noritoshi; Yoshida, Akihiro; Naito, Michitaka; Kitamura, Masayasu; Osawa, Toshihiko

2009-01-01

The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 +/- 0.6 (DiY), 1.4 +/- 0.4 (NY), 3.8 +/- 0.3 (BrY), and 0.7 +/- 0.1 (DiBrY) micromol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and N(epsilon)-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people.

Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

PubMed

Otero-Lobato, María José; Kaats-Richters, Veronica E M; Havenith, Remco W A; Jenneskens, Leonardus W; Seinen, Willem

2004-11-14

To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

Structural Basis of Differential Ligand Recognition by Two Classes of bis-(3-5)-cyclic Dimeric Guanosine Monophosphate-binding Riboswitches

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

K Smith; C Shanahan; E Moore

2011-12-31

The bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA receptors in this pathway. We have solved the structure of a c-di-GMP-II riboswitch, which reveals that the ligand is bound as part of a triplex formed with a pseudoknot. The structure also shows that the guanine bases of c-di-GMP are recognized through noncanonical pairings and that the phosphodiester backbonemore » is not contacted by the RNA. Recognition is quite different from that observed in the c-di-GMP-I riboswitch, demonstrating that at least two independent solutions for RNA second messenger binding have evolved. We exploited these differences to design a c-di-GMP analog that selectively binds the c-di-GMP-II aptamer over the c-di-GMP-I RNA. There are several bacterial species that contain both types of riboswitches, and this approach holds promise as an important tool for targeting one riboswitch, and thus one gene, over another in a selective fashion.« less

DR2DI: a powerful computational tool for predicting novel drug-disease associations

NASA Astrophysics Data System (ADS)

Lu, Lu; Yu, Hua

2018-05-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

Biofilm Formation by the Acidophile Bacterium Acidithiobacillus thiooxidans Involves c-di-GMP Pathway and Pel exopolysaccharide.

PubMed

Díaz, Mauricio; Castro, Matias; Copaja, Sylvia; Guiliani, Nicolas

2018-02-21

Acidophile bacteria belonging to the Acidithiobacillus genus are pivotal players for the bioleaching of metallic values such as copper. Cell adherence to ores and biofilm formation, mediated by the production of extracellular polymeric substances, strongly favors bioleaching activity. In recent years, the second messenger cyclic diguanylate (c-di-GMP) has emerged as a central regulator for biofilm formation in bacteria. C-di-GMP pathways have been reported in different Acidithiobacillus species; however, c-di-GMP effectors and signal transduction networks are still largely uncharacterized in these extremophile species. Here we investigated Pel exopolysaccharide and its role in biofilm formation by sulfur-oxidizing species Acidithiobacillus thiooxidans . We identified 39 open reading frames (ORFs) encoding proteins involved in c-di-GMP metabolism and signal transduction, including the c-di-GMP effector protein PelD, a structural component of the biosynthesis apparatus for Pel exopolysaccharide production. We found that intracellular c-di-GMP concentrations and transcription levels of pel genes were higher in At . thiooxidans biofilm cells compared to planktonic ones. By developing an At . thiooxidans Δ pelD null-mutant strain we revealed that Pel exopolysaccharide is involved in biofilm structure and development. Further studies are still necessary to understand how Pel biosynthesis is regulated in Acidithiobacillus species, nevertheless these results represent the first characterization of a c-di-GMP effector protein involved in biofilm formation by acidophile species.

DR2DI: a powerful computational tool for predicting novel drug-disease associations

NASA Astrophysics Data System (ADS)

Lu, Lu; Yu, Hua

2018-04-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

PubMed Central

Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

1980-01-01

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition. PMID:7441565

Diabetes insipidus.

PubMed

Leroy, Clara; Karrouz, Wassila; Douillard, Claire; Do Cao, Christine; Cortet, Christine; Wémeau, Jean-Louis; Vantyghem, Marie-Christine

2013-12-01

Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of dehydration, bladder distention, pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome, granulomatosis and cancer is required. The diagnosis is based on biological assessment, pituitary magnetic resonance imaging (MRI) and results of a desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years, and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to hypopituitarism, including DI in 2% of cases. Transient or permanent DI is present in 8-9% of endoscopic transphenoidal surgeries. Current advances in DI concern the etiological work-up, with in particular the identification of IgG4-related hypophysitis or many genetic abnormalities, opening the field of targeted therapies in the years to come. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

In vitro biosynthesis of 17 alpha,20 alpha,20 beta-dihydroxy-4-pegnen-3-one by the ovaries, testes, and head kidneys of the Atlantic salmon Salmo salar

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

Sangalang, G.B.; Freeman, H.C.

Ovaries, testes, and head kidneys of sexually mature Atlantic salmon, Salmo salar, biosynthesized 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-diOHP) from equimolar amounts of (/sup 3/H)pregnenolone plus (4-/sup 14/C)progesterone in vitro. The /sup 3/H:/sup 14/C isotope ratios of steroid metabolites indicated that the biosynthetic pathways to 17 alpha,20 beta-diOHP in the testes differed from those observed in the ovaries and head kidneys. (4-/sup 14/C)progesterone appeared to be the principal precursor of 17 alpha,20 beta-diOHP in the testes, whereas both precursors were efficiently biotransformed to 17 alpha,20 beta-diOPH in the ovaries and head kidneys. 17 alpha-Hydroxy-4-pregnen-3-one (17 alpha-OHP) was the immediate precursormore » to 17 alpha,20 beta-diOHP in all tissues. However, appreciable amounts of 17 alpha,20 beta-diOHP accumulated in vitro in the testes only in the presence of exogenous (/sup 14/C)progesterone. Incubation of the testes, ovaries, and head kidneys with (/sup 14/C)pregnenolone resulted in high yields of 17 alpha,20 beta-diOHP in the ovaries and head kidneys but no detectable amounts of the steroid in the testes. The results confirm that progesterone is the favored precursor to 17 alpha,20 beta-diOHP in the testes. The results also suggest that the head kidneys may be an excellent cellular source of 17 alpha,20 beta-diOHP in both male and female. Atlantic salmon and may play an important role in the sexual maturation process in this fish. It is suggested that biosynthetic control mechanism affecting 17 alpha,20 beta-diOHP synthesis and/or spermiation and ovulation may differ in male and female Atlantic salmon.« less

Comparison of esophagogastric junction distensibility changes during POEM and Heller myotomy using intraoperative FLIP.

PubMed

Teitelbaum, Ezra N; Boris, Lubomyr; Arafat, Fahd O; Nicodème, Frédéric; Lin, Zhiyue; Kahrilas, Peter J; Pandolfino, John E; Soper, Nathaniel J; Hungness, Eric S

2013-12-01

Peroral endoscopic myotomy (POEM) is a novel endoscopic surgical procedure for the treatment of achalasia. The comparative effects of POEM and laparoscopic Heller myotomy (LHM) on esophagogastric junction (EGJ) physiology are unknown. A novel measurement catheter, the functional lumen imaging probe (FLIP), allows for intraoperative evaluation of EGJ compliance by measuring luminal geometry and pressure during volume-controlled distensions. Distensibility index (DI) (defined as the minimum cross-sectional area at the EGJ divided by pressure) was measured with FLIP intraoperatively in patients undergoing LHM and POEM. Separate measurements were taken after each operative step. During LHM, measurements were performed after: (1) induction of anesthesia, (2) insufflation of pneumoperitoneum, (3) hiatal dissection and esophageal mobilization, (4) myotomy, (5) partial fundoplication, and (6) deinsufflation. During POEM, they were performed after: (1) induction of anesthesia, (2) submucosal tunnel creation, and (3) myotomy. Eleven LHM and 14 POEM patients underwent intraoperative FLIP. Baseline DI was similar between groups. LHM resulted in an overall increase in mean DI (pre 1.4 vs. post 7.6 mm(2)/mmHg, using a 40-ml distension volume; p < 0.001). Insufflation of pneumoperitoneum and hiatal dissection did not affect DI. Myotomy caused an increase in DI. Partial fundoplication (6 Toupet, 5 Dor) caused a decrease in DI, and deinsufflation caused an increase in DI. POEM also resulted in an overall increase in mean DI (pre 1.4 vs. post 7.9 mm(2)/mmHg; p < 0.001). Measured individually, both submucosal tunnel creation and myotomy caused increases in DI. When overall changes were compared, there were no differences in the amount of DI increase between LHM and POEM. POEM and LHM result in a similar improvement in EGJ distensibility intraoperatively. Further study is needed to correlate intraoperative FLIP measurements with postoperative symptomatic and physiologic outcomes.

Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats.

PubMed

Demeter, Kornél; Török, Bibiána; Fodor, Anna; Varga, János; Ferenczi, Szilamér; Kovács, Krisztina J; Eszik, Ildikó; Szegedi, Viktor; Zelena, Dóra

2016-03-01

Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases. Copyright © 2015 Elsevier B.V. All rights reserved.

Active Sensing Air Pressure Using Differential Absorption Barometric Radar

NASA Astrophysics Data System (ADS)

Lin, B.

2016-12-01

Tropical storms and other severe weathers cause huge life losses and property damages and have major impacts on public safety and national security. Their observations and predictions need to be significantly improved. This effort tries to develop a feasible active microwave approach that measures surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at 50-55 GHz O2 absorption band in order to constrain assimilated dynamic fields of numerical weather Prediction (NWP) models close to actual conditions. Air pressure is the most important variable that drives atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Even over land there is no uniform coverage of surface air pressure measurements. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as 4mb ( 1mb) under all weather conditions. NASA Langley research team has made substantial progresses in advancing the DiBAR concept. The feasibility assessment clearly shows the potential of surface barometry using existing radar technologies. The team has also developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted laboratory, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. The precision and accuracy of radar surface pressure measurements are within the range of the theoretical analysis of the DiBAR concept. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will provide us an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.

Lipid Raft-Mediated Membrane Tethering and Delivery of Hydrophobic Cargos from Liquid Crystal-Based Nanocarriers.

PubMed

Nag, Okhil K; Naciri, Jawad; Oh, Eunkeu; Spillmann, Christopher M; Delehanty, James B

2016-04-20

A main goal of bionanotechnology and nanoparticle (NP)-mediated drug delivery (NMDD) continues to be the development of novel biomaterials that can controllably modulate the activity of the NP-associated therapeutic cargo. One of the desired subcellular locations for targeted delivery in NMDD is the plasma membrane. However, the controlled delivery of hydrophobic cargos to the membrane bilayer poses significant challenges including cargo precipitation and lack of specificity. Here, we employ a liquid crystal NP (LCNP)-based delivery system for the controlled partitioning of a model dye cargo from within the NP core into the plasma membrane bilayer. During synthesis of the NPs, the water-insoluble model dye cargo, 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), was efficiently incorporated into the hydrophobic LCNP core as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) facilitated the localization of the dye-loaded NPs to lipid raft microdomains in the plasma membrane in HEK 293T/17 cell. Analysis of DiO cellular internalization kinetics revealed that when delivered as a LCNP-PEG-Chol NP, the half-life of DiO membrane residence time (30 min) was twice that of free DiO (DiO(free)) (15 min) delivered from bulk solution. Time-resolved laser scanning confocal microscopy was employed to visualize the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer as confirmed by Förster resonance energy transfer (FRET) imaging. Finally, the delivery of DiO as a LCNP-PEG-Chol complex resulted in the attenuation of its cytotoxicity; the NP form of DiO exhibited ∼30-40% less toxicity compared to DiO(free). Our data demonstrate the utility of the LCNP platform as an efficient vehicle for the combined membrane-targeted delivery and physicochemical modulation of molecular cargos using lipid raft-mediated tethering.

PET imaging of Hsp90 expression in pancreatic cancer using a new 64Cu-labeled dimeric Sansalvamide A decapeptide.

PubMed

Wang, Xiaohui; Zhang, Jun; Wu, Hubing; Li, Yumin; Conti, Peter S; Chen, Kai

2018-04-24

Heat shock protein 90 (Hsp90) plays a vital role in the progress of malignant disease and elevated Hsp90 expression has been reported in pancreatic cancer. In this study, we radiolabeled a dimeric Sansalvamide A derivative (Di-San A1) with 64 Cu, and evaluated the feasibility of using 64 Cu-Di-San A1 for PET imaging of Hsp90 expression in a mouse model of pancreatic cancer. A macrocyclic chelator NOTA (1,4,7-triazacyclononane-1,4,7-trisacetic acid) was conjugated to Di-San A1. 64 Cu-Di-San A1 was successfully prepared in a radiochemical yield > 97% with a radiochemical purity > 98%. 64 Cu-Di-San A1 is stable in PBS and mouse serum with > 92% of parent probe intact after 4 h incubation. The cell binding and uptake revealed that 64 Cu-Di-San A1 binds to Hsp90-positive PL45 pancreatic cancer cells, and the binding can be effectively blocked by an Hsp90 inhibitor (17AAG). For microPET study, 64 Cu-Di-San A1 shows good in vivo performance in terms of tumor uptake in nude mice bearing PL45 tumors. The Hsp90-specific tumor activity accumulation of 64 Cu-Di-San A1 was further demonstrated by significant reduction of PL45 tumor uptake with a pre-injected blocking dose of 17AAG. The ex vivo PET imaging and biodistribution results were consistent with the quantitative analysis of PET imaging, demonstrating good tumor-to-muscle ratio (5.35 ± 0.46) of 64 Cu-Di-San A1 at 4 h post-injection in PL45 tumor mouse xenografts. 64 Cu-Di-San A1 allows PET imaging of Hsp90 expression in PL45 tumors, which may provide a non-invasive method to quantitatively characterize Hsp90 expression in pancreatic cancer.

Cloned Defective Interfering Influenza Virus Protects Ferrets from Pandemic 2009 Influenza A Virus and Allows Protective Immunity to Be Established

PubMed Central

Dimmock, Nigel J.; Taylor, Irene; Cheung, Linda; Hallis, Bassam; Marriott, Anthony C.; Carroll, Miles W.; Easton, Andrew J.

2012-01-01

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes. PMID:23251341

Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

PubMed Central

Chen, Li-Hong; Köseoğlu, Volkan K.; Güvener, Zehra T.; Myers-Morales, Tanya; Reed, Joseph M.; D'Orazio, Sarah E. F.; Miller, Kurt W.; Gomelsky, Mark

2014-01-01

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

Seismogenic structures of the 2006 ML4.0 Dangan Island earthquake offshore Hong Kong

NASA Astrophysics Data System (ADS)

Xia, Shaohong; Cao, Jinghe; Sun, Jinlong; Lv, Jinshui; Xu, Huilong; Zhang, Xiang; Wan, Kuiyuan; Fan, Chaoyan; Zhou, Pengxiang

2018-02-01

The northern margin of the South China Sea, as a typical extensional continental margin, has relatively strong intraplate seismicity. Compared with the active zones of Nanao Island, Yangjiang, and Heyuan, seismicity in the Pearl River Estuary is relatively low. However, a ML4.0 earthquake in 2006 occurred near Dangan Island (DI) offshore Hong Kong, and this site was adjacent to the source of the historical M5.8 earthquake in 1874. To reveal the seismogenic mechanism of intraplate earthquakes in DI, we systematically analyzed the structural characteristics in the source area of the 2006 DI earthquake using integrated 24-channel seismic profiles, onshore-offshore wide-angle seismic tomography, and natural earthquake parameters. We ascertained the locations of NW- and NE-trending faults in the DI sea and found that the NE-trending DI fault mainly dipped southeast at a high angle and cut through the crust with an obvious low-velocity anomaly. The NW-trending fault dipped southwest with a similar high angle. The 2006 DI earthquake was adjacent to the intersection of the NE- and NW-trending faults, which suggested that the intersection of the two faults with different strikes could provide a favorable condition for the generation and triggering of intraplate earthquakes. Crustal velocity model showed that the high-velocity anomaly was imaged in the west of DI, but a distinct entity with low-velocity anomaly in the upper crust and high-velocity anomaly in the lower crust was found in the south of DI. Both the 1874 and 2006 DI earthquakes occurred along the edge of the distinct entity. Two vertical cross-sections nearly perpendicular to the strikes of the intersecting faults revealed good spatial correlations between the 2006 DI earthquake and the low to high speed transition in the distinct entity. This result indicated that the transitional zone might be a weakly structural body that can store strain energy and release it as a brittle failure, resulting in an earthquake-prone area.

Mediterranean diet and Alzheimer disease mortality

PubMed Central

Scarmeas, Nikolaos; Luchsinger, Jose A.; Mayeux, Richard; Stern, Yaakov

2009-01-01

Background We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. Objectives To examine the association between MeDi and mortality in patients with AD. Methods A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. Results Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003). Conclusion Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect. PMID:17846408

List of Participants

NASA Astrophysics Data System (ADS)

2008-11-01

Mohab Abou ZeidInstitut des Hautes Études Scientifiques, Bures-sur-Yvette Ido AdamMax-Planck-Institut für Gravitationsphysik (AEI), Potsdam Henrik AdorfLeibniz Universität Hannover Mohammad Ali-AkbariIPM, Tehran Antonio Amariti Università di Milano-Bicocca Nicola Ambrosetti Université de Neuchâtel Martin Ammon Max-Planck-Institut für Physik, München Christopher AndreyÉcole Polytechnique Fédérale de Lausanne (EPFL) Laura AndrianopoliPolitecnico di Torino David AndriotLPTHE, Université UPMC Paris VI Carlo Angelantonj Università di Torino Pantelis ApostolopoulosUniversitat de les Illes Balears, Palma Gleb ArutyunovInstitute for Theoretical Physics, Utrecht University Davide AstolfiUniversità di Perugia Spyros AvramisUniversité de Neuchâtel Mirela BabalicChalmers University, Göteborg Foday BahDigicom Ioannis Bakas University of Patras Igor BandosUniversidad de Valencia Jose L F BarbonIFTE UAM/CSIC Madrid Till BargheerMax-Planck-Institut für Gravitationsphysik (AEI), Potsdam Marco Baumgartl Eidgenössische Technische Hochschule (ETH), Zürich James BedfordImperial College London Raphael BenichouLaboratoire de Physique Théorique, École Normale Supérieure, Paris Francesco Benini SISSA, Trieste Eric Bergshoeff Centre for Theoretical Physics, University of Groningen Alice BernamontiVrije Universiteit, Brussel Julia BernardLaboratoire de Physique Théorique, École Normale Supérieure, Paris Adel Bilal Laboratoire de Physique Théorique, École Normale Supérieure, Paris Marco Billo' Università di Torino Matthias Blau Université de Neuchâtel Guillaume BossardAlbert-Einstein-Institut, Golm Leonardo BriziÉcole Polytechnique Fédérale de Lausanne (EPFL) Johannes BroedelLeibniz Universität Hannover (AEI) Tom BrownQueen Mary, University of London Ilka BrunnerEidgenössische Technische Hochschule (ETH), Zürich Erling BrynjolfssonUniversity of Iceland Dmitri BykovSteklov Institute, Moscow and Trinity College, Dublin Joan CampsUniversitat de Barcelona Davide CassaniLaboratoire de Physique Théorique, École Normale Supérieure, Paris Alejandra CastroUniversity of Michigan Claudio Caviezel Max-Planck-Institut für Physik, München Alessio Celi Universitat de Barcelona Anna Ceresole Istituto Nazionale di Fisica Nucleare, Università di Torino Athanasios ChatzistavrakidisNational Technical University of Athens Wissam ChemissanyCentre for Theoretical Physics, University of Groningen Eugen-Mihaita CioroianuUniversity of Craiova Andres CollinucciTechnische Universität Wien Paul CookUniversità di Roma, Tor Vergata Lorenzo CornalbaUniversità di Milano-Bicocca Aldo CotroneKatholieke Universiteit Leuven Ben Craps Vrije Universiteit, Brussel Stefano Cremonesi SISSA, Trieste Riccardo D'AuriaPolitecnico di Torino Gianguido Dall'AgataUniversity of Padova Jose A de AzcarragaUniversidad de Valencia Jan de BoerInstituut voor Theoretische Fysica, Universiteit van Amsterdam Sophie de BuylInstitut des Hautes Études Scientifiques, Bures-sur-Yvette Marius de LeeuwUtrecht University Frederik De RooVrije Universiteit, Brussel Jan De Rydt Katholieke Universiteit Leuven and CERN, Geneva Bernard de WitInstitute for Theoretical Physics, Utrecht University Stephane DetournayIstituto Nazionale di Fisica Nucleare, Sezione di Milano Paolo Di Vecchia Niels Bohr Institute, København Eugen DiaconuUniversity of Craiova Vladimir Dobrev Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, Sofia Nick DoreyUniversity of Cambridge Hajar Ebrahim NajafabadiIPM, Tehran Federico Elmetti Università di Milano Oleg Evnin Vrije Universiteit, Brussel Francesco Fiamberti Università di Milano Davide Forcella SISSA, Trieste and CERN, Geneva Valentina Forini Humboldt-Universität zu Berlin Angelos Fotopoulos Università di Torino Denis Frank Université de Neuchâtel Marialuisa Frau Università di Torino Matthias Gaberdiel Eidgenössische Technische Hochschule (ETH), Zürich Diego Gallego SISSA/ISAS, Trieste Maria Pilar Garcia del MoralIstituto Nazionale di Fisica Nucleare, Università di Torino Valentina Giangreco Marotta PulettiUppsala University Valeria L GiliQueen Mary, University of London Luciano GirardelloUniversità di Milano-Bicocca Gian GiudiceCERN, Geneva Kevin Goldstein Institute for Theoretical Physics, Utrecht University Joaquim Gomis Universitat de Barcelona Pietro Antonio GrassiUniversità del Piemonte Orientale, Alessandria Viviane GraßLudwig-Maximilians-Universität, München Gianluca Grignani Università di Perugia Luca Griguolo Università di Parma Johannes GrosseJagiellonian University, Krakow Umut Gursoy École Polytechnique, Palaiseau Norberto Gutierrez RodriguezUniversity of Oviedo Babak HaghighatPhysikalisches Institut, Universität Bonn Troels Harmark Niels Bohr Institute, København Robert HaslhoferEidgenössische Technische Hochschule (ETH), Zürich Tae-Won HaPhysikalisches Institut, Universität Bonn Alexander HauptImperial College London and Max-Planck-Institut für Gravitationsphysik (AEI), Potsdam Marc HenneauxUniversité Libre de Bruxelles Johannes HennLAPTH, Annecy-le-Vieux Shinji HiranoNiels Bohr Institute, København Stefan HoheneggerEidgenössische Technische Hochschule (ETH), Zürich Jan HomannLudwig-Maximilians-Universität, München Gabriele Honecker CERN, Geneva Joost HoogeveenInstituut voor Theoretische Fysica, Universiteit van Amsterdam Mechthild HuebscherUniversidad Autónoma de Madrid Chris HullImperial College London Carmen-Liliana IonescuUniversity of Craiova Ella JasminUniversité Libre de Bruxelles Konstantin KanishchevInstitute of Theoretical Physics, University of Warsaw Stefanos Katmadas Utrecht University Alexandros KehagiasNational Technical University of Athens Christoph Keller Eidgenössische Technische Hochschule (ETH), Zürich Patrick Kerner Max-Planck-Institut für Physik, München Rebiai KhaledLaboratoire de Physique Mathématique et Physique Subatomique, Université Mentouri, Constantine Elias Kiritsis Centre de Physique Théorique, École Polytechnique, Palaiseau and University of Crete Denis KleversPhysikalisches Institut, Universität Bonn Paul Koerber Max-Planck-Institut für Physik, München Simon Koers Max-Planck-Institut für Physik, München Karl KollerLudwig-Maximilians-Universität, München Peter Koroteev Institute for Theoretical and Experimental Physics (ITEP), Moscow and Max-Planck-Institut für Gravitationsphysik (AEI), Potsdam Alexey KoshelevVrije Universiteit, Brussel Costas KounnasÉcole Normale Supérieure, Paris Daniel KreflCERN, Geneva Charlotte KristjansenNiels Bohr Institute, København Finn LarsenCERN, Geneva and University of Michigan Arnaud Le DiffonÉcole Normale Supérieure, Lyon Michael LennekCentre de Physique Théorique, École Polytechnique, Palaiseau Alberto Lerda Università del Piemonte Orientale, Alessandria Andreas LiberisUniversity of Patras Maria A Lledo Universidad de Valencia Oscar Loaiza-Brito CINVESTAV, Mexico Florian Loebbert Max-Planck-Institut für Gravitationsphysik (AEI), Potsdam Yolanda Lozano University of Oviedo Dieter Luest Ludwig-Maximilians-Universität, München Tomasz Łukowski Jagiellonian University, Krakow Diego Mansi University of Crete Alberto Mariotti Università di Milano-Bicocca Raffaele Marotta Istituto Nazionale di Fisica Nucleare, Napoli Alessio Marrani Istituto Nazionale di Fisica Nucleare and LNF, Firenze Andrea Mauri University of Crete Liuba Mazzanti École Polytechnique, Palaiseau Sean McReynoldsUniversità di Milano-Bicocca AKM Moinul Haque Meaze Chittagong University Patrick Meessen Instituto de Física Teórica, Universidad Autónoma de Madrid Carlo MeneghelliUniversità di Parma and Albert-Einstein-Institut, Golm Lotta Mether University of Helsinki and CERN, Geneva René Meyer Max-Planck-Institut für Physik, München Georgios MichalogiorgakisCenter de Physique Théorique, École Polytechnique, Palaiseau Giuseppe Milanesi Eidgenössische Technische Hochschule (ETH), Zürich Samuel Monnier Université de Genève Wolfgang MueckUniversità di Napoli Federico II Elena Méndez Escobar University of Edinburgh Iulian Negru University of Craiova Emil NissimovInstitute for Nuclear Research and Nuclear Energy, Sofia Teake NutmaCentre for Theoretical Physics, University of Groningen Niels Obers Niels Bohr Institute, København Olof Ohlsson SaxUppsala University Rodrigo OleaIstituto Nazionale di Fisica Nucleare, Sezione di Milano Domenico OrlandoUniversité de Neuchâtel Marta Orselli Niels Bohr Institute, København Tomas OrtinInstituto de Física Teórica, Universidad Autónoma de Madrid Yaron OzTel Aviv University Enrico PajerLudwig-Maximilians-Universität, München Angel Paredes GalanUtrecht University Sara PasquettiUniversité de Neuchâtel Silvia PenatiUniversità di Milano-Bicocca Jan PerzKatholieke Universiteit Leuven Igor PesandoUniversità di Torino Tassos PetkouUniversity of Crete Marios PetropoulosCenter de Physique Théorique, École Polytechnique, Palaiseau Franco PezzellaIstituto Nazionale di Fisica Nucleare, Sezione di Napoli Moises Picon PonceUniversity of Padova Marco PirroneUniversità di Milano-Bicocca Andrea PrinslooUniversity of Cape Town Joris RaeymaekersKatholieke Universiteit Leuven Alfonso RamalloUniversidade de Santiago de Compostela Carlo Alberto RattiUniversità di Milano-Bicocca Marco RauchPhysikalisches Institut, Universität Bonn Ronald Reid-EdwardsUniversity of Hamburg Patricia RitterUniversity of Edinburgh Peter RoenneDESY, Hamburg Jan RosseelUniversità di Torino Clement RuefService de Physique Théorique, CEA Saclay Felix RustMax-Planck-Institut für Physik, München Thomas RyttovNiels Bohr Institute, København and CERN, Geneva Agustin Sabio VeraCERN, Geneva Christian SaemannTrinity College, Dublin Houman Safaai SISSA, Trieste Henning SamtlebenÉcole Normale Supérieure, Lyon Alberto SantambrogioIstituto Nazionale di Fisica Nucleare, Sezione di Milano Silviu Constantin SararuUniversity of Craiova Ricardo SchiappaCERN, Geneva Ionut Romeo SchiopuChalmers University, Göteborg Cornelius Schmidt-ColinetEidgenössische Technische Hochschule (ETH), Zürich Johannes SchmudeSwansea University Waldemar SchulginLaboratoire de Physique Théorique, École Normale Supérieure, Paris Domenico SeminaraUniversità di Firenze Alexander SevrinVrije Universiteit, Brussel Konstadinos SfetsosUniversity of Patras Igor ShenderovichSt Petersburg State University Jonathan ShockUniversidade de Santiago de Compostela Massimo SianiUniversità di Milano-Bicocca Christoph SiegUniversità Degli Studi di Milano Joan SimonUniversity of Edinburgh Paul SmythUniversity of Hamburg Luca SommovigoUniversidad de Valencia Dmitri Sorokin Istituto Nazionale di Fisica Nucleare, Padova Christos SourdisUniversity of Patras Wieland StaessensVrije Universiteit, Brussel Ivan StefanovUniversity of Patras Sigurdur StefanssonUniversity of Iceland Kellogg Stelle Imperial College London Giovanni Tagliabue Università di Milano Laura Tamassia Katholieke Universiteit Leuven Javier TarrioUniversidade de Santiago de Compostela Dimitri TerrynVrije Universiteit, Brussel Larus Thorlacius University of Iceland Mario ToninDipartimento Di Fisica, Sezione Di Padova Mario Trigiante Politecnico di Torino Efstratios TsatisUniversity of Patras Arkady TseytlinImperial College London Pantelis TziveloglouCornell University, New York and CERN, Geneva Angel Uranga CERN, Geneva Dieter Van den Bleeken Katholieke Universiteit Leuven Ernst van Eijk Università di Napoli Federico II Antoine Van Proeyen Katholieke Universiteit Leuven Maaike van ZalkUtrecht University Pierre Vanhove Service de Physique Théorique, CEA Saclay Silvia Vaula Instituto de Física Teórica, Universidad Autónoma de Madrid Cristian Vergu Service de Physique Théorique, CEA Saclay Alessandro VichiÉcole Polytechnique Fédérale de Lausanne (EPFL) Marlene WeissCERN, Geneva and Eidgenössische Technische Hochschule (ETH), Zürich Sebastian Weiss Université de Neuchâtel Alexander WijnsUniversity of Iceland Linus WulffUniversity of Padova Thomas WyderKatholieke Universiteit Leuven Ahmed YoussefAstroParticule et Cosmologie (APC), Université Paris Diderot Daniela ZanonUniversità Degli Studi di Milano Andrea ZanziPhysikalisches Institut, Universität Bonn Andrey ZayakinInstitute for Theoretical and Experimental Physics (ITEP), Moscow Tobias ZinggUniversity of Iceland Dimitrios ZoakosUniversidade de Santiago de Compostela Emanuele ZorzanUniversità di Milano Konstantinos ZoubosNiels Bohr Institute, København

DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum.

PubMed

Saltman, Anna J; Barakat, May; Bryant, Donald M; Brodovskaya, Anastasia; Whited, Jessica L

2017-06-16

Perfusion techniques have been used for centuries to visualize the circulation of tissues. Axolotl (Ambystoma mexicanum) is a species of salamander that has emerged as an essential model for regeneration studies. Little is known about how revascularization occurs in the context of regeneration in these animals. Here we report a simple method for visualization of the vasculature in axolotl via perfusion of 1,1'-Dioctadecy-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). DiI is a lipophilic carbocyanine dye that inserts into the plasma membrane of endothelial cells instantaneously. Perfusion is done using a peristaltic pump such that DiI enters the circulation through the aorta. During perfusion, dye flows through the axolotl's blood vessels and incorporates into the lipid bilayer of vascular endothelial cells upon contact. The perfusion procedure takes approximately one hour for an eight-inch axolotl. Immediately after perfusion with DiI, the axolotl can be visualized with a confocal fluorescent microscope. The DiI emits light in the red-orange range when excited with a green fluorescent filter. This DiI perfusion procedure can be used to visualize the vascular structure of axolotls or to demonstrate patterns of revascularization in regenerating tissues.

Modulating Effects of Dicaffeoylquinic Acids from Ilex kudingcha on Intestinal Microecology in Vitro.

PubMed

Xie, Minhao; Chen, Guijie; Wan, Peng; Dai, Zhuqing; Hu, Bing; Chen, Ligen; Ou, Shiyi; Zeng, Xiaoxiong; Sun, Yi

2017-11-29

Dietary polyphenols have been considered as novel prebiotics, and polyphenols could exert their functions through modulating intestinal microbiota. The diverse bioactivities of kudingcha could derive from its phenolic compounds, but the effects of dicaffeoylquinic acids (diCQAs) from Ilex kudingcha on intestinal microbiota have not been investigated. In the present study, high-throughput sequencing and anaerobic fermentation in vitro were utilized to investigate the microecology-modulating function of I. kudingcha diCQAs. As a result, diCQAs raised the diversity and exhibited a more considerable impact than a carbon source on the microbial profile. DiCQAs increased the relative abundances of Alistipes, Bacteroides, Bifidobacterium, Butyricimonas, Clostridium sensu stricto, Escherichia/Shigella, Parasutterella, Romboutsia, Oscillibacter, Veillonella, Phascolarctobacterium, Lachnospiracea incertae sedis, Gemmiger, Streptococcus, and Haemophilus and decreased the relative abundances of Ruminococcus, Anaerostipes, Dialister, Megasphaera, Megamonas, and Prevotella. DiCQAs also affected the generation of short-chain fatty acids through microbiota. The contents of acetic and lactic acids were raised, while the production of propionic and butyric acids was reduced. Conclusively, diCQAs from I. kudingcha had significant modulating effects on intestinal microbiota in vitro, which might be the fundamental of diCQAs exerting their bioactivities.

Adaptation, reliability and validity testing of a Persian version of the Health Assessment Questionnaire-Disability Index in Iranian patients with rheumatoid arthritis.

PubMed

Nazary-Moghadam, Salman; Zeinalzadeh, Afsaneh; Salavati, Mahyar; Almasi, Simin; Negahban, Hossein

2017-01-01

The aim of the present study was to culturally adapt and evaluate reliability and validity of Health Assessment Questionnaire-Disability Index (HAQ-DI) in Iranian patients with rheumatoid arthritis (RA). 234 patients with RA for validation study, Eighty-six participants for reliability study. Test-retest relative reliability and internal consistency of Persian version of HAQ-DI were examined by intraclass correlation coefficient (ICC) and Cronbach's alpha, respectively. Additionally, HAQ-DI construct validity (Spearman's correlation) was examined using Persian version of Short-Form 36 Health survey (SF-36), activity and severity parameters. Persian version of HAQ-DI total score showed excellent test-retest reliability (ICC = 0.98) and internal consistency (Cronbach's alpha = 0.95). Spearman's correlations between the total PHAQ-DI score and activity and severity parameters were above 0.55. Correlation between PHAQ-DI and SF-36 Physical Health were higher as compared with SF-36 Mental Health. Persian version of HAQ-DI is a reliable and valid culturally-adapted instrument in order to measure functional limitations in Iranian people with RA. Copyright © 2016 Elsevier Ltd. All rights reserved.

The growth in applications for Social Security Disability Insurance: a spillover effect from workers' compensation.

PubMed

Guo, Xuguang; Burton, John F

2012-01-01

We investigate the determinants of application for Social Security Disability Insurance (DI) benefits in approximately 45 jurisdictions between 1981 and 1999. We reproduce findings of previous studies of the determinants of DI application then test the additional influence of changes to workers' compensation program benefits and rules on DI application rates. Our findings indicate that the programs are interrelated: When workers' compensation benefits declined and eligibility rules tightened in the 1990s, the DI application rate increased.

Information Resource Management in the DCSPLANS (Deputy Chief of Staff for Plans) Branch of the U.S. Army Military Personnel Center

DTIC Science & Technology

1986-11-15

Richard E. Broome [Broome 1985], Major Robert M. DiBona [ DiBona 1985], Major Robert A. Kirsch II [Kirsch 1985], and Major Alan F. Noel, Jr. [Noel 1985...Major Kirsch expanded this prototype to be compatible with the emerging Federal standards for dictionary systems. Major DiBona analyzed data validation...described in [Noel 1985, Kirsch 1985]. The implementation of edit validation rules in a dictionary environment is covered in [ DiBona 1985] and implementation

Monitoring Changes of Tropical Extreme Rainfall Events Using Differential Absorption Barometric Radar (DiBAR)

NASA Technical Reports Server (NTRS)

Lin, Bing; Harrah, Steven; Lawrence, R. Wes; Hu, Yongxiang; Min, Qilong

2015-01-01

This work studies the potential of monitoring changes in tropical extreme rainfall events such as tropical storms from space using a Differential-absorption BArometric Radar (DiBAR) operating at 50-55 gigahertz O2 absorption band to remotely measure sea surface air pressure. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 5 millibars (approximately 1 millibar) under all weather conditions. With these sea level pressure measurements, the forecasts, analyses and understanding of these extreme events in both short and long time scales can be improved. Severe weathers, especially hurricanes, are listed as one of core areas that need improved observations and predictions in WCRP (World Climate Research Program) and NASA Decadal Survey (DS) and have major impacts on public safety and national security through disaster mitigation. Since the development of the DiBAR concept about a decade ago, our team has made substantial progress in advancing the concept. Our feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. We have developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with our instrumentation goals. Observational system simulation experiments for space DiBAR performance show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on tropical extreme rainfall weather and climate conditions.

Cu@C nanoporous composites containing little copper oxides derived from dimethyl imidazole modified MOF199 as electrocatalysts for hydrogen evolution reaction

NASA Astrophysics Data System (ADS)

Wei, Xuedong; Li, Na; Zhang, Xianming

2017-12-01

It remains a huge challenge to develop non precious electrocatalysts with high activity to substitute commercial Pt catalysts for hydrogen evolution reactions (HER). Here, the C-Cu-DI and C-Cu materials with the copper based nanoporous carbon structures were synthesized by carbonizing MOF199 and DI-MOF199. The composite structure and HER electrocatalytic properties of the C-Cu-DI and C-Cu materials are studied. The results show that C-Cu-DI and C-Cu samples exhibit good catalytic activity. And C-Cu-DI sample through the addition of Dimethyl imidazole(DI) in the DI-MOF199 precursor has higher electrocatalytic activity than the C-Cu sample. The superior catalytic activity is attributed to the special composite structure of nanoscale deposition particles on the framework with plenty of nano pores and nano copper and few copper oxidation particles distributed or wrapped into the amorphous porous carbon phase. The nano copper and few copper oxidation particles in the C-Cu and C-Cu-DI catalysts maybe provide the more effective catalytic activity sites. The C-Cu-DI composite with large size spherical hollow deposition particles has higher conductivity, better BET surface area and reasonable micro-meso-macro porous distribution, so the overpotentials at the current density of 1 mA cm-2 and 10 mA cm-2 are respectively 270 mV and 390 mV vs. RHE. Although the HER activity has a big gap with commercial platinum catalyst, this study can provide an important experimental exploration for the design of copper based non noble metal/nano porous carbon composite HER electrocatalyst.

DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

PubMed Central

Scornik, Fabiana S.; Bucciero, Ronald S.; Wu, Yuesheng; Selga, Elisabet; Bosch Calero, Cristina; Brugada, Ramon

2013-01-01

The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK) channel activator with selectivity for its β1- or β4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming α-subunit and a smooth muscle-abundant regulatory β1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the β1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its α-subunit. We studied BK channels from wild-type and transgenic β1-knockout mice in excised patches. BK channels from brain arteries, with or without the β1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) (∼30 μM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as −300 mV. This “sweet spot” for persistent activation is independent of Ca2+ and/or the β1–4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. PMID:23542916

Cyclic di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions.

PubMed

Zeden, Merve S; Schuster, Christopher F; Bowman, Lisa; Zhong, Qiyun; Williams, Huw D; Gründling, Angelika

2018-03-02

Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such as Staphylococcus aureus However, the exact role of this molecule has not been identified. dacA , the S. aureus gene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that an S. aureus dacA mutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality of dacA were identified in alsT and opuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in S. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained in hepS, hemB, ctaA, and qoxB, coding proteins required for respiration. Furthermore, we show that dacA is dispensable for growth in anaerobic conditions. Together, these findings reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration in S. aureus . © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Imaging of Alkaline Phosphatase Activity in Bone Tissue

PubMed Central

Gade, Terence P.; Motley, Matthew W.; Beattie, Bradley J.; Bhakta, Roshni; Boskey, Adele L.; Koutcher, Jason A.; Mayer-Kuckuk, Philipp

2011-01-01

The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP) using a small imaging molecule in combination with 19Flourine magnetic resonance spectroscopic imaging (19FMRSI). 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP), a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using 19Fluorine magnetic resonance spectroscopy (19FMRS) and 19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. 19FMRS and 19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. 19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized 19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of 19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, 19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications. PMID:21799916

Within-prison drug injection among HIV-infected male prisoners in Indonesia: a highly constrained choice.

PubMed

Culbert, Gabriel J; Waluyo, Agung; Iriyanti, Mariska; Muchransyah, Azalia P; Kamarulzaman, Adeeba; Altice, Frederick L

2015-04-01

In Indonesia, incarceration of people who inject drugs (PWID) and access to drugs in prison potentiate within-prison drug injection (WP-DI), a preventable and extremely high-risk behavior that may contribute substantially to HIV transmission in prison and communities to which prisoners are released. This mixed method study examined the prevalence, correlates, and social context of WP-DI among HIV-infected male prisoners in Indonesia. 102 randomly selected HIV-infected male prisoners completed semi-structured voice-recorded interviews about drug use changes after arrest, drug use cues within prison, and impact of WP-DI on HIV and addiction treatment. Logistic regression identified multivariate correlates of WP-DI and thematic analysis of interview transcripts used grounded-theory. Over half (56%) of participants reported previous WP-DI. Of those, 93% shared injection equipment in prison, and 78.6% estimated sharing needles with ≥ 10 other prisoners. Multivariate analyses independently correlated WP-DI with being incarcerated for drug offenses (AOR = 3.29, 95%CI = 1.30-8.31, p = 0.011) and daily drug injection before arrest (AOR = 5.23, 95%CI = 1.42-19.25, p = 0.013). Drug availability and proximity to drug users while incarcerated were associated with frequent drug craving and escalating drug use risk behaviors after arrest. Energetic heroin marketing and stigmatizing attitudes toward methadone contribute to WP-DI and impede addiction and HIV treatment. Frequent WP-DI and needle sharing among these HIV-infected Indonesian prison inmates indicate the need for structural interventions that reduce overcrowding, drug supply, and needle sharing, and improve detection and treatment of substance use disorders upon incarceration to minimize WP-DI and associated harm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Relative amplitude of medium-scale traveling ionospheric disturbances as deduced from global GPS network

NASA Astrophysics Data System (ADS)

Voeykov, S. V.; Afraimovich, E. L.; Kosogorov, E. A.; Perevalova, N. P.; Zhivetiev, I. V.

We worked out a new method for estimation of relative amplitude dI I of total electron content TEC variations corresponding to medium-scale 30-300 km traveling ionospheric disturbances MS TIDs Daily and latitudinal dependences of dI I and dI I probability distributions are obtained for 52 days of 1999-2005 with different level of geomagnetic activity Statistical estimations were obtained for the analysis of 10 6 series of TEC with 2 3-hour duration To obtain statistically significant results three latitudinal regions were chosen North America high-latitudinal region 50-80 r N 200-300 r E 59 GPS receivers North America mid-latitudinal region 20-50 r N 200-300 r E 817 receivers equatorial belt -20 20 r N 0-360 r E 76 receivers We found that average daily value of the relative amplitude of TEC variations dI I changes from 0 3 to 10 proportionally to the value of geomagnetic index Kp This dependence is strong at high latitudes dI I 0 37 cdot Kp 1 5 and it is some weaker at mid latitudes dI I 0 2 cdot Kp 0 35 At the equator belt we found the weakest dependence dI I on the geomagnetic activity level dI I 0 1 cdot Kp 0 6 The most important and the most interesting result of our work is that during geomagnetic quiet conditions the relative amplitude of TEC variations at night considerably exceeds daily values by 3-5 times at equatorial and at high latitudes and by 2 times at mid latitudes But during strong magnetic storms the relative amplitude dI I at high

Defective interfering particles of poliovirus: mapping of the deletion and evidence that the deletions in the genomes of DI(1), (2), and (3) are located in the same region

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

Nomoto, A.; Jacobson, A.; Lee, Y.F.

1979-01-01

The deletions in RNAs of three defective interfering (DI) particles of poliovirus type 1 have been located and their approximate extent determined by three methods. (1) Digestion with RNase III of DI RNAs yields the same 3'-terminal fragments as digestion wth RNase III of standard virus RNA. The longest 3'-terminal located in the 5'-terminal half of the polio genome. (2) Fingerprints of RNase T/sub 1/-resistant oligonucleotides of all three DI RNAs are identical and lack four large oligonucleotides as compared to the fingerprints of standard virus, an observation suggesting that the deletions in all three DI RNAs are located inmore » the same reregion of the viral genome. The deletion-specific oligonucleotides have also been shown to be within the 5'-terminal half of the viral genome by alkali fragmentation of the RNA and fingerprinting poly(A)-linked (3'-terminal) fragments of decreasing size. (3) Virion RNA of DI(2) particles was annealed with denatured double-stranded RNA (RF) of standard virus and the hybrid heteroduplex molcules examined in the electron microscope. A single loop, approximately 900 nucleotides long and 20% from one end of the molecules, was observed. Both the size and extent of individual deletions is somewhat variable in different hetereoduplex molecules, an observation suggesting heterogeneity in the size of the deletion in RNA of the DI(2) population. Our data show that the DI RNAs of poliovirus contain an internal deletion in that region of the viral genome known to specify the capsid polypeptides. This result provides an explanation as to why poliovirus DI particles are unable to synthesize viral coat proteins.« less

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c

PubMed Central

Rotcheewaphan, Suwatchareeporn; Belisle, John T.; Webb, Kristofor J.; Kim, Hee-Jin; Spencer, John S.

2016-01-01

The second messenger, bis-(3′,5′)-cyclic dimeric guanosine monophosphate (cyclic di-GMP), is involved in the control of multiple bacterial phenotypes, including those that impact host–pathogen interactions. Bioinformatics analyses predicted that Mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. In contrast, the related pathogen Mycobacterium tuberculosis encodes only a single diguanylate cyclase. One of the M. leprae unique diguanylate cyclases (ML1419c) was previously shown to be produced early during the course of leprosy. Thus, functional analysis of ML1419c was performed. The gene encoding ML1419c was cloned and expressed in Pseudomonas aeruginosa PAO1 to allow for assessment of cyclic di-GMP production and cyclic di-GMP-mediated phenotypes. Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. Direct measurement of cyclic di-GMP levels by liquid chromatography–mass spectrometry confirmed that ml1419c expression increased cyclic di-GMP production in P. aeruginosa PAO1 cultures in comparison to the vector control. The observed phenotypes and increased levels of cyclic di-GMP detected in P. aeruginosa expressing ml1419c could be abrogated by mutation of the active site in ML1419c. These studies demonstrated that ML1419c of M. leprae functions as diguanylate cyclase to synthesize cyclic di-GMP. Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae. PMID:27450520

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c.

PubMed

Rotcheewaphan, Suwatchareeporn; Belisle, John T; Webb, Kristofor J; Kim, Hee-Jin; Spencer, John S; Borlee, Bradley R

2016-09-01

The second messenger, bis-(3',5')-cyclic dimeric guanosine monophosphate (cyclic di-GMP), is involved in the control of multiple bacterial phenotypes, including those that impact host-pathogen interactions. Bioinformatics analyses predicted that Mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. In contrast, the related pathogen Mycobacterium tuberculosis encodes only a single diguanylate cyclase. One of the M. leprae unique diguanylate cyclases (ML1419c) was previously shown to be produced early during the course of leprosy. Thus, functional analysis of ML1419c was performed. The gene encoding ML1419c was cloned and expressed in Pseudomonas aeruginosa PAO1 to allow for assessment of cyclic di-GMP production and cyclic di-GMP-mediated phenotypes. Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. Direct measurement of cyclic di-GMP levels by liquid chromatography-mass spectrometry confirmed that ml1419c expression increased cyclic di-GMP production in P. aeruginosa PAO1 cultures in comparison to the vector control. The observed phenotypes and increased levels of cyclic di-GMP detected in P. aeruginosa expressing ml1419c could be abrogated by mutation of the active site in ML1419c. These studies demonstrated that ML1419c of M. leprae functions as diguanylate cyclase to synthesize cyclic di-GMP. Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae.

Distress intolerance moderation of motivated attention to cannabis and negative stimuli after induced stress among cannabis users: an ERP study.

PubMed

Macatee, Richard J; Okey, Sarah A; Albanese, Brian J; Schmidt, Norman B; Cougle, Jesse R

2018-05-07

Prevalence of cannabis use is increasing, but many regular users do not develop cannabis use disorder (CUD); thus, CUD risk identification among current users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to tolerate negative affect, may be linked to CUD, but no studies have tested possible neurophysiological mechanisms. Increased motivated attentional processing of cannabis and negative emotional stimuli as indexed by neurophysiology [i.e. the late positive potential (LPP)], particularly during acute stress, may contribute to CUD among high DI users. Frequent cannabis users with high (n = 61) and low DI (n = 44) viewed cannabis, negative, and matched neutral images during electroencephalography (EEG) recording before and after a laboratory stressor. Cannabis cue-elicited modulation of the 1000- to 3000-milliseconds LPP was larger in high DI users at post-stressor only, although the effect was only robust in the 1000- to 2000-milliseconds window. Further, modulation magnitude in the high DI group covaried with stress-relief craving and some CUD indices in the 400- to 1000-milliseconds and 1000- to 3000-milliseconds windows, respectively. No significant effects of DI on negative stimuli-elicited LPP modulation were found, although inverse associations with some CUD indices were observed. Finally, exploratory analyses revealed some evidence for DI moderation of the relation between subjective stressor reactivity and negative stimuli-elicited LPP modulation such that greater stressor reactivity was associated with blunted versus enhanced modulation in the high and low DI groups, respectively. Negative and cannabis stimuli-elicited LPP modulation appear to index distinct, CUD-relevant neural processes in high DI cannabis users. © 2018 Society for the Study of Addiction.

Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella

PubMed Central

Solano, Cristina; García, Begoña; Latasa, Cristina; Toledo-Arana, Alejandro; Zorraquino, Violeta; Valle, Jaione; Casals, Joan; Pedroso, Enrique; Lasa, Iñigo

2009-01-01

Bacteria have developed an exclusive signal transduction system involving multiple diguanylate cyclase and phosphodiesterase domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) that modulate the levels of the same diffusible molecule, 3′-5′-cyclic diguanylic acid (c-di-GMP), to transmit signals and obtain specific cellular responses. Current knowledge about c-di-GMP signaling has been inferred mainly from the analysis of recombinant bacteria that either lack or overproduce individual members of the pathway, without addressing potential compensatory effects or interferences between them. Here, we dissected c-di-GMP signaling by constructing a Salmonella strain lacking all GGDEF-domain proteins and then producing derivatives, each restoring 1 protein. Our analysis showed that most GGDEF proteins are constitutively expressed and that their expression levels are not interdependent. Complete deletion of genes encoding GGDEF-domain proteins abrogated virulence, motility, long-term survival, and cellulose and fimbriae synthesis. Separate restoration revealed that 4 proteins from Salmonella and 1 from Yersinia pestis exclusively restored cellulose synthesis in a c-di-GMP–dependent manner, indicating that c-di-GMP produced by different GGDEF proteins can activate the same target. However, the restored strain containing the STM4551-encoding gene recovered all other phenotypes by means of gene expression modulation independently of c-di-GMP. Specifically, fimbriae synthesis and virulence were recovered through regulation of csgD and the plasmid-encoded spvAB mRNA levels, respectively. This study provides evidence that the regulation of the GGDEF-domain proteins network occurs at 2 levels: a level that strictly requires c-di-GMP to control enzymatic activities directly, restricted to cellulose synthesis in our experimental conditions, and another that involves gene regulation for which c-di-GMP synthesis can be dispensable. PMID:19416883

Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

DOE PAGES

Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; ...

2015-12-28

Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

Within-Prison Drug Injection among HIV-infected Male Prisoners in Indonesia: A Highly Constrained Choice

PubMed Central

Culbert, Gabriel J.; Waluyo, Agung; Iriyanti, Mariska; Muchransyah, Azalia P.; Kamarulzaman, Adeeba; Altice, Frederick L.

2016-01-01

Background In Indonesia, incarceration of people who inject drugs (PWID) and access to drugs in prison potentiate within-prison drug injection (WP-DI), a preventable and extremely high-risk behavior that may contribute substantially to HIV transmission in prison and communities to which prisoners are released. Aims This mixed method study examined the prevalence, correlates, and social context of WP-DI among HIV-infected male prisoners in Indonesia. Methods 102 randomly selected HIV-infected male prisoners completed semi-structured voice-recorded interviews about drug use changes after arrest, drug use cues within prison, and impact of WP-DI on HIV and addiction treatment. Logistic regression identified multivariate correlates of WP-DI and thematic analysis of interview transcripts used grounded-theory. Results Over half (56%) of participants reported previous WP-DI. Of those, 93% shared injection equipment in prison, and 78.6% estimated sharing needles with ≥10 other prisoners. Multivariate analyses independently correlated WP-DI with being incarcerated for drug offenses (AOR=3.29, 95%CI=1.30–8.31, p=0.011) and daily drug injection before arrest (AOR=5.23, 95%CI=1.42–19.25, p=0.013). Drug availability and proximity to drug users while incarcerated were associated with frequent drug craving and escalating drug use risk behaviors after arrest. Energetic heroin marketing and stigmatizing attitudes toward methadone contribute to WP-DI and impede addiction and HIV treatment. Conclusions Frequent WP-DI and needle sharing among these HIV-infected Indonesian prison inmates indicate the need for structural interventions that reduce overcrowding, drug supply, and needle sharing, and improve detection and treatment of substance use disorders upon incarceration to minimize WP-DI and associated harm. PMID:25659895

Standardization of transfusion practice in organ donors using the Digital Intern, an electronic decision support algorithm.

PubMed

Connor, Joseph P; Cunningham, Ashley M; Raife, Thomas; Rose, William N; Medow, Joshua E

2017-06-01

Prospective clinical trials support restrictive thresholds for red blood cell (RBC) transfusion. Nonsurvivable donors are a major source of organs for transplantation. The Digital Intern (DI) is a computer algorithm to standardize donor care that includes a more restrictive transfusion threshold. The impact of standardized and restrictive RBC transfusion in organ donors, as determined by the DI, has not been reported. We conducted a retrospective cohort study to compare the transfusion practice of the DI (n = 100) to a historic group of physician-managed donors (n = 90). Transfusion rates, the number of units transfused, and pretransfusion laboratory values were compared between groups. The variability of these parameters was also compared between groups. Finally, the number of transplanted organs per donor in each group was compared. The mean time as a donor was 25.9 ± 15.2 hours and was not different between the groups. In the DI group 19% were transfused compared to 26% in the control group (p = 0.3). The number of units transfused was less in the DI group (1 unit vs. 2 units per transfusion, p = 0.03) and the pretransfusion hematocrit was lower in the DI group (23% vs. 27%, p = 0.01). The variability in the latter two parameters was significantly lower in the DI group. The number of transplanted organs per donor was similar in both groups (3.24 [DI] vs. 3.03 [control], p = 0.37). The DI provides a more standardization transfusion practice in organ donors and reduces blood use without compromising transplantable organs. © 2017 AABB.

Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

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

Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine

Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

PubMed Central

Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; Harwood, Caroline S.; Sondermann, Holger; Navarro, Marcos V. A. S.

2016-01-01

Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs. PMID:26712005

Directional Convexity and Finite Optimality Conditions.

DTIC Science & Technology

1984-03-01

system, Necessary Conditions for optimality. Work Unit Number 5 (Optimization and Large Scale Systems) *Istituto di Matematica Applicata, Universita...that R(T) is convex would then imply x(u,T) e int R(T). Cletituto di Matematica Applicata, Universita di Padova, 35100 ITALY. Sponsored by the United

General Education Teachers' Differentiated Instruction in Elementary Inclusion

ERIC Educational Resources Information Center

Deason, Jennifer

2014-01-01

Inclusion teachers at the elementary level face challenges in differentiating instruction for all students. Despite inclusion teachers' willingness to use differentiated instruction (DI), many teachers struggle implementing DI because of teachers' understanding of DI, insufficient time for planning, and insufficient training and resources. The…

Coastal Ocean Circulation Experiment off Senegal (COCES)

DTIC Science & Technology

2008-09-30

Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy Phone: +39 040 2140322 Fax: +39 040 2140266 Email...NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo

Mapping training needs for dissemination and implementation research: lessons from a synthesis of existing D&I research training programs.

PubMed

Chambers, David A; Proctor, Enola K; Brownson, Ross C; Straus, Sharon E

2017-09-01

With recent growth in the field of dissemination and implementation (D&I) research, multiple training programs have been developed to build capacity, including summer training institutes, graduate courses, degree programs, workshops, and conferences. While opportunities for D&I research training have expanded, course organizers acknowledge that available slots are insufficient to meet demand within the scientific and practitioner community. In addition, individual programs have struggled to best fit various needs of trainees, sometimes splitting coursework between specific D&I content and more introductory grant writing material. This article, stemming from a 2013 NIH workshop, reviews experiences across multiple training programs to align training needs, career stage and role, and availability of programs. We briefly review D&I needs and opportunities by career stage and role, discuss variations among existing training programs in format, mentoring relationships, and other characteristics, identify challenges of mapping needs of trainees to programs, and present recommendations for future D&I research training.

Cloned Defective Interfering Influenza RNA and a Possible Pan-Specific Treatment of Respiratory Virus Diseases

PubMed Central

Dimmock, Nigel J.; Easton, Andrew J.

2015-01-01

Defective interfering (DI) genomes are characterised by their ability to interfere with the replication of the virus from which they were derived, and other genetically compatible viruses. DI genomes are synthesized by nearly all known viruses and represent a vast natural reservoir of antivirals that can potentially be exploited for use in the clinic. This review describes the application of DI virus to protect from virus-associated diseases in vivo using as an example a highly active cloned influenza A DI genome and virus that protects broadly in preclinical trials against different subtypes of influenza A and against non-influenza A respiratory viruses. This influenza A-derived DI genome protects by two totally different mechanisms: molecular interference with influenza A replication and by stimulating innate immunity that acts against non-influenza A viruses. The review considers what is needed to develop DI genomes to the point of entry into clinical trials. PMID:26184282

Reconciling findings on the employment effect of disability insurance.

PubMed

Bound, John; Lindner, Stephan; Waidmann, Timothy

2014-12-01

Over the last 25 years, the Social Security Disability Insurance Program (DI) has grown dramatically. During the same period, employment rates for men with work limitations showed substantial declines in both absolute and relative terms. While the timing of these trends suggests that the expansion of DI was a major contributor to employment decline among this group, raising questions about the targeting of disability benefits, studies using denied applicants suggest a more modest role of the DI expansion. To reconcile these findings, we decompose total employment changes into population and employment changes for three categories: DI beneficiaries, denied applicants, and non-applicants. Our results show that during the early 1990s, the growth in DI can fully explain the employment decline for men only under an extreme assumption about the employment potential of beneficiaries. For the period after the mid-1990s, we find little role for the DI program in explaining the continuing employment decline for men with work limitations.

Reconciling findings on the employment effect of disability insurance

PubMed Central

Bound, John; Lindner, Stephan; Waidmann, Timothy

2016-01-01

Over the last 25 years, the Social Security Disability Insurance Program (DI) has grown dramatically. During the same period, employment rates for men with work limitations showed substantial declines in both absolute and relative terms. While the timing of these trends suggests that the expansion of DI was a major contributor to employment decline among this group, raising questions about the targeting of disability benefits, studies using denied applicants suggest a more modest role of the DI expansion. To reconcile these findings, we decompose total employment changes into population and employment changes for three categories: DI beneficiaries, denied applicants, and non-applicants. Our results show that during the early 1990s, the growth in DI can fully explain the employment decline for men only under an extreme assumption about the employment potential of beneficiaries. For the period after the mid-1990s, we find little role for the DI program in explaining the continuing employment decline for men with work limitations. PMID:27158580

Success in School for Justice-Involved Girls: Do Specific Aspects of Developmental Immaturity Matter?

PubMed Central

Haney-Caron, Emily; Goldstein, Naomi E. S.; Giallella, Christy L.; Kemp, Kathleen; Romaine, Christina Riggs

2016-01-01

Developmental immaturity (DI) may help explain some of the variability in aspects of academic achievement among girls in the juvenile justice system, a population with high rates of truancy, dropout, and school failure. This study examined the relationships among the decision making and independent functioning components of DI, verbal intelligence, and academic achievement within this population. Using data from 60 girls in residential juvenile justice facilities, multiple regression analyses indicated that verbal IQ moderated the relationship between the DI construct of decision making and academic achievement. Self-reported school attendance and number of previous arrests did not significantly mediate the relationship between DI and academic achievement. These results may indicate that the decision-making factor of DI may be particularly important, and, if results are replicated, future intervention efforts could focus more on improving this skill within this juvenile justice population. Additionally, the overall importance of the full DI construct is an important area of future study. PMID:28082833

Elettrodinamica classica

NASA Astrophysics Data System (ADS)

Lechner, Kurt

Nella scoperta della Relatività Ristretta l'Elettrodinamica, rappresentando una teoria relativistica per eccellenza, ha giocato un ruolo fondamentale. Il principio di relativit` a einsteiniana, che afferma che tutte le leggi della fisica devono avere la stessa forma in tutti i sistemi di riferimento inerziali, è emerso con forza da questa teoria ed è andato consolidandosi sempre di più, man mano che le nostre conoscenze del mondo microscopico sono diventate più complete: tutte le interazioni fondamentali rispettano infatti tale principio. Il modo più semplice ed elegante per implementarlo — difatti l'unico di un'utilità concreta — è rappresentato dal paradigma della covarianza a vista nell'ambito del calcolo tensoriale. Questo paradigma è stato applicato con successo a tutte le teorie di carattere fondamentale, come le teorie che descrivono le quattro interazioni fondamentali e le più speculative teorie di superstringa, e mantiene la sua piena efficacia anche in teoria quantistica. La nostra esposizione dell'Elettrodinamica classica si baserà dunque a ragione su questo paradigma.

Diabetes insipidus: Differential diagnosis and management.

PubMed

Robertson, Gary L

2016-03-01

Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of dilute urine. It can be caused by any of 4 fundamentally different defects that must be distinguished for safe and effective management. They are: (1) pituitary DI, due to inadequate production and secretion of antidiuretic hormone, arginine-vasopressin (AVP); (2) gestational DI due to degradation of AVP by an enzyme made in placenta; (3) primary polydipsia, due to suppression of AVP secretion by excessive fluid intake; and (4) nephrogenic DI due to renal insensitivity to the antidiuretic effect of AVP. This review describes several methods of differential diagnosis, indicates the advantages and disadvantages of each and presents a new approach that is simpler and less costly but just as reliable as the best of the older methods. The various treatments for the different types of DI and recent findings on the genetic basis of the familial forms of DI are also discussed with emphasis on their contributions to improved diagnosis and management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dietary choline deficiency and excess induced intestinal inflammation and alteration of intestinal tight junction protein transcription potentially by modulating NF-κB, STAT and p38 MAPK signaling molecules in juvenile Jian carp.

PubMed

Wu, Pei; Jiang, Wei-Dan; Jiang, Jun; Zhao, Juan; Liu, Yang; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

2016-11-01

This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Meanwhile, compared with the optimal choline group, choline deficiency decreased the activities of lysozyme and acid phosphatase, contents of complement 3 and IgM in the intestine, downregulated the mRNA levels of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti-inflammatory cytokines (interleukin (IL) 10 and transforming growth factor β2 in the PI, MI and DI), and signaling molecule IκB in the PI, MI and DI; while upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor necrosis factor α in the MI and DI, interferon γ2b in the PI and MI, IL-1β and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STAT) 4 and STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that choline deficiency caused inflammation and immunity depression in the intestine of fish. But choline deficiency decreased the PI IL-6a mRNA level, and increased the DI LEAP-2A and defensin-3 mRNA levels with unknown reasons. Furthermore, dietary choline deficiency downregulated mRNA levels of tight junction (TJ) proteins (claudin 3c in the PI and MI, claudin 7, claudin 11 and occludin in the PI, MI and DI) and signaling molecule mitogen-activated protein kinases p38 in the PI, MI and DI of juvenile Jian carp, whereas upregulated the mRNA levels of claudin 3b in the MI and DI, and claudin 3c in the DI. Moreover, the excessive choline exhibited negative effects on intestinal immunity and TJ proteins that were similar to the choline deficiency. In summary, dietary choline deficiency or excess caused the depression of intestinal mucosal immune by inducing inflammation and dysfunction of the intestinal physical barrier, and regulating related signaling molecules of fish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accuracy of digital American Board of Orthodontics Discrepancy Index measurements.

PubMed

Dragstrem, Kristina; Galang-Boquiren, Maria Therese S; Obrez, Ales; Costa Viana, Maria Grace; Grubb, John E; Kusnoto, Budi

2015-07-01

A digital analysis that is shown to be accurate will ease the demonstration of initial case complexity. To date, no literature exists on the accuracy of the digital American Board of Orthodontics Discrepancy Index (DI) calculations when applied to pretreatment digital models. Plaster models were obtained from 45 previous patients with varying degrees of malocclusion. Total DI scores and the target disorders were computed manually with a periodontal probe on the original plaster casts (gold standard) and digitally using Ortho Insight 3D (Motion View Software, Hixson, Tenn) and OrthoCAD (Cadent, Carlstadt, NJ). Intrarater and interrater reliabilities were assessed for 15 subjects using the Spearman rho correlation test. Accuracies of the DI scores and target disorders were assessed for all 45 subjects using Wilcoxon signed ranks tests. Intrarater and interrater reliabilities were high for total DI scores and most target disorders (r > 0.8). No significant difference was found between total DI score when measured with OrthoCAD compared with manual calculations. The total DI scores calculated by Ortho Insight 3D were found to be significantly greater than those by manual calculation by 2.71 points. The findings indicate that a DI calculated by Ortho Insight 3D may lead the clinician to overestimate case complexity. OrthoCAD's DI module was demonstrated to be a clinically acceptable alternative to manual calculation of the total scores. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

New pH-sensitive liposomes containing phosphatidylethanolamine and a bacterial dirhamnolipid.

PubMed

Sánchez, Marina; Aranda, Francisco J; Teruel, José A; Ortiz, Antonio

2011-01-01

Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions have been described as efficient systems for cytoplasmic delivery of molecules into cells. Incorporation of an amphiphile of appropriate structure is needed for the stabilization and performance of these vesicles. Among the wide variety of interesting activities displayed by Pseudomonas aeruginosa dirhamnolipids (diRL), is their capacity to stabilize bilayer structures in phosphatidylethanolamine systems. In this work, X-ray scattering, dynamic light scattering, fluorescence spectroscopy and fluorescence microscopy have been used to study the structure and pH-dependent behaviour of phosphatidylethanolamine/diRL liposomes. We show that diRL, in combination with dioleoylphosphatidylethanolamine (DOPE), forms stable multilamellar and unilamellar liposomes. Acidification of DOPE/diRL vesicles leads to membrane destabilization, fusion, and release of entrapped aqueous vesicle contents. Finally, DOPE/diRL pH-sensitive liposomes act as efficient vehicles for the cytoplasmic delivery of fluorescent probes into cultured cells. It is concluded that DOPE/diRL form stable pH-sensitive liposomes, and that these liposomes are incorporated into cultured cells through the endocytic pathway, delivering its contents into the cytoplasm, which means a potential use of these liposomes for the delivery of foreign substances into living cells. Our results establish a new application of diRL as a bilayer stabilizer in phospholipid vesicles, and the use of diRL-containing pH-sensitive liposomes as delivery vehicles. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal

NASA Astrophysics Data System (ADS)

Chang, Jung-Wei; Lee, Ching-Chang; Pan, Wen-Harn; Chou, Wei-Chun; Huang, Han-Bin; Chiang, Hung-Che; Huang, Po-Chin

2017-03-01

A food scandal occurred in Taiwan in 2011 because the DEHP (di-2-ethylhexyl phthalate) had been intentionally used in food products. We assessed the daily intakes (DIs) and cumulative risk of phthalates in Taiwan’s general population after the scandal. The DIs of 6 phthalates, including di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), and DEHP, were evaluated using urinary phthalate metabolites. Hazard quotients of phthalates classified as affecting the reproductive (HQrep) and hepatic (HQhep) systems were assessed using cumulative approach. The creatinine-based model showed that the highest DI values in children 7-to 12- years-old were for DEHP (males: median: 4.79 μg/kg bw/d; females: median: 2.62 μg/kg bw/d). The 95th percentile (P95) of HQrep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQhep values were all >1 in the 7- to 18- year-old male groups. Most of the HQrep was attributable to the HQs of DnBP and DiBP (53.9-84.7%), and DEHP contributed most to HQhep (83.1-98.6%), which reveals that DnBP, DiBP and DEHP were the main risk of phthalate exposure for Taiwanese. Taiwan’s general population is widely exposed to DnBP, DiBP and DEHP, especially for young children.

Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry

PubMed Central

Kato, Yoji; Dozaki, Natsuko; Nakamura, Toshiyuki; Kitamoto, Noritoshi; Yoshida, Akihiro; Naito, Michitaka; Kitamura, Masayasu; Osawa, Toshihiko

2009-01-01

The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 ± 0.6 (DiY), 1.4 ± 0.4 (NY), 3.8 ± 0.3 (BrY), and 0.7 ± 0.1 (DiBrY) µmol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and Nε-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people. PMID:19177191

Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa

DOE PAGES

Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.; ...

2015-05-15

Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZmore » domain fold with a dimerization mode not previously observed for this family of proteins. Moreover, calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. Our results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.« less

Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa

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

Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.

Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZmore » domain fold with a dimerization mode not previously observed for this family of proteins. Moreover, calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. Our results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.« less

Accelerated Photobleaching of a Cyanine Dye in the Presence of a Ternary Target DNA, PNA Probe, Dye Catalytic Complex: A Molecular Diagnostic

PubMed Central

Wang, M.; Holmes-Davis, R.; Rafinski, Z.; Jedrzejewska, B.; Choi, K. Y.; Zwick, M.; Bupp, C.; Izmailov, A.; Paczkowski, J.; Warner, B.; Koshinsky, H.

2009-01-01

In many settings, molecular testing is needed but unavailable due to complexity and cost. Simple, rapid, and specific DNA detection technologies would provide important alternatives to existing detection methods. Here we report a novel, rapid nucleic acid detection method based on the accelerated photobleaching of the light-sensitive cyanine dye, 3,3′-diethylthiacarbocyanine iodide (DiSC2(3) I−), in the presence of a target genomic DNA and a complementary peptide nucleic acid (PNA) probe. On the basis of the UV–vis, circular dichroism, and fluorescence spectra of DiSC2(3) with PNA–DNA oligomer duplexes and on characterization of a product of photolysis of DiSC2(3) I−, a possible reaction mechanism is proposed. We propose that (1) a novel complex forms between dye, PNA, and DNA, (2) this complex functions as a photosensitizer producing 1O2, and (3) the 1O2 produced promotes photobleaching of dye molecules in the mixture. Similar cyanine dyes (DiSC3(3), DiSC4(3), DiSC5(3), and DiSCpy(3)) interact with preformed PNA–DNA oligomer duplexes but do not demonstrate an equivalent accelerated photobleaching effect in the presence of PNA and target genomic DNA. The feasibility of developing molecular diagnostic assays based on the accelerated photobleaching (the smartDNA assay) that results from the novel complex formed between DiSC2(3) and PNA–DNA is under way. PMID:19231844

Causality Analysis of fMRI Data Based on the Directed Information Theory Framework.

PubMed

Wang, Zhe; Alahmadi, Ahmed; Zhu, David C; Li, Tongtong

2016-05-01

This paper aims to conduct fMRI-based causality analysis in brain connectivity by exploiting the directed information (DI) theory framework. Unlike the well-known Granger causality (GC) analysis, which relies on the linear prediction technique, the DI theory framework does not have any modeling constraints on the sequences to be evaluated and ensures estimation convergence. Moreover, it can be used to generate the GC graphs. In this paper, first, we introduce the core concepts in the DI framework. Second, we present how to conduct causality analysis using DI measures between two time series. We provide the detailed procedure on how to calculate the DI for two finite-time series. The two major steps involved here are optimal bin size selection for data digitization and probability estimation. Finally, we demonstrate the applicability of DI-based causality analysis using both the simulated data and experimental fMRI data, and compare the results with that of the GC analysis. Our analysis indicates that GC analysis is effective in detecting linear or nearly linear causal relationship, but may have difficulty in capturing nonlinear causal relationships. On the other hand, DI-based causality analysis is more effective in capturing both linear and nonlinear causal relationships. Moreover, it is observed that brain connectivity among different regions generally involves dynamic two-way information transmissions between them. Our results show that when bidirectional information flow is present, DI is more effective than GC to quantify the overall causal relationship.

Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa*

PubMed Central

Whitney, John C.; Whitfield, Gregory B.; Marmont, Lindsey S.; Yip, Patrick; Neculai, A. Mirela; Lobsanov, Yuri D.; Robinson, Howard; Ohman, Dennis E.; Howell, P. Lynne

2015-01-01

Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa. PMID:25817996

Giornalismo Matematico "A Carattere Elementare" Nella Seconda Meta Dell'Ottocento.

ERIC Educational Resources Information Center

Furinghetti, Fulvia; Somaglia, Annamaria

1992-01-01

Considers the Italian mathematical journals of the second half of the nineteenth century oriented to the teaching of mathematics at different school levels. Focuses on three journals: "Rivista di matematica elementare,""Periodico di matematica," and "Rivista di Matematica." Analyzes elements that help outline their…

Numerical Solution of Hamilton-Jacobi Equations in High Dimension

DTIC Science & Technology

2012-11-23

high dimension FA9550-10-1-0029 Maurizio Falcone Dipartimento di Matematica SAPIENZA-Universita di Roma P. Aldo Moro, 2 00185 ROMA AH930...solution of Hamilton-Jacobi equations in high dimension AFOSR contract n. FA9550-10-1-0029 Maurizio Falcone Dipartimento di Matematica SAPIENZA

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl...

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl...

40 CFR 464.41 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85.... naphthalene 65. phenol 66. bis (2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85...) 55. naphthalene 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 85...

40 CFR 464.41 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85.... naphthalene 65. phenol 66. bis (2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85...) 55. naphthalene 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 85...

DiGeorge syndrome and unilateral symbrachydactyly.

PubMed

Devriendt, K; De Smet, L; De Boeck, K; Fryns, J P

1997-01-01

We describe a child with DiGeorge syndrome due to a del22(q11) and a symbrachydactyly of the left hand. The underlying cardiovascular malformations in DiGeorge syndrome may lead to an increased susceptibility to vascular disruptions, giving further support to the subclavian-artery-disruption-sequence theory.

AN ASSESSMENT OF PHTHALATE ESTER TOXICITY TO FRESHWATER BENTHOS: 2. SEDIMENT EXPOSURES

EPA Science Inventory

Seven phthalate esters were evaluated for their stability and 10-d acute toxicity to the freshwater invertebrates Hyalella azteca and Chironomus tentans following incorporation into sediment. The chemicals were diethyl (DEP), di-n-butyl (DBP), di-n-hyxyl (DHP), di-[2-ethylhexyl] ...

78 FR 49993 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

....regulations.gov : Follow online instructions for submitting comments. Email: Nefertiti DiCosmo, Remedial... [email protected] . Fax: Gladys Beard at (312) 697-2077. Mail: Nefertiti DiCosmo, Remedial Project... FURTHER INFORMATION CONTACT: Nefertiti DiCosmo, Remedial Project Manager, U.S. Environmental Protection...

77 FR 64790 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... DiCosmo, Remedial Project Manager, at [email protected] or David Novak, Community Involvement...: Nefertiti DiCosmo, Remedial Project Manager, U.S. Environmental Protection Agency (SR-6J), 77 West Jackson... FURTHER INFORMATION CONTACT: Nefertiti DiCosmo, Remedial Project Manager, U.S. Environmental Protection...

78 FR 49939 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... : Follow online instructions for submitting comments. Email: Nefertiti DiCosmo, Remedial Project Manager... . Fax: Gladys Beard at (312) 697-2077. Mail: Nefertiti DiCosmo, Remedial Project Manager, U.S... FURTHER INFORMATION CONTACT: Nefertiti DiCosmo, Remedial Project Manager, U.S. Environmental Protection...

Evaluation of Drugs for Prevention of Hyperthermia in Rats Exposed to Microwave Irradiation.

DTIC Science & Technology

1987-03-04

is deficient in antidiuretic hormone (ADH) and has diabetes insipidus (DI). The latter condition causes unusually high water intake and urine...ADH) and consequently has diabetes ihsipidus (DI). A DI-rat, also known as Brattleboro rat, has both unusually high water intake and rate of

40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal..., reaction products with polyethylene-polypropylene glycol Bu glycidal ether. (a) Chemical substance and... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal..., reaction products with polyethylene-polypropylene glycol Bu glycidal ether. (a) Chemical substance and... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

On the Development of Constitutive Relations for Plain and Reinforced Concrete.

DTIC Science & Technology

1982-04-09

Costitutive e Con- dizioni di Rottura del Calcestruzzo in Stati de Tensione Mono e Pluriassiali." Costruzione in Cemento Armato, Studi e Rendiconti...leggi, costitutive e con- dizioni di rottura del calcestruzzo in stati di tensione mono e pluriassiali." Construzione in Cemento Armato, Studi e

Physics, Nonlinear Time Series Analysis, Data Assimilation and Hyperfast Modeling of Nonlinear Ocean Waves

DTIC Science & Technology

2010-09-30

Hyperfast Modeling of Nonlinear Ocean Waves A. R. Osborne Dipartimento di Fisica Generale, Università di Torino Via Pietro Giuria 1, 10125...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Universit?i Torino,Dipartimento di Fisica Generale,Via Pietro Giuria 1,10125 Torino, Italy, 8. PERFORMING

Hyperfast Numerical Integration of Ocean Surface Wave Dynamics Extensions to Higher Order

DTIC Science & Technology

2008-09-30

Osborne Dipartimento di Fisica Generale, Università di Torino Via Pietro Giuria 1 10125 Torino, Italy Phone: (+39) 11-670-7451 or (+39) 11-329...Universit?i Torino,Dipartimento di Fisica Generale,Via Pietro Giuria 1,10125 Torino, Italy, , 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING

Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions.

PubMed

Eison, A S; Iversen, S D; Sandberg, B E; Watson, S P; Hanley, M R; Iversen, L L

1982-01-08

A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.

Proceedings of the Course on Algorithms and Data Structures for Geometric Computations Held at CISM (Centre International des Sciences Mecaniques) in Udine (Italy) on 8-12 July 1985,

DTIC Science & Technology

1985-07-26

Science Student Via alla Roggia, 9a 6962 Viganello Switzerland CHAABAN Moustafa, Professor Ain Shams University Faculty of Engineering 15, El Farik El ...Masri st. Almaza, Heliopolis, Cairo Egypt DELLA RICCIA Giacomo, Professor Universita’ di Udine Ist. di Matematica , Informatica e Sistemistica Via...Ro cq uencourt , B . P . 105 78153 Le Chesnay Cedex France .%c Page 5 TASSO Carlo, Assoc. Professor U1niversita’ di Udine 1st. di Matematica

t-Butyl-Oxycarbonylated Diamines as Building Blocks for Isocyanate-Free Polyurethane/Urea Dispersions and Coatings.

PubMed

Ma, Shuang; Zhang, Huiyi; Sablong, Rafaël J; Koning, Cor E; van Benthem, Rolf A T M

2018-05-01

t-Butyl-oxycarbonylated diamines ("di-Boc-carbamates") are investigated as dicarbamate monomers for diamine/dicarbamate polymerizations. Polyureas (PUs) and polyurethanes (PURs) with high molecular weights are prepared from stoichiometric polymerizations of diamines or diols with N-N'-di-t-butyl-oxycarbonyl isophorone diamine (DiBoc-IPDC) using KOt-Bu as a catalyst, while gelation is observed when an excess of DiBoc-IPDC is used with respect to the diamines or diols. Stable dispersions are obtained from PUs and PURs with 3,3'-diamino-N-methyldipropylamine (DMDPA) as internal dispersing agent. The corresponding PU-based coatings exhibit superior mechanical properties and solvent resistances compared to the polyurethane urea coatings synthesized from diols, DiBoc-IPDC, and DMDPA. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vibrio cholerae VpsT Regulates Matrix Production and Motility by Directly Sensing Cyclic di-GMP

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

Krasteva, P.; Fong, J; Shikuma, N

2010-01-01

Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerizationmore » on c-di-GMP binding.« less

Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

PubMed

Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

2015-04-01

Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

Composition and method for encapsulating photovoltaic devices

DOEpatents

Pern, Fu-Jann

2000-01-01

A composition and method for encapsulating a photovoltaic device which minimizes discoloration of the encapsulant. The composition includes an ethylene-vinyl acetate encapsulant, a curing agent, an optional ultraviolet light stabilizer, and/or an optional antioxidant. The curing agent is preferably 1,1-di-(t-butylperoxy)-3,3,5-trimethylcyclohexane; the ultraviolet light stabilizer is bis-(N-octyloxy-tetramethyl) piperidinyl sebacate and the antioxidant is selected from the group consisting of tris (2,4-di-tert-butylphenyl) phosphite, tetrakis methylene (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) methane, octadecyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate, and 2,2'-ethylidene bis(4,6-di-t-butylphenyl) fluorophosponite. The composition is applied to a solar cell then cured. The cured product contains a minimal concentration of curing-generated chromophores and resists UV-induced degradation.

Design, Synthesis and Evaluation of Novel Isoxazolines/Oxime Sulfonates of 2‧(2‧,6‧)-(Di)Chloropodophyllotoxins as Insecticidal Agents

NASA Astrophysics Data System (ADS)

Yu, Mingqiao; Liu, Guangci; Zhang, Yuanyuan; Feng, Tao; Xu, Ming; Xu, Hui

2016-09-01

A series of 2‧(2‧,6‧)-(di)halogeno-isoxazolopodophyllic acids-based esters, and oxime sulfonates of 2‧(2‧,6‧)-(di)halogenopodophyllones were prepared by structural modifications of podophyllotoxin as insecticidal agents against Mythimna separata Walker. It was found that when 2‧(2‧,6‧)-(di)halogenopodophyllones or 2‧(2‧,6‧)-(di)chloropicropodophyllones reacted with hydroxylamine hydrochloride, the desired products were related with the configuration of their lactones. Three key single-crystal structures of Ie, IIe and IIIb were determined by X-ray diffraction. Especially compounds IIc and Vc showed the highest insecticidal activity. Moreover, some interesting results of structure-insecticidal activity relationships of tested compounds were also observed.

Concocting that Magic Elixir: Successful Grant Application Writing in Dissemination and Implementation Research.

PubMed

Brownson, Ross C; Colditz, Graham A; Dobbins, Maureen; Emmons, Karen M; Kerner, Jon F; Padek, Margaret; Proctor, Enola K; Stange, Kurt C

2015-12-01

This paper reports core competencies for dissemination and implementation (D&I) grant application writing and provides tips for writing a successful proposal. Two related phases were used to collect the data: a card sorting process among D&I researchers and an expert review among a smaller set of researchers. Card sorting was completed by 123 respondents. In the second phase, a series of grant application writing tips were developed based on the combined 170 years of grant review experience of the writing team. The card sorting resulted in 12 core competencies for D&I grant application writing that covered the main sections in a grant application to the US National Institutes of Health: (a) specific aims that provide clear rationale, objectives, and an overview of the research plan; (b) significance that frames and justifies the importance of a D&I question; (c) innovation that articulates novel products and new knowledge; and (d) approach that uses a relevant D&I model, addresses measurement and the D&I context, and includes an analysis plan well-tied to the aims and measures. Writing a successful D&I grant application is a skill that can be learned with experience and attention to the core competencies articulated in this paper. © 2015 Wiley Periodicals, Inc.

Bioactivity of 2'-deoxyinosine-incorporated aptamer AS1411.

PubMed

Fan, Xinmeng; Sun, Lidan; Wu, Yun; Zhang, Lihe; Yang, Zhenjun

2016-05-19

Aptamers can be chemically modified to enhance nuclease resistance and increase target affinity. In this study, we performed chemical modification of 2'-deoxyinosine in AS1411, an anti-proliferative G-rich oligodeoxynucleotide aptamer, which binds selectively to the nucleolin protein. Its function was augmented when 2'-deoxyinosine was incorporated at positions 12, 13, 15, and 24 of AS1411, respectively. In addition, double incorporation of 2'-deoxyinosine at positions 12 and 24 (FAN-1224dI), 13 and 24 (FAN-1324dI), and 15 and 24 (FAN-1524dI) promoted G-quartet formation, as well as inhibition of DNA replication and tumor cell growth, and induced S-phase cell cycle arrest. In further animal experiments, FAN-1224dI, FAN-1324dI and FAN-1524dI resulted in enhanced treatment effects than AS1411 alone. These results suggested that the position and number of modification substituents in AS1411 are critical parameters to improve the diagnostic and therapeutic function of the aptamer. Structural investigations of the FAN-1524dI/nucleolin complex structure, using molecular dynamics simulation, revealed the critical interactions involving nucleolin and 2'-dI incorporated AS1411 compared with AS1411 alone. These findings augment understanding of the role of 2'-deoxyinosine moieties in interactive binding processes.

Concocting that Magic Elixir: Successful Grant Application Writing in Dissemination and Implementation Research

PubMed Central

Colditz, Graham A.; Dobbins, Maureen; Emmons, Karen M.; Kerner, Jon F.; Padek, Margaret; Proctor, Enola K.; Stange, Kurt C.

2015-01-01

Abstract Background This paper reports core competencies for dissemination and implementation (D&I) grant application writing and provides tips for writing a successful proposal. Methods Two related phases were used to collect the data: a card sorting process among D&I researchers and an expert review among a smaller set of researchers. Card sorting was completed by 123 respondents. In the second phase, a series of grant application writing tips were developed based on the combined 170 years of grant review experience of the writing team. Results The card sorting resulted in 12 core competencies for D&I grant application writing that covered the main sections in a grant application to the US National Institutes of Health: (a) specific aims that provide clear rationale, objectives, and an overview of the research plan; (b) significance that frames and justifies the importance of a D&I question; (c) innovation that articulates novel products and new knowledge; and (d) approach that uses a relevant D&I model, addresses measurement and the D&I context, and includes an analysis plan well‐tied to the aims and measures. Conclusions Writing a successful D&I grant application is a skill that can be learned with experience and attention to the core competencies articulated in this paper. PMID:26577630

Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers

PubMed Central

Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

2015-01-01

The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

Ordering Diagnostic Imaging: A Survey of Ontario Physiotherapists' Opinions on an Expanded Scope of Practice

PubMed Central

Chong, Jodie Ng Fuk; De Luca, Krista; Goldan, Sana; Imam, Abdullah; Li, Boris; Zabjek, Karl; Chu, Anna

2015-01-01

ABSTRACT Purpose: To explore Ontario physiotherapists' opinions on their ability to order diagnostic imaging (DI). Methods: An online questionnaire was sent to all registered members of the College of Physiotherapists of Ontario. Descriptive statistics were calculated using response frequencies. Practice characteristics were compared using χ2 tests and Wilcoxon rank–sum tests. Results: Of 1,574 respondents (21% response rate), 42% practised in orthopaedics and 53% in the public sector. Most physiotherapists were interested in ordering DI (72% MRI/diagnostic ultrasound, 78% X-rays/computed tomography scans). Respondents with an orthopaedic caseload of 50% or more (p<0.001) and those in the private sector (p<0.001) were more interested in ordering DI. Respondents preferred a DI course that combined face-to-face and Web-based components and one that was specific to their area of practice. Most respondents perceived minimal barriers to the uptake of ordering DI, and most agreed that support from other health care professionals would facilitate uptake. Conclusion: The majority of Ontario physiotherapists are interested in ordering DI. For successful implementation of a health care change, such as physiotherapists' ability to order DI, educational needs and barriers to and facilitators of the uptake of the authorized activity should be considered. PMID:25931666

A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

PubMed

Shak, S; Perez, H D; Goldstein, I M

1983-12-25

We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

Enzymatic synthesis of 1,3-dihydroxyphenylacetoyl-sn-glycerol: Optimization by response surface methodology and evaluation of its antioxidant and antibacterial activities.

PubMed

Kharrat, Nadia; Aissa, Imen; Dgachi, Youssef; Aloui, Fatma; Chabchoub, Fakher; Bouaziz, Mohamed; Gargouri, Youssef

2017-12-01

In this study, the enzymatic synthesis of phenylacetoyl glycerol ester was carried out as a response to the increasing consumer demand for natural compounds. 1,3-dihydroxyphenylacetoyl-sn-Glycerol (1,3-di-HPA-Gly), labeled as "natural" compound with interesting biological properties, has been successfully synthesized for the first time in good yield by a direct esterification of glycerol (Gly) with p-hydroxyphenylacetic acid (p-HPA) using immobilized Candida antarctica lipase as a biocatalyst. Spectroscopic analyses of purified esters showed that the glycerol was mono- or di-esterified on the primary hydroxyl group. These compounds were evaluated for their antioxidant activity using two different tests. The glycerol di-esters (1,3-di-HPA-Gly) showed a higher antiradical capacity than that of the butyl hydroxytoluene. Furthermore, compared to the p-HPA, synthesized ester (1,3-di-HPA-Gly) exhibited the most antibacterial effect mainly against Gram + bacteria. Among synthesized esters the 1,3-di-HPA-Gly was most effective as antioxidant and antibacterial compound. These findings could be the basis for a further exploitation of the new compound, 1,3-di-HPA-Gly, as antioxidant and antibacterial active ingredient in the cosmetic and pharmaceutical fields. Copyright © 2017. Published by Elsevier Inc.

Device overlay method for high volume manufacturing

NASA Astrophysics Data System (ADS)

Lee, Honggoo; Han, Sangjun; Kim, Youngsik; Kim, Myoungsoo; Heo, Hoyoung; Jeon, Sanghuck; Choi, DongSub; Nabeth, Jeremy; Brinster, Irina; Pierson, Bill; Robinson, John C.

2016-03-01

Advancing technology nodes with smaller process margins require improved photolithography overlay control. Overlay control at develop inspection (DI) based on optical metrology targets is well established in semiconductor manufacturing. Advances in target design and metrology technology have enabled significant improvements in overlay precision and accuracy. One approach to represent in-die on-device as-etched overlay is to measure at final inspection (FI) with a scanning electron microscope (SEM). Disadvantages to this approach include inability to rework, limited layer coverage due to lack of transparency, and higher cost of ownership (CoO). A hybrid approach is investigated in this report whereby infrequent DI/FI bias is characterized and the results are used to compensate the frequent DI overlay results. The bias characterization is done on an infrequent basis, either based on time or triggered from change points. On a per-device and per-layer basis, the optical target overlay at DI is compared with SEM on-device overlay at FI. The bias characterization results are validated and tracked for use in compensating the DI APC controller. Results of the DI/FI bias characterization and sources of variation are presented, as well as the impact on the DI correctables feeding the APC system. Implementation details in a high volume manufacturing (HVM) wafer fab will be reviewed. Finally future directions of the investigation will be discussed.

Screening for strains with 11α-hydroxylase activity for 17α-hydroxy progesterone biotransformation.

PubMed

Gao, Qian; Qiao, Yuqian; Shen, Yanbing; Wang, Min; Wang, Xibo; Liu, Yang

2017-08-01

Various corticosteroids are prepared by using 11α,17α-diOH-progesterone (11α,17α-diOH-PROG) as an important intermediate and raw material. Hence, strains that can improve the yields of 11α,17α-diOH-PROG should be screened. Cunninghamella elegans CICC40250 was singled out from five common 11α hydroxylation strains. The reaction parameters of 11α,17α-diOH-PROG production were also investigated. C. elegans CICC40250 could efficiently catalyze the hydroxylation of 17α-hydroxy progesterone (17α-OH-PROG) at C-11α position. This strain could also effectively convert 11α,17α-diOH-PROG at high substrate concentrations (up to 30g/L). After the coenzyme precursor glucose was added, the rate of 11α,17α-diOH-PROG formation reached 84.2%, which was 11.4% higher than that of the control group. Our study established a simple and feasible mechanism to increase 11α,17α-diOH-PROG production levels. This mechanism involves C. elegans CICC40250 that can be efficiently applied to induce the biotransformation of 17α-OH-PROG with a hydroxylation biocatalytic ability. Copyright © 2017. Published by Elsevier Inc.

Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology

NASA Astrophysics Data System (ADS)

Tomasi, G.; Kimberley, S.; Rosso, L.; Aboagye, E.; Turkheimer, F.

2012-04-01

In positron emission tomography (PET) studies involving organs different from the brain, ignoring the metabolite contribution to the tissue time-activity curves (TAC), as in the standard single-input (SI) models, may compromise the accuracy of the estimated parameters. We employed here double-input (DI) compartmental modeling (CM), previously used for [11C]thymidine, and a novel DI spectral analysis (SA) approach on the tracers 5-[18F]fluorouracil (5-[18F]FU) and [18F]fluorothymidine ([18F]FLT). CM and SA were performed initially with a SI approach using the parent plasma TAC as an input function. These methods were then employed using a DI approach with the metabolite plasma TAC as an additional input function. Regions of interest (ROIs) corresponding to healthy liver, kidneys and liver metastases for 5-[18F]FU and to tumor, vertebra and liver for [18F]FLT were analyzed. For 5-[18F]FU, the improvement of the fit quality with the DI approaches was remarkable; in CM, the Akaike information criterion (AIC) always selected the DI over the SI model. Volume of distribution estimates obtained with DI CM and DI SA were in excellent agreement, for both parent 5-[18F]FU (R2 = 0.91) and metabolite [18F]FBAL (R2 = 0.99). For [18F]FLT, the DI methods provided notable improvements but less substantial than for 5-[18F]FU due to the lower rate of metabolism of [18F]FLT. On the basis of the AIC values, agreement between [18F]FLT Ki estimated with the SI and DI models was good (R2 = 0.75) for the ROIs where the metabolite contribution was negligible, indicating that the additional input did not bias the parent tracer only-related estimates. When the AIC suggested a substantial contribution of the metabolite [18F]FLT-glucuronide, on the other hand, the change in the parent tracer only-related parameters was significant (R2 = 0.33 for Ki). Our results indicated that improvements of DI over SI approaches can range from moderate to substantial and are more significant for tracers with a high rate of metabolism. Furthermore, they showed that SA is suitable for DI modeling and can be used effectively in the analysis of PET data.

Esophagogastric junction distensibility measurements during Heller myotomy and POEM for achalasia predict postoperative symptomatic outcomes

PubMed Central

Teitelbaum, Ezra N.; Soper, Nathaniel J.; Pandolfino, John E.; Kahrilas, Peter J.; Hirano, Ikuo; Boris, Lubomyr; Nicodème, Frédéric; Lin, Zhiyue; Hungness, Eric S.

2015-01-01

Background The functional lumen imaging probe (FLIP) is a novel diagnostic tool that can be used to measure esophagogastric junction (EGJ) distensibility. In this study we performed intraoperative FLIP measurements during laparoscopic Heller myotomy (LHM) and peroral esophageal myotomy (POEM) for treatment of achalasia and evaluated the relationship between EGJ distensibility and postoperative symptoms. Methods Distensibility index (DI) (defined as the minimum cross-sectional area at the EGJ divided by distensive pressure) was measured with FLIP at two time points during LHM and POEM: 1) at baseline after induction of anesthesia, and 2) after operation completion. Results Measurements were performed in 20 patients undergoing LHM and 36 undergoing POEM. Both operations resulted in an increase in DI, although this increase was larger with POEM (7±3.1 vs. 5.1±3.4mm2/mmHg, p<.05). The two patients (both LHM) with the smallest increases in DI (1 and 1.6mm2/mmHg) both had persistent symptoms postoperatively and, overall, LHM patients with larger increases in DI had lower postoperative Eckardt scores. In the POEM group, there was no correlation between change in DI and symptoms; however, all POEM patients experienced an increase in DI of >3mm2/mmHg. When all patients were divided into thirds based on final DI, none in the lowest DI group (<6mm2/mmHg) had symptoms suggestive of reflux (i.e., GerdQ score >7), as compared with 20% in the middle third (6–9mm2/mmHg) and 36% in the highest third (>9mm2/mmHg). Patients within an “ideal” final DI range (4.5–8.5 mm2/mmHg) had optimal symptomatic outcomes (i.e. Eckardt≤1 and GerdQ≤7) in 88% of cases, compared with 47% in those with a final DI above or below that range (p<.05). Conclusions Intraoperative EGJ distensibility measurements with FLIP were predictive of postoperative symptomatic outcomes. These results provide initial evidence that FLIP has the potential to act as a useful calibration tool during operations for achalasia. PMID:25055891

Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

PubMed

Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

2006-05-01

To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

Mediterranean Diet and Mild Cognitive Impairment

PubMed Central

Scarmeas, Nikolaos; Stern, Yaakov; Mayeux, Richard; Manly, Jennifer; Schupf, Nicole; Luchsinger, Jose A.

2009-01-01

Background Higher adherence to the Mediterranean diet (MeDi) may protect from Alzheimer’s disease (AD) but its association with Mild Cognitive Impairment (MCI) has not been explored. Objective To investigate the association between MeDi and MCI. Design, Setting, Patients, Outcomes In a multiethnic community study in New York, we used Cox proportional hazards to investigate the association between adherence to the MeDi (0 – 9 scale; higher scores higher adherence) and (1) incidence of MCI and (2) progression from MCI to AD. All models were adjusted for cohort, age, gender, ethnicity, education, APOE genotype, caloric intake, body mass index and time duration between baseline dietary assessment and baseline diagnosis. Results There were 1393 cognitively normal participants, 275 of whom developed MCI during 4.5 (± 2.7, 0.9–16.4) years of follow-up. Compared to subjects in the lowest MeDi adherence tertile, subjects in the middle MeDi tertile had 17 % (HR, 0.83; 95% CI, 0.62 – 1.12; p=0.24) less risk of developing MCI, while those at the highest MeDi adherence tertile had 28 % (HR, 0.72; 95% CI, 0.52 – 1.00; p=0.05) less risk of developing MCI (trend HR, 0.85; 95% CI, 0.72 – 1.00; p for trend= 0.05). There were 482 subjects with MCI, 106 of whom developed AD during 4.3 (± 2.7, 1.0 – 13.8) years of follow-up. Compared to subjects in the lowest MeDi adherence tertile, subjects in the middle MeDi adherence tertile had 45 % (HR, 0.55; 95% CI, 0.34 – 0.90; p=0.01) less risk of developing AD, while those at the highest MeDi adherence tertile had 48 % (HR, 0.52; 95% CI, 0.30 – 0.91; p=0.02) less risk of developing AD (trend HR, 0.71; 95% CI, 0.53 – 0.95; p for trend= 0.02). Conclusions Higher adherence to the MeDi is associated with a trend for reduced risk for developing MCI and with reduced risk for MCI conversion to AD. PMID:19204158

Mediterranean diet and carotid atherosclerosis in the Northern Manhattan Study

PubMed Central

Gardener, Hannah; Wright, Clinton B.; Cabral, Digna; Scarmeas, Nikolaos; Gu, Yian; Cheung, Ken; Elkind, Mitchell S.V.; Sacco, Ralph L.; Rundek, Tatjana

2015-01-01

Objective Adherence to a Mediterranean-style diet (MeDi) may protect against clinical vascular events by reducing atherosclerosis, but data is limited. This is the first observational study of the association between MeDi adherence and carotid plaque thickness and area. Methods The study included 1374 participants of the population-based Northern Manhattan Study with diet assessed and carotid intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean age 66 ± 9 years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi adherence score (range = 0–9, 9 representing maximal adherence) was examined continuously and in quintiles (3/4/5/6 –9 vs. 0–2). Results Mean cIMT = 0.9 ± 0.1 mm and 57% had plaque (median plaque thickness = 1.5 mm, 75th percentile = 2.2; median plaque area = 4.2 mm2, 75th percentile = 15.8). There was no association between MeDi and cIMT or plaque presence. MeDi adherence was inversely associated with the 75th percentile of plaque thickness and median of plaque area in quantile regression analyses. These associations persisted after controlling for demographics, smoking, physical activity, and total energy consumption (effect of a 1-point increase in MeDi score on the 75th percentile of plaque thickness = −0.049 mm, p = 0.03; median of plaque area = −0.371 mm2, p = 0.03), and when additionally controlling for vascular disease biomarkers, medication use, BMI, and previous cardiac disease. The protective associations appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0–2 (bottom quintile). Differential effects of a MeDi on plaque thickness and area across race/ethnic groups was suggested. Conclusions Moderate and strict adherence to a MeDi may protect against a higher burden of carotid atherosclerotic plaque, which may mediate the protection against clinical vascular events. Efforts to improve adherence to a MeDi are critical to reducing the burden of atherosclerotic disease. PMID:24721190

Mediterranean diet and carotid atherosclerosis in the Northern Manhattan Study.

PubMed

Gardener, Hannah; Wright, Clinton B; Cabral, Digna; Scarmeas, Nikolaos; Gu, Yian; Cheung, Ken; Elkind, Mitchell S V; Sacco, Ralph L; Rundek, Tatjana

2014-06-01

Adherence to a Mediterranean-style diet (MeDi) may protect against clinical vascular events by reducing atherosclerosis, but data is limited. This is the first observational study of the association between MeDi adherence and carotid plaque thickness and area. The study included 1374 participants of the population-based Northern Manhattan Study with diet assessed and carotid intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean age 66 ± 9 years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi adherence score (range = 0-9, 9 representing maximal adherence) was examined continuously and in quintiles (3/4/5/6-9 vs. 0-2). Mean cIMT = 0.9 ± 0.1 mm and 57% had plaque (median plaque thickness = 1.5 mm, 75th percentile = 2.2; median plaque area = 4.2 mm(2), 75th percentile = 15.8). There was no association between MeDi and cIMT or plaque presence. MeDi adherence was inversely associated with the 75th percentile of plaque thickness and median of plaque area in quantile regression analyses. These associations persisted after controlling for demographics, smoking, physical activity, and total energy consumption (effect of a 1-point increase in MeDi score on the 75th percentile of plaque thickness = -0.049 mm, p = 0.03; median of plaque area = -0.371 mm(2), p = 0.03), and when additionally controlling for vascular disease biomarkers, medication use, BMI, and previous cardiac disease. The protective associations appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0-2 (bottom quintile). Differential effects of a MeDi on plaque thickness and area across race/ethnic groups was suggested. Moderate and strict adherence to a MeDi may protect against a higher burden of carotid atherosclerotic plaque, which may mediate the protection against clinical vascular events. Efforts to improve adherence to a MeDi are critical to reducing the burden of atherosclerotic disease. Copyright © 2014. Published by Elsevier Ireland Ltd.

Validation of the dyspnea index in adolescents with exercise-induced paradoxical vocal fold motion.

PubMed

De Guzman, Vanessa; Ballif, Catherine L; Maurer, Rie; Hartnick, Christopher J; Raol, Nikhila

2014-09-01

Paradoxical vocal fold motion (PVFM) affects almost 1 million adolescents in the United States. However, to date, no disease-specific objective measure exists to assess symptom severity and response to treatment in adolescents with exercise-induced PVFM. To validate the Dyspnea Index (DI) quality-of-life instrument (previously validated for adults with breathing disorders) in children aged 12 to 18 years with exercise-induced PVFM and to determine the minimum significant DI change corresponding to patient-reported or caregiver-reported improvement or worsening of symptoms. A longitudinal study of 56 patients (age range, 12-18 years) diagnosed as having exercise-induced PVFM and their caregivers from February 1, 2013, to September 30, 2013, in an outpatient pediatric otolaryngology office practice. The DI was administered to patients and caregivers, with items modified to reflect the perspective of caregivers. Appropriate DI change was measured to reflect improvement or worsening of symptoms. Test-retest reliability was accomplished by having a subset of patients and caregivers complete the instrument twice within 2 weeks before therapy. Internal consistency was assessed by calculation of Cronbach α. Discriminant validity and convergent validity were determined by comparing DIs with assessment of global change in symptoms. The patient and caregiver mean (SD) DI changes were -12.9 (9.6) and -14.7 (9.3), respectively (P < .001 for both). Reliability was established by test-retest analysis with an intraclass correlation coefficient of 0.8 and by calculation of Cronbach α = 0.80, demonstrating internal consistency. Discriminant validity was determined by assessing for a significant DI change when patients globally perceived that a change existed after treatment (P < .001). A DI change of 8 or higher (P < .001) correlated with patient-reported significant change. Convergent validity was demonstrated by evaluating for significant DI change when no change was reported following treatment (P < .001). The DI appears to be a valid and reliable instrument to assess quality of life in exercise-induced pediatric PVFM. A DI change of 8 or higher seems significant. This instrument can serve as an objective tool to assess change in exercise-induced pediatric PVFM following speech therapy.

Transition metal complexes of 2-amino-3,5-dihalopyridines: Syntheses, structures and magnetic properties of (3,5-diCAPH)2CuX4 and (3,5-diBAPH)2CuX4.

PubMed

Tremelling, Grant W; Foxman, Bruce M; Landee, Christopher P; Turnbull, Mark M; Willett, Roger D

2009-12-21

A family of bis(2-amino-3,5-dihalopyridinium)tetrahalocuprate(II) compounds has been synthesized, including (3,5-diCAPH)2CuCl4 (1), (3,5-diCAPH)2CuBr4 (2), (3,5-diBAPH)2CuCl4 (3), and (3,5-diBAPH)2CuBr4 (4) [3,5-diCAPH = 2-amino-3,5-dichloropyridinium; 3,5-diBAPH = 2-amino-3,5-dibromopyridinium]. These complexes have been analyzed through single crystal X-ray diffraction and temperature dependent magnetic susceptibility. Compound 1 crystallizes in the P-1 space group and the tetrachlorocuprate ion is best described as possessing a distorted square planar geometry. Compounds 2-4 are structurally similar and crystallized in the P2(1)/n, P2(1)/c, and P2(1)/n space groups respectively. The tetrahalocuprate ions are best described as distorted tetrahedra. All four compounds show antiferromagnetic interactions and were fit to the uniform chain Heisenberg model with resulting 2J/kB values of -11.71(2) K, -2.21(1) K, -12.43 (2) K, and -1.36(1) K, respectively. The exchange values correlate well with the two-halide exchange pathway parameters. The unusual observation that the chloride complexes show stronger magnetic exchange than the bromide complexes provides strong support that the exchange can be strongly dependent upon the Cu-X...X angles and Cu-X...X-Cu torsion angles.

Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

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

Smith, K.; Lipchock, S; Livingston,

2010-01-01

The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that themore » most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 {angstrom}) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3{prime}-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.« less

Diagnosis of diabetes insipidus observed in Swiss Duroc boars.

PubMed

Grahofer, Alexander; Wiedemar, Natalie; Gurtner, Corinne; Drögemüller, Cord; Nathues, Heiko

2016-01-29

Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses Inflammatory Responses Through TRPV1 Activation.

PubMed

Kim, Yiseul; Kim, Jung Tae; Park, Joonwoo; Son, Hee Jin; Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

2017-10-01

Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca 2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC 50  = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations.

PubMed

Pfaller, Christian K; Mastorakos, George M; Matchett, William E; Ma, Xiao; Samuel, Charles E; Cattaneo, Roberto

2015-08-01

Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and other infectious diseases. The efficacy of MV-based vectors depends on their replication proficiency and immune activation capacity. Here we document that copy-back defective interfering RNAs (DI-RNAs) are generated by recombinant vaccine and wild-type MVs immediately after rescue. The MV C protein interferes with DI-RNA generation and may enhance the processivity of the viral polymerase. We frequently detected clusters of A-to-G or U-to-C transitions and noted that sequences flanking individual mutations contain motifs favoring recognition by the adenosine deaminase acting on RNA-1 (ADAR1). The consistent type of transitions on the DI-RNAs indicates that these are direct substrates for editing by ADAR1. The ADAR1-mediated biased hypermutation events are consistent with the protein kinase R (PKR)-ADAR1 balancing model of innate immunity activation. We show by coinfection that the C-defective phenotype is dominant. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations

PubMed Central

Pfaller, Christian K.; Mastorakos, George M.; Matchett, William E.; Ma, Xiao; Samuel, Charles E.

2015-01-01

ABSTRACT Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. IMPORTANCE Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and other infectious diseases. The efficacy of MV-based vectors depends on their replication proficiency and immune activation capacity. Here we document that copy-back defective interfering RNAs (DI-RNAs) are generated by recombinant vaccine and wild-type MVs immediately after rescue. The MV C protein interferes with DI-RNA generation and may enhance the processivity of the viral polymerase. We frequently detected clusters of A-to-G or U-to-C transitions and noted that sequences flanking individual mutations contain motifs favoring recognition by the adenosine deaminase acting on RNA-1 (ADAR1). The consistent type of transitions on the DI-RNAs indicates that these are direct substrates for editing by ADAR1. The ADAR1-mediated biased hypermutation events are consistent with the protein kinase R (PKR)-ADAR1 balancing model of innate immunity activation. We show by coinfection that the C-defective phenotype is dominant. PMID:25972541

76 FR 23973 - Certain Pasta From Italy: Notice of Partial Rescission of Antidumping Duty Administrative Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... S.r.L. (``Afeltra''), Pasta Zara SpA (``Zara''), Pastificio Di Martino Gaetano & F.lli SpA (``Di..., P.A.P., Riscossa, Rustichella, and Zara (collectively ``certain non-mandatory respondents..., dated November 24, 2010. On November 29, 2010, Di Martino, Felicetti, and Zara withdrew their requests...

76 FR 48125 - Certain Pasta From Italy: Notice of Preliminary Results of Antidumping Duty Administrative Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... Zara SpA (``Zara''), Pastificio Di Martino Gaetano & F.lli SpA (``Di Martino''), Pastificio Fabianelli...., Riscossa, Rustichella, and Zara (collectively ``certain non-mandatory respondents'') requested that the..., 2010. On November 29, 2010, Di Martino, Felicetti, and Zara withdrew its request for a review. \\5\\ See...

Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

USDA-ARS?s Scientific Manuscript database

To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcD...

OCTANOL/WATER PARTITION COEFFICIENTS AND WATER SOLUBILITIES OF PHTHALATE ESTERS

EPA Science Inventory

Measurements of the octanol/water partition coefficients (K-ow) and water solubilities of di-n-octyl phthalate (DnOP) and di-n-decyl phthalate (DnDP) by the slow-stirring method are reported. The water solubility was also measured for di-n-hexyl phthalate (DnHP). The log K-ow val...

PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

EPA Science Inventory

PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

The plasticizer Di (2-ethylhexyl) phtha...

Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

PubMed Central

Bui, Tuan V; Stifani, Nicolas; Akay, Turgay; Brownstone, Robert M

2016-01-01

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery. DOI: http://dx.doi.org/10.7554/eLife.21715.001 PMID:27977000

Cyclic diguanylate signaling in Gram-positive bacteria

PubMed Central

Purcell, Erin B.; Tamayo, Rita

2016-01-01

The nucleotide second messenger 3′-5′ cyclic diguanylate monophosphate (c-di-GMP) is a central regulator of the transition between motile and non-motile lifestyles in bacteria, favoring sessility. Most research investigating the functions of c-di-GMP has focused on Gram-negative species, especially pathogens. Recent work in Gram-positive species has revealed that c-di-GMP plays similar roles in Gram-positives, though the precise targets and mechanisms of regulation may differ. The majority of bacterial life exists in a surface-associated state, with motility allowing bacteria to disseminate and colonize new environments. c-di-GMP signaling regulates flagellum biosynthesis and production of adherence factors and appears to be a primary mechanism by which bacteria sense and respond to surfaces. Ultimately, c-di-GMP influences the ability of a bacterium to alter its transcriptional program, physiology and behavior upon surface contact. This review discusses how bacteria are able to sense a surface via flagella and type IV pili, and the role of c-di-GMP in regulating the response to surfaces, with emphasis on studies of Gram-positive bacteria. PMID:27354347

Structural Insight into the Mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.

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

Tchigvintsev, A.; Xu, X.; Singer, A.

2010-08-01

Cyclic diguanylate (or bis-(3'-5') cyclic dimeric guanosine monophosphate; c-di-GMP) is a ubiquitous second messenger that regulates diverse cellular functions, including motility, biofilm formation, cell cycle progression, and virulence in bacteria. In the cell, degradation of c-di-GMP is catalyzed by highly specific EAL domain phosphodiesterases whose catalytic mechanism is still unclear. Here, we purified 13 EAL domain proteins from various organisms and demonstrated that their catalytic activity is associated with the presence of 10 conserved EAL domain residues. The crystal structure of the TBD1265 EAL domain was determined in free state (1.8 {angstrom}) and in complex with c-di-GMP (2.35 {angstrom}), andmore » unveiled the role of conserved residues in substrate binding and catalysis. The structure revealed the presence of two metal ions directly coordinated by six conserved residues, two oxygens of c-di-GMP phosphate, and potential catalytic water molecule. Our results support a two-metal-ion catalytic mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.« less

[Analysis of interdependence of temperament, neuroendocrine control and psychophysiological status during dry immersion].

PubMed

Nichiporuk, I A

2008-01-01

Interdependence of temperament, hormonal and psychophysiological status was investigated in 8 young volunteers for 7-d dry immersion (DI). Blood levels of insulin, sex, steroid, thyroid hormones and psychomotor parameters were determined on DI days 3 and 7, and on day 7 of recovery. Before DI, the volunteers filled in the Kettelle personality questionnaire. During DI, anxious subjects spent less time to compare visual patterns demonstrating high and stable speed of reactions but made a bit more errors. Extraverts showed high speed of reactions and stability of psychomotor parameters and did not increase the number of errors. Easy-tempered and introvert subjects preserved inherently high insulin concentrations in DI. Support deprivation was attended by drop of the levels of triiodothyronine and cortisol and rise of prolactin and thyroxin. Results of multiple correlation analysis led to the conclusion that DI accentuates the role of original extra-introversion and dampens origin anxiety. Successfulness can be attained by adequate alteration of the levels of steroid and thyroid hormones with effectively balanced vagoinsulin-sympathoadrenal neuroendocrine control and monoaminergic CNV activity.

Diabetes insipidus: The other diabetes

PubMed Central

Kalra, Sanjay; Zargar, Abdul Hamid; Jain, Sunil M.; Sethi, Bipin; Chowdhury, Subhankar; Singh, Awadhesh Kumar; Thomas, Nihal; Unnikrishnan, A. G.; Thakkar, Piya Ballani; Malve, Harshad

2016-01-01

Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefits over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin. PMID:26904464

Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report.

PubMed

Ma, Hongbing; Yang, Jing; Xiang, Bing; Jia, Yongqian

2015-06-01

Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 ( EVI1 )-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression (- 7/EVI1 + ) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with - 7/EVI1 + and without a 3q aberration. The possible mechanisms associated with EVI1 , monosomy 7 and DI were investigated.

12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake.

PubMed

Stanford, Kristin I; Lynes, Matthew D; Takahashi, Hirokazu; Baer, Lisa A; Arts, Peter J; May, Francis J; Lehnig, Adam C; Middelbeek, Roeland J W; Richard, Jeffrey J; So, Kawai; Chen, Emily Y; Gao, Fei; Narain, Niven R; Distefano, Giovanna; Shettigar, Vikram K; Hirshman, Michael F; Ziolo, Mark T; Kiebish, Michael A; Tseng, Yu-Hua; Coen, Paul M; Goodyear, Laurie J

2018-05-01

Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

Transformation of the Ionic X-Ray Contrast Agent Diatrizoate and Related Triiodinated Benzoates by Trametes versicolor

PubMed Central

Rode, Ulrike; Müller, Rudolf

1998-01-01

Iodinated X-ray contrast agents are considered to be nondegradable by microorganisms. The decomposition of the ionic X-ray contrast agents Diatrizoate (3,5-di(acetamido)-2,4,6-triiodobenzoic acid) and Iodipamide (3,3′-adipoyl-diimino-di(2,4,6-triiodobenzoic acid) and related triiodinated benzoates (Acetrizoate [3-acetylamino-2,4,6-triiodobenzoic acid] and Aminotrizoate [3-amino-2,4,6-triiodobenzoic acid]) by Trametes versicolor has been investigated. The fungus was able to transform all tested triiodinated benzoates cometabolically. During transformation of these compounds, iodide was released, but deiodination was not complete. T. versicolor liberated traces of 14CO2 from uniformly ring-14C-labeled Diatrizoate (3,5-di(acetamido)-2,4,6-triiodobenzoate). Various extracellular metabolites were detected during transformation of the different substances. In the transformation of Diatrizoate, the three main metabolites were identified as 3,5-di(acetamido)-2,6-diiodobenzoic acid, 3,5-di(acetamido)-2,4-diiodobenzoic acid, and 3,5-di(acetamido)-2-iodobenzoic acid, suggesting reductive deiodinations in steps as initial transformation steps. PMID:9687487

Exploring the Psychological Profile of Patients with Delusional Infestation.

PubMed

Shah, Reena; Taylor, Ruth E; Bewley, Anthony

2017-01-04

Delusional infestation (DI) is an uncommon psychiatric disorder in which patients present with the false and fixed belief (i.e. a delusion) that their skin and/or their environment is infested despite objective evidence to the contrary. Within psychodermatology specialist clinics there is a high rate of DI referrals. What is not known is the level of psychiatric and psychological co-morbidities associated with DI and whether psychiatric or psychological assessment would be warranted. One-hundred and thirty-eight adult patients with DI attending an outpatient psychodermatology clinic were given 3 standardised questionnaires. The results showed that 81% had a poor quality of life; 52% with anxiety, 41.6% with depression and 49% with appearance-related concerns. This study indicates high levels of psychiatric and psychological disorders in DI which require assessment and appropriate intervention.

The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS.

PubMed

Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C; Greaves-Lord, Kirstin

2015-06-01

The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3 Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3 Di and ADOS, in 186 children referred to six mental health centers. The parent report showed excellent correspondence to an ASD classification according to the 3 Di and both the 3 Di and ADOS. The teacher report added significantly to the screening accuracy over and above the parent report when compared with the ADOS classification. Findings support the screening utility of the parent-reported SRS among clinically referred children and indicate that different informants may provide unique information relevant for ASD assessment.

Combination of diOlistic labeling with retrograde tract tracing and immunohistochemistry.

PubMed

Neely, M Diana; Stanwood, Gregg D; Deutch, Ariel Y

2009-11-15

Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. DiOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has recently been introduced as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the restricted use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies.

Combination of DiOlistic Labeling with Retrograde Tract Tracing and Immunohistochemistry

PubMed Central

Diana Neely, M.; Stanwood, Gregg D; Deutch, Ariel Y.

2009-01-01

Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. Recently diOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has been developed as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies. PMID:19712695

List of Participants

NASA Astrophysics Data System (ADS)

2007-11-01

Mohab Abou ZeidVrije Universiteit, Brussel Joke AdamKatholieke Universiteit Leuven Nikolas AkerblomMax-Planck-Institut für Physik, München Luis Fernando Alday Utrecht University Stelios Alexandris University of Patras Antonio Amariti Università di Milano-Bicocca Nicola Ambrosetti Université de Neuchâtel Pascal Anastasopoulos Università di Roma Tor Vergata Laura Andrianopoli Enrico Fermi Center Carlo Angelantonj Università di Torino Lilia Anguelova Queen Mary, University of London Daniel AreanUniversidade de Santiago de Compostela Gleb ArutyunovUtrecht University Spyros Avramis NTU Athens—University of Patras Ioannis Bakas University of Patras Subrata Bal Dublin Institute for Advanced Studies Igor Bandos Valencia University Jessica Barrett University of Iceland Marco Baumgartl Eidgenössische Technische Hochschule, Zürich Jacopo Bechi Università di Firenze James Bedford Queen Mary, University of London Jorge Bellorin Universidad Autonoma de Madrid Francesco Benini SISSA, Trieste Eric Bergshoeff Centre for Theoretical Physics, University of Groningen Gaetano BertoldiUniversity of Wales, Swansea Adel Bilal Laboratoire de Physique Théorique, École Normale Superieure, Paris Matthias Blau Université de Neuchâtel Johannes BroedelUniversität Hannover Felix Brümmer Universität Heidelberg Julio Cesar Bueno de Andrade São Paulo State University—UNESP Cliff Burgess McMaster University Agostino Butti Laboratoire de Physique Théorique, École Normale Superieure, Paris Marco Caldarelli Universitat de Barcelona Pablo G Camara Centre de Physique Théorique, École Polytechnique, Palaiseau Joan Camps Universitat de Barcelona Felipe Canoura FernandezUniversidade de Santiago de Compostela Luigi Cappiello Università di Napoli Federico II Luca Carlevaro École Polytechnique, Palaiseau Roberto Casero Centre de Physique Théorique, École Polytechnique, Palaiseau Claudio Caviezel Max-Planck-Institut für Physik, München Alessio Celi Universitat de Barcelona Anna Ceresole Istituto Nazionale di Fisica Nucleare and Università di Torino Kang Sin Choi University of Bonn Michele Cirafici University of Patras Andres Collinucci Katholieke Universiteit Leuven Aldo Cotrone Universitat de Barcelona Ben Craps Vrije Universiteit, Brussel Stefano Cremonesi SISSA, Trieste Gianguido Dall'Agata Padova University Sanjit Das Indian Institute of Technology, Kharagpur Forcella Davide SISSA, Trieste Jose A de Azcarraga Valencia University and Instituto de Fìsica Corpuscular (CSIC-UVEG), Valencia Sophie de BuylInstitut des Hautes Études Scientifiques, Bures-sur-Yvette Jean-Pierre Derendinger Université de Neuchâtel Stephane Detournay Università Degli Studi di Milano Paolo Di Vecchia NORDITA, København Oscar Dias Universitat de Barcelona Vladimir Dobrev Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, Sofia Joel Ekstrand Department of Theoretical Physics, Uppsala University Federico Elmetti Università di Milano I Diaconu Eugen University of Craiova Oleg Evnin Vrije Universiteit, Brussel Bo Feng Imperial College, London Livia Ferro Università di Torino Pau Figueras Universitat de Barcelona Raphael Flauger University of Texas at Austin Valentina Forini Università di Perugia Angelos Fotopoulos Università di Torino Denis Frank Université de Neuchâtel Lisa Freyhult Albert-Einstein-Institut, Golm Carlos Fuertes Instituto de Física Teórica, Madrid Matthias Gaberdiel Eidgenössische Technische Hochschule, Zürich Maria Pilar Garcia del Moral Università di Torino Daniel Gerber Instituto de Física Teórica, Madrid Valentina Giangreco Marotta Puletti Uppsala University Joaquim Gomis Universitat de Barcelona Gianluca Grignani Università di Perugia Luca Griguolo Università di Parma Umut Gursoy École Polytechnique, Palaiseau and École Normale Supérieure, Paris Michael Haack Ludwig-Maximilians-Universität, München Troels Harmark Niels Bohr Institute, København Alexander Haupt Imperial College, London Michal Heller Jagiellonian University, Krakow Samuli Hemming University of Iceland Yasuaki Hikida DESY, Hamburg Christian Hillmann Max-Planck-Institut für Gravitationsphysik, Potsdam Stephan Hoehne Max-Planck-Institut für Physik, München Gabriele Honecker CERN, Geneva Carlos Hoyos University of Wales, Swansea Mechthild Huebscher Consejo Superior de Investigaciones Cientificas, Madrid Matthias Ihl University of Texas at Austin Emiliano Imeroni University of Wales, Swansea Nikos Irges University of Crete Negru Iulian University of Craiova Matthias Kaminski Ludwig-Maximilians-Universität, München Stefanos Katmadas Universiteit Utrecht Shoichi Kawamoto Oxford University Christoph Keller Eidgenössische Technische Hochschule, Zürich Arjan Keurentjes Vrije Universiteit, Brussel Sadi Khodaee Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran Michael Kiermaier Massachusetts Institute of Technology, Cambridge, MA Elias Kiritsis Centre de Physique Théorique, École Polytechnique, Palaiseau and University of Crete Ingo KirschEidgenössische Technische Hochschule, Zürich Johanna Knapp CERN, Geneva Paul Koerber Max-Planck-Institut für Physik, München Simon Koers Max-Planck-Institut für Physik, München Anatoly Konechny Heriot-Watt University, Edinburgh Peter Koroteev Institute for Theoretical and Experimental Physics (ITEP), Moscow Daniel KreflLudwig-Maximilians-Universität and Max-Planck-Institut für Physik, München Chethan KrishnanUniversité Libre de Bruxelles Stanislav Kuperstein Université Libre de Bruxelles Alberto Lerda Università del Piemonte Orientale, Alessandria Roman Linares Universidad Autonoma Metropolitana, Iztapalapa, México Maria A Lledo Universidad de Valencia Dieter Luest Ludwig-Maximilians-Universität and Max-Planck-Institut für Physik, München Joseph Lykken Fermi National Accelerator Laboratory (Fermilab), Batavia, IL Carlo Maccaferri Vrije Universiteit, Brussel Oscar Macia Universidad de Valencia Tristan Maillard Centre de Physique Théorique, École Polytechnique, Palaiseau Diego Mansi Università Degli Studi di Milano Matteo Marescotti Università del Piemonte Orientale, Alessandria Alberto Mariotti Università di Milano-Bicocca Raffaele Marotta Istituto Nazionale di Fisica Nucleare, Napoli Alessio Marrani Istituto Nazionale di Fisica Nucleare and LNF, Firenze Luca Martucci Instituto de Física Teórica, Madrid and Katholieke Universiteit Leuven David Mateos University of California, Santa Barbara Andrea Mauri Università di Milano Liuba Mazzanti Università di Milano-Bicocca Patrick Meessen Instituto de Física Teórica, Universidad Autónoma de Madrid Lotta Mether Helsinki Institute of Physics Rene Meyer Max-Planck-Institut für Physik, München Giuseppe Milanesi SISSA, Trieste Cesar Miquel-Espanya Universitat de Valencia and Instituto de Física Corpuscular, Valencia Alexander Monin Institute for Theoretical and Experimental Physics (ITEP), Moscow and Moscow State University (MSU) Samuel Monnier Université de Genève Sergio Montero Instituto de Física Teórica, Madrid Nicola Mori Università di Firenze Alexander Marcel Morisse University of California, Santa Cruz Sebastian Moster Max-Planck-Institut für Physik, München Adele Nasti Queen Mary, University of London Vasilis Niarchos École Polytechnique, Palaiseau Emil Nissimov Institute for Nuclear Research and Nuclear Energy, Sofia Francesco Nitti École Polytechnique, Palaiseau Eoin O'Colgain Imperial College, London Niels Obers Niels Bohr Institute, København Rodrigo Olea Università Degli Studi di Milano Marta Orselli Niels Bohr Institute, København Enrico PajerLudwig-Maximilians-Universität, München Eran PaltiOxford University Georgios PapathanasiouBrown University, Providence, RI Angel ParedesCentre de Physique Théorique, École Polytechnique, Palaiseau Jeong-Hyuck ParkMax-Planck-Institut für Physik, München Sara PasquettiUniversità di Parma Silvia PenatiUniversità di Milano-Bicocca Igor PesandoUniversità di Torino Marios PetropoulosÉcole Polytechnique, Palaiseau Roberto PettorinoUniversità di Napoli Federico II Franco PezzellaIstituto Nazionale di Fisica Nucleare, Napoli Moises Picon PonceIstituto Nazionale di Fisica Nucleare, Padova Marco PirroneUniversità di Milano-Bicocca Erik PlauschinnMax-Planck-Institut für Physik, München Andre PloeghCentre for Theoretical Physics, University of Groningen Giuseppe PolicastroLaboratoire de Physique Théorique, École Normale Superieure, Paris Josep PonsUniversitat de Barcelona S Prem KumarUniversity of Wales, Swansea Nikolaos PrezasCERN, Geneva Carlo Alberto RattiUniversità di Milano-Bicocca Riccardo RicciImperial College, London Alejandro RiveroEscuela Universitaria Politécnica de Teruel, Universidad de Zaragoza Irene RodriguezInstituto de Física Teórica, Madrid Maria Jose RodriguezUniversitat de Barcelona Diederik RoestUniversitat de Barcelona Alberto RomagnoniLaboratoire de Physique Théorique d'Orsay, Paris Christian RomelsbergerDublin Institute for Advanced Studies Jan RosseelKatholieke Universiteit Leuven Sebastiano RossiEidgenössische Technische Hochschule, Zürich Felix RustMax-Planck-Institut für Physik, München Cheol RyouPohang University of Science and Technology (POSTECH) Christian SaemannDublin Institute for Advanced Studies Houman Safaai SISSA, Trieste Alberto SantambrogioIstituto Nazionale di Fisica Nucleare, Sezione di Milano Frank SaueressigUniversiteit Utrecht Ricardo SchiappaCERN, Geneva Cornelius Schmidt-ColinetEidgenössische Technische Hochschule, Zürich Maximilian Schmidt-SommerfeldMax-Planck-Institut für Physik, München Waldemar SchulginMax-Planck-Institut für Physik, München Claudio ScruccaUniversité de Neuchâtel Nathan SeibergInstitute of Advanced Studies, Princeton, NJ Domenico SeminaraUniversità di Firenze Alexander SevrinVrije Universiteit, Brussel Konstadinos SfetsosUniversity of Patras Kostas SiamposUniversity of Patras Christoph SiegUniversità Degli Studi di Milano Vaula Silvia Instituto de Física Teórica, Madrid Aaron Sim Imperial College, London Woojoo Sim Pohang University of Science and Technology (POSTECH) Sergey Slizovskiy Department of Theoretical Physics, Uppsala University Paul Smyth Katholieke Universiteit Leuven Corneliu Sochichiu Laboratori Nazionali di Frascati Dmitri Sorokin Istituto Nazionale di Fisica Nucleare, Padova Kellogg Stelle Imperial College, London Piotr Surowka Jagiellonian University, Krakow Yasutoshi Takayama Niels Bohr Institute, København Laura Tamassia Katholieke Universiteit Leuven Radu Tatar University of Liverpool Larus Thorlacius University of Iceland Paavo Tiitola Helsinki Institute of Physics Diego Trancanelli Stony Brook University, NY Michele TraplettiInstitut für Theoretische Physik, Universität Heidelberg Mario Trigiante Politecnico di Torino Angel Uranga CERN, Geneva and Instituto de Física Teórica, Madrid Roberto Valandro SISSA, Trieste Dieter Van den Bleeken Katholieke Universiteit Leuven Antoine Van Proeyen Katholieke Universiteit Leuven Thomas Van Riet Centre for Theoretical Physics, University of Groningen Pierre Vanhove Service de Physique Théorique, Saclay Oscar Varela Universidad de Valencia Alessandro Vichi Scuola Normale Superiore di Pisa Massimiliano VinconQueen Mary, University of London John Ward Queen Mary, University of London and CERN, Geneva Brian Wecht Massachusetts Institute of Technology, Cambridge, MA Marlene Weiss Eidgenössische Technische Hochschule, Zürich and CERN, Geneva Sebastian Weiss Université de Neuchâtel Alexander Wijns Vrije Universiteit, Brussel Przemek Witaszczyk Jagiellonian University, Krakow Timm Wrase University of Texas at Austin Jun-Bao Wu SISSA, Trieste Amos Yarom Ludwig-Maximilians-Universität, München Marco Zagermann Max-Planck-Institut für Physik, München Daniela Zanon Dipartimento di Fisica, Università di Milano Andrea Zanzi University of Bonn Andrey Zayakin Moscow State University (MSU) and Institute for Theoretical and Experimental Physics (ITEP), Moscow Konstantinos Zoubos Queen Mary, University of London

Homozygote Depression in Gamete-Derived Dragon-Fruit (Hylocereus) Lines

PubMed Central

Li, Daqing; Arroyave Martinez, Maria F.; Shaked, Ruth; Tel-Zur, Noemi

2018-01-01

Putative gamete-derived progenies from two Hylocereus species, the diploid H. monacanthus and the tetraploid H. megalanthus, were studied with the dual aims to confirm their gamete origin and to evaluate their potential use as genetic resources. An additional goal was to determine the origin (allotetraploid vs. autotetraploid) of H. megalanthus by exploring morphological variations in the di-haploid (2x) H. megalanthus progeny. Gamete origin was proved in all five H. monacanthus lines obtained and in 49 of the 70 H. megalanthus lines by using flow cytometry and simple sequence repeat (SSR) markers. The five double-haploid (2x) H. monacanthus lines showed low vigor and abnormal flower development, with malformed ovules and aborted pollen grains. Only one flower set fruit, giving several viable seeds. For H. megalanthus, both abnormal ovules and defective anthers were observed in the di-haploid (2x) and double di-haploid (4x) lines. Among the 46 di-haploid lines, only 14 set fruit. Another 13 di-haploid lines formed flower buds that abscised before anthesis or soon after pollination. The severe sterility of the double-haploid H. monacanthus and the reduced fertility of all the di-haploid and double di-haploid H. megalanthus lines can be linked to their reduced heterozygosity, which drastically affected the development of normal female and male organs. We thus concluded that chromosome doubling, as occurred spontaneously in the double-haploid H. monacanthus and the double di-haploid H. megalanthus, is not sufficient to restore fertility in Hylocereus. We also observed very low gametoclonal variation among the di-haploid (2x) H. megalanthus lines, a finding that supported an autotetraploid, rather than an allotetraploid, origin of this species. Nonetheless, despite the above-described challenging limitations, these gamete-derived lines are currently being bred as the seed parent, offering unique possibilities for genetic research and additional breeding. PMID:29354138

The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

PubMed Central

Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

2014-01-01

Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

PubMed

Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

2015-01-01

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Prospective validation study of the International Classification of Functioning, Disability and Health score in Crohn's disease and ulcerative colitis.

PubMed

Leong, Rupert W L; Huang, Tony; Ko, Yanna; Jeon, Ari; Chang, Jeff; Kohler, Friedbert; Kariyawasam, Viraj

2014-10-01

Inflammatory bowel diseases (IBD) may result in disability. We aim to validate a novel scoring system for the IBD disability index (IBD-DI), and identify predictors of disability and its correlation with work absenteeism. This prospective IBD ambulatory clinic cohort study measured IBD-DI, Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) or partial Mayo score (pMayo) for ulcerative colitis (UC), IBDQ quality-of-life, and Work Productivity and Activity Impairment. Negative IBD-DI represented greater disability. Validation tests were performed and predictors and extent of work absenteeism were determined. 166 consecutive subjects were recruited (75 CD, 41 UC, 50 controls). IBD-DI correlated with CDAI (r=-0.77, P<0.001), pMayo (r=-0.82, P<0.001) and IBDQ (r=0.86, P<0.001). IBD-DI differentiated CD, and UC from controls (medians -7, -4, +10; P<0.001) with a score of >3.5 identifying controls with 94% sensitivity and 83% specificity (area-under-curve 0.92). Stable patients had unchanged IBD-DI (P=ns) but not in those who relapsed (P<0.001). Intraclass correlation was 0.89 and Cronbach's alpha of internal consistency was 0.94. Diagnosis age, sex, phenotype, perianal disease, prior surgery, steroid-use and disease duration did not influence the IBD-DI but active use of biological agents significantly reduced disability (P=0.03). 21.6% of IBD patients had moderate-severe disability equating to missing >25% of work hours in the previous week. Multivariate analysis identified that only IBD-DI to be predictive of unemployment status (OR: 0.94; 95% CI: 0.89-0.99). The IBD-DI is a valid tool measuring disability in both CD and UC and correlates with workforce participation. It is a potential useful tool in the assessment of participation restriction and activity limitation. ACTRN12613000903785. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

PubMed Central

Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs

2017-01-01

ABSTRACT The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli. This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. PMID:28928205

WE-G-204-02: Utility of a Channelized Hotelling Model Observer Over a Large Range of Angiographic Exposure Levels

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

Fetterly, K; Favazza, C

2015-06-15

Purpose: Mathematical model observers provide a figure of merit that simultaneously considers a test object and the contrast, noise, and spatial resolution properties of an imaging system. The purpose of this work was to investigate the utility of a channelized Hotelling model observer (CHO) to assess system performance over a large range of angiographic exposure conditions. Methods: A 4 mm diameter disk shaped, iodine contrast test object was placed on a 20 cm thick Lucite phantom and 1204 image frames were acquired using fixed x-ray beam quality and for several detector target dose (DTD) values in the range 6 tomore » 240 nGy. The CHO was implemented in the spatial domain utilizing 96 Gabor functions as channels. Detectability index (DI) estimates were calculated using the “resubstitution” and “holdout” methods to train the CHO. Also, DI values calculated using discrete subsets of the data were used to estimate a minimally biased DI as might be expected from an infinitely large dataset. The relationship between DI, independently measured CNR, and changes in results expected assuming a quantum limited detector were assessed over the DTD range. Results: CNR measurements demonstrated that the angiography system is not quantum limited due to relatively increasing contamination from electronic noise that reduces CNR for low DTD. Direct comparison of DI versus CNR indicates that the CHO relatively overestimates DI for low DTD and/or underestimates DI values for high DTD. The relative magnitude of the apparent bias error in the DI values was ∼20% over the 40x DTD range investigated. Conclusion: For the angiography system investigated, the CHO can provide a minimally biased figure of merit if implemented over a restricted exposure range. However, bias leads to overestimates of DI for low exposures. This work emphasizes the need to verify CHO model performance during real-world application.« less

Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area induces reinstatement of cocaine-seeking behaviour in rats.

PubMed

Placenza, Franca M; Fletcher, Paul J; Rotzinger, Susan; Vaccarino, Franco J

2004-12-01

The mesocorticolimbic dopamine (DA) system is critically involved in mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a neuropeptide that significantly interacts with the mesocorticolimbic system, therefore suggesting a possible role for the SP system in the mediation of relapse. This study examined the effects of injections of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of cocaine-seeking behaviour, as well as on locomotor activity in rats. Additionally, this study examined whether these effects are DA-dependent. Rats were trained to self-administer cocaine for 15 days followed by 15 days of extinction. Reinstatement of cocaine-seeking behaviour was then measured in response to bilateral intra-VTA microinjections of DiMe-C7 (0, 0.1, 0.5 and 2.5 microg). In a separate group of rats, locomotor activity was measured in response to intra-VTA injections of DiMe-C7 (0, 0.5, 1.5 and 3 microg). The effects of pre-treatment with DA receptor antagonists on DiMe-C7-induced reinstatement and locomotor activity were also examined. Animals were pre-treated with the D(1) and D(2) receptor antagonists, SCH23390 and haloperidol (0, 0.01 and 0.03 mg/kg, IP), respectively, prior to receiving intra-VTA injections of DiMe-C7 (0 and 2.5 microg). Infusion of DiMe-C7 into the VTA increased locomotor activity and induced reinstatement of cocaine-seeking behaviour. Both SCH23390 and haloperidol blocked intra-VTA DiMe-C7-induced locomotor activation. In addition, SCH23390 attenuated DiMe-C7-induced reinstatement of cocaine-seeking behaviour, while haloperidol had no effect. These results suggest that interactions between SP and the mesocorticolimbic DA system may play a role in mediating reinstatement of cocaine-seeking behaviour and that the involvement of these interactions in reinstatement are dependent upon D(1) receptor mechanisms.

Value of supervised learning events in predicting doctors in difficulty.

PubMed

Patel, Mumtaz; Agius, Steven; Wilkinson, Jack; Patel, Leena; Baker, Paul

2016-07-01

In the UK, supervised learning events (SLE) replaced traditional workplace-based assessments for foundation-year trainees in 2012. A key element of SLEs was to incorporate trainee reflection and assessor feedback in order to drive learning and identify training issues early. Few studies, however, have investigated the value of SLEs in predicting doctors in difficulty. This study aimed to identify principles that would inform understanding about how and why SLEs work or not in identifying doctors in difficulty (DiD). A retrospective case-control study of North West Foundation School trainees' electronic portfolios was conducted. Cases comprised all known DiD. Controls were randomly selected from the same cohort. Free-text supervisor comments from each SLE were assessed for the four domains defined in the General Medical Council's Good Medical Practice Guidelines and each scored blindly for level of concern using a three-point ordinal scale. Cumulative scores for each SLE were then analysed quantitatively for their predictive value of actual DiD. A qualitative thematic analysis was also conducted. The prevalence of DiD in this sample was 6.5%. Receiver operator characteristic curve analysis showed that Team Assessment of Behaviour (TAB) was the only SLE strongly predictive of actual DiD status. The Educational Supervisor Report (ESR) was also strongly predictive of DiD status. Fisher's test showed significant associations of TAB and ESR for both predicted and actual DiD status and also the health and performance subtypes. None of the other SLEs showed significant associations. Qualitative data analysis revealed inadequate completion and lack of constructive, particularly negative, feedback. This indicated that SLEs were not used to their full potential. TAB and the ESR are strongly predictive of DiD. However, SLEs are not being used to their full potential, and the quality of completion of reports on SLEs and feedback needs to be improved in order to better identify and manage DiD. © 2016 John Wiley & Sons Ltd.

Polyfluoroalkyl phosphate esters and perfluoroalkyl carboxylic acids in target food samples and packaging--method development and screening.

PubMed

Gebbink, Wouter A; Ullah, Shahid; Sandblom, Oskar; Berger, Urs

2013-11-01

Polyfluoroalkyl phosphate mono-, di-, and tri-esters (mono-, di-, and triPAPs) are used to water- and grease-proof food packaging materials, and these chemicals are known precursors to perfluoroalkyl carboxylic acids (PFCAs). Existing analytical methods for PAPs lack sample clean-up steps in the sample preparation. In the present study, a method based on ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC/MS/MS) was developed and optimized for the analysis of mono-, di-, and triPAPs, including a clean-up step for the raw extracts. The method was applied to food samples and their PAP-containing packaging materials. The optimized UPLC/MS/MS method enabled the separation and identification of a total of 4 monoPAPs, 16 diPAPs, and 7 triPAPs in the technical mixture Zonyl®-RP. For sample clean-up, weak anion exchange solid phase extraction columns were tested. PAPs standard solutions spiked onto the columns were separated into a fraction containing neutral compounds (triPAPs) and a fraction with ionic compounds (mono- and diPAPs) with recoveries between 72-110%. Method limits of quantification for food samples were in the sub to low picogram per gram range. For quantitative analysis of PAPs, compound-specific labeled internal standards showed to be essential as sorption and matrix effects were observed. Mono-, di-, and/or triPAPs were detected in all food packaging materials obtained from the Swedish market. Up to nine diPAPs were detected in the food samples, with the 6:2/6:2 and 6:2/8:2 diPAPs as the dominant compounds. DiPAP concentrations in the food samples ranged from 0.9 to 36 pg/g, which was comparable to individual PFCA concentrations in the same samples. Consumption of food packed in PAP-containing materials could be an indirect source of human exposure to PFCAs.

Dissociative Ionization of Pyridine by Electron Impact

NASA Technical Reports Server (NTRS)

Dateo, Christopher; Huo, Winifred; Kwak, Dochan (Technical Monitor)

2002-01-01

In order to understand the damage of biomolecules by electrons, a process important in radiation damage, we undertake a study of the dissociative ionization (DI) of pyridine (C5H5N) from the low-lying ionization channels. The methodology used is the same as in the benzene study. While no experimental DI data are available, we compare the dissociation products from our calculations with the dissociative photoionization measurements of Tixier et al. using dipole (e, e(+) ion) coincidence spectroscopy. Comparisons with the DI of benzene is also made so as to understand the difference in DI between a heterocyclic and an aromatic molecule.

Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5' deiodinase deficiency.

PubMed

Berry, M J; Grieco, D; Taylor, B A; Maia, A L; Kieffer, J D; Beamer, W; Glover, E; Poland, A; Larsen, P R

1993-09-01

Inbred mouse strains differ in their capacity to deiodinate iododioxin and iodothyronines, with strains segregating into high or low activity groups. Metabolism of iododioxin occurs via the type I iodothyronine 5'deiodinase (5'DI), one of two enzymes that metabolize thyroxine (T4) to 3,5,3'-triiodothyronine (T3). Recombinant inbred strains derived from crosses between high and low activity strains exhibit segregation characteristic of a single allele difference. Hepatic and renal 5'DI mRNA in a high (C57BL/6J) and low (C3H/HeJ) strain paralleled enzyme activity and concentration, in agreement with a recent report. 5'DI-deficient mice had twofold higher serum free T4 but normal free T3 and thyrotropin. Brown adipose tissue 5'DII was invariant between the two strains. Southern analyses using a 5'DI probe identified a restriction fragment length variant that segregated with 5'DI activity in 33 of 35 recombinant inbred strains derived from four different pairs of high and low activity parental strains. Recombination frequencies using previously mapped loci allowed assignment of the 5'DI gene to mouse chromosome 4 and identified its approximate chromosomal position. We propose the symbol Dio1 to denote the mouse 5'DI gene. Conserved linkage between this segment of mouse chromosome 4 and human HSA1p predicts this location for human Dio1.

The extremophile Acidithiobacillus ferrooxidans possesses a c-di-GMP signalling pathway that could play a significant role during bioleaching of minerals.

PubMed

Ruiz, L M; Castro, M; Barriga, A; Jerez, C A; Guiliani, N

2012-02-01

  The primary goal of this study was to characterize the existence of a functional c-di-GMP pathway in the bioleaching bacterium Acidithiobacillus ferrooxidans.   A bioinformatic search revealed that the genome sequence of At. ferrooxidans ATCC 23270 codes for several proteins involved in the c-di-GMP pathway, including diguanylate cyclases (DGC), phosphodiesterases and PilZ effector proteins. Overexpression in Escherichia coli demonstrated that four At. ferrooxidans genes code for proteins containing GGDEF/EAL domains with functional DGC activity. MS/MS analysis allowed the identification of c-di-GMP in nucleotide preparations obtained from At. ferrooxidans cells. In addition, c-di-GMP levels in cells grown on the surface of solid energetic substrates such as sulfur prills or pyrite were higher than those measured in ferrous iron planktonic cells.   At. ferrooxidans possesses a functional c-di-GMP pathway that could play a key role in At. ferrooxidans biofilm formation during bioleaching processes.   This is the first global study about the c-di-GMP pathway in an acidophilic bacterium of great interest for the biomining industry. It opens a new way to explore the regulation of biofilm formation by biomining micro-organisms during the bioleaching process. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy.

PubMed

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-24

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL 'opens' to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

Disegno dello studio genomico, ambientale, microbiomico e metabolomico sulla celiachia: un approccio al futuro della prevenzione personalizzata della celiachia

PubMed Central

SERENA, GLORIA; LEONARD, MAUREEN M.; CAMHI, STEPHANIE; HUEDO-MEDINA, TANIA B.; FASANO, ALESSIO

2017-01-01

Riassunto Negli ultimi anni abbiamo assistito a un fiorire di novità cliniche e scientifiche sulla celiachia (CE), ma forse la novità più importante che influenzerà il futuro della ricerca e della clinica in questo campo riguarda la storia naturale della malattia. Per molti anni si è creduto che la predisposizione genetica e l’esposizione al glutine fossero necessarie e sufficienti allo sviluppo della CE. Studi recenti, però suggeriscono che la perdita di tolleranza al glutine possa apparire in qualsiasi momento della vita a seguito di altri elementi. Inoltre, diversi fattori ambientali conosciuti per il loro ruolo nell’influenzare la composizione della microflora intestinale sono anche stati considerati legati allo sviluppo della CE. Tra questi fattori sono inclusi la modalità di parto, la dieta dell’infante e l’uso di antibiotici. A tutt’oggi, nessuno studio longitudinale di ampia scala ha determinato se e come la composizione del microbioma e il suo profilo metabolomico possano influenzare la perdita di tolleranza al glutine e il successivo sviluppo della CE in soggetti geneticamente predisposti. In questo articolo descriviamo uno studio prospettico, multicentrico e longitudinale su infanti a rischio per la CE che utilizzerà diverse tecniche per approfondire il ruolo che il microbioma intestinale ha durante i primi passaggi dello sviluppo della malattia autoimmune. PMID:27362724

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

NASA Astrophysics Data System (ADS)

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-01

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

Acute diabetes insipidus mediated by vasopressinase after placental abruption.

PubMed

Wallia, Amisha; Bizhanova, Aigerim; Huang, Wenyu; Goldsmith, Susan L; Gossett, Dana R; Kopp, Peter

2013-03-01

Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

External validity of the pediatric cardiac quality of life inventory

PubMed Central

Marino, Bradley S.; Drotar, Dennis; Cassedy, Amy; Davis, Richard; Tomlinson, Ryan S.; Mellion, Katelyn; Mussatto, Kathleen; Mahony, Lynn; Newburger, Jane W.; Tong, Elizabeth; Cohen, Mitchell I.; Helfaer, Mark A.; Kazak, Anne E.; Wray, Jo; Wernovsky, Gil; Shea, Judy A.; Ittenbach, Richard

2012-01-01

Purpose The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific, health-related quality of life (HRQOL) measure for pediatric heart disease (HD). The purpose of this study was to demonstrate the external validity of PCQLI scores. Methods The PCQLI development site (Development sample) and six geographically diverse centers in the United States (Composite sample) recruited pediatric patients with acquired or congenital HD. Item response option variability, scores [Total (TS); Disease Impact (DI) and Psychosocial Impact (PI) subscales], patterns of correlation, and internal consistency were compared between samples. Results A total of 3,128 patients and parent participants (1,113 Development; 2,015 Composite) were analyzed. Response option variability patterns of all items in both samples were acceptable. Inter-sample score comparisons revealed no differences. Median item–total (Development, 0.57; Composite, 0.59) and item–subscale (Development, DI 0.58, PI 0.59; Composite, DI 0.58, PI 0.56) correlations were moderate. Subscale–subscale (0.79 for both samples) and subscale–total (Development, DI 0.95, PI 0.95; Composite, DI 0.95, PI 0.94) correlations and internal consistency (Development, TS 0.93, DI 0.90, PI 0.84; Composite, TS 0.93, DI 0.89, PI 0.85) were high in both samples. Conclusion PCQLI scores are externally valid across the US pediatric HD population and may be used for multi-center HRQOL studies. PMID:21188538

Chemical Synthesis and Evaluation of a Disialic Acid-Containing Dextran Polymer as an Inhibitor for the Interaction between Siglec 7 and Its Ligand.

PubMed

Yamaguchi, Sho; Yoshimura, Atsushi; Yasuda, Yu; Mori, Airi; Tanaka, Hiroshi; Takahashi, Takashi; Kitajima, Ken; Sato, Chihiro

2017-07-04

A new sialic acid (Sia)-containing glycopolymer-a fluorescent probe with high-density disialic acid (diSia) on the surface of polysaccharide dextran (diSia-Dex)-was synthesized as a key molecule to regulate the Sia recognition lectins, Siglecs, that are involved in the immune system. According to our original methods, diSia was synthesized by α-selective sialylation, and a dextran template possessing terminal acetylenes and amino groups was prepared. A diSia and a fluorescent molecule were subsequently introduced to surface-modified dextran by Hüisgen reaction and amidation, respectively. The modulatory activity of Siglec7 was evaluated by using synthetic probes. DiSia-Dex showed high binding avidity toward Siglec7, with a K D value of 5.87×10 -10  m, and a high inhibitory activity for the interaction between Siglec7 and a ligand (GD3), with a IC 50 value of 1.0 nm. Notably, diSia-Dex was able to release Siglec7 from the pre-existing Siglec7-GD3 complex, possibly due to its unique properties of a slow dissociation rate and a high association rate. Together, these data show that diSia-Dex can be widely applicable as a modulator of Siglec7 functions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of cyclic diguanylate in affecting microbial community shifts at different pH during the operation of simultaneous partial nitrification, anammox and denitrification process.

PubMed

Wang, Chao; Liu, Sitong; Xu, Xiaochen; Guo, Yongzhao; Yang, Fenglin; Wang, Dong

2018-05-08

The intracellular cyclic diguanylate acid (c-di-GMP) has emerged as a prominent second signal molecule that coordinates sessile-motile transition and biofilm formation in many bacteria. Herein, we study the role of c-di-GMP in affecting microbial community shifts at different pH levels during simultaneous partial nitrification, anammox and denitrification process (SNAD) in integrated fixed film activated sludge (IFAS) reactor. The results demonstrated that the contents of c-di-GMP notably decreased in suspended sludge, whereas the contents of c-di-GMP in biofilm had no significant change as pH gradually increased from 7.5 to 8.5. Most of the bacteria (Blastocatella, Brevundimonas) with flagella that have been reported to be regulated by c-di-GMP were present in suspended sludge, and the microbial community structure of suspended sludge had obvious change than biofilm. The increased alkaline pH reduced intracellular c-di-GMP content for increasing the motility of bacteria to be washed out from the reactor, causing the microbial community shifts in suspended sludge. This change would lead to the increase of nitrite-oxidizing bacteria which would inhibit anammox activity. Overall, this study provided more comprehensive information regarding the shifts of microbial community induced by c-di-GMP in SNAD-IFAS reactor. Copyright © 2018. Published by Elsevier B.V.

40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and Silicones, di-Me, Me... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as Siloxanes and Silicones...

40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and Silicones, di-Me, Me... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as Siloxanes and Silicones...

40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

75 FR 27185 - Revisions to the Authorization for Validated End-User Applied Materials China, Ltd.

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-14

... Service Center, No. 1 North Di Sheng Street, BDA, Beijing, China 100176. Applied Materials South East Asia..., Shanghai, China 201203. Applied Materials (China), Inc.--Beijing Depot, No. 1 North Di Sheng Street, BDA... Di Sheng Street, BDA Beijing, China 100176. Applied Materials South East Asia Pte. Ltd.-- Wuxi Depot...

Interdisciplinary investigations in support of project DI-MOD

NASA Technical Reports Server (NTRS)

Starks, Scott A.

1991-01-01

Interdisciplinary investigations in support of project DI-MOD are discussed. The following subject areas were covered: (1) potential extensions of Project DI-MOD to additional sites in Central America; (2) human migration patterns and their impact on malaria transmission; and (3) an investigation into possible computer-based approaches to the analysis of remotely sensed multispectral data.

32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development (HUD). 644.336 Section 644.336... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development...

Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology.

PubMed

Tomasi, G; Kimberley, S; Rosso, L; Aboagye, E; Turkheimer, F

2012-04-07

In positron emission tomography (PET) studies involving organs different from the brain, ignoring the metabolite contribution to the tissue time-activity curves (TAC), as in the standard single-input (SI) models, may compromise the accuracy of the estimated parameters. We employed here double-input (DI) compartmental modeling (CM), previously used for [¹¹C]thymidine, and a novel DI spectral analysis (SA) approach on the tracers 5-[¹⁸F]fluorouracil (5-[¹⁸F]FU) and [¹⁸F]fluorothymidine ([¹⁸F]FLT). CM and SA were performed initially with a SI approach using the parent plasma TAC as an input function. These methods were then employed using a DI approach with the metabolite plasma TAC as an additional input function. Regions of interest (ROIs) corresponding to healthy liver, kidneys and liver metastases for 5-[¹⁸F]FU and to tumor, vertebra and liver for [¹⁸F]FLT were analyzed. For 5-[¹⁸F]FU, the improvement of the fit quality with the DI approaches was remarkable; in CM, the Akaike information criterion (AIC) always selected the DI over the SI model. Volume of distribution estimates obtained with DI CM and DI SA were in excellent agreement, for both parent 5-[¹⁸F]FU (R(2) = 0.91) and metabolite [¹⁸F]FBAL (R(2) = 0.99). For [¹⁸F]FLT, the DI methods provided notable improvements but less substantial than for 5-[¹⁸F]FU due to the lower rate of metabolism of [¹⁸F]FLT. On the basis of the AIC values, agreement between [¹⁸F]FLT K(i) estimated with the SI and DI models was good (R² = 0.75) for the ROIs where the metabolite contribution was negligible, indicating that the additional input did not bias the parent tracer only-related estimates. When the AIC suggested a substantial contribution of the metabolite [¹⁸F]FLT-glucuronide, on the other hand, the change in the parent tracer only-related parameters was significant (R² = 0.33 for K(i)). Our results indicated that improvements of DI over SI approaches can range from moderate to substantial and are more significant for tracers with a high rate of metabolism. Furthermore, they showed that SA is suitable for DI modeling and can be used effectively in the analysis of PET data.

Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors.

PubMed

Hayashi, Yasuhiko; Kita, Daisuke; Watanabe, Takuya; Fukui, Issei; Sasagawa, Yasuo; Oishi, Masahiro; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi

2016-12-01

Diabetes insipidus (DI) remains a complication of transsphenoidal surgery (TSS) for sellar and parasellar tumors. Antidiuretic hormone (ADH) appears as hyper intensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport. This retrospective study included 172 patients undergoing TSS for sellar tumors at our institute from 2006 to 2014. Sequential T1-weighted MR images without enhancement were evaluated for HI in the pituitary stalk and the posterior lobe to assess the localization of ADH before and at intervals after TSS. DI was assessed pre- and postoperatively. HI in the pituitary stalk showed the following morphology: (1) ovoid in the distal end of the pituitary stalk (group A), (2) linear in the distal part of the pituitary stalk (group B), (3) linear in the whole pituitary stalk (group C). Preoperative DI occurred in 6 patients (3.5 %) with no HI observed in the posterior lobe. Postoperative DI was transient in 82 patients (47.7 %), and permanent in 11 (6.4 %). One week after surgery, HI was absent in the posterior lobe in 74 patients (43.0 %), and present in the pituitary stalk in 99 patients (57.6 %); both were significantly correlated with postoperative DI (p < 0.001). The absence of HI in the posterior lobe (A, 48.9 %; B, 68.3 %; C, 92.3 %), persistence of DI (A, 3.7 days; B, 45.9 days; C, 20.5 months), and duration until HI recovery in the posterior lobe (A, 3.6 months; B, 6.8 months; C, 22.9 months) were greatest in group C, followed by group B, and then group A. Fourteen group A patients did not have postoperative DI despite having HI in the pituitary stalk and the posterior lobe. Four group C patients developed permanent DI with persistence HI in the pituitary stalk. HI in the pituitary stalk and its absence in the posterior lobe indicated postoperative DI, which was transient if HI was detected in the pituitary stalk. DI duration could be predicted by the length of HI in the pituitary stalk, which corresponded to the degree of ADH transport obstruction.

Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

PubMed Central

Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

2016-01-01

The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

Spectroscopic and metal-binding properties of DF3: an artificial protein able to accommodate different metal ions

PubMed Central

Torres Martin de Rosales, Rafael; Faiella, Marina; Farquhar, Erik; Que, Lawrence; Andreozzi, Concetta; Pavone, Vincenzo; Maglio, Ornella; Nastri, Flavia

2010-01-01

The design, synthesis, and metal-binding properties of DF3, a new de novo designed di-iron protein model are described (“DF” represents due ferri, Italian for “two iron,” “di-iron”). DF3 is the latest member of the DF family of synthetic proteins. They consist of helix–loop–helix hairpins, designed to dimerize and form an antiparallel four-helix bundle that encompasses a metal-binding site similar to those of non-heme carboxylate-bridged di-iron proteins. Unlike previous DF proteins, DF3 is highly soluble in water (up to 3 mM) and forms stable complexes with several metal ions (Zn, Co, and Mn), with the desired secondary structure and the expected stoichiometry of two ions per protein. UV–vis studies of Co(II) and Fe(III) complexes confirm a metal-binding environment similar to previous di-Co(II)- and di-Fe(III)-DF proteins, including the presence of a µ-oxo-di-Fe(III) unit. Interestingly, UV–vis, EPR, and resonance Raman studies suggest the interaction of a tyro-sine adjacent to the di-Fe(III) center. The design of DF3 was aimed at increasing the accessibility of small molecules to the active site of the four-helix bundle. Indeed, binding of azide to the di-Fe(III) site demonstrates a more accessible metal site compared with previous DFs. In fact, fitting of the binding curve to the Hill equation allows us to quantify a 150% accessibility enhancement, with respect to DF2. All these results represent a significant step towards the development of a functional synthetic DF metalloprotein. PMID:20225070

Using Stage- and Slit-Scanning to Improve Contrast and Optical Sectioning in Dual-View Inverted Light Sheet Microscopy (diSPIM)

PubMed Central

KUMAR, ABHISHEK; CHRISTENSEN, RYAN; GUO, MIN; CHANDRIS, PANOS; DUNCAN, WILLIAM; WU, YICONG; SANTELLA, ANTHONY; MOYLE, MARK; WINTER, PETER W.; COLÓN-RAMOS, DANIEL; BAO, ZHIRONG; SHROFF, HARI

2017-01-01

Dual-view inverted selective plane illumination microscopy (diSPIM) enables high-speed, long-term, fourdimensional (4D) imaging with isotropic spatial resolution. It is also compatible with conventional sample mounting on glass coverslips. However, broadening of the light sheet at distances far from the beam waist and sample-induced scattering degrades diSPIM contrast and optical sectioning. We describe two simple improvements that address both issues and entail no additional hardware modifications to the base diSPIM. First, we demonstrate improved diSPIM sectioning by keeping the light sheet and detection optics stationary, and scanning the sample through the stationary light sheet (rather than scanning the broadening light sheet and detection plane through the stationary sample, as in conventional diSPIM). This stage-scanning approach allows a thinner sheet to be used when imaging laterally extended samples, such as fixed microtubules or motile mitochondria in cell monolayers, and produces finer contrast than does conventional diSPIM. We also used stage-scanning diSPIM to obtain high-quality, 4D nuclear datasets derived from an uncompressed nematode embryo, and performed lineaging analysis to track 97% of cells until twitching. Second, we describe the improvement of contrast in thick, scattering specimens by synchronizing light-sheet synthesis with the rolling, electronic shutter of our scientific complementary metal-oxide-semiconductor (sCMOS) detector. This maneuver forms a virtual confocal slit in the detection path, partially removing out-of-focus light. We demonstrate the applicability of our combined stage- and slit-scanning-methods by imaging pollen grains and nuclear and neuronal structures in live nematode embryos. All acquisition and analysis code is freely available online. PMID:27638693

Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

PubMed

Castro, Matías; Deane, Shelly M; Ruiz, Lina; Rawlings, Douglas E; Guiliani, Nicolas

2015-01-01

An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

PubMed

Sirima, S B; Durier, C; Kara, L; Houard, S; Gansane, A; Loulergue, P; Bahuaud, M; Benhamouda, N; Nebié, I; Faber, B; Remarque, E; Launay, O

2017-10-27

Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. ClinicalTrials.gov NCT02014727; PACTR201402000719423. Copyright © 2017. Published by Elsevier Ltd.

Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review.

PubMed

Bohl, Michael A; Forseth, James; Nakaji, Peter

2017-01-01

Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis. A series of 6 neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP. To our knowledge, no previous reports of this phenomenon in neurosurgical patients have been published. We reviewed the clinical histories, intensive care unit treatment, medication administration records, and laboratory values of these patients, and we found recurrent elevated serum sodium and urine output and decreased urine specific gravity after discontinuation of AVP. Resolution of tDI occurred upon resumption of AVP or administration of desmopressin. Elevated serum sodium levels were often severe, resulting in worsened clinical outcomes. When AVP was resumed, tDI typically recurred if AVP was again tapered and discontinued. Routine administration of desmopressin was useful in controlling sodium levels until the tDI resolved. Recognition of this phenomenon has caused us to change our clinical management of neurosurgical patients receiving AVP. We hypothesize that tDI is caused by downregulation of the V2 receptor mass in the renal distal convoluted tubule and collecting duct cells. When AVP is discontinued, patients develop nephrogenic tDI secondary to decreased V2 receptor binding, which explains why desmopressin is effective in correcting tDI. Future research includes a large prospective study to determine risk factors for tDI, its incidence, and its pathophysiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and characterization of novel 8-plex DiLeu isobaric labels for quantitative proteomics and peptidomics

PubMed Central

Frost, Dustin C.; Greer, Tyler; Xiang, Feng; Liang, Zhidan; Li, Lingjun

2015-01-01

Rationale Relative quantification of proteins via their enzymatically digested peptide products determines disease biomarker candidate lists in discovery studies. Isobaric label-based strategies using TMT and iTRAQ allow for up to 10 samples to be multiplexed in one experiment, but their expense limits their use. The demand for cost-effective tagging reagents capable of multiplexing many samples led us to develop an 8-plex version of our isobaric labeling reagent, DiLeu. Methods The original 4-plex DiLeu reagent was extended to an 8-plex set by coupling isotopic variants of dimethylated leucine to an alanine balance group designed to offset the increasing mass of the label’s reporter group. Tryptic peptides from a single protein digest, a protein mixture digest, and Saccharomyces cerevisiae lysate digest were labeled with 8-plex DiLeu and analyzed via nanoLC-MS2 on a Q-Exactive Orbitrap mass spectrometer. Characteristics of 8-plex DiLeu-labeled peptides, including quantitative accuracy and fragmentation, were examined. Results An 8-plex set of DiLeu reagents with 1 Da-spaced reporters was synthesized at a yield of 36%. The average cost to label eight 100 μg peptide samples was calculated to be approximately $15. Normalized collision energy tests on the Q-Exactive revealed that a higher-energy collisional dissociation value of 27 generated the optimum number of high-quality spectral matches. Relative quantification of DiLeu-labeled peptides yielded normalized median ratios accurate to within 12% of their expected values. Conclusions Cost-effective 8-plex DiLeu reagents can be synthesized and applied to relative peptide and protein quantification. These labels increase the multiplexing capacity of our previous 4-plex implementation without requiring high-resolution instrumentation to resolve reporter ion signals. PMID:25981542

Diguanylate Cyclase Null Mutant Reveals That C-Di-GMP Pathway Regulates the Motility and Adherence of the Extremophile Bacterium Acidithiobacillus caldus

PubMed Central

Castro, Matías; Deane, Shelly M.; Ruiz, Lina; Rawlings, Douglas E.; Guiliani, Nicolas

2015-01-01

An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process. PMID:25689133

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults

PubMed Central

Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina

2017-01-01

Background Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods One hundred seven frail, obese older adults were randomized into the control (N = 27), diet (N = 26), exercise (N = 26), and diet-exercise (N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2 = 0.140 and 0.107) and diet-exercise (∆R2 = 0.427 and 0.243) groups (P < 0.05 for all). Conclusions Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107. PMID:28951766

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.

PubMed

Colleluori, Georgia; Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina; Villareal, Dennis T

2017-01-01

Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. One hundred seven frail, obese older adults were randomized into the control ( N = 27), diet ( N = 26), exercise ( N = 26), and diet-exercise ( N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). UcOC increased in the diet group (36 ± 11.6%) but not in the other groups ( P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months ( P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only ( R 2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆ R 2 = 0.140 and 0.107) and diet-exercise (∆ R 2 = 0.427 and 0.243) groups ( P < 0.05 for all). Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

Identification and Functional Characterization of Monofunctional ent-Copalyl Diphosphate and ent-Kaurene Synthases in White Spruce Reveal Different Patterns for Diterpene Synthase Evolution for Primary and Secondary Metabolism in Gymnosperms1[W][OA

PubMed Central

Keeling, Christopher I.; Dullat, Harpreet K.; Yuen, Mack; Ralph, Steven G.; Jancsik, Sharon; Bohlmann, Jörg

2010-01-01

The biosynthesis of the tetracyclic diterpene ent-kaurene is a critical step in the general (primary) metabolism of gibberellin hormones. ent-Kaurene is formed by a two-step cyclization of geranylgeranyl diphosphate via the intermediate ent-copalyl diphosphate. In a lower land plant, the moss Physcomitrella patens, a single bifunctional diterpene synthase (diTPS) catalyzes both steps. In contrast, in angiosperms, the two consecutive cyclizations are catalyzed by two distinct monofunctional enzymes, ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS). The enzyme, or enzymes, responsible for ent-kaurene biosynthesis in gymnosperms has been elusive. However, several bifunctional diTPS of specialized (secondary) metabolism have previously been characterized in gymnosperms, and all known diTPSs for resin acid biosynthesis in conifers are bifunctional. To further understand the evolution of ent-kaurene biosynthesis as well as the evolution of general and specialized diterpenoid metabolisms in gymnosperms, we set out to determine whether conifers use a single bifunctional diTPS or two monofunctional diTPSs in the ent-kaurene pathway. Using a combination of expressed sequence tag, full-length cDNA, genomic DNA, and targeted bacterial artificial chromosome sequencing, we identified two candidate CPS and KS genes from white spruce (Picea glauca) and their orthologs in Sitka spruce (Picea sitchensis). Functional characterization of the recombinant enzymes established that ent-kaurene biosynthesis in white spruce is catalyzed by two monofunctional diTPSs, PgCPS and PgKS. Comparative analysis of gene structures and enzyme functions highlights the molecular evolution of these diTPSs as conserved between gymnosperms and angiosperms. In contrast, diTPSs for specialized metabolism have evolved differently in angiosperms and gymnosperms. PMID:20044448

DiAlert: a prevention program for overweight first degree relatives of type 2 diabetes patients: results of a pilot study to test feasibility and acceptability.

PubMed

Heideman, Wieke H; de Wit, Maartje; Middelkoop, Barend J C; Nierkens, Vera; Stronks, Karien; Verhoeff, Arnoud P; Snoek, Frank J

2012-09-27

Prevalence of type 2 diabetes mellitus is increasing due to lifestyle changes, particularly affecting those genetically at risk. We developed DiAlert as a targeted group-based intervention aimed to promote intrinsic motivation and action planning for lifestyle changes and weight loss in first degree relatives of patients with type 2 diabetes mellitus.The main objective of the pilot of the DiAlert intervention was to assess fidelity, feasibility and acceptability prior to starting the randomized controlled trial. Individuals with a family history of type 2 diabetes mellitus were self-identified and screened for eligibility. DiAlert consists of two group sessions. Feasibility, fidelity, acceptability and self-reported perceptions and behavioral determinants were evaluated in a pre-post study using questionnaires and observations. Determinants of behavior change were analyzed using paired-samples t tests and Wilcoxon signed rank tests. DiAlert was delivered to two groups of first degree relatives of patients with type 2 diabetes mellitus (N = 9 and N = 12). Feasibility and fidelity were confirmed. Overall, the DiAlert group sessions were positively evaluated (8.0 on a scale of 1 to 10) by participants. The intervention did not impact perceived susceptibility or worry about personal diabetes risk. Action planning with regard to changing diet and physical activity increased. DiAlert proved feasible and was well-accepted by participants. Positive trends in action planning indicate increased likelihood of actual behavior change following DiAlert. Testing the effectiveness in a randomized controlled trial is imperative. Netherlands National Trial Register (NTR): NTR2036.

Factors Associated with Postoperative Diabetes Insipidus after Pituitary Surgery.

PubMed

Faltado, Antonio L; Macalalad-Josue, Anna Angelica; Li, Ralph Jason S; Quisumbing, John Paul M; Yu, Marc Gregory Y; Jimeno, Cecilia A

2017-12-01

Determining risk factors for diabetes insipidus (DI) after pituitary surgery is important in improving patient care. Our objective is to determine the factors associated with DI after pituitary surgery. We reviewed records of patients who underwent pituitary surgery from 2011 to 2015 at Philippine General Hospital. Patients with preoperative DI were excluded. Multiple logistic regression analysis was performed and a predictive model was generated. The discrimination abilities of the predictive model and individual variables were assessed using the receiving operator characteristic curve. A total of 230 patients were included. The rate of postoperative DI was 27.8%. Percent change in serum Na (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.15 to 1.69); preoperative serum Na (OR, 1.19; 95% CI, 1.02 to 1.40); and performance of craniotomy (OR, 5.48; 95% CI, 1.60 to 18.80) remained significantly associated with an increased incidence of postoperative DI, while percent change in urine specific gravity (USG) (OR, 0.53; 95% CI, 0.33 to 0.87) and meningioma on histopathology (OR, 0.05; 95% CI, 0.04 to 0.70) were significantly associated with a decreased incidence. The predictive model generated has good diagnostic accuracy in predicting postoperative DI with an area under curve of 0.83. Greater percent change in serum Na, preoperative serum Na, and performance of craniotomy significantly increased the likelihood of postoperative DI while percent change in USG and meningioma on histopathology were significantly associated with a decreased incidence. The predictive model can be used to generate a scoring system in estimating the risk of postoperative DI. Copyright © 2017 Korean Endocrine Society

Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study.

PubMed

Gardener, Hannah; Wright, Clinton B; Gu, Yian; Demmer, Ryan T; Boden-Albala, Bernadette; Elkind, Mitchell S V; Sacco, Ralph L; Scarmeas, Nikolaos

2011-12-01

A dietary pattern common in regions near the Mediterranean appears to reduce risk of all-cause mortality and ischemic heart disease. Data on blacks and Hispanics in the United States are lacking, and to our knowledge only one study has examined a Mediterranean-style diet (MeDi) in relation to stroke. In this study, we examined an MeDi in relation to vascular events. The Northern Manhattan Study is a population-based cohort to determine stroke incidence and risk factors (mean ± SD age of participants: 69 ± 10 y; 64% women; 55% Hispanic, 21% white, and 24% black). Diet was assessed at baseline by using a food-frequency questionnaire in 2568 participants. A higher score on a 0-9 scale represented increased adherence to an MeDi. The relation between the MeDi score and risk of ischemic stroke, myocardial infarction (MI), and vascular death was assessed with Cox models, with control for sociodemographic and vascular risk factors. The MeDi-score distribution was as follows: 0-2 (14%), 3 (17%), 4 (22%), 5 (22%), and 6-9 (25%). Over a mean follow-up of 9 y, 518 vascular events accrued (171 ischemic strokes, 133 MIs, and 314 vascular deaths). The MeDi score was inversely associated with risk of the composite outcome of ischemic stroke, MI, or vascular death (P-trend = 0.04) and with vascular death specifically (P-trend = 0.02). Moderate and high MeDi scores were marginally associated with decreased risk of MI. There was no association with ischemic stroke. Higher consumption of an MeDi was associated with decreased risk of vascular events. Results support the role of a diet rich in fruit, vegetables, whole grains, fish, and olive oil in the promotion of ideal cardiovascular health.

Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal

PubMed Central

Martinez, Bridget; Soñanez-Organis, José G.; Vázquez-Medina, José Pablo; Viscarra, Jose A.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

2013-01-01

SUMMARY Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5–7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic–pituitary–thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism. PMID:24307712

Low-Cost WDM-PON With Colorless Bidirectional Transceivers

NASA Astrophysics Data System (ADS)

Shin, Dong Jae; Keh, Y. C.; Kwon, J. W.; Lee, E. H.; Lee, J. K.; Park, M. K.; Park, J. W.; Oh, Y. K.; Kim, S. W.; Yun, I. K.; Shin, H. C.; Heo, D.; Lee, J. S.; Shin, H. S.; Kim, H. S.; Park, S. B.; Jung, D. K.; Hwang, Seongtaek; Oh, Y. J.; Jang, D. H.; Shim, C. S.

2006-01-01

This paper presents a low-cost bidirectional (BiDi) wavelength-division-multiplexed passive optical network (WDM-PON) employing colorless uncooled BiDi transceivers (TRxs) and superluminescent diode (SLD)-based broadband light sources (BLSs). The C band is allocated for upstream and the E+ band for downstream in consideration of BiDi packaging, SLD development, and wavelength alignment of dual-window arrayed waveguide gratings (AWGs). The BiDi TRx integrates an uncooled Fabry-Pérot laser diode (FP-LD), a p-i-n photodiode (PD), and a 45°-angled thin-film filter in a small-form-factor (SFF) package. The SLD-based BLSs provide 13-dBm amplified spontaneous emissions (ASEs) with spectral ripples of < 3 dB and polarization dependencies of < 1 dB. Colorless operations over 32 100-GHz-spaced channels are demonstrated from -20 to 80°C in 155-Mb/s BiDi transmissions over 25 km.

Diabetes Insipidus.

PubMed

Lu, H A Jenny

2017-01-01

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

Dens invaginatus with necrotic pulp in a right maxillary lateral incisor with preserved vitality.

PubMed

Alessandro, Lanza; Fabrizio, Di Francesco; Gennaro, De Marco; Dario, Di Stasio; Eugenio, Guidetti; Letizia, Perillo; Luigi, Femiano; Felice, Femiano

2018-01-01

Dens invaginatus (DI) is a dental malformation occurring in several morphologic types. Consequently, treatment of teeth affected by DI can get complicated because of the complex root canal anatomy. The aim is to describe how to manage a rare report of a DI with necrotic pulp held within the vital pulp of a maxillary lateral incisor. Oral fistula was found on the buccal mucosa of the apex of the vital maxillary lateral incisor with a DI having necrotic pulp. Endodontic treatment of the maxillary lateral incisor and of the tract canal of DI was realized. Clinical disappearance of oral sinus tract was observed after 10 days. On the contrary, the disappearance of radiolucent area occurred after 6 months. A proper and prompt diagnosis is necessary to carry out effective prevention protocols or prevent consequences generating nonrecoverable endo-perio diseases.

Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

PubMed Central

Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Sitong; Bian, Tingwei; Han, Chunmao; Meng, Qin

2016-01-01

Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring. PMID:27901027

Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5

ERIC Educational Resources Information Center

Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C.; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin

2016-01-01

The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical…

40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

Kinetics of Slow Neutrons in a Time-of-flight Spectrometer. II. Probability of Transmission Across a Rotating Slit and Distribution after the Flight of Neutrons with Velocity Spectrum F (v); CINETICA DEI NEUTRONI LENTI IN UNO SPETTROMETRO A TEMPO DI VOLO. II. PROBABILITA DI TRANSMISSIONE ATTRAVERSO UNA FENDITURA RUOTANTE E DISTRIBUZIONE DOPO IL VOLO DI NEUTRONI CON SPETTRO DI VELOCITA F (V)

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

Marsequerra, M.; Pauli, G.

1958-12-01

On the basis of the results obtained in Part I (CNC-1), expressions are derived for the transmission probability through a revolving curved slit for neutrons having a velocity distribution f(v), the distribution shown by the neutrons after the flight, and the uncertainty in the energy of neutrons detected in an infinitesimal time interval. (auth)

Limb anomalies in DiGeorge and CHARGE syndromes

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

Prasad, C.; Quackenbush, E.J.; Whiteman, D.

1997-01-20

Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with CHARGE syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with CHARGE syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies. 14 refs., 4 figs.

Dischi (E Jet) Nelle Stelle Massicce Giovani

NASA Astrophysics Data System (ADS)

Cesaroni, Riccardo

2017-11-01

In questo contributo verrà discussa l'importanza dei dischi e jet ad essi asso- ciati per la formazione delle stelle di tipo spettrale OB e verranno presentati i risultati recentemente ottenuti con ALMA in questo ambito. In particolare mostr- eremo che la struttura del disco sembra risentire della complessità dell'ambiente circostante e che la probabilità di rivelare un disco attorno alle stelle di più alta massa è massima in una fase evolutiva intermedia. Infine discuteremo la possibilità che il fenomeno di accrescimento dal disco sulla stella possa avvenire in maniera discontinua mediante "burst", probabilmente dovuti ad instabilità nel disco.

Enhanced di-Higgs boson production in the complex Higgs singlet model

DOE PAGES

Dawson, S.; Sullivan, M.

2018-01-31

Here, we consider the standard model (SM) extended by the addition of a complex scalar singlet, with no assumptions about additional symmetries of the potential. This model provides for resonant di-Higgs production of Higgs particles with different masses. We demonstrate that regions of parameter space allowed by precision electroweak measurements, experimental limits on single Higgs production, and perturbative unitarity allow for large di-Higgs production rates relative to the SM rates. In this scenario, the dominant production mechanism of the new scalar states is di-Higgs production. Results are presented formore » $$\\sqrt{s}$$ = 13, 27 and 100 TeV.« less

Bacterial nucleotide-based second messengers.

PubMed

Pesavento, Christina; Hengge, Regine

2009-04-01

In all domains of life nucleotide-based second messengers transduce signals originating from changes in the environment or in intracellular conditions into appropriate cellular responses. In prokaryotes cyclic di-GMP has emerged as an important and ubiquitous second messenger regulating bacterial life-style transitions relevant for biofilm formation, virulence, and many other bacterial functions. This review describes similarities and differences in the architecture of the cAMP, (p)ppGpp, and c-di-GMP signaling systems and their underlying signaling principles. Moreover, recent advances in c-di-GMP-mediated signaling will be presented and the integration of c-di-GMP signaling with other nucleotide-based signaling systems will be discussed.

Enhanced di-Higgs boson production in the complex Higgs singlet model

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

Dawson, S.; Sullivan, M.

Here, we consider the standard model (SM) extended by the addition of a complex scalar singlet, with no assumptions about additional symmetries of the potential. This model provides for resonant di-Higgs production of Higgs particles with different masses. We demonstrate that regions of parameter space allowed by precision electroweak measurements, experimental limits on single Higgs production, and perturbative unitarity allow for large di-Higgs production rates relative to the SM rates. In this scenario, the dominant production mechanism of the new scalar states is di-Higgs production. Results are presented formore » $$\\sqrt{s}$$ = 13, 27 and 100 TeV.« less

[Qualitative analysis of bis-(3'-5')-cyclic dimeric adenosine monophosphate of Porphyromonas gingivalis by high performance liquid chromatography coupled with mass spectrometry].

PubMed

Yongmei, Tan; Xiaojun, Yang; Juan, Du; Wanghong, Zhao; Xiaodan, Chen; Jin, Hou

2016-06-01

To test whether Porphyromonas gingivalis (P. gingivalis) could produce bacterial signal molecule, bis-(3'-5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and lay the foundation for explorations of its roles in life metabolism and periodontitis immunity of P. gingivalis. P. gingivalis standard strain ATCC33277 was used as the experimental strain to extract nucleic acids from the bacteria. Then, c-di-AMP was detected using high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Subsequently, HPLC was used to validate the sample further. Based on the signal/noise (S/N) for 3 : 1, the limit of determination of HPLC-MS/MS for peak time of c-di-AMP standard substances was 7.49 min and nucleic acid extractions from P. gingivalis was 8.82 min (S/N > 3). Further confirmation of HPLC showed that nucleic acid extractions from both P. gingivalis and c-di-AMP standard substances pre- sented goal absorbent peaks at 15.7 min, with the same ultraviolet absorbent spectrum. The nucleic acid extrac- tions from P. gingivalis contained c-di-AMP, which shows that P. gingivalis could produce c-di-AMP.

Theory of the development of alternans in the heart during controlled diastolic interval pacing

NASA Astrophysics Data System (ADS)

Otani, Niels F.

2017-09-01

The beat-to-beat alternation in action potential durations (APDs) in the heart, called APD alternans, has been linked to the development of serious cardiac rhythm disorders, including ventricular tachycardia and fibrillation. The length of the period between action potentials, called the diastolic interval (DI), is a key dynamical variable in the standard theory of alternans development. Thus, methods that control the DI may be useful in preventing dangerous cardiac rhythms. In this study, we examine the dynamics of alternans during controlled-DI pacing using a series of single-cell and one-dimensional (1D) fiber models of alternans dynamics. We find that a model that combines a so-called memory model with a calcium cycling model can reasonably explain two key experimental results: the possibility of alternans during constant-DI pacing and the phase lag of APDs behind DIs during sinusoidal-DI pacing. We also find that these results can be replicated by incorporating the memory model into an amplitude equation description of a 1D fiber. The 1D fiber result is potentially concerning because it seems to suggest that constant-DI control of alternans can only be effective over only a limited region in space.

Evaluation of Direct Infusion-Multiple Reaction Monitoring Mass Spectrometry for Quantification of Heat Shock Proteins

PubMed Central

Xiang, Yun; Koomen, John M.

2012-01-01

Protein quantification with liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) has emerged as a powerful platform for assessing panels of biomarkers. In this study, direct infusion, using automated, chip-based nanoelectrospray ionization, coupled with MRM (DI-MRM) is used for protein quantification. Removal of the LC separation step increases the importance of evaluating the ratios between the transitions. Therefore, the effects of solvent composition, analyte concentration, spray voltage, and quadrupole resolution settings on fragmentation patterns have been studied using peptide and protein standards. After DI-MRM quantification was evaluated for standards, quantitative assays for the expression of heat shock proteins (HSPs) were translated from LC-MRM to DI-MRM for implementation in cell line models of multiple myeloma. Requirements for DI-MRM assay development are described. Then, the two methods are compared; criteria for effective DI-MRM analysis are reported based on the analysis of HSP expression in digests of whole cell lysates. The increased throughput of DI-MRM analysis is useful for rapid analysis of large batches of similar samples, such as time course measurements of cellular responses to therapy. PMID:22293045

Ganglioneuroblastoma: Case report and review of the literature.

PubMed

Alessi, S; Grignani, M; Carone, L

2011-06-01

Neuroblastoma are among the most important tumors of extracranial origin in pediatric patients. They arise from embryonal cells involved in the development of the sympathetic nervous system, whose differentiation has been arrested [1,2]. They are the tumors most frequently diagnosed during the first decade of life. Their evolution is unpredictable, ranging from progression to spontaneous regression or maturation, and their location and metastatic potential vary. Little is known about the cause of these tumors and the risk factors associated with their development. This article describes a typical case of ganglioneuroblastoma and provides a review of the literature on this type of tumor.Sommario Il neuroblastoma è uno dei più importanti tumori pediatrici di derivazione extracranica; esso origina dalle cellule embrionali coinvolte nello sviluppo del sistema nervoso simpatico a causa di un blocco nel loro processo di differenziamento [1,2]. È la più frequente neoplasia della prima decade di vita; la sua progressione biologica è imprevedibile, regressione spontanea, maturazione a ganglioneuroma, localizzazione e metastatizzazione variabili. Poco è noto a riguardo dei fattori di rischio e della sua eziopatogenesi. Viene presentato un caso tipico di ganglioneuroblastoma e riesaminata la letteratura su questa neoplasia.

Revisiting the Diego Blood Group System in Amerindians: Evidence for Gene-Culture Comigration.

PubMed

Bégat, Christophe; Bailly, Pascal; Chiaroni, Jacques; Mazières, Stéphane

2015-01-01

Six decades ago the DI*A allele of the Diego blood group system was instrumental in proving Native American populations originated from Siberia. Since then, it has received scant attention. The present study was undertaken to reappraise distribution of the DI*A allele in 144 Native American populations based on current knowledge. Using analysis of variance tests, frequency distribution was studied according to geographical, environmental, and cultural parameters. Frequencies were highest in Amazonian populations. In contrast, DI*A was undetectable in subarctic, Fuegian, Panamanian, Chaco and Yanomama populations. Closer study revealed a correlation that this unequal distribution was correlated with language, suggesting that linguistic divergence was a driving force in the expansion of DI*A among Native Americans. The absence of DI*A in circumpolar Eskimo-Aleut and Na-Dene speakers was consistent with a late migratory event confined to North America. Distribution of DI*A in subtropical areas indicated that gene and culture exchanges were more intense within than between ecozones. Bolstering the utility of classical genetic markers in biological anthropology, the present study of the expansion of Diego blood group genetic polymorphism in Native Americans shows strong evidence of gene-culture comigration.

Transformation of methylparaben during water chlorination: Effects of bromide and dissolved organic matter on reaction kinetics and transformation pathways.

PubMed

Yoom, Hoonsik; Shin, Jaedon; Ra, Jiwoon; Son, Heejong; Ryu, Dongchoon; Kim, Changwon; Lee, Yunho

2018-09-01

The reaction kinetics, products, and pathways of methylparaben (MeP) during water chlorination with and without bromide (Br - ) were investigated to better understand the fate of parabens in chlorinated waters. During the chlorination of MeP-spiked waters without Br - , MeP was transformed into mono-Cl-MeP and di-Cl-MeP with apparent second-order rate constants (k app ) of 64M -1 s -1 and 243M -1 s -1 at pH7, respectively, while further chlorination of di-Cl-MeP was relatively slower (k app =1.3M -1 s -1 at pH7). With increasing Br - concentration, brominated MePs, such as mono-Br-MeP, Br-Cl-MeP, and di-Br-MeP, became major transformation products. The di-halogenated MePs (di-Cl-MeP, Br,Cl-MeP, and di-Br-MeP) showed relatively low reactivity to chlorine at pH7 (k app =1.3-4.6M -1 s -1 ) and bromine (k app =32-71M -1 s -1 ), which explains the observed high stability of di-halogenated MePs in chlorinated waters. With increasing pH from 7 to 8.5, the transformation of di-halogenated MePs was further slowed due to the decreasing reactivity of di-MePs to chlorine. The formation of the di-halogenated MePs and their further transformation become considerably faster at Br - concentrations higher than 0.5μM (40μg/L). Nonetheless, the accelerating effect of Br - diminishes in the presence of dissolved organic matter (DOM) extract (Suwannee River humic acid (SRHA)) due to a more rapid consumption of bromine by DOM than chlorine. The effect of Br - on the fate of MeP was less in the tested real water matrices, possibly due to a more rapid bromine consumption by the real water DOM compared to SRHA. A kinetic model was developed based on the determined species-specific second-order rate constants for chlorination/bromination of MeP and its chlorinated and brominated MePs and the transformation pathway information, which could reasonably simulate the transformation of MePs during the chlorination of water in the presence of Br - and selected DOM. Copyright © 2017 Elsevier B.V. All rights reserved.

Bringing it home: expanding the local reach of dissemination and implementation training via a university-based workshop.

PubMed

Morrato, Elaine H; Rabin, Borsika; Proctor, Jeff; Cicutto, Lisa C; Battaglia, Catherine T; Lambert-Kerzner, Anne; Leeman-Castillo, Bonnie; Prahl-Wretling, Michelle; Nuechterlein, Bridget; Glasgow, Russell E; Kempe, Allison

2015-07-04

Currently, national training programs do not have the capacity to meet the growing demand for dissemination and implementation (D&I) workforce education and development. The Colorado Research in Implementation Science Program (CRISP) developed and delivered an introductory D&I workshop adapted from national programs to extend training reach and foster a local learning community for D&I. To gauge interest and assess learning needs, a pre-registration survey was administered. Based on feedback, a 1.5-day workshop was designed. Day 1 introduced D&I frameworks, strategies, and evaluation principles. Local and national D&I experts provided ignite-style talks on key lessons followed by panel discussion. Breakout sessions discussed community engagement and applying for D&I grants. A workbook was developed to enhance the training and provided exercises for application to an individual's projects. Day 2 offered expert-led mentoring sessions with selected participants who desired advanced instruction. Two follow-up surveys (immediate post-workshop, 6 months) assessed knowledge gained from participation and utilization of workshop content. Ninety-three workshop registrants completed an assessment survey to inform workshop objectives and curriculum design; 43 % were new and 54 % reported a basic understanding of the D&I field. Pre-registrants intended to use the training to "apply for a D&I grant" (73 %); "incorporate D&I into existing projects" (76 %), and for quality improvement (51 %). Sixty-eight individuals attended Day 1; 11 also attended Day 2 mentoring sessions. In the 1-week post-workshop survey (n = 34), 100 % strongly agreed they were satisfied with the training; 97 % strongly agreed the workshop workbook was a valuable resource. All Day 2 participants strongly agreed that working closely with faculty and experts increased their overall confidence. In the 6-month follow-up evaluation (n = 23), evidence of new D&I-related manuscripts and grant proposals was found. Training materials were published online ( www.ucdenver.edu/implementation/workshops ) and disseminated via the National Institutes of Health (NIH) Clinical and Translational Science Awards Consortium. To sustain reach, CRISP adapted the materials into an interactive e-book ( www.CRISPebooks.org ) and launched a new graduate course. Local D&I training workshops can extend the reach of national training programs.

Concentrations of phthalates and bisphenol A in Norwegian foods and beverages and estimated dietary exposure in adults.

PubMed

Sakhi, Amrit K; Lillegaard, Inger Therese L; Voorspoels, Stefan; Carlsen, Monica H; Løken, Elin B; Brantsæter, Anne L; Haugen, Margaretha; Meltzer, Helle M; Thomsen, Cathrine

2014-12-01

Phthalates and bisphenol A (BPA) are ubiquitous in our environment. These chemicals have been characterized as endocrine disruptors that can cause functional impairment of development and reproduction. Processed and packaged foods are among the major sources of human exposure to these chemicals. No previous report showing the levels of these chemicals in food items purchased in Norway is available. The aim of the present study was to determine the concentration of ten different phthalates and BPA in foods and beverages purchased on the Norwegian market and estimate the daily dietary exposure in the Norwegian adult population. Commonly consumed foods and beverages in Norway were purchased in a grocery store and analysed using gas- and liquid chromatography coupled with mass spectrometry. Daily dietary exposures to these chemicals in the Norwegian adult population were estimated using the latest National dietary survey, Norkost 3 (2010-2011). This study showed that phthalates and BPA are found in all foods and beverages that are common to consume in Norway. The detection frequency of phthalates in the food items varied from 11% for dicyclohexyl phthalate (DCHP) to 84% for di-iso-nonyl phthalate (DiNP), one of the substitutes for bis(2-ethylhexyl) phthalate (DEHP). BPA was found in 54% of the food items analysed. Among the different phthalates, the highest concentrations were found for DEHP and DiNP in the food items. Estimated dietary exposures were also equally high and dominated by DEHP and DiNP (400-500 ng/kg body weight (bw)/day), followed by di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DiDP) (30-40 ng/kg bw/day). Dimethyl phthalate (DMP), diethylphthalate (DEP) and DCHP had the lowest concentrations and the exposures were around 10-20 ng/kg bw/day. Estimated dietary exposure to BPA was 5 ng/kg bw/day. In general, levels of phthalates and BPA in foods and beverages from the Norwegian market are comparable to other countries worldwide. Grain and meat products were the major contributors of exposure to these chemicals in the Norwegian adult population. The estimated dietary exposures to these chemicals were considerably lower than their respective tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of solid phase microextraction on dental composite resin analysis.

PubMed

Wang, Ven-Shing; Chang, Ta-Yuan; Lai, Chien-Chen; Chen, San-Yue; Huang, Long-Chen; Chao, Keh-Ping

2012-08-15

A direct immersion solid phase microextraction (DI-SPME) method was developed for the analysis of dentin monomers in saliva. Dentine monomers, such as triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA) and 2,2-bis-[4-(2-hydroxy-3-methacryloyloxypropoxy) phenyl]-propane (Bis-GMA), have a high molecular weight and a low vapor pressure. The polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber with a medium polarity was employed for DI-SPME, and 215 nm of detection wavelength was found to be optimum in the chromatogram of HPLC measurement. The calibration range for DI-SPME was 0.30-300 μg/mL with correlation coefficients (r) greater than 0.998 for each analyte. The DI-SPME method achieved good accuracy (recovery 96.1-101.2%) and precision (2.30-8.15% CV) for both intra- and inter-day assays of quality control samples for three target compounds. Method validation was performed on standards dissolved in blank saliva, and there was no significant difference (p>0.2) between the DI-SPME method and the liquid injection method. However, the detection limit of DI-SPME was as low as 0.03, 0.27 and 0.06 μg/mL for TEGDMA, UDMA and Bis-GMA, respectively. Real sample analyses were performed on commercial dentin products after curing for the leaching measurement. In summary, DI-SPME is a more sensitive method that requires less sample pretreatment procedures to measure the resin materials leached in saliva. Copyright © 2012 Elsevier B.V. All rights reserved.

DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.

PubMed

Gándara, Carolina; Alonso, Juan C

2015-03-01

Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth. Copyright © 2015 Elsevier B.V. All rights reserved.

Alamethicin in lipid bilayers: combined use of X-ray scattering and MD simulations.

PubMed

Pan, Jianjun; Tieleman, D Peter; Nagle, John F; Kucerka, Norbert; Tristram-Nagle, Stephanie

2009-06-01

We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted transmembrane at high humidity and high concentrations, in agreement with earlier results. The X-ray scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/DOPC. In contrast, the X-ray data indicate that the thicker diC22:1PC membrane thins with added Alm, a total decrease in thickness of 4 A at 1/10 Alm/diC22:1PC. The different effect of Alm on the thickness changes of the two bilayers is consistent with Alm having a hydrophobic thickness close to the hydrophobic thickness of 27 A for DOPC; Alm is then mismatched with the 7 A thicker diC22:1PC bilayer. The X-ray data indicate that Alm decreases the bending modulus (K(C)) by a factor of approximately 2 in DOPC and a factor of approximately 10 in diC22:1PC membranes (P/L approximately 1/10). The van der Waals and fluctuational interactions between bilayers are also evaluated through determination of the anisotropic B compressibility modulus.

Distinguishing mechanisms for alternans in cardiac cells using constant-diastolic-interval pacing

NASA Astrophysics Data System (ADS)

Cherry, Elizabeth M.

2017-09-01

Alternans, a proarrhythmic dynamical state in which cardiac action potentials alternate between long and short durations despite a constant pacing period, traditionally has been explained at the cellular level using nonlinear dynamics principles under the assumption that the action potential duration (APD) is determined solely by the time elapsed since the end of the previous action potential, called the diastolic interval (DI). In this scenario, APDs at a steady state should be the same provided that the preceding DIs are the same. Nevertheless, experiments attempting to eliminate alternans by dynamically adjusting the timing of pacing stimuli to keep the DI constant showed that alternans persisted, contradicting the traditional theory. It is now widely known that alternans also can arise from a different mechanism associated with intracellular calcium cycling. Our goal is to determine whether intracellular calcium dynamics can explain the experimental findings regarding the persistence of alternans despite a constant DI. For this, we use mathematical models capable of producing alternans through both voltage- and calcium-mediated mechanisms. We show that for voltage-driven alternans, action potentials elicited from a constant-DI protocol are always the same. However, in the case of calcium-driven alternans, the constant-DI protocol can result in alternans. Reducing the strength of the calcium instability progressively reduces and finally eliminates constant-DI alternans. Our findings suggest that screening for the presence of alternans using a constant-DI protocol has the potential for differentiating between voltage-driven and calcium-driven alternans.

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

PubMed

Deniz, Ferhat; Kepez, Alper; Ay, Seyit Ahmet; Ergogan, Okan; Baskoy, Kamil; Guncıkan, Mustafa Nuri; Dogan, Zekeriya; Yonem, Arif

2015-11-01

There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

The carbocyanine dye DiD labels in vitro and in vivo neural stem cells of the subventricular zone as well as myelinated structures following in vivo injection in the lateral ventricle.

PubMed

Carradori, Dario; Barreau, Kristell; Eyer, Joël

2016-02-01

Carbocyanines are fluorescent lipophilic cationic dyes used since the early 1980s as neuronal tracers. Several applications of these compounds have been developed thanks to their low cell toxicity, lateral diffusion within the cellular membranes, and good photostability. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine 4-chlorobenzenesulfonate (DiD) is an interesting component of this family because, in addition to the classic carbocyanine properties, it has a longer wavelength compared with its analogues. That makes DiD an excellent carbocyanine for labeling cells and tissues with significant intrinsic fluorescence. Drug encapsulation, drug delivery, and cellular transplantation are also fields using DiD-based systems where having detailed knowledge about its behavior as a single entity is important. Recently, promising studies concerned neural stem cells from the subventricular zone of the lateral ventricle in the brain (their natural niche) and their potential therapeutic use. Here, we show that DiD is able to label these stem cells in vitro and present basilar information concerning its pharmacokinetics, concentrations, and microscope protocols. Moreover, when DiD is injected in vivo in the cerebrospinal fluid present in the lateral ventricle of rat, it also labels stem cells as well as myelinated structures of the caudoputamen. This analysis provides a database to consult when planning experiments concerning DiD and neural stem cells from the subventricular zone. © 2015 Wiley Periodicals, Inc.

BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

PubMed

Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

2017-09-19

The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several mechanisms to cope with environmental stresses. BolA-like proteins are widely conserved from prokaryotes to eukaryotes, and in Escherichia coli , in addition to its pleiotropic effects, this protein plays a determinant role in bacterial motility and biofilm formation regulation. Similarly, the bacterial second messenger c-di-GMP is a molecule with high importance in coordinating the switch between planktonic and sessile life in bacteria. Here we have unravelled the importance of accurate regulation of cross-talk between BolA and c-di-GMP for a proper response in the regulation of these bacterial lifestyles. This finding underlines the complexity of bacterial cell regulation, revealing the existence of one additional tool for fine-tuning such important cellular molecular mechanisms. The relationship between BolA and c-di-GMP gives new perspectives regarding biofilm formation and opens the possibility to extend our studies to other organisms with relevance for human health. Copyright © 2017 Moreira et al.

40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

Code of Federal Regulations, 2012 CFR

2012-07-01

...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

Code of Federal Regulations, 2013 CFR

2013-07-01

...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

Code of Federal Regulations, 2014 CFR

2014-07-01

...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

[Answers to queries on absence of "heart related to fire" theory in the western Han Dynasty].

PubMed

Tian, S; Wang, J

1995-01-01

This paper claims that all the materials, including the first chapter of Lu's Chun Qiu Shi Er Ji, the theory of Heart Related to Fire in Huai Nan Zi Di Xing Xun, and "Chi Di Zi kills Bai Di Zi" are all later interpolations and are, therefore, unconvincing. The author offers ten questions conflicting with the old sayings.

21 CFR 178.2650 - Organotin stabilizers in vinyl chloride plastics.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) (1), (2), (3), (4), (5), (6), and (7) of this section. (1) Di(n-octyl)tin S,S′-bis(isooctylmercaptoacetate) is an octyltin chemical having 15.1 to 16.4 percent by weight of tin (Sn) and having 8.1 to 8.9 percent by weight of mercapto sulfur. It is made from di(n-octyl)tin dichloride or di(n-octyl)tin oxide...

21 CFR 178.2650 - Organotin stabilizers in vinyl chloride plastics.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) (1), (2), (3), (4), (5), (6), and (7) of this section. (1) Di(n-octyl)tin S,S′-bis(isooctylmercaptoacetate) is an octyltin chemical having 15.1 to 16.4 percent by weight of tin (Sn) and having 8.1 to 8.9 percent by weight of mercapto sulfur. It is made from di(n-octyl)tin dichloride or di(n-octyl)tin oxide...

21 CFR 178.2650 - Organotin stabilizers in vinyl chloride plastics.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) (1), (2), (3), (4), (5), (6), and (7) of this section. (1) Di(n-octyl)tin S,S′-bis(isooctylmercaptoacetate) is an octyltin chemical having 15.1 to 16.4 percent by weight of tin (Sn) and having 8.1 to 8.9 percent by weight of mercapto sulfur. It is made from di(n-octyl)tin dichloride or di(n-octyl)tin oxide...

21 CFR 178.2650 - Organotin stabilizers in vinyl chloride plastics.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) (1), (2), (3), (4), (5), (6), and (7) of this section. (1) Di(n-octyl)tin S,S′-bis(isooctylmercaptoacetate) is an octyltin chemical having 15.1 to 16.4 percent by weight of tin (Sn) and having 8.1 to 8.9 percent by weight of mercapto sulfur. It is made from di(n-octyl)tin dichloride or di(n-octyl)tin oxide...

The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS

ERIC Educational Resources Information Center

Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C.; Greaves-Lord, Kirstin

2015-01-01

The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3Di and ADOS, in 186 children referred to…

40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.

PubMed

Bowman, Lisa; Zeden, Merve S; Schuster, Christopher F; Kaever, Volkhard; Gründling, Angelika

2016-12-30

Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5'-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus*

PubMed Central

Bowman, Lisa; Zeden, Merve S.; Kaever, Volkhard

2016-01-01

Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5′-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. PMID:27834680

Dissociative Ionization of Aromatic and Heterocyclic Molecules

NASA Technical Reports Server (NTRS)

Huo, Winifred M.

2003-01-01

Space radiation poses a major health hazard to humans in space flight. The high-energy charged particles in space radiation ranging from protons to high atomic number, high-energy (HZE) particles, and the secondary species they produce, attack DNA, cells, and tissues. Of the potential hazards, long-term health effects such as carcinogenesis are likely linked to the DNA lesions caused by secondary electrons in the 1 - 30 eV range. Dissociative ionization (DI) is one of the electron collision processes that can damage the DNA, either directly by causing a DNA lesion, or indirectly by producing radicals and cations that attack the DNA. To understand this process, we have developed a theoretical model for DI. Our model makes use of the fact that electron motion is much faster than nuclear motion and assumes DI proceeds through a two-step process. The first step is electron-impact ionization resulting in a particular state of the molecular ion in the geometry of the neutral molecule. In the second step the ion undergoes unimolecular dissociation. Thus the DI cross section sigma(sup DI)(sub a) for channel a is given by sigma(sup DI)(sub a) = sigma(sup I)(sub a) P(sub D) with sigma(sup I)(sub a) the ionization cross section of channel a and P(sub D) the dissociation probability. This model has been applied to study the DI of H2O, NH3, and CH4, with results in good agreement with experiment. The ionization cross section sigma(sup I)(sub a) was calculated using the improved binary encounter-dipole model and the unimolecular dissociation probability P(sub D) obtained by following the minimum energy path determined by the gradients and Hessians of the electronic energy with respect to the nuclear coordinates of the ion. This model is used to study the DI from the low-lying channels of benzene and pyridine to understand the different product formation in aromatic and heterocyclic molecules. DI study of the DNA base thymine is underway. Solvent effects will also be discussed.

The Nutrient Profile of Foods Consumed Using the British Food Standards Agency Nutrient Profiling System Is Associated with Metabolic Syndrome in the SU.VI.MAX Cohort.

PubMed

Julia, Chantal; Fézeu, Léopold K; Ducrot, Pauline; Méjean, Caroline; Péneau, Sandrine; Touvier, Mathilde; Hercberg, Serge; Kesse-Guyot, Emmanuelle

2015-10-01

Metabolic syndrome (MetS), comprising high waist circumference, blood pressure, glycemia, and triglycerides, and lower HDL cholesterol could in part be prevented by adequate nutrition. Nutrient profiling systems could be useful public health tools to help consumers make healthier food choices. An individual dietary index (DI) based on nutrient profiling of foods consumed could characterize dietary patterns in relation to the onset of MetS. The objective of this study was to prospectively investigate the association between the Food Standards Agency (FSA) Nutrient Profiling System (NPS) DI and the onset of MetS in a middle-aged French cohort. Participants from the SUpplémentation en VItamines et Minéraux AntioXydants cohort (SU.VI.MAX, n = 3741) were included in the present study. The FSA NPS DI was computed by using dietary data from 24 h records at inclusion. MetS was identified at baseline and at year 13 of follow-up with the use of self-reported medication, data from clinical investigations, and biological measurements. A prospective association between the FSA NPS DI (in quartiles and continuous) and the onset of MetS was investigated by using logistic regression. Poorer diets identified with the use of the FSA NPS DI were significantly associated with a higher risk of developing MetS (OR for poorer vs. healthier FSA NPS DI: 1.43; 95% CI: 1.08, 1.89; P-trend across quartiles = 0.02). The FSA NPS DI was significantly associated with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) components of MetS (difference between healthier vs. poorer FSA NPS DI: 2.16 mm Hg for SBP and 1.5 mm Hg for DBP, P-trend across quartiles = 0.02). The FSA NPS DI was prospectively associated with the onset of MetS in a middle-aged French population. The application of NPSs in public health initiatives may help the population make healthier food choices, which might reduce the risk of developing MetS. © 2015 American Society for Nutrition.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

PubMed

Duque, Gustavo Salgado; Silva, Dayse Aparecida da; Albuquerque, Felipe Neves de; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; Albuquerque, Denilson Campos de

2016-11-01

Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Avaliar a frequência dos polimorfismos genéticos da ECA em pacientes com IC de etiologia isquêmica de uma população do Rio de Janeiro e sua associação com achados ecocardiográficos. Avaliação genética do polimorfismo I/D da ECA associada a análise de dados clínicos, laboratoriais e ecocardiográficos de 99 pacientes. Foram encontrados 53 alelos I, 145 alelos D, quanto aos genótipos da ECA: 49,5% DD, 47,48% DI, 3,02% II. O tratamento medicamentoso foi otimizado com 98% usando betabloqueadores e 84,8%, IECA ou bloqueador do receptor de angiotensina. Achados ecocardiográficos: diferença entre os diâmetros diastólicos do ventrículo esquerdo (ΔVED): 2,98±8,94 (DD) vs. 0,68±8,12 (DI) vs. -11,0±7,00 (II), p=0,018; piora evolutiva do diâmetro sistólico do VE (VES): 65,3 % DD vs. 19,0 % DI vs. 0,0 % II, p=0,01; do diâmetro diastólico do VE (VED): 65,3 % DD vs. 46,8 % DI vs. 0,0 % II, p=0,03; e da fração de ejeção do VE (FEVE): 67,3 % DD vs. 40,4 % DI vs. 33,3 % II, p=0,024. Correlação com alelo D: ΔFEVE, ΔVES, ΔVED. Foram identificados mais pacientes com piora evolutiva da FEVE e dos diâmetros cavitários do VE no genótipo DD, seguido do DI, sendo o II o de melhor evolução. O mesmo padrão foi observado na ΔVED.

Propulsion Diagnostic Method Evaluation Strategy (ProDiMES) User's Guide

NASA Technical Reports Server (NTRS)

Simon, Donald L.

2010-01-01

This report is a User's Guide for the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES). ProDiMES is a standard benchmarking problem and a set of evaluation metrics to enable the comparison of candidate aircraft engine gas path diagnostic methods. This Matlab (The Mathworks, Inc.) based software tool enables users to independently develop and evaluate diagnostic methods. Additionally, a set of blind test case data is also distributed as part of the software. This will enable the side-by-side comparison of diagnostic approaches developed by multiple users. The Users Guide describes the various components of ProDiMES, and provides instructions for the installation and operation of the tool.

Congo Red Stain Identifies Matrix Overproduction and Is an Indirect Measurement for c-di-GMP in Many Species of Bacteria.

PubMed

Jones, Christopher J; Wozniak, Daniel J

2017-01-01

Congo red is a diazo textile dye that has been used to visualize the production of amyloid fibers for nearly a century. Microbiological applications were later developed, especially in identifying strains that produce amyloid appendages called curli and overexpressing polysaccharides in the biofilm matrix. The second messenger cyclic diguanylate (c-di-GMP) regulates the production of biofilm matrix polysaccharides, and therefore Congo red staining of samples can be utilized as an indirect measurement of elevated c-di-GMP production in bacteria. Congo red allows the identification of strains producing high c-di-GMP in an inexpensive, quantitative, and high-throughput manner.

Using Ultradeep Pyrosequencing to Study HIV-1 Coreceptor Usage in Primary and Dual Infection

PubMed Central

Wagner, Gabriel A.; Pacold, Mary E.; Vigil, Edgar; Caballero, Gemma; Morris, Sheldon R.; Kosakovsky Pond, Sergei L.; Little, Susan J.; Richman, Douglas D.; Gianella, Sara; Smith, Davey M.

2013-01-01

HIV-1 dual infection (DI) and CXCR4 (X4) coreceptor usage are associated with accelerated disease progression but frequency and dynamics of coreceptor usage during DI is unknown. Ultradeep sequencing was used to interrogate for DI and infer coreceptor usage in longitudinal blood samples of 102 subjects. At baseline, X4 usage was high (23 subjects harbored X4 variants) and was not associated with infection duration or DI. Coreceptor usage changed over time in 12 of 47 participants, and X4 usage emerged in 4 of 41 monoinfections vs 2 of 5 superinfections (P = .12), suggesting a weak statistical trend toward occurrence of superinfection and acquiring X4 usage. PMID:23599311

Investigating the Source Mechanisms of Deflation-Inflation Events at Kilauea Volcano, Hawai`i

NASA Astrophysics Data System (ADS)

Johnson, J. H.; Anderson, K. R.; Poland, M. P.; Miklius, A.

2012-12-01

At Kilauea Volcano, Hawai`i, cyclic deflation-inflation ("DI") events have been observed on tiltmeters since 1988. Most DI events begin with deflation at the summit that generally lasts 12-72 hours and accumulate ~1-5 microradians of tilt as measured on the rim of Kilauea Caldera, followed by inflation that is initially rapid but wanes over the course of 12-48 hours as the net deformation approaches pre-event levels. This gives the tilt events a V- or U-shaped appearance in the tilt time series, depending on the onset deflation rates. DI events are also manifested at the Pu`u `O`o eruptive vent on Kilauea's east rift zone, about 20 km along the rift from the summit, and lag summit deformation by approximately 30-90 minutes (except during 2005-2007, when summit DI events were not detected at Pu`u `O`o). The temporal correlation of tilt at the caldera and east rift zone indicates that these events affect much of Kilauea's magma plumbing system, from the summit magma reservoir to the eruption site. Large-magnitude DI events are visible in data from continuously-recording GPS stations both at Kilauea's summit and at Pu`u `O`o, and some DI events have been imaged using InSAR. Tilt events with long-lived (several days) deflation phases are usually associated with decreases in lava effusion or even eruptive pauses on the east rift zone, while large inflationary phases are often accompanied by surges in lava effusion, new breakouts, and thus increased lava flow hazard. The lava level within the summit eruptive vent, which has been continuously visible since early 2010, correlates with tilt deformation associated with DI events. Seismic tremor levels measured at Kilauea summit at times also display a relation with DI events, sometimes correlated and sometimes anti-correlated. Tilt events have become more common since the onset of Kilauea's summit eruption in March 2008, increasing from about 5-10 per year before 2008 to more than 80 in the 8 months of 2012. Two possibly inter-related mechanisms have been suggested to explain the DI events: (1) blockage and subsequent clearing of the transport pathway that feeds the shallow summit magma system and conduit to Pu`u `O`o, and (2) convective overturns caused by replacement of degassed magma with gas-rich magma. Using a simple kinematic forward model, we invert deformation data from more than 400 DI events to estimate the location and volume change of the shallow summit source generating the ground tilt, and look for changes associated with the evolution of eruptive behaviour at Kilauea. More insight into the DI events can be gained by developing a physics-based model capable of linking magmatic processes with the temporal evolution of individual DI events. We will construct multiphysics finite element models (FEMs) to simulate deformation caused by the two proposed mechanisms to link the observations to the physical processes that drive DI events. The FEMs allow us to investigate complicated model configurations that account for 3D geometric configurations, distributions of rheologic properties, and multiple deformation sources. Crucially, the models also allow for temporal variation of fluid flow and subsurface pressurization, which will provide insights into the unique patterns of tilt observed at Kilauea.

Dissemination and implementation of comparative effectiveness evidence: key informant interviews with Clinical and Translational Science Award institutions.

PubMed

Morrato, Elaine H; Concannon, Thomas W; Meissner, Paul; Shah, Nilay D; Turner, Barbara J

2013-03-01

To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems.

Dissemination and implementation of comparative effectiveness evidence: key informant interviews with Clinical and Translational Science Award institutions

PubMed Central

Morrato, Elaine H; Concannon, Thomas W; Meissner, Paul; Shah, Nilay D; Turner, Barbara J

2014-01-01

Aim To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. Materials & methods Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. Results & conclusions The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems. PMID:24236560

Synthetic phenolic antioxidants, including butylated hydroxytoluene (BHT), in resin-based dental sealants

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

Wang, Wei; Kannan, Pranav; Xue, Jingchuan

Resin-based dental sealants (also referred to as pit-and-fissure sealants) have been studied for their contribution to bisphenol A (BPA) exposure in children. Nevertheless, little attention has been paid to the occurrence of other potentially toxic chemicals in dental sealants. In this study, the occurrence of six synthetic phenolic antioxidants (SPAs), including 2,6-di-tert-butyl-4-hydroxytoluene (BHT), 2,6-di-tert-butyl-4-(hydroxyethyl)phenol (BHT-OH), 3,5-di-tert-butyl-4-hydroxy-benzaldehyde (BHT-CHO), 2,6-di-tert-butylcyclohexa-2,5-diene-1,4-dione (BHT-Q), 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) and 2-tert-butyl-4-methoxyphenol (BHA), was examined in 63 dental sealant products purchased from the U.S. market. BHT was found in all dental sealants at median and maximum concentrations of 56.8 and 1020 µg/g, respectively. The metabolites of BHT andmore » BHA were detected in 39–67% of samples, at concentration ranges of« less

Dark Current Characterization of SW HgCdTe IRFPAs Detectors on Si Substrate with Long Time Integration

NASA Astrophysics Data System (ADS)

Song, P. Y.; Ye, Z. H.; Huang, A. B.; Chen, H. L.; Hu, X. N.; Ding, R. J.; He, L.

2016-09-01

The dark currents of two short wave (SW) HgCdTe infrared focal plane arrays (IRFPA) detectors hybridized with direct injection (DI) readout and capacitance transimpedance amplifier (CTIA) with long time integration were investigated. The cutoff wavelength of the two SW IRFPAs is about 2.6 μm at 84 K. The dark current densities of DI and CTIA samples are approximately 8.0 × 10-12 A/cm2 and 7.2 × 10-10 A/cm2 at 110 K, respectively. The large divergence of the dark current density might arise from the injection efficiency difference of the two readouts. The low injection efficiency of the DI readout, compared with the high injection efficiency of the CTIA readout at low temperature, makes the dark current density of the DI sample much lower than that of the CTIA sample. The experimental value of injection efficiency of the DI sample was evaluated as 1.1% which is consistent with its theoretical value.

Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness.

PubMed

Staubo, Sara C; Aakre, Jeremiah A; Vemuri, Prashanthi; Syrjanen, Jeremy A; Mielke, Michelle M; Geda, Yonas E; Kremers, Walter K; Machulda, Mary M; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Roberts, Rosebud O

2017-02-01

The Mediterranean diet (MeDi) is associated with reduced risk of cognitive impairment, but it is unclear whether it is associated with better brain imaging biomarkers. Among 672 cognitively normal participants (mean age, 79.8 years, 52.5% men), we investigated associations of MeDi score and MeDi components with magnetic resonance imaging measures of cortical thickness for the four lobes separately and averaged (average lobar). Higher MeDi score was associated with larger frontal, parietal, occipital, and average lobar cortical thickness. Higher legume and fish intakes were associated with larger cortical thickness: legumes with larger superior parietal, inferior parietal, precuneus, parietal, occipital, lingual, and fish with larger precuneus, superior parietal, posterior cingulate, parietal, and inferior parietal. Higher carbohydrate and sugar intakes were associated with lower entorhinal cortical thickness. In this sample of elderly persons, higher adherence to MeDi was associated with larger cortical thickness. These cross-sectional findings require validation in prospective studies. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Driving Intervention for Returning Combat Veterans.

PubMed

Classen, Sherrilene; Winter, Sandra; Monahan, Miriam; Yarney, Abraham; Link Lutz, Amanda; Platek, Kyle; Levy, Charles

2017-04-01

Increased crash incidence following deployment and veterans' reports of driving difficulty spurred traffic safety research for this population. We conducted an interim analysis on the efficacy of a simulator-based occupational therapy driving intervention (OT-DI) compared with traffic safety education (TSE) in a randomized controlled trial. During baseline and post-testing, OT-Driver Rehabilitation Specialists and one OT-Certified Driver Rehabilitation Specialist measured driving performance errors on a DriveSafety CDS-250 high-fidelity simulator. The intervention group ( n = 13) received three OT-DI sessions addressing driving errors and visual-search retraining. The control group ( n = 13) received three TSE sessions addressing personal factors and defensive driving. Based on Wilcoxon rank-sum analysis, the OT-DI group's errors were significantly reduced when comparing baseline with Post-Test 1 ( p < .0001) and comparing the OT-DI group with the TSE group at Post-Test 1 ( p = .01). These findings provide support for the efficacy of the OT-DI and set the stage for a future effectiveness study.

Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

PubMed

Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

2015-01-01

Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

Modeling radiation induced segregation in Iron-Chromium alloys

DOE PAGES

Senninger, Oriane; Soisson, Frederic; Martinez Saez, Enrique; ...

2015-10-16

Radiation induced segregation in ferritic Fe-Cr alloys is studied by Atomistic Kinetic Monte Carlo simulations that include di usion of chemical species by vacancy and interstitial migration, recombination, and elimination at sinks. The parameters of the di usion model are tted to DFT calculations. Transport coe cients that control the coupling between di usion of defects and chemical species are measured in dilute and concentrated alloys. Radiation induced segregation near grain boundaries is directly simulated with this model. We nd that the di usion of vacancies toward sinks leads to a Cr depletion. Meanwhile, the di usion of self-interstitials causesmore » an enrichment of Cr in the vicinity of sinks. For concentrations lower than 15%Cr, we predict that sinks will be enriched with Cr for temperatures lower than a threshold. When the temperature is above this threshold value, the sinks will be depleted in Cr. These results are compared to previous experimental studies and models. Cases of radiation induced precipitation and radiation accelerated precipitation are considered.« less

Experimentally determined compositions of diopside-jadeite pyroxene in equilibrium with albite and quartz at 1200-1350°C and 15-34 kbar

NASA Astrophysics Data System (ADS)

Gasparik, Tibor

1985-03-01

Equilibrium compositions of diopside-jadeite pyroxene coexisting with albite and quartz were experimentally determined at 25 different P-T conditions, using an electron microprobe for analysis. The new data and the 600°C data of HOLLAND (1983) provided the following mixing properties of the diopside (Di)-jadeite (Jd) solid solution (J, K): Gxs = XJdXDi[12600 - 9.45 T + (12600 - 7.6 T)( XJd - XDi) - (21400 - 16.2 T)( XJd - XDi) 2]. The Di-Jd solution is close to ideal above 1000°C but immiscible below 565°C. The Di-Jd solvus is slightly asymmetric with the crest at composition Di 42.4Jd 57.6. Excess enthalpy is positive but smaller than indicated by the enthalpy of solution measurements of WOODet al. (1980). Disorder in the Di-Jd solution is significantly smaller than complete disorder implied by the ionic two-site model.

An Interactive Computer Forecasting Model to Determine the Effects of Policy Changes on the Valuation of the Military Retirement System.

DTIC Science & Technology

1986-12-01

adjustment determined on CPI percentage increase from June to - December and December to June, respectively (Chiles Amendment). 1980 Deleted the semi-annual...ll1-(1/q))/di) 4 01595 print using ’Present value of future retirement benefits =tzlh9U S.f’lpre 01600 t2((I+di)** los1 )- 01605 nc=pre*(di/t) 01610

Di(hydroxyphenyl)- benzimidazole monomers

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

1993-01-01

Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

A novel tank for DI water reduction in MEMS manufacturing

NASA Astrophysics Data System (ADS)

Raccurt, O.; Tardif, F.; Kerber, L.; Lardin, T.; Vareine, T.

2003-05-01

A new rinsing process is proposed based on the conclusions obtained by simulations. It consists of a combination of piston flows and internal top-to-bottom recycling steps, which decreases the DI water consumption (and associated cost) for the same rinsing efficiency. This novel concept re-using the DI water in situ in the rinsing tank is demonstrated using an industrial bath recently proposed on the market.

Retrieval of Water Channels by Endocytosis in Renal Epithelia.

DTIC Science & Technology

1998-07-01

1983) and conformational changes ( DiBona , 1983) during enhanced water flow. Following cessation of hormone actions or receptor down regulation...and DiBona , 1982; Pearl and Taylor, 1983; Hays et al., 1994). In our studies, we report the role of proteins associated with microfilaments that may...vasopressin-activated transport. Proc. Soc. Exptl. Biol. Med. Invited Review. (Accepted). DiBona , D.R. 1983. Cytoplasmic involvement in ADH-mediated osmosis

Aluminum corrosion mitigation in alkaline electrolytes containing hybrid inorganic/organic inhibitor system for power sources applications

NASA Astrophysics Data System (ADS)

Gelman, Danny; Lasman, Itay; Elfimchev, Sergey; Starosvetsky, David; Ein-Eli, Yair

2015-07-01

The severe corrosion accompanied with hydrogen evolution process is the main obstacle preventing the implementation of Al as an anode in alkaline batteries. It impairs the functionality of alkaline battery, due to a drastic capacity loss and a short shelf life. The possibility to reduce Al corrosion rate in alkaline solution with the use of hybrid organic∖inorganic inhibitor based on poly (ethylene glycol) di-acid (PEG di-acid) and zinc oxide (ZnO) was examined in this work. A correlation between an Al corrosion rates and the concentrations of both PEG di-acid and ZnO in alkaline is shown. Selecting 5000 ppm PEG di-acid and 16 gr/l ZnO provides substantial corrosion protection of Al, reducing the corrosion rate in a strong alkaline solution by more than one order of magnitude. Moreover, utilizing the same formulation results in increase in Al-air battery discharge capacity, from 44.5 (for a battery utilizing only KOH in the electrolyte) to 70 mhA/cm2 (for a battery utilizing ZnO/PEG di-acid hybrid inhibitor in the electrolyte). The morphology and composition of the Al electrode surface (studied by SEM, EDS, and XRD) depend on PEG di-acid and ZnO concentrations.

16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

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

Walden, T.L. Jr.; Patchen, M.; Snyder, S.L.

1987-03-01

16,16-Dimethyl prostaglandin E2 (DiPGE2), a stable analog of PGE2, increases the LD50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 micrograms of DiPGE2 30 min prior to /sup 60/Co gamma irradiation extends the LD50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose reduction factor of 1.72 (95% confidence limits: 1.62, 1.82). The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90%more » survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs postinjection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.« less

Improvement in smile esthetics following orthodontic treatment: a retrospective study utilizing standardized smile analysis.

PubMed

Maganzini, Anthony L; Schroetter, Sarah B; Freeman, Kathy

2014-05-01

To quantify smile esthetics following orthodontic treatment and determine whether these changes are correlated to the severity of the initial malocclusion. A standardized smile mesh analysis that evaluated nine lip-tooth characteristics was applied to two groups of successfully treated patients: group 1 (initial American Board of Orthodontics Discrepancy Index [DI] score<20) and group 2 (initial DI score>20). T-tests were used to detect significant differences between the low-DI and high-DI groups for baseline pretreatment measurements, baseline posttreatment measurements, and changes from pre- to posttreatment. A Spearman correlation test compared the initial DI values with the changes in the nine smile measurements. Five of the smile measurements were improved in both groups following orthodontic treatment. Both groups demonstrated improved incisor exposure, an improved gingival smile line, an increase in smile width, a decreased buccal corridor space, and an improvement in smile consonance. Spearman correlation tests showed that initial DI value was not correlated to changes in any of the individual smile measurements. Smile esthetics is improved by orthodontic treatment regardless of the initial severity of the malocclusion. In other words, patients with more complex orthodontic issues and their counterparts with minor malocclusions benefitted equally from treatment in terms of their smile esthetics.

Studying distributed cognition of simulation-based team training with DiCoT.

PubMed

Rybing, Jonas; Nilsson, Heléne; Jonson, Carl-Oscar; Bang, Magnus

2016-03-01

Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology's usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System® simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System®. We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design.

Exposure to phthalates in house dust and associated allergies in children aged 6-12years.

PubMed

Ait Bamai, Yu; Araki, Atsuko; Kawai, Toshio; Tsuboi, Tazuru; Saito, Ikue; Yoshioka, Eiji; Cong, Shi; Kishi, Reiko

2016-11-01

Phthalates are widely used as plasticizers in household products. Several studies have reported an association between phthalate exposure and an increased risk of allergies. The present study estimated phthalate exposure in children aged 6-12years and assessed potential correlations with allergies. House dust samples were collected from floors and multi-surface objects >35cm above the floor. Urine samples were collected from the first morning void of the day. Daily phthalate intake (DI dust and DI) was estimated using both house dust and urinary metabolite concentrations. Exposure to di-2-ethylhexyl phthalate (DEHP) in floor dust was associated with parental-reported rhino-conjunctivitis. After stratification by gender, this trend was found to only occur in boys. Furthermore, urinary mono-isobutyl phthalate was inversely associated with parental-reported wheeze in boys. DI dust of benzyl butyl phthalate (BBzP) and DEHP were significantly correlated with DI_BBzP and DI_DEHP, respectively. These correlations were stronger with floor than with multi-surface dust. Our results suggest that, among Japanese children, house dust from low surfaces, such as living room floors, might play a meaningful role in the indoor environmental exposure pathway for BBzP and DEHP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contributions of nanodiamond abrasives and deionized water in magnetorheological finishing of aluminum oxynitriden

NASA Astrophysics Data System (ADS)

Miao, Chunlin; Lambropoulos, John C.; Romanofsky, Henry; Shafrir, Shai N.; Jacobs, Stephen D.

2009-08-01

Magnetorheological finishing (MRF) is a sub-aperture deterministic process for fabricating high-precision optics by removing material and smoothing the surface. The goal of this work is to study the relative contribution of nanodiamonds and water in material removal for MRF of aluminum oxynitride ceramic (ALON) based upon a nonaqueous magnetorheological (MR) fluid. Removal was enhanced by a high carbonyl iron concentration and the addition of nanodiamond abrasives. Small amounts of deionized (DI) water were introduced into the nonaqueous MR fluid to further influence the material removal process. Material removal data were collected with a spot-taking machine. Drag force (Fd) and normal force (Fn) before and after adding nanodiamonds or DI water were measured with a dual load cell. Both drag force and normal force were insensitive to the addition of nanodiamonds but increased with DI water content in the nonaqueous MR fluid. Shear stress (i.e., drag force divided by spot area) was calculated, and examined as a function of nanodiamond concentration and DI water concentration. Volumetric removal rate increased with increasing shear stress, which was shown to be a result of increasing viscosity after adding nanodiamonds and DI water. This work demonstrates that removal rate for a hard ceramic with MRF can be enhanced by adding DI water into a nonaqueous MR fluid.

Bioactivity of 2′-deoxyinosine-incorporated aptamer AS1411

PubMed Central

Fan, Xinmeng; Sun, Lidan; Wu, Yun; Zhang, Lihe; Yang, Zhenjun

2016-01-01

Aptamers can be chemically modified to enhance nuclease resistance and increase target affinity. In this study, we performed chemical modification of 2′-deoxyinosine in AS1411, an anti-proliferative G-rich oligodeoxynucleotide aptamer, which binds selectively to the nucleolin protein. Its function was augmented when 2′-deoxyinosine was incorporated at positions 12, 13, 15, and 24 of AS1411, respectively. In addition, double incorporation of 2′-deoxyinosine at positions 12 and 24 (FAN-1224dI), 13 and 24 (FAN-1324dI), and 15 and 24 (FAN-1524dI) promoted G-quartet formation, as well as inhibition of DNA replication and tumor cell growth, and induced S-phase cell cycle arrest. In further animal experiments, FAN-1224dI, FAN-1324dI and FAN-1524dI resulted in enhanced treatment effects than AS1411 alone. These results suggested that the position and number of modification substituents in AS1411 are critical parameters to improve the diagnostic and therapeutic function of the aptamer. Structural investigations of the FAN-1524dI/nucleolin complex structure, using molecular dynamics simulation, revealed the critical interactions involving nucleolin and 2′-dI incorporated AS1411 compared with AS1411 alone. These findings augment understanding of the role of 2′-deoxyinosine moieties in interactive binding processes. PMID:27194215

Simultaneous Detection of Two Chemicals Using a TE20-Mode Substrate-Integrated Waveguide Resonator

PubMed Central

Salim, Ahmed

2018-01-01

Microwave resonators working as sensors can detect only a single analyte at a time. To address this issue, a TE20-mode substrate-integrated waveguide (SIW) resonator is exploited, owing to its two distinct regions of high-intensity electric fields, which can be manipulated by loading two chemicals. Two microfluidic channels with unequal fluid-carrying capacities, engraved in a polydimethylsiloxane (PDMS) sheet, can perturb the symmetric electric fields even if loaded with the two extreme cases of dielectric [ethanol (E), deionized water (DI)] and [deionized water, ethanol]. The four layers of the sandwiched structure considered in this study consisted of a top conductive pattern and a bottom ground, both realized on a Rogers RT/Duroid 5880. PDMS-based channels attached with an adhesive serve as the middle layers. The TE20-mode SIW with empty channels resonates at 8.26 GHz and exhibits a −25 dB return loss with an unloaded quality factor of Q ≈ 28. We simultaneously load E and DI and demonstrate the detection of the four possible combinations: [E, DI], [DI, E], [E, E], and [DI, DI]. The performance of our proposed method showed increases in sensitivity (MHz/εr) of 7.5%, 216%, and 1170% compared with three previously existing multichannel microwave chemical sensors. PMID:29518981

Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis.

PubMed

Ren, Gai-Xian; Fan, Sai; Guo, Xiao-Peng; Chen, Shiyun; Sun, Yi-Cheng

2016-01-01

Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments.

Episodic deflation-inflation events at Kīlauea Volcano and implications for the shallow magma system: Chapter 11

USGS Publications Warehouse

Anderson, Kyle R.; Poland, Michael; Johnson, Jessica H.; Miklius, Asta; Carey, Rebecca; Cayol, Valérie; Poland, Michael P.; Weis, Dominique

2015-01-01

Episodic variations in magma pressures and flow rates at Kīlauea Volcano, defined by a characteristic temporal evolution and termed deflation-inflation (DI) events, have been observed since at least the 1990s. DI events consist of transient, days-long deflations and subsequent reinflations of the summit region, accompanied since 2008 by fluctuations in the surface height of Kīlauea's summit lava lake. After a delay of minutes to hours, these events also often appear along the volcano's East Rift Zone in ground deformation data and as temporary reductions in eruption rate (sometimes followed by brief surges). Notable pauses in DI activity have preceded many eruptive events at Kīlauea. We analyzed more than 500 DI events recorded by borehole tiltmeters at the summit during 2000–2013. Inverse modeling suggests that DI-related ground deformation at the summit is generated by pressure transients in a shallow magma reservoir located beneath the east margin of Halema‘uma‘u Crater and that this reservoir has remained remarkably stable for more than a decade. Utilizing tilt data and variation in the level of the summit lava lake during a large DI event, we estimate a reservoir volume of approximately 1 km3 (0.2–5.5 km3 at 95% confidence).

Z-depth integration: a new technique for manipulating z-depth properties in composited scenes

NASA Astrophysics Data System (ADS)

Steckel, Kayla; Whittinghill, David

2014-02-01

This paper presents a new technique in the production pipeline of asset creation for virtual environments called Z-Depth Integration (ZeDI). ZeDI is intended to reduce the time required to place elements at the appropriate z-depth within a scene. Though ZeDI is intended for use primarily in two-dimensional scene composition, depth-dependent "flat" animated objects are often critical elements of augmented and virtual reality applications (AR/VR). ZeDI is derived from "deep image compositing", a capacity implemented within the OpenEXR file format. In order to trick the human eye into perceiving overlapping scene elements as being in front of or behind one another, the developer must manually manipulate which pixels of an element are visible in relation to other objects embedded within the environment's image sequence. ZeDI improves on this process by providing a means for interacting with procedurally extracted z-depth data from a virtual environment scene. By streamlining the process of defining objects' depth characteristics, it is expected that the time and energy required for developers to create compelling AR/VR scenes will be reduced. In the proof of concept presented in this manuscript, ZeDI is implemented for pre-rendered virtual scene construction via an AfterEffects software plug-in.

The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control

PubMed Central

Lindenberg, Sandra; Klauck, Gisela; Pesavento, Christina; Klauck, Eberhard; Hengge, Regine

2013-01-01

C-di-GMP—which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)—is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and—by direct and specific interaction—activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling. PMID:23708798

Measurement of membrane potential and [Ca2+]i in cell ensembles: application to the study of glutamate taste in mice.

PubMed Central

Hayashi, Y; Zviman, M M; Brand, J G; Teeter, J H; Restrepo, D

1996-01-01

We have studied the spectral properties of the voltage-sensitive dye, 1-(3-sulfonatopropyl)-4-[beta [2-(di-n-octylamino)-6-naphtyl]vinyl] pyridinium betaine (di-8-ANEPPS), and the Ca(2+)-sensitive dye, fura-2, in azolectin liposomes and in isolated taste buds from mouse. We find that the fluorescence excitation spectra of di-8-ANEPPS and fura-2 are largely nonoverlapping, allowing alternate ratio measurements of membrane potential and intracellular calcium ([Ca2+]i). There is a small spillover of di-8-ANEPPS fluorescence at the excitation wavelengths used for fura-2 (340 and 360 nm). However, voltage-induced changes in the fluorescence of di-8-ANEPPS, excited at the fura-2 wavelengths, are small. In addition, di-8-ANEPPS fluorescence is localized to the membrane, whereas fura-2 fluorescence is distributed throughout the cytoplasm. Because of this, the effect of spillover of di-8-ANEPPS fluorescence in the [Ca2+]i estimate is < 1%, under the appropriate conditions. We have applied this method to study of the responses of multiple taste cells within isolated taste buds. We show that membrane potential and [Ca2+]i can be measured alternately in isolated taste buds from mouse. Stimulation with glutamate and glutamate analogs indicates that taste cells express both metabotropic and ionotropic receptors. The data suggest that the receptors responding to 2-amino-4-phosphonobutyrate (L-AP4), presumably metabotropic L-glutamate receptors, do not mediate excitatory glutamate taste responses. Images FIGURE 5 PMID:8842242

Fluctuating asymmetry and developmental instability in evolutionary biology: past, present and future.

PubMed

Dongen, S V

2006-11-01

The role of developmental instability (DI), as measured by fluctuating asymmetry (FA), in evolutionary biology has been the focus of a wealth of research for more than half a century. In spite of this long period and many published papers, our current state of knowledge reviewed here only allows us to conclude that patterns are heterogeneous and that very little is known about the underlying causes of this heterogeneity. In addition, the statistical properties of FA as a measure of DI are only poorly grasped because of a general lack of understanding of the underlying mechanisms that drive DI. If we want to avoid that this area of research becomes abandoned, more efforts should be made to understand the observed heterogeneity, and attempts should be made to develop a unifying statistical protocol. More specifically, and perhaps most importantly, it is argued here that more attention should be paid to the usefulness of FA as a measure of DI since many factors might blur this relationship. Furthermore, the genetic architecture, associations with fitness and the importance of compensatory growth should be investigated under a variety of stress situations. In addition, more focus should be directed to the underlying mechanisms of DI as well as how these processes map to the observable phenotype. These insights could yield more efficient statistical models and a unified approach to the analysis of patterns in FA and DI. The study of both DI and canalization is indispensable to obtain better insights in their possible common origin, especially because both have been suggested to play a role in both micro- and macro-evolutionary processes.

Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection.

PubMed

Feng, Liangzhu; Tao, Danlei; Dong, Ziliang; Chen, Qian; Chao, Yu; Liu, Zhuang; Chen, Meiwan

2017-05-01

Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin. Copyright © 2016. Published by Elsevier Ltd.

Low-frequency pitch perception in children with cochlear implants in comparison to normal hearing peers.

PubMed

Dincer D'Alessandro, Hilal; Filipo, Roberto; Ballantyne, Deborah; Attanasio, Giuseppe; Bosco, Ersilia; Nicastri, Maria; Mancini, Patrizia

2015-11-01

The aim of the present study was to investigate the application of two new pitch perception tests in children with cochlear implants (CI) and to compare CI outcomes to normal hearing (NH) children, as well as investigating the effect of chronological age on performance. The tests were believed to be linked to the availability of Temporal Fine Structure (TFS) cues. 20 profoundly deaf children with CI (5-17 years) and 31 NH peers participated in the study. Harmonic Intonation (HI) and Disharmonic Intonation (DI) tests were used to measure low-frequency pitch perception. HI/DI outcomes were found poorer in children with CI. CI and NH groups showed a statistically significant difference (p < 0.001). HI scores were better than those of DI test (p < 0.001). Chronological age had a significant effect on DI performance in NH group (p < 0.05); children under the age of 8.5 years showed larger inter-subject-variability; however, the majority of NH children showed outcomes that were considered normal at adult-level. For the DI test, bimodal listeners had better performance than when listening with CI alone. HI/DI tests were applicable as clinical tools in the pediatric population. The majority of CI users showed abnormal outcomes on both tests confirming poor TFS processing in the hearing-impaired population. Findings indicated that the DI test provided more differential low-frequency pitch perception outcomes in that it reflected phase locking and TFS processing capacities of the ear, whereas HI test provided information of its place coding capacity as well.

Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review.

PubMed

Fenske, Wiebke; Allolio, Bruno

2012-10-01

The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term "polyuria polydipsia syndrome" was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

PubMed Central

Corley, Janie; Cox, Simon R.; Valdés Hernández, Maria C.; Craig, Leone C.A.; Dickie, David Alexander; Karama, Sherif; McNeill, Geraldine M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

2017-01-01

Objective: To assess the association between Mediterranean-type diet (MeDi) and change in brain MRI volumetric measures and mean cortical thickness across a 3-year period in older age (73–76 years). Methods: We focused on 2 longitudinal brain volumes (total and gray matter; n = 401 and 398, respectively) plus a longitudinal measurement of cortical thickness (n = 323), for which the previous cross-sectional evidence of an association with the MeDi was strongest. Adherence to the MeDi was calculated from data gathered from a food frequency questionnaire at age 70, 3 years prior to the baseline imaging data collection. Results: In regression models adjusting for relevant demographic and physical health indicators, we found that lower adherence to the MeDi was associated with greater 3-year reduction in total brain volume (explaining 0.5% of variance, p < 0.05). This effect was half the size of the largest covariate effect (i.e., age). Cross-sectional associations between MeDi and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume. Conclusions: Lower adherence to the MeDi in an older Scottish cohort is predictive of total brain atrophy over a 3-year interval. Fish and meat consumption does not drive this change, suggesting that other components of the MeDi or, possibly, all of its components in combination are responsible for the association. PMID:28053008

Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

PubMed

Sharma, Parveen; Ignatchenko, Vladimir; Grace, Kevin; Ursprung, Claudia; Kislinger, Thomas; Gramolini, Anthony O

2010-07-09

Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase, which transports Ca(2+) into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation. Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO) annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins. We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

Diabetes Insipidus Contributes to Traumatic Brain Injury Pathology Via CD36 Neuroinflammation

PubMed Central

Staples, Meaghan; Borlongan, Mia C.; Hernandez, Diana; Acosta, Sandra

2013-01-01

Each year, over one million people in the United States are affected by traumatic brain injury (TBI). Symptoms of both acute and chronic neuroinflammation follow TBI, coinciding with a robust immune response and activation of the brain’s endogenous repair mechanisms. TBI can lead to endocrine failure as a result of damage to the thalamic region of the brain, evidenced by excessive thirst and polyuria often accompanying TBI. These symptoms indicate the presence of diabetes insipidus (DI), a disruption of water homeostasis due to antidiuretic hormone deficiency. This deficiency accompanies a mechanical or neuroinflammatory damage to the thalamic region during TBI, evidenced by increased expression of inflammatory microglial marker MHCII in this brain region. Excessive thirst and urinations, which are typical DI symptoms, in our chronic TBI rats also suggest a close connection between TBI and DI. We seek to bridge this gap between TBI and DI through investigation of the Cluster of Differentiation 36 (CD36) receptor. This receptor is associated with Low-Density Lipoprotein (LDL) deregulation, proinflammatory events, and innate immunity regulation. We posit that CD36 exacerbates TBI through immune activation and subsequent neuroinflammation. Indeed, scientific evidence already supports pathological interaction of CD36 in other neurological disorders including stroke and Alzheimer’s disease. We propose that DI contributes to TBI pathology via CD36 neuroinflammation. Use of CD36 as a biomarker may provide insights into treatment and disease pathology of TBI and DI. This unexplored avenue of research holds potential for a better understanding and treatment of TBI and DI. PMID:24021616

The gas chromatographic determination of volatile fatty acids in wastewater samples: evaluation of experimental biases in direct injection method against thermal desorption method.

PubMed

Ullah, Md Ahsan; Kim, Ki-Hyun; Szulejko, Jan E; Cho, Jinwoo

2014-04-11

The production of short-chained volatile fatty acids (VFAs) by the anaerobic bacterial digestion of sewage (wastewater) affords an excellent opportunity to alternative greener viable bio-energy fuels (i.e., microbial fuel cell). VFAs in wastewater (sewage) samples are commonly quantified through direct injection (DI) into a gas chromatograph with a flame ionization detector (GC-FID). In this study, the reliability of VFA analysis by the DI-GC method has been examined against a thermal desorption (TD-GC) method. The results indicate that the VFA concentrations determined from an aliquot from each wastewater sample by the DI-GC method were generally underestimated, e.g., reductions of 7% (acetic acid) to 93.4% (hexanoic acid) relative to the TD-GC method. The observed differences between the two methods suggest the possibly important role of the matrix effect to give rise to the negative biases in DI-GC analysis. To further explore this possibility, an ancillary experiment was performed to examine bias patterns of three DI-GC approaches. For instance, the results of the standard addition (SA) method confirm the definite role of matrix effect when analyzing wastewater samples by DI-GC. More importantly, their biases tend to increase systematically with increasing molecular weight and decreasing VFA concentrations. As such, the use of DI-GC method, if applied for the analysis of samples with a complicated matrix, needs a thorough validation to improve the reliability in data acquisition. Copyright © 2014 Elsevier B.V. All rights reserved.

Acyl-chain remodeling of dioctanoyl-phosphatidylcholine in Saccharomyces cerevisiae mutant defective in de novo and salvage phosphatidylcholine synthesis

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

Kishino, Hideyuki; Eguchi, Hiroki; Takagi, Keiko

2014-03-07

Highlights: • Dioctanoyl-PC (diC8PC) supported growth of a yeast mutant defective in PC synthesis. • diC8PC was converted to PC species containing longer acyl residues in the mutant. • Both acyl residues of diC8PC were replaced by longer fatty acids in vitro. • This system will contribute to the elucidation of the acyl chain remodeling of PC. - Abstract: A yeast strain, in which endogenous phosphatidylcholine (PC) synthesis is controllable, was constructed by the replacement of the promoter of PCT1, encoding CTP:phosphocholine cytidylyltransferase, with GAL1 promoter in a double deletion mutant of PEM1 and PEM2, encoding phosphatidylethanolamine methyltransferase and phospholipidmore » methyltransferase, respectively. This mutant did not grow in the glucose-containing medium, but the addition of dioctanoyl-phosphatidylcholine (diC8PC) supported its growth. Analyses of the metabolism of {sup 13}C-labeled diC8PC ((methyl-{sup 13}C){sub 3}-diC8PC) in this strain using electrospray ionization tandem mass spectrometry revealed that it was converted to PC species containing acyl residues of 16 or 18 carbons at both sn-1 and sn-2 positions. In addition, both acyl residues of (methyl-{sup 13}C){sub 3}-diC8PC were replaced with 16:1 acyl chains in the in vitro reaction using the yeast cell extract in the presence of palmitoleoyl-CoA. These results indicate that PC containing short acyl residues was remodeled to those with acyl chains of physiological length in yeast.« less

Characterization of Austempered Ferritic Ductile Iron

NASA Astrophysics Data System (ADS)

Dakre, Vinayak S.; Peshwe, D. R.; Pathak, S. U.; Likhite, A. A.

2018-04-01

The ductile iron (DI) has graphite nodules enclose in ferrite envelop in pearlitic matrix. The pearlitic matrix in DI was converted to ferritic matrix through heat treatment. This heat treatment includes austenitization of DI at 900°C for 1h, followed by furnace cooling to 750°C & hold for 1h, then again furnace cooling to 690°C hold for 2h, then samples were allowed to cool in furnace. The new heat treated DI has graphite nodules in ferritic matrix and called as ferritic ductile iron (FDI). Both DIs were austenitized at 900°C for 1h and then quenched into salt bath at 325°C. The samples were soaked in salt bath for 60, 120, 180, 240 and 300 min followed by air cooling. The austempered samples were characterized with help of optical microscopy, SEM and X-ray diffraction analysis. Austempering of ferritic ductile iron resulted in finer ausferrite matrix as compared to ADI. Area fraction of graphite, ferrite and austenite were determining using AXIOVISION-SE64 software. Area fraction of graphite was more in FDI than that of as cast DI. The area fraction of graphite remains unaffected due to austempering heat treatment. Ausferritic matrix coarsened (feathered) with increasing in austempering time for both DI and FDI. Bulk hardness test was carried on Rockwell Hardness Tester with load of 150 kgf and diamond indenter. Hardness obtained in as cast DI is 28 HRC which decreased to 6 HRC in FDI due conversion of pearlitic matrix to ferritic matrix. Hardness is improved by austempering process.

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother-Child Cohort Study.

PubMed

Soomro, Munawar Hussain; Baiz, Nour; Philippat, Claire; Vernet, Celine; Siroux, Valerie; Nichole Maesano, Cara; Sanyal, Shreosi; Slama, Remy; Bornehag, Carl-Gustaf; Annesi-Maesano, Isabella

2018-02-02

Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di- n -butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p =0.01 and HR=1.87 (95% CI: 1.01, 3.48), p =0.04, respectively}. Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829.

Perceptions of orthodontic case complexity among orthodontists, general practitioners, orthodontic residents, and dental students.

PubMed

Heath, Elizabeth M; English, Jeryl D; Johnson, Cleverick D; Swearingen, Elizabeth B; Akyalcin, Sercan

2017-02-01

Our aims were to assess the perceptions of orthodontic case complexity among orthodontists, general dentists, orthodontic residents, and dental students and to compare their perceptions with the American Board of Orthodontics Discrepancy Index (DI). Orthodontists, general dentists, orthodontic residents, and dental students (n = 343) participated in a Web-based survey. Pretreatment orthodontic records of 29 cases with varying DI scores were obtained. Respondents were asked to evaluate case complexity on a 100-point visual analog scale. Additional information was collected on participants' orthodontic education and orthodontic treatment preferences. Pearson correlation coefficients were used to assess the relationship between the average complexity score and the DI score. Repeated measures analysis with linear mixed models was used to assess the association between the average complexity score and the DI score and whether the association between the 2 scores varied by level of difficulty or panel group. The level of significance for all analyses was set at P <0.05. The results showed that 71.6% of general dentists provided some orthodontic services, with 21.0% providing full fixed appliances and 38.3% providing clear aligners. DI score was significantly associated with complexity perceptions (P = 0.0168). Associations between average complexity and DI score varied significantly by provider group (P = 0.0033), with orthodontists and residents showing the strongest associations. When the DI score was greater than 15, orthodontists and residents perceived cases as more complex than did the other provider groups. Orthodontists and orthodontic residents had better judgments for evaluating orthodontic case complexity. The high correlation between orthodontic professionals' perceptions and DI scores suggested that additional orthodontic education and training have an influence on the ability to recognize case complexity. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Does the CDC Definition of Fever Accurately Predict Inflammation and Infection in Persons With SCI?

PubMed

Trbovich, Michelle; Li, Carol; Lee, Shuko

2016-01-01

Background: Pneumonia and septicemia have the greatest impact on reduced life expectancy in persons with spinal cord injury (SCI). Fever is often the first presenting symptom of infection or inflammation. Thermoregulatory dysfunction in persons with SCI may preclude a typical febrile response to infection or inflammation and thus delay diagnostic workup. Objective: To determine the core temperature of persons with SCI in the setting of infection or inflammation and the frequency with which it meets criteria for the CDC definition of fever (>100.4°F). Methods: Retrospective review of hospitalized SCI patients over 5 years with a diagnosis of infection or inflammation (DI), defined by serum leukocytosis. In this study, 458 persons with paraplegia (PP) and 483 persons with tetraplegia (TP) had 4,191 DI episodes. Aural temperatures (T au ) on the day of DI, 7 days prior, and 14 days afterwards were abstracted from medical records. Main outcome measures were average T au at DI, frequency of temperatures >100.4°F at DI, and average baseline temperatures before and after DI. Results: Average T au at DI was 98.2°F (±1.5) and 98.2°F (±1.4) in the TP and PP groups, respectively, with only 11.6% to 14% of DI resulting in T au >100.4°F. Baseline temperatures ranged from 97.9°F (±0.7) to 98.0°F (±0.8). Conclusion: SCI persons with leukocytosis infrequently mount a fever as defined by the CDC, and baseline temperatures were subnormal (<98.6°F). Thermoregulatory dysfunction likely accounts for these findings. T au >100.4°F is not a sensitive predictor of infection or inflammation in persons with SCI. Clinicians should be vigilant for alternative symptoms of infection and inflammation in these patients, so diagnostic workup is not delayed.

The incidence of complications associated with loop duodeno-ileostomy after single-anastomosis duodenal switch procedures among 1328 patients: a multicenter experience.

PubMed

Surve, Amit; Cottam, Daniel; Sanchez-Pernaute, Andres; Torres, Antonio; Roller, Joshua; Kwon, Yong; Mourot, Joshua; Schniederjan, Bleu; Neichoy, Bo; Enochs, Paul; Tyner, Michael; Bruce, Jon; Bovard, Scott; Roslin, Mitchell; Jawad, Muhammad; Teixeira, Andre; Srikanth, Myur; Free, Jason; Zaveri, Hinali; Pilati, David; Bull, Jamie; Belnap, LeGrand; Richards, Christina; Medlin, Walter; Moon, Rena; Cottam, Austin; Sabrudin, Sarah; Cottam, Samuel; Dhorepatil, Aneesh

2018-02-02

The single-anastomosis duodenal switch procedure is a type of duodenal switch that involves a loop anastomosis rather than traditional Roux-en-Y reconstruction. To date, there have been no multicenter studies looking at the complications associated with post-pyloric loop reconstruction. The aim of the study was to report the incidence of complications associated with loop duodeno-ileostomy (DI) following single-anastomosis duodenal switch (SADS) procedures. Mixed of private and teaching facilities. The medical records of 1328 patients who underwent primary SADS procedure (single-anastomosis duodeno-ileal bypass with sleeve gastrectomy or stomach intestinal pylorus-sparing surgery) by 17 surgeons from 3 countries (United States, Spain, and Australia) at 9 centers over a 6-year period were retrospectively reviewed, and their results were compared with articles in the literature. Mean preoperative body mass index was 51.6 kg/m 2 . Of 1328 patients, 123 patients received a linear stapled duodeno-ileostomy (DI) and 1205 patients a hand-sewn DI. In the overall series, the anastomotic leak, ulcer, and bile reflux occurred in .6% (9/1328), .1% (2/1328), and .1% (2/1328), respectively. None of our patients experienced volvulus at the DI or an internal hernia. Overall, 5 patients (.3%) (3/123 [2.4%] with linear stapled DI versus 2/1205 [.1%] with hand-sewn DI [P<.05]) experienced stricture at the DI in this series. The overall incidence of complications associated with loop DI was lower than the reported incidence of anastomotic complications after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch. SADS procedures may cause much fewer anastomotic complications compared with Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Exposure assessment of particulates of diesel and natural gas fuelled buses in silico.

PubMed

Pietikäinen, Mari; Oravisjärvi, Kati; Rautio, Arja; Voutilainen, Arto; Ruuskanen, Juhani; Keiski, Riitta L

2009-12-15

Lung deposition estimates of particulate emissions of diesel and natural gas (CNG) fuelled vehicles were studied by using in silico methodology. Particulate emissions and particulate number size distributions of two Euro 2 petroleum based diesel buses and one Euro 3 gas bus were measured. One of the petroleum based diesel buses used in the study was equipped with an oxidation catalyst on the vehicle (DI-OC) while the second had a partial-DPF catalyst (DI-pDPF). The third bus used was the gas bus with an oxidation catalyst on the vehicle (CNG-OC). The measurements were done using a transient chassis dynamometer test cycle (Braunschweig cycle) and an Electric Low Pressure Impactor (ELPI) with formed particulates in the size range of 7 nm to 10 microm. The total amounts of the emitted diesel particulates were 88-fold for DI-OC and 57-fold for DI-pDPF compared to the total amount of emitted CNG particulates. Estimates for the deposited particulates were computed with a lung deposition model ICRP 66 using in-house MATLAB scripts. The results were given as particulate numbers and percentages deposited in five different regions of the respiratory system. The percentages of particulates deposited in the respiratory system were 56% for DI-OC, 51% for DI-pDPF and 77% for CNG-OC of all the inhaled particulates. The result shows that under similar conditions the total lung dose of particulates originating from petroleum diesel fuelled engines DI-OC and DI-pDPF was more than 60-fold and 35-fold, respectively, compared to the lung dose of particulates originating from the CNG fuelled engine. The results also indicate that a majority (35-50%) of the inhaled particulates emitted from the tested petroleum diesel and CNG engines penetrate deep into the unciliated regions of the lung where gas-exchange occurs.

Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil.

PubMed

Liu, Chen; Liu, Jinxia

2016-05-01

Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure Assessment Issues in Epidemiology Studies of Phthalates

PubMed Central

Johns, Lauren E.; Cooper, Glinda S.; Galizia, Audrey; Meeker, John D.

2015-01-01

Purpose The purpose of this paper is to review exposure assessment issues that need to be addressed in designing and interpreting epidemiology studies of phthalates, a class of chemicals commonly used in consumer and personal care products. Specific issues include population trends in exposure, temporal reliability of a urinary metabolite measurement, and how well a single urine sample may represent longer-term exposure. The focus of this review is on seven specific phthalates: diethyl phthalate (DEP); di-n-butyl phthalate (DBP); diisobutyl phthalate (DiBP); butyl benzyl phthalate (BBzP); di(2-ethylhexyl) phthalate (DEHP); diisononyl phthalate (DiNP); and diisodecyl phthalate (DiDP). Methods Comprehensive literature search using multiple search strategies Results Since 2001, declines in population exposure to DEP, BBzP, DBP, and DEHP have been reported in the United States and Germany, but DEHP exposure has increased in China. Although the half-lives of various phthalate metabolites are relatively short (3 to 18 hours), the intraclass correlation coefficients (ICCs) for phthalate metabolites, based on spot and first morning urine samples collected over a week to several months, range from weak to moderate, with a tendency toward higher ICCs (greater temporal stability) for metabolites of the shorter-chained (DEP, DBP, DiBP and BBzP, ICCs generally 0.3 to 0.6) compared with those of the longer-chained (DEHP, DiNP, DiDP, ICCs generally 0.1 to 0.3) phthalates. Additional research on optimal approaches to addressing the issue of urine dilution in studies of associations between biomarkers and different type of health effects is needed. Conclusions In conclusion, the measurement of urinary metabolite concentrations in urine could serve as a valuable approach to estimating exposure to phthalates in environmental epidemiology studies. Careful consideration of the strengths and limitations of this approach when interpreting study results is required. PMID:26313703

Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

PubMed Central

Carlstedt, Fredrik; Jönsson, Bo AG.; Lindh, Christian H.; Jensen, Tina K.; Bodin, Anna; Jonsson, Carin; Janson, Staffan; Swan, Shanna H.

2014-01-01

Background: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)—the distance from the anus to the genitals—has been used to assess reproductive toxicity. Objective: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. Methods: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. Results: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. Conclusions: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally. Citation: Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH. 2015. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect 123:101–107; http://dx.doi.org/10.1289/ehp.1408163 PMID:25353625

Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic Variation

PubMed Central

Houard, Sophie; Havelange, Nicolas; Drossard, Jürgen; Mertens, Hubert; Croon, Alexander; Kastilan, Robin; Byrne, Richard; van der Werff, Nicole; van der Eijk, Marjolein; Thomas, Alan W.; Kocken, Clemens H. M.; Remarque, Edmond J.

2016-01-01

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and 1.3 gram, respectively. N-terminal determinations showed that approximately 50% of each of the proteins lost 12 residues from their N-terminus, in accordance with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of limited proteolytic cleavage within a disulphide bonded region became evident. The three proteins quantitatively bound to the mAb 4G2 that recognizes a conformational epitope, suggesting proper folding of the proteins. The lyophilized Drug Product (1:1:1 mixture of PfAMA1-DiCo1, DiCo2, DiCo3) fulfilled all pre-set release criteria (appearance, dissolution rate, identity, purity, protein content, moisture content, sub-visible particles, immuno-potency (after reconstitution with adjuvant), abnormal toxicity, sterility and endotoxin), was stable in accelerated and real-time stability studies at -20°C for over 24 months. When formulated with adjuvants selected for clinical phase I evaluation, the Drug Product did not show adverse effect in a repeated-dose toxicity study in rabbits. The Drug Product has entered a phase Ia/Ib clinical trial. PMID:27695087

Does the CDC Definition of Fever Accurately Predict Inflammation and Infection in Persons With SCI?

PubMed Central

Li, Carol; Lee, Shuko

2016-01-01

Background: Pneumonia and septicemia have the greatest impact on reduced life expectancy in persons with spinal cord injury (SCI). Fever is often the first presenting symptom of infection or inflammation. Thermoregulatory dysfunction in persons with SCI may preclude a typical febrile response to infection or inflammation and thus delay diagnostic workup. Objective: To determine the core temperature of persons with SCI in the setting of infection or inflammation and the frequency with which it meets criteria for the CDC definition of fever (>100.4°F). Methods: Retrospective review of hospitalized SCI patients over 5 years with a diagnosis of infection or inflammation (DI), defined by serum leukocytosis. In this study, 458 persons with paraplegia (PP) and 483 persons with tetraplegia (TP) had 4,191 DI episodes. Aural temperatures (Tau) on the day of DI, 7 days prior, and 14 days afterwards were abstracted from medical records. Main outcome measures were average Tau at DI, frequency of temperatures >100.4°F at DI, and average baseline temperatures before and after DI. Results: Average Tau at DI was 98.2°F (±1.5) and 98.2°F (±1.4) in the TP and PP groups, respectively, with only 11.6% to 14% of DI resulting in Tau >100.4°F. Baseline temperatures ranged from 97.9°F (±0.7) to 98.0°F (±0.8). Conclusion: SCI persons with leukocytosis infrequently mount a fever as defined by the CDC, and baseline temperatures were subnormal (<98.6°F). Thermoregulatory dysfunction likely accounts for these findings. Tau >100.4°F is not a sensitive predictor of infection or inflammation in persons with SCI. Clinicians should be vigilant for alternative symptoms of infection and inflammation in these patients, so diagnostic workup is not delayed. PMID:29339867

A systematic analysis of the in vitro and in vivo functions of the HD-GYP domain proteins of Vibrio cholerae.

PubMed

McKee, Robert W; Kariisa, Ankunda; Mudrak, Benjamin; Whitaker, Courtney; Tamayo, Rita

2014-10-25

The second messenger cyclic diguanylate (c-di-GMP) plays a central role in bacterial adaptation to extracellular stimuli, controlling processes such as motility, biofilm development, cell development and, in some pathogens, virulence. The intracellular level of c-di-GMP is controlled by the complementary activities of diguanylate cyclases containing a GGDEF domain and two classes of c-di-GMP phosphodiesterases containing an EAL or HD-GYP hydrolytic domain. Compared to the GGDEF and EAL domains, the functions of HD-GYP domain family proteins are poorly characterized. The human diarrheal pathogen Vibrio cholerae encodes nine putative HD-GYP domain proteins. To determine the contributions of HD-GYP domain proteins to c-di-GMP signaling in V. cholerae, we systematically analyzed the enzymatic functionality of each protein and their involvement in processes known to be regulated by c-di-GMP: motility, biofilm development and virulence. Complementary in vitro and in vivo experiments showed that four HD-GYP domain proteins are active c-di-GMP phosphodiesterases: VC1295, VC1348, VCA0210 and VCA0681. Mutation of individual HD-GYP domain genes, as well as combinatorial mutations of multiple HD-GYP domain genes, had no effect on motility or biofilm formation of V. cholerae under the conditions tested. Furthermore, no single HD-GYP domain gene affected intestinal colonization by V. cholerae in an infant mouse model. However, inactivation of multiple HD-GYP domain genes, including the four encoding functional phosphodiesterases, significantly attenuated colonization. These results indicate that the HD-GYP family of c-di-GMP phosphodiesterases impacts signaling by this second messenger during infection. Altogether, this work greatly furthers the understanding of this important family of c-di-GMP metabolic enzymes and demonstrates a role for HD-GYP domain proteins in the virulence of V. cholerae.

Analysis of a thread used in the Kshara Sutra treatment in the Ayurvedic medicinal system.

PubMed

Gewali, M B; Pilapitiya, U; Hattori, M; Namba, T

1990-05-01

From a Kshara Sutra thread which is used in the therapy of fistula in the Ayurvedic medicinal system, euphol, 3,12-di-O-acetyl-8-O-benzoylingol, 3,12-di-O-acetyl-8-O-tigloylingol, curcumin, p-coumaroylferuloylmethane and di-p-courmaroylmethane were isolated and characterized. In addition, GLC and GC/MS confirmed the presence of euphol, antiquol B, cycloeucalenol and 24-methylene cycloartanol in the thread.

National Security Consequences of U.S. Oil Dependency

DTIC Science & Technology

2006-11-09

J. DiBona Sentient Council Jessica P. Einhorn Paul H. Nitze School of Advanced International Studies Martin S. Feldstein National Bureau of Economic...Croft James R. Schlesinger John Deutch Peter Schwartz Charles J. DiBona Philip R. Sharp Jessica P. Einhorn James B. Steinberg Martin S. Feldstein Linda G...Director of Central Intelligence. Charles J. DiBona is the current Chairman of the Sentient Council and retired Chairman of the Board of Logistics

The HADES-RICH upgrade using Hamamatsu H12700 MAPMTs with DiRICH FEE + Readout

NASA Astrophysics Data System (ADS)

Patel, V.; Traxler, M.

2018-03-01

The High Acceptance Di-Electron Spectrometer (HADES) is operational since the year 2000 and uses a hadron blind RICH detector for electron identification. The RICH photon detector is currently replaced by Hamamatsu H12700 MAPMTs with a readout system based on the DiRICH front-end module. The electronic readout chain is being developed as a joint effort of the HADES-, CBM- and PANDA collaborations and will also be used in the photon detectors for the upcoming Compressed Baryonic Matter (CBM) and PANDA experiments at FAIR . This article gives a brief overview on the photomultipliers and their quality assurance test measurements, as well as first measurements of the new DiRICH front-end module in final configurations.

4-(Di­methyl­amino)­pyridinium trichlorido[4-(di­methyl­amino)­pyridine-κN]cobaltate(II)

PubMed Central

Guenifa, Fatiha; Hadjadj, Nasreddine; Zeghouan, Ouahida; Bendjeddou, Lamia; Merazig, Hocine

2013-01-01

In the anion of the title compound, (C7H11N2)[CoCl3(C7H10N2)], the CoII ion is coordinated by one N atom from a 4-(di­methyl­amino)­pyridine (DMAP) ligand and three Cl atoms, forming a CoNCl3 polyhedron with a distorted tetra­hedral geometry. In the crystal, cations and anions are linked via weak N—H⋯Cl and C—H⋯Cl hydrogen bonds. Double layers of complex anions stack along the b- axis direction, which alternate with double layers of 4-(di­methyl­amino)-pyridinium cations. PMID:24046560

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma.

PubMed

Raghunathan, Veena; Dhaliwal, Maninder Singh; Gupta, Aditya; Jevalikar, Ganesh

2015-03-01

Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

PREFACE: Young Researcher Meeting in Rome 2012

NASA Astrophysics Data System (ADS)

Agostini, Fabio; Cattani, Giordano; Mazzaferro, Luca; Migliaccio, Marina; Pietrobon, Davide; Ricci Pacifici, Daniel; Stellato, Francesco; Veneziani, Marcella

2012-10-01

Conference logo At its third edition, the Young Researcher Meeting in Rome (YRMR) proves to be a growing event in the Italian scientific panorama. The high-quality content of the abstracts submitted to the scientific committee resulted in an exciting conference, held, for the second time, at the University of Rome 'Tor Vergata' on 20 January 2012. A busy schedule covered a large variety of cutting-edge science topics: fundamental interactions, particle physics, cosmology, astrophysics, condensed matter and biomedical physics. The broad range of the subjects discussed is the distinctive feature of the YRMR, a meeting aimed at enhancing the synergy among complementary branches of science by stimulating a fruitful exchange between theoretical, experimental and computational physics. Promoting collaborations between PhD students, postdoctoral fellows and young researchers creates a solid scientific network with an open-minded approach to discovery. In this volume, we collect the contributions that have been presented both in the form of talks and of posters. YRMR Organising and Editorial Committee Fabio Agostini (fabio.agostini@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Giordano Cattani (giordano.cattani@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' INFN sezione di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Luca Mazzaferro (luca.mazzaferro@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' INFN sezione di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Marina Migliaccio (migliaccio@ifca.unican.es) Instituto de Fisica de Cantabria, Edificio Juan Jorda, Avenida de los Castros, E-39005 Santander, Cantabria Spain Davide Pietrobon (davide.pietrobon@jpl.nasa.gov) Jet Propulsion Laboratory - California Institute of Technology 4800 Oak Grove Drive 169-237 91109 Pasadena, CA USA Daniel Ricci Pacifici (Daniel.Ricci.Pacifici@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' INFN sezione di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Francesco Stellato (francesco.stellato@cfel.de) Center for Free Electron Laser science c/o DESY 22607 Hamburg Germany Marcella Veneziani (marcella.veneziani@caltech.edu) California Institute of Technology 1200 California Blvd, Pasadena, 91125, CA USA Institution logos Acknowledgments The organizers of the 3rd Young Researcher Meeting in Rome would like to thank all the scientists who participated in the meeting. We thank the Science Faculty of the University of Rome 'Tor Vergata' for hosting the conference. The 'Tor Vergata' Division of the National Institute for Nuclear Physics (INFN) and the Department of Physics of the University of Rome 'Tor Vergata' who have sponsored the event, covering the organization costs and allowing for travel grants to the speakers. We are grateful to Professor Francesco Fucito, Professor Piergiorgio Picozza, Professor Rinaldo Santonico, Dr Jose Francisco Morales and Ms Francesca Luna for their valuable support.

Measurement of q ˆ in Relativistic Heavy Ion Collisions using di-hadron correlations

DOE PAGES

Tannenbaum, M. J.

2017-06-06

The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficientmore » $$\\hat{q}$$ and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum p T, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle p Tt and associated p Ta transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, j T, is dominated by k T, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger k T in A+A than in p+p collisions. The present work introduces the observation that the k T measured in p+p collisions for di-hadrons with p Tt and p Ta must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the k T measured with the same di-hadron p Tt and p Ta in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result <$$\\hat{q}$$L>=2.1±0.6 GeV 2. This is more precise but in agreement with a theoretical calculation of <$$\\hat{q}$$L>=14$$+42\\atop{-14}$$ GeV 2 using the same data. Assuming a length ≈7 fm for central Au+Au collisions the present result gives $$\\hat{q}$$≈0.30±0.09 GeV 2/fm, in fair agreement with the JET collaboration result from single hadron suppression of $$\\hat{q}$$≈1.2±0.3 GeV 2/fm at an initial time τ 0=0.6 fm/c in Au+Au collisions at √sNN=200 GeV.« less

Measurement of q ˆ in Relativistic Heavy Ion Collisions using di-hadron correlations

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

Tannenbaum, M. J.

The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficientmore » $$\\hat{q}$$ and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum p T, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle p Tt and associated p Ta transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, j T, is dominated by k T, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger k T in A+A than in p+p collisions. The present work introduces the observation that the k T measured in p+p collisions for di-hadrons with p Tt and p Ta must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the k T measured with the same di-hadron p Tt and p Ta in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result <$$\\hat{q}$$L>=2.1±0.6 GeV 2. This is more precise but in agreement with a theoretical calculation of <$$\\hat{q}$$L>=14$$+42\\atop{-14}$$ GeV 2 using the same data. Assuming a length ≈7 fm for central Au+Au collisions the present result gives $$\\hat{q}$$≈0.30±0.09 GeV 2/fm, in fair agreement with the JET collaboration result from single hadron suppression of $$\\hat{q}$$≈1.2±0.3 GeV 2/fm at an initial time τ 0=0.6 fm/c in Au+Au collisions at √sNN=200 GeV.« less

Trajectories of disposable income among people of working ages diagnosed with multiple sclerosis: a nationwide register-based cohort study in Sweden 7 years before to 4 years after diagnosis with a population-based reference group

PubMed Central

Mogard, Olof; Alexanderson, Kristina; Karampampa, Korinna; Friberg, Emilie; Tinghög, Petter

2018-01-01

Objectives To describe how disposable income (DI) and three main components changed, and analyse whether DI development differed from working-aged people with multiple sclerosis (MS) to a reference group from 7 years before to 4 years after diagnosis in Sweden. Design Population-based cohort study, 12-year follow-up (7 years before to 4 years after diagnosis). Setting Swedish working-age population with microdata linked from two nationwide registers. Participants Residents diagnosed with MS in 2009 aged 25–59 years (n=785), and references without MS (n=7847) randomly selected with stratified matching (sex, age, education and country of birth). Primary and secondary outcome measures DI was defined as the annual after tax sum of incomes (earnings and benefits) to measure individual economic welfare. Three main components of DI were analysed as annual sums: earnings, sickness absence benefits and disability pension benefits. Results We found no differences in mean annual DI between people with and without MS by independent t-tests (p values between 0.15 and 0.96). Differences were found for all studied components of DI from diagnosis year by independent t-tests, for example, in the final study year (2013): earnings (−64 867 Swedish Krona (SEK); 95% CI−79 203 to −50 528); sickness absence benefits (13 330 SEK; 95% CI 10 042 to 16 500); and disability pension benefits (21 360 SEK; 95% CI 17 380 to 25 350). A generalised estimating equation evaluated DI trajectory development between people with and without MS to find both trajectories developed in parallel, both before (−4039 SEK; 95% CI −10 536 to 2458) and after (−781 SEK; 95% CI −6988 to 5360) diagnosis. Conclusions The key finding of parallel DI trajectory development between working-aged MS and references suggests minimal economic impact within the first 4 years of diagnosis. The Swedish welfare system was responsive to the observed reductions in earnings around MS diagnosis through balancing DI with morbidity-related benefits. Future decreases in economic welfare may be experienced as the disease progresses, although thorough investigation with future studies of modern cohorts are required. PMID:29743325

Effects of four dim vs high intensity red color light regimens on growth performance and welfare of broilers.

PubMed

Senaratna, D; Samarakone, T S; Gunawardena, W W D A

2018-01-01

Broilers show clear preference towards red color light (RL). However setting of an optimum light intensity is difficult since dim intensities that favor growth reduce welfare. This experiment was conducted to test the most effective RL intensity regimen (Dim [5 lux; DI] vs high [320 lux; HI]) in combination applied at different growth stages that favors for both performance and welfare. Complete randomize design was adopted with 6 replicates. Treatments were; T1 = early DI (8-21 d)+latter HI (22-35 d); T2 = early DI (8-28 d)+latter HI (29-35 d), T3 = early HI (8-21 d)+latter DI (22-35 d), T4 = early HI (8-28 d)+latter DI (29-35 d) and T5 = control (white light; WT) (8-35 d) at medium intensity (20 lux). Body weight (BW), weight gain (WG), water/feed intake and ratio, feed conversion ratios (FCR) were assessed. Common behaviours (15) were recorded by scan sampling method. Lameness, foot pad dermatitis, breast blisters, hock burning damage were assessed as welfare parameters. Fear reactions were tested using Tonic Immobility Test. Ocular and carcass evaluations were done. Meat and tibiae were analyzed for fat and bone ash respectively. On 35 d, the highest BW (2,155.72±176 g), WG (1,967.78±174 g) were recorded by T2 compared to WT (BW WT = 1,878.22±155, WG WT = 1,691.83±160). But, application of RL, either DI, or HI during early/latter stage had no significant effect on FCR. Under HI, birds showed much higher active behaviours. DI encourages eating. Though LI changed from DI to HI, same trend could be seen even under HI. The highest leg strength (218.5±120 s) was recorded by T2. The lowest leg strength (64.58±33 s) and the highest ocular weight (2.48±1 g) were recorded by T1. Significantly (p<0.05) the highest skin weight (162.17±6 g) but the lowest fat% in meat (13.03%±5%) was recorded by T2. Early exposure to DI-RL up to 28 days followed by exposure to HI-RL is the most favorable lighting regimen for optimizing production, better welfare of broilers and improving health benefits of meat.

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

Acknowledgements

NASA Astrophysics Data System (ADS)

2016-07-01

The Meeting was sponsored by the Istituto Nazionale di Fisica Nucleare (INFN), the Società Italiana di Fisica (SIF), the European Physics Society (EPS), the University of Pisa and the University of Siena.

Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis.

PubMed

Kalia, Dimpy; Merey, Gökçe; Nakayama, Shizuka; Zheng, Yue; Zhou, Jie; Luo, Yiling; Guo, Min; Roembke, Benjamin T; Sintim, Herman O

2013-01-07

For an organism to survive, it must be able to sense its environment and regulate physiological processes accordingly. Understanding how bacteria integrate signals from various environmental factors and quorum sensing autoinducers to regulate the metabolism of various nucleotide second messengers c-di-GMP, c-di-AMP, cGMP, cAMP and ppGpp, which control several key processes required for adaptation is key for efforts to develop agents to curb bacterial infections. In this review, we provide an update of nucleotide signaling in bacteria and show how these signals intersect or integrate to regulate the bacterial phenotype. The intracellular concentrations of nucleotide second messengers in bacteria are regulated by synthases and phosphodiesterases and a significant number of these metabolism enzymes had been biochemically characterized but it is only in the last few years that the effector proteins and RNA riboswitches, which regulate bacterial physiology upon binding to nucleotides, have been identified and characterized by biochemical and structural methods. C-di-GMP, in particular, has attracted immense interest because it is found in many bacteria and regulate both biofilm formation and virulence factors production. In this review, we discuss how the activities of various c-di-GMP effector proteins and riboswitches are modulated upon c-di-GMP binding. Using V. cholerae, E. coli and B. subtilis as models, we discuss how both environmental factors and quorum sensing autoinducers regulate the metabolism and/or processing of nucleotide second messengers. The chemical syntheses of the various nucleotide second messengers and the use of analogs thereof as antibiofilm or immune modulators are also discussed.