Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH.

PubMed Central

Rossignol, M; Kolb-Cheynel, I; Egly, J M

1997-01-01

The transcription/DNA repair factor TFIIH consists of nine subunits, several exhibiting known functions: helicase/ATPase, kinase activity and DNA binding. Three subunits of TFIIH, cdk7, cyclin H and MAT1, form a ternary complex, cdk-activating kinase (CAK), found either on its own or as part of TFIIH. In the present work, we demonstrate that purified human CAK complex (free CAK) and recombinant CAK (rCAK) produced in insect cells exhibit a strong preference for the cyclin-dependent kinase 2 (cdk2) over a ctd oligopeptide substrate (which mimics the carboxy-terminal domain of the RNA polymerase II). In contrast, TFIIH preferentially phosphorylates the ctd as well as TFIIE alpha, but not cdk2. TFIIH was resolved into four subcomplexes: the kinase complex composed of cdk7, cyclin H and MAT1; the core TFIIH which contains XPB, p62, p52, p44 and p34; and two other subcomplexes in which XPD is found associated with either the kinase complex or with the core TFIIH. Using these fractions, we demonstrate that TFIIH lacking the CAK subcomplex completely recovers its transcriptional activity in the presence of free CAK. Furthermore, studies examining the interactions between TFIIH subunits provide evidence that CAK is integrated within TFIIH via XPB and XPD. PMID:9130708

Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH.

PubMed Central

Marinoni, J C; Roy, R; Vermeulen, W; Miniou, P; Lutz, Y; Weeda, G; Seroz, T; Gomez, D M; Hoeijmakers, J H; Egly, J M

1997-01-01

TFIIH is a multiprotein factor involved in transcription and DNA repair and is implicated in DNA repair/transcription deficiency disorders such as xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Eight out of the nine genes encoding the subunits forming TFIIH have already been cloned. We report here the identification, cDNA cloning and gene structure of the 52 kDa polypeptide and its homology with the yeast counterpart TFB2. This protein, along with p89/XPB, p62, p44 and p34, forms the core of TFIIH. Moreover, using in vitro reconstituted transcription and nucleotide excision repair (NER) assays and microinjection experiments, we demonstrate that p52 is directly involved in both transcription and DNA repair mechanisms in vitro and in vivo. PMID:9118947

Double-stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA polymerase II open complex formation.

PubMed

Fishburn, James; Tomko, Eric; Galburt, Eric; Hahn, Steven

2015-03-31

Formation of the RNA polymerase II (Pol II) open complex (OC) requires DNA unwinding mediated by the transcription factor TFIIH helicase-related subunit XPB/Ssl2. Because XPB/Ssl2 binds DNA downstream from the location of DNA unwinding, it cannot function using a conventional helicase mechanism. Here we show that yeast TFIIH contains an Ssl2-dependent double-stranded DNA translocase activity. Ssl2 tracks along one DNA strand in the 5' → 3' direction, implying it uses the nontemplate promoter strand to reel downstream DNA into the Pol II cleft, creating torsional strain and leading to DNA unwinding. Analysis of the Ssl2 and DNA-dependent ATPase activity of TFIIH suggests that Ssl2 has a processivity of approximately one DNA turn, consistent with the length of DNA unwound during transcription initiation. Our results can explain why maintaining the OC requires continuous ATP hydrolysis and the function of TFIIH in promoter escape. Our results also suggest that XPB/Ssl2 uses this translocase mechanism during DNA repair rather than physically wedging open damaged DNA.

Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo.

PubMed

Hoogstraten, Deborah; Nigg, Alex L; Heath, Helen; Mullenders, Leon H F; van Driel, Roel; Hoeijmakers, Jan H J; Vermeulen, Wim; Houtsmuller, Adriaan B

2002-11-01

The transcription/repair factor TFIIH operates as a DNA helix opener in RNA polymerase II (RNAP2) transcription and nucleotide excision repair. To study TFIIH in vivo, we generated cell lines expressing functional GFP-tagged TFIIH. TFIIH was homogeneously distributed throughout the nucleus with nucleolar accumulations. We provide in vivo evidence for involvement of TFIIH in RNA polymerase I (RNAP1) transcription. Photobleaching revealed that TFIIH moves freely and gets engaged in RNAP1 and RNAP2 transcription for approximately 25 and approximately 6 s, respectively. TFIIH readily switches between transcription and repair sites (where it is immobilized for approximately 4 min) without large-scale alterations in composition. Our findings support a model of diffusion and random collision of individual components that permits a quick and versatile response to changing conditions.

GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy

PubMed Central

Kuschal, Christiane; Botta, Elena; Orioli, Donata; Digiovanna, John J.; Seneca, Sara; Keymolen, Kathelijn; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G.; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A.; Stephens, Robert; Zhao, Yongmei; Lehmann, Alan R.; Baranello, Laura; Levens, David; Kraemer, Kenneth H.; Stefanini, Miria

2016-01-01

The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEβ). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEα and TFIIEβ) as well as decreased phosphorylation of TFIIEα in cells from both children. Interestingly, decreased phosphorylation of TFIIEα was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. PMID:26996949

Heat-shock inactivation of the TFIIH-associated kinase and change in the phosphorylation sites on the C-terminal domain of RNA polymerase II.

PubMed

Dubois, M F; Vincent, M; Vigneron, M; Adamczewski, J; Egly, J M; Bensaude, O

1997-02-15

The C-terminal domain (CTD) of the RNA polymerase II largest subunit (RPB1) plays a central role in transcription. The CTD is unphosphorylated when the polymerase assembles into a preinitiation complex of transcription and becomes heavily phosphorylated during promoter clearance and entry into elongation of transcription. A kinase associated to the general transcription factor TFIIH, in the preinitiation complex, phosphorylates the CTD. The TFIIH-associated CTD kinase activity was found to decrease in extracts from heat-shocked HeLa cells compared to unstressed cells. This loss of activity correlated with a decreased solubility of the TFIIH factor. The TFIIH-kinase impairment during heat-shock was accompanied by the disappearance of a particular phosphoepitope (CC-3) on the RPB1 subunit. The CC-3 epitope was localized on the C-terminal end of the CTD and generated in vitro when the RPB1 subunit was phosphorylated by the TFIIH-associated kinase but not by another CTD kinase such as MAP kinase. In apparent discrepancy, the overall RPB1 subunit phosphorylation increased during heat-shock. The decreased activity in vivo of the TFIIH kinase might be compensated by a stress-activated CTD kinase such as MAP kinase. These results also suggest that heat-shock gene transcription may have a weak requirement for TFIIH kinase activity.

Molecular insights into the recruitment of TFIIH to sites of DNA damage

PubMed Central

Oksenych, Valentyn; de Jesus, Bruno Bernardes; Zhovmer, Alexander; Egly, Jean-Marc; Coin, Frédéric

2009-01-01

XPB and XPD subunits of TFIIH are central genome caretakers involved in nucleotide excision repair (NER), although their respective role within this DNA repair pathway remains difficult to delineate. To obtain insight into the function of XPB and XPD, we studied cell lines expressing XPB or XPD ATPase-deficient complexes. We show the involvement of XPB, but not XPD, in the accumulation of TFIIH to sites of DNA damage. Recruitment of TFIIH occurs independently of the helicase activity of XPB, but requires two recently identified motifs, a R-E-D residue loop and a Thumb-like domain. Furthermore, we show that these motifs are specifically involved in the DNA-induced stimulation of the ATPase activity of XPB. Together, our data demonstrate that the recruitment of TFIIH to sites of damage is an active process, under the control of the ATPase motifs of XPB and suggest that this subunit functions as an ATP-driven hook to stabilize the binding of the TFIIH to damaged DNA. PMID:19713942

Phosphorylation of XPB helicase regulates TFIIH nucleotide excision repair activity

PubMed Central

Coin, Frédéric; Auriol, Jérome; Tapias, Angel; Clivio, Pascale; Vermeulen, Wim; Egly, Jean-Marc

2004-01-01

Nucleotide excision repair (NER) removes damage from DNA in a tightly regulated multiprotein process. The xeroderma pigmentosum group B (XPB) helicase subunit of TFIIH functions in NER and transcription. The serine 751 (S751) residue of XPB was found to be phosphorylated in vivo. This phosphorylation inhibits NER and the microinjection of a phosphomimicking XPB-S751E mutant is unable to correct the NER defect of XP-B cells. Conversely, XPB-S751 dephosphorylation or its substitution with alanine (S751A) restores NER both in vivo and in vitro. Surprisingly, phospho/dephosphorylation of S751 spares TFIIH-dependent transcription. Finally, the phosphorylation of XPB-S751 does not impair the TFIIH unwinding of the DNA around the lesion, but rather prevents the 5′ incision triggered by the ERCC1-XPF endonuclease. These data support an additional role for XPB in promoting the incision of the damaged fragment and reveal a point of NER regulation on TFIIH without interference in its transcription activity. PMID:15549133

Heat-shock inactivation of the TFIIH-associated kinase and change in the phosphorylation sites on the C-terminal domain of RNA polymerase II.

PubMed Central

Dubois, M F; Vincent, M; Vigneron, M; Adamczewski, J; Egly, J M; Bensaude, O

1997-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit (RPB1) plays a central role in transcription. The CTD is unphosphorylated when the polymerase assembles into a preinitiation complex of transcription and becomes heavily phosphorylated during promoter clearance and entry into elongation of transcription. A kinase associated to the general transcription factor TFIIH, in the preinitiation complex, phosphorylates the CTD. The TFIIH-associated CTD kinase activity was found to decrease in extracts from heat-shocked HeLa cells compared to unstressed cells. This loss of activity correlated with a decreased solubility of the TFIIH factor. The TFIIH-kinase impairment during heat-shock was accompanied by the disappearance of a particular phosphoepitope (CC-3) on the RPB1 subunit. The CC-3 epitope was localized on the C-terminal end of the CTD and generated in vitro when the RPB1 subunit was phosphorylated by the TFIIH-associated kinase but not by another CTD kinase such as MAP kinase. In apparent discrepancy, the overall RPB1 subunit phosphorylation increased during heat-shock. The decreased activity in vivo of the TFIIH kinase might be compensated by a stress-activated CTD kinase such as MAP kinase. These results also suggest that heat-shock gene transcription may have a weak requirement for TFIIH kinase activity. PMID:9016617

IIHS head restraint ratings and insurance injury claim rates.

PubMed

Trempel, Rebecca E; Zuby, David S; Edwards, Marcy A

2016-08-17

The Insurance Institute for Highway Safety (IIHS) rates front seat/head restraint designs using a combination of static and dynamic measurements following RCAR-IIWPG procedures. The purpose of this study was to determine whether vehicles with better IIHS-rated seats/head restraints had lower injury risk in rear-end collisions and how the effect of better rated seats interacted with driver gender and age. The presence of an associated insurance injury claim was determined for rear-impact crashes using 2001-2014 model year cars and SUVs. Logistic regression was used to compare injury risk for vehicles with good, acceptable, and marginal IIHS-rated seats/head restraints with poor-rated seats/head restraints. Analyses were run by gender and driver age and also by the rate of more severe injury claims. Injury rates were 11.2% lower for vehicles with seats/head restraints rated good compared to vehicles with seats/head restraints rated poor. The percentage reduction for good- versus poor-rated seats was greater for females (12.7%) than males (8.9%). Comparing good- with poor-rated seats, driver ages 15-24 had the largest reduction at 19.8%, followed by 10.7% for driver ages 45-64 and 10.4% for driver ages 25-44. Seats/head restraints with better IIHS ratings are associated with lower injury rates in rear-impact collisions than seats rated poor. The reductions in injury rates were strongest for females and for young-to-middle-age drivers. The strong reductions in injury rates for these groups are encouraging given their high initial injury rates.

MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH.

PubMed

Adamczewski, J P; Rossignol, M; Tassan, J P; Nigg, E A; Moncollin, V; Egly, J M

1996-04-15

MAT1, cyclin H and cdk7 are part of TFIIH, a class II transcription factor which possesses numerous subunits of which several have been shown to be involved in processes other than transcription. Two of them, XPD (ERCC2) and XPB (ERCC3), are helicases involved in nucleotide excision repair (NER), whereas cdk7, cyclin H and MAT1 are thought to participate in cell cycle regulation. MAT1, cyclin H and cdk7 exist as a ternary complex either free or associated with TFIIH from which the latter can be dissociated at high salt concentration. MAT1 is strongly associated with cdk7 and cyclin H. Although not strictly required for the formation and activity of the complex, it stimulates its kinase activity. The kinase activity of TFIIH, which is constant during the cell cycle, is reduced after UV light irradiation.

Biallelic mutations in CYP24A1 or SLC34A1 as a cause of infantile idiopathic hypercalcemia (IIH) with vitamin D hypersensitivity: molecular study of 11 historical IIH cases.

PubMed

Pronicka, Ewa; Ciara, Elżbieta; Halat, Paulina; Janiec, Agnieszka; Wójcik, Marek; Rowińska, Elżbieta; Rokicki, Dariusz; Płudowski, Paweł; Wojciechowska, Ewa; Wierzbicka, Aldona; Książyk, Janusz B; Jacoszek, Agnieszka; Konrad, Martin; Schlingmann, Karl P; Litwin, Mieczysław

2017-08-01

Idiopathic infantile hypercalcemia (IIH) is a mineral metabolism disorder characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. The periodical increase in incidence of IIH, which occurred in the twentieth century in the United Kingdom, Poland, and West Germany, turned out to be a side effect of rickets over-prophylaxis. It was recently discovered that the condition is linked to two genes, CYP24A1 and SLC34A1. The aim of the study was to search for pathogenic variants of the genes in adult persons who were shortlisted in infancy as IIH caused by "hypersensitivity to vit. D". All persons were found to carry mutations in CYP24A1 or SLC34A1, nine and two persons respectively. The changes were biallelic, with one exception. Incidence of IIH in Polish population estimated on the basis of allele frequency of recurrent p.R396W CYP24A1 variant, is 1:32,465 births. It indicates that at least a thousand homozygotes and compound heterozygotes with risk of IIH live in the country. Differences in mechanism of developing hypercalcemia indicate that its prevention may vary in both IIH defects. Theoretically, vit. D restriction is a first indication for CYP24A1 defect (which disturbs 1,25(OH) 2 D degradation) and phosphate supplementation for SLC34A1 defect (which impairs renal phosphate transport). In conclusion, we suggest that molecular testing for CYP24A1 and SLC34A1 mutations should be performed in each case of idiopathic hypercalcemia/hypercalciuria, both in children and adults, to determine the proper way for acute treatment and complications prevention.

NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62.

PubMed

Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

2011-07-01

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH.

PubMed Central

Adamczewski, J P; Rossignol, M; Tassan, J P; Nigg, E A; Moncollin, V; Egly, J M

1996-01-01

MAT1, cyclin H and cdk7 are part of TFIIH, a class II transcription factor which possesses numerous subunits of which several have been shown to be involved in processes other than transcription. Two of them, XPD (ERCC2) and XPB (ERCC3), are helicases involved in nucleotide excision repair (NER), whereas cdk7, cyclin H and MAT1 are thought to participate in cell cycle regulation. MAT1, cyclin H and cdk7 exist as a ternary complex either free or associated with TFIIH from which the latter can be dissociated at high salt concentration. MAT1 is strongly associated with cdk7 and cyclin H. Although not strictly required for the formation and activity of the complex, it stimulates its kinase activity. The kinase activity of TFIIH, which is constant during the cell cycle, is reduced after UV light irradiation. Images PMID:8617234

Disruption of TTDA Results in Complete Nucleotide Excision Repair Deficiency and Embryonic Lethality

PubMed Central

Theil, Arjan F.; Nonnekens, Julie; Steurer, Barbara; Mari, Pierre-Olivier; de Wit, Jan; Lemaitre, Charlène; Marteijn, Jurgen A.; Raams, Anja; Maas, Alex; Vermeij, Marcel; Essers, Jeroen; Hoeijmakers, Jan H. J.; Giglia-Mari, Giuseppina; Vermeulen, Wim

2013-01-01

The ten-subunit transcription factor IIH (TFIIH) plays a crucial role in transcription and nucleotide excision repair (NER). Inactivating mutations in the smallest 8-kDa TFB5/TTDA subunit cause the neurodevelopmental progeroid repair syndrome trichothiodystrophy A (TTD-A). Previous studies have shown that TTDA is the only TFIIH subunit that appears not to be essential for NER, transcription, or viability. We studied the consequences of TTDA inactivation by generating a Ttda knock-out (Ttda−/−) mouse-model resembling TTD-A patients. Unexpectedly, Ttda−/− mice were embryonic lethal. However, in contrast to full disruption of all other TFIIH subunits, viability of Ttda−/− cells was not affected. Surprisingly, Ttda−/− cells were completely NER deficient, contrary to the incomplete NER deficiency of TTD-A patient-derived cells. We further showed that TTD-A patient mutations only partially inactivate TTDA function, explaining the relatively mild repair phenotype of TTD-A cells. Moreover, Ttda−/− cells were also highly sensitive to oxidizing agents. These findings reveal an essential role of TTDA for life, nucleotide excision repair, and oxidative DNA damage repair and identify Ttda−/− cells as a unique class of TFIIH mutants. PMID:23637614

Domain architecture of the p62 subunit from the human transcription/repair factor TFIIH deduced by limited proteolysis and mass spectrometry analysis.

PubMed

Jawhari, Anass; Boussert, Stéphanie; Lamour, Valérie; Atkinson, R Andrew; Kieffer, Bruno; Poch, Olivier; Potier, Noelle; van Dorsselaer, Alain; Moras, Dino; Poterszman, Arnaud

2004-11-16

TFIIH is a multiprotein complex that plays a central role in both transcription and DNA repair. The subunit p62 is a structural component of the TFIIH core that is known to interact with VP16, p53, Eralpha, and E2F1 in the context of activated transcription, as well as with the endonuclease XPG in DNA repair. We used limited proteolysis experiments coupled to mass spectrometry to define structural domains within the conserved N-terminal part of the molecule. The first domain identified resulted from spontaneous proteolysis and corresponds to residues 1-108. The second domain encompasses residues 186-240, and biophysical characterization by fluorescence studies and NMR analysis indicated that it is at least partially folded and thus may correspond to a structural entity. This module contains a region of high sequence conservation with an invariant FWxxPhiPhi motif (Phi representing either tyrosine or phenylalanine), which was also found in other protein families and could play a key role as a protein-protein recognition module within TFIIH. The approach used in this study is general and can be straightforwardly applied to other multidomain proteins and/or multiprotein assemblies.

NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62▿

PubMed Central

Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

2011-01-01

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus. PMID:21543505

Role of Vitamin A Metabolism in IIH: Results from the Idiopathic Intracranial Hypertension Treatment Trial

PubMed Central

Libien, J; Kupersmith, MJ; Blaner, W; McDermott, MP; Gao, S; Liu, Y; Corbett, J; Wall, M

2017-01-01

Introduction Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. Methods Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months. Results At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33 nM) and controls (median 5.04 nM, p = 0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p = 0.02) and CSF ATRA (p = 0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r = −0.44, p = 0.006) and the change in CSF retinol (r = −0.61, p = 0.02). Conclusion Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior

Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

PubMed

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

2014-03-01

The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

PubMed Central

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

2014-01-01

ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

PubMed Central

van Vuuren, A J; Vermeulen, W; Ma, L; Weeda, G; Appeldoorn, E; Jaspers, N G; van der Eb, A J; Bootsma, D; Hoeijmakers, J H; Humbert, S

1994-01-01

ERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibility that it is not directly involved in NER but that it regulates the transcription of one or more NER genes. Using an in vivo microinjection repair assay and an in vitro NER system based on cell-free extracts we demonstrate that ERCC3 in BTF2 is directly implicated in excision repair. Antibody depletion experiments support the idea that the p62 BTF2 subunit and perhaps the entire transcription factor function in NER. Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3 subunits in the complex. Expression of a dominant negative K436-->R ERCC3 mutant, expected to have lost all helicase activity, completely abrogates NER and transcription and concomitantly induces a dramatic chromatin collapse. These findings establish the role of ERCC3 and probably the entire BTF2 complex in transcription in vivo which was hitherto only demonstrated in vitro. The results strongly suggest that transcription itself is a critical component for maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and transcription provides a clue in understanding the complex clinical features of some inherited repair syndromes. Images PMID:8157004

The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies.

PubMed Central

Jordan, P; Cunha, C; Carmo-Fonseca, M

1997-01-01

TFIIH is a general transcription factor for RNA polymerase II that in addition is involved in DNA excision repair. TFIIH is composed of eight or nine subunits and we show that at least four of them, namely cdk7, cyclin H, MAT1, and p62 are localized in the coiled body, a distinct subnuclear structure that is transcription dependent and highly enriched in small nuclear ribonucleoproteins. Although coiled bodies do not correspond to sites of transcription, in vivo incorporation of bromo-UTP shows that they are surrounded by transcription foci. Immunofluorescence analysis using antibodies directed against the essential repair factors proliferating cell nuclear antigen and XPG did not reveal labeling of the coiled body in either untreated cells or cells irradiated with UV light, arguing that coiled bodies are probably not involved in DNA repair mechanisms. The localization of cyclin H in the coiled body was predominantly detected during the G1 and S-phases of the cell cycle, whereas in G2 coiled bodies were very small or not detected. Finally, both cyclin H and cdk7 did not colocalize with P80 coilin after disruption of the coiled body, indicating that these proteins are specifically targeted to the small nuclear ribonucleoprotein-containing domain. Images PMID:9243502

IIHS side crash test ratings and occupant death risk in real-world crashes.

PubMed

Teoh, Eric R; Lund, Adrian K

2011-10-01

To evaluate how well the Insurance Institute for Highway Safety (IIHS) side crash test ratings predict real-world occupant death risk in side-impact crashes. The IIHS has been evaluating passenger vehicle side crashworthiness since 2003. In the IIHS side crash test, a vehicle is impacted perpendicularly on the driver's side by a moving deformable barrier simulating a typical sport utility vehicle (SUV) or pickup. Injury ratings are computed for the head/neck, torso, and pelvis/leg, and vehicles are rated based on their ability to protect occupants' heads and resist occupant compartment intrusion. Component ratings are combined into an overall rating of good, acceptable, marginal, or poor. A driver-only rating was recalculated by omitting rear passenger dummy data. Data were extracted from the Fatality Analysis Reporting System (FARS) and National Automotive Sampling System/General Estimates System (NASS/GES) for the years 2000-2009. Analyses were restricted to vehicles with driver side air bags with head and torso protection as standard features. The risk of driver death was computed as the number of drivers killed (FARS) divided by the number involved (NASS/GES) in left-side impacts and was modeled using logistic regression to control for the effects of driver age and gender and vehicle type and curb weight. Death rates per million registered vehicle years were computed for all outboard occupants and compared by overall rating. Based on the driver-only rating, drivers of vehicles rated good were 70 percent less likely to die when involved in left-side crashes than drivers of vehicles rated poor, after controlling for driver and vehicle factors. Compared with vehicles rated poor, driver death risk was 64 percent lower for vehicles rated acceptable and 49 percent lower for vehicles rated marginal. All 3 results were statistically significant. Among components, vehicle structure rating exhibited the strongest relationship with driver death risk. The vehicle

The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor.

PubMed Central

Schaeffer, L; Moncollin, V; Roy, R; Staub, A; Mezzina, M; Sarasin, A; Weeda, G; Hoeijmakers, J H; Egly, J M

1994-01-01

ERCC2 is involved in the DNA repair syndrome xeroderma pigmentosum (XP) group D and was found to copurify with the RNA polymerase II (B) transcription factor BTF2/TFIIH that possesses a bidirectional helicase activity. Antibodies directed towards the 89 kDa (ERCC3) or the p62 subunit of BTF2 are able to either immunoprecipitate ERCC2 or shift the polypeptide in a glycerol gradient. Conversely, an antibody directed towards ERCC2 also retains or shifts BTF2. ERCC2 could be resolved from the other characterized components of BTF2 upon salt treatment, while its readdition enhanced BTF2 transcription activity. ERCC2, ERCC3 and p44 are three repair proteins found in association with BTF2. Two of them, ERCC2 and ERCC3, are responsible for atypical forms of XP disorders which confer a high predisposition to skin cancer. This includes clinical features that lack an adequate rationalization on the basis of nucleotide excision repair (NER) deficiency but which may now be explained better in terms of a partial transcription deficiency. Images PMID:8194528

The TFIIH subunit Tfb3 regulates cullin neddylation

PubMed Central

Rabut, Gwenaël; Le Dez, Gaëlle; Verma, Rati; Makhnevych, Taras; Knebel, Axel; Kurz, Thimo; Boone, Charles; Deshaies, Raymond J.; Peter, Matthias

2011-01-01

Summary Cullin proteins are scaffolds for the assembly of multi-subunit ubiquitin ligases, which ubiquitylate a large number of proteins involved in widely-varying cellular functions. Multiple mechanisms cooperate to regulate cullin activity, including neddylation of their C-terminal domain. Interestingly, we found that the yeast Cul4-type cullin Rtt101 is not only neddylated but also ubiquitylated, and both modifications promote Rtt101 function in vivo. Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING-domain of Hrt1 nor did it require the Nedd8 ligase Dcn1. Instead, ubiquitylation of Rtt101 was dependent on the ubiquitin-conjugating enzyme Ubc4, while efficient neddylation involves the RING-domain protein Tfb3, a subunit of the transcription factor TFIIH. Tfb3 also controls Cul3 neddylation and activity in vivo, and physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 as well as the Hrt1/Rtt101 complex. Together, these results suggest that the conserved RING-domain protein Tfb3 controls activation of a subset of cullins. PMID:21816351

Def1 interacts with TFIIH and modulates RNA polymerase II transcription.

PubMed

Damodaren, Nivedita; Van Eeuwen, Trevor; Zamel, Joanna; Lin-Shiao, Enrique; Kalisman, Nir; Murakami, Kenji

2017-12-12

The DNA damage response is an essential process for the survival of living cells. In a subset of stress-responsive genes in humans, Elongin controls transcription in response to multiple stimuli, such as DNA damage, oxidative stress, and heat shock. Yeast Elongin (Ela1-Elc1), along with Def1, is known to facilitate ubiquitylation and degradation of RNA polymerase II (pol II) in response to multiple stimuli, yet transcription activity has not been examined. We have found that Def1 copurifies from yeast whole-cell extract with TFIIH, the largest general transcription factor required for transcription initiation and nucleotide excision repair. The addition of recombinant Def1 and Ela1-Elc1 enhanced transcription initiation in an in vitro reconstituted system including pol II, the general transcription factors, and TFIIS. Def1 also enhanced transcription restart from TFIIS-induced cleavage in a pol II transcribing complex. In the Δdef1 strain, heat shock genes were misregulated, indicating that Def1 is required for induction of some stress-responsive genes in yeast. Taken together, our results extend the understanding of the molecular mechanism of transcription regulation on cellular stress and reveal functional similarities to the mammalian system.

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum.

PubMed

Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

2013-08-01

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum

PubMed Central

Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

2013-01-01

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD. PMID:23232694

Venous sinus stenting for reduction of intracranial pressure in IIH: a prospective pilot study.

PubMed

Liu, Kenneth C; Starke, Robert M; Durst, Christopher R; Wang, Tony R; Ding, Dale; Crowley, R Webster; Newman, Steven A

2017-11-01

OBJECTIVE Idiopathic intracranial hypertension (IIH) may cause blindness due to elevated intracranial pressure (ICP). Venous sinus stenosis has been identified in select patients, leading to stenting as a potential treatment, but its effects on global ICP have not been completely defined. The purpose of this pilot study was to assess the effects of venous sinus stenting on ICP in a small group of patients with IIH. METHODS Ten patients for whom medical therapy had failed were prospectively followed. Ophthalmological examinations were assessed, and patients with venous sinus stenosis on MR angiography proceeded to catheter angiography, venography with assessment of pressure gradient, and ICP monitoring. Patients with elevated ICP measurements and an elevated pressure gradient across the stenosis were treated with stent placement. RESULTS All patients had elevated venous pressure (mean 39.5 ± 14.9 mm Hg), an elevated gradient across the venous sinus stenosis (30.0 ± 13.2 mm Hg), and elevated ICP (42.2 ± 15.9 mm Hg). Following stent placement, all patients had resolution of the stenosis and gradient (1 ± 1 mm Hg). The ICP values showed an immediate decrease (to a mean of 17.0 ± 8.3 mm Hg), and further decreased overnight (to a mean of 8 ± 4.2 mm Hg). All patients had subjective and objective improvement, and all but one improved during follow-up (median 23.4 months; range 15.7-31.6 months). Two patients developed stent-adjacent stenosis; retreatment abolished the stenosis and gradient in both cases. Patients presenting with papilledema had resolution on follow-up funduscopic imaging and optical coherence tomography (OCT) and improvement on visual field testing. Patients presenting with optic atrophy had optic nerve thinning on follow-up OCT, but improved visual fields. CONCLUSIONS For selected patients with IIH and venous sinus stenosis with an elevated pressure gradient and elevated ICP, venous sinus stenting results in resolution of the venous pressure

Strength Enhancement of Car Front Bumper for Slow Speed Impact by FEA Method as per IIHS Regulation

NASA Astrophysics Data System (ADS)

Sonawane, Chandrakant Rameshchandra; Shelar, Ajit Lavaji

2017-05-01

Low speed collisions happen significantly due to on road slow moving heavy traffic as well as during parking of vehicles. The bumpers are provided in front and back side of a vehicle has two main purposes: first is to absorb the energy generated during these kinds of slow speed impacts and secondly to protect the expensive parts like main engine parts, radiators and connected engine cooling mechanism, headlights, taillights, etc, by slowing down the vehicles. The problem often in various cars bumper is that they doesn't line-up vertically during low speed impact and leads to damage of various parts which are costly to repair. Many a times bumper design does not have sufficient capacity to absorb the energy generated during these impact. Guideline by International Institute Highway Safety (IIHS) regulation provides useful insight for such low speed impact study. In this paper, slow speed impact test were conducted as per IIHS regulation in three positions namely central impact, left hand corner impact and right hand corner impact. Parameters including bumper material, shape, thickness and impact condition are analyzed using fine element analysis (FEA) to enhance crashworthiness design in low speed impact. Then the vehicle front structure has been modified suitably. It has been observed that lining up the front metal bumper with suitable stiffness provides the best result which ultimately reduces the damage to the vehicle parts.

Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases.

PubMed

Seroz, T; Winkler, G S; Auriol, J; Verhage, R A; Vermeulen, W; Smit, B; Brouwer, J; Eker, A P; Weeda, G; Egly, J M; Hoeijmakers, J H

2000-11-15

Nucleotide excision repair (NER) removes UV-induced photoproducts and numerous other DNA lesions in a highly conserved 'cut-and-paste' reaction that involves approximately 25 core components. In addition, several other proteins have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellular processes. An intriguing example is the Saccharomyces cerevisiae Mms19 protein that has an unknown dual function in NER and RNA polymerase II transcription. Here we report the cloning and characterization of a human homolog, designated hMMS19, that encodes a 1030 amino acid protein with 26% identity and 51% similarity to S.cerevisiae Mms19p and with a strikingly similar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription factor TFIIH. These findings extend the conservation of the NER apparatus and the link between NER and basal transcription and suggest that hMMS19 exerts its function in repair and transcription by interacting with the XPB and XPD helicases.

Core Mediator structure at 3.4 Å extends model of transcription initiation complex.

PubMed

Nozawa, Kayo; Schneider, Thomas R; Cramer, Patrick

2017-05-11

Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.

Puberty as a risk factor for less favorable visual outcome in idiopathic intracranial hypertension.

PubMed

Stiebel-Kalish, Hadas; Kalish, Yuval; Lusky, Moshe; Gaton, Dan D; Ehrlich, Rita; Shuper, Avinoam

2006-08-01

To test the hypothesis that puberty is a risk factor for poorer visual outcome in idiopathic intracranial hypertension (IIH). Retrospective chart review case series. Tertiary referral center, neuro-ophthalmology unit. Ninety-six patients with IIH followed for a minimum of one year. Age (grouped into prepubertal, pubertal, teenage, or adult), obesity, initial intracranial pressure (ICP), measurements and presence of hypertension, anemia, or renal failure were correlated with final visual outcome using chi(2), stepwise logistic regression, and model-selection log linear analyses. Visual outcome was graded into "excellent" -- no evidence of an optic neuropathy or any permanent visual field defect in either eye, "moderate"-- evidence of an optic neuropathy and/or a mild (nasal constriction) visual field defect, or "poor outcome" (peripheral constriction) -- permanent visual field defect. Outcome data were complete for 96 patients. Moderate to poor visual outcome, as opposed to excellent, was significantly associated with puberty (P = .007 using the gender-specific definition of puberty, .0002 using the broad definition). Moderate-poor visual outcome occurred in none of seven IIH patients of prepubertal age (<9 years), in 15 of 26 patients presenting between nine to 16 years, in two of six patients aged 17 to 22 years, and in seven of 57 adult patients over the age of 23 years. In this series of 96 patients with IIH, visual outcome was less favorable in pubertal patients than in prepubertal, teenage, and adult patients. We recommend that clinicians maintain a high index of awareness when caring for pubescent children with IIH.

Risk factors for idiopathic intracranial hypertension in men: a case-control study

PubMed Central

Fraser, J. Alexander; Bruce, Beau B.; Rucker, Janet; Fraser, Lisa-Ann; Atkins, Edward J.; Newman, Nancy J.; Biousse, Valérie

2009-01-01

Objective To identify risk factors for idiopathic intracranial hypertension (IIH) in men Design Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis. Setting Outpatient clinics in two US tertiary care centers Participants The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category. Main Outcome Measures Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching. Results Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03). Conclusions Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men. PMID:19945715

Ordered Conformational Changes in Damaged DNA Induced by Nucleotide Excision Repair Factors*

PubMed Central

Tapias, Angels; Auriol, Jerome; Forget, Diane; Enzlin, Jacqueline H.; Schärer, Orlando D; Coin, Frederic; Coulombe, Benoit; Egly, Jean-Marc

2015-01-01

In response to genotoxic attacks, cells activate sophisticated DNA repair pathways such as nucleotide excision repair (NER), which consists of damage removal via dual incision and DNA resynthesis. Using permanganate footprinting as well as highly purified factors, we show that NER is a dynamic process that takes place in a number of successive steps during which the DNA is remodeled around the lesion in response to the various NER factors. XPC/HR23B first recognizes the damaged structure and initiates the opening of the helix from position −3 to +6. TFIIH is then recruited and, in the presence of ATP, extends the opening from position −6 to +6; it also displaces XPC downstream from the lesion, thereby providing the topological structure for recruiting XPA and RPA, which will enlarge the opening. Once targeted by XPG, the damaged DNA is further melted from position −19 to +8. XPG and XPF/ERCC1 endo-nucleases then cut the damaged DNA at the limit of the opened structure that was previously “labeled” by the positioning of XPC/HR23B and TFIIH. PMID:14981083

Preventing passenger vehicle occupant injuries by vehicle design--a historical perspective from IIHS.

PubMed

O'Neill, Brian

2009-04-01

and chest injury measures recorded on driver and front-seat test dummies. NHTSA later added side crash tests and rollover ratings to the U.S. NCAP. Consumer crash testing spread worldwide in the 1990s. In 1995, the Insurance Institute for Highway Safety (IIHS) began using frontal offset crash tests to rate and compare frontal crashworthiness and later added side and rear crash assessments. Shortly after, Europe launched EuroNCAP to assesses new car performance including front, side, and front-end pedestrian tests. The influence of these consumer-oriented crash test programs on vehicle designs has been major. From the beginning, U.S. NCAP results prompted manufacturers to improve seat belt performance. Frontal offset tests from IIHS and EuroNCAP resulted in greatly improved front-end crumple zones and occupant compartments. Side impact tests have similarly resulted in improved side structures and accelerated the introduction of side impact airbags, especially those designed to protect occupant's heads. Vehicle safety designs, initially driven by regulations and later by consumer demand because of crash testing, have proven to be very successful public health measures. Since they were first introduced in the late 1960s, vehicle safety designs have saved hundreds of thousands of lives and prevented countless injuries worldwide. The designs that improved vehicle crashworthiness have been particularly effective. Some newer crash avoidance designs also have the potential to be effective-e.g., electronic stability control is already saving many lives in single-vehicle crashes. However, determining the actual effectiveness of these new technologies is a slow process and needs real-world crash experience because there are no assessment equivalent of crash tests for crash avoidance designs.

Heat-shock-specific phosphorylation and transcriptional activity of RNA polymerase II.

PubMed

Egyházi, E; Ossoinak, A; Lee, J M; Greenleaf, A L; Mäkelä, T P; Pigon, A

1998-07-10

The carboxyl-terminal domain (CTD) of the largest RNA polymerase II (pol II) subunit is a target for extensive phosphorylation in vivo. Using in vitro kinase assays it was found that several different protein kinases can phosphorylate the CTD including the transcription factor IIH-associated CDK-activating CDK7 kinase (R. Roy, J. P. Adamczewski, T. Seroz, W. Vermeulen, J. P. Tassan, L. Schaeffer, E. A. Nigg, J. H. Hoeijmakers, and J. M. Egly, 1994, Cell 79, 1093-1101). Here we report the colocalization of CDK7 and the phosphorylated form of CTD (phosphoCTD) to actively transcribing genes in intact salivary gland cells of Chironomus tentans. Following a heat-shock treatment, both CDK7 and pol II staining disappear from non-heat-shock genes concomitantly with the abolishment of transcriptional activity of these genes. In contrast, the actively transcribing heat-shock genes, manifested as chromosomal puff 5C on chromosome IV (IV-5C), stain intensely for phosphoCTD, but are devoid of CDK7. Furthermore, the staining of puff IV-5C with anti-PCTD antibodies was not detectably influenced by the TFIIH kinase and transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Following heat-shock treatment, the transcription of non-heat-shock genes was completely eliminated, while newly formed heat-shock gene transcripts emerged in a DRB-resistant manner. Thus, heat shock in these cells induces a rapid clearance of CDK7 from the non-heat-shock genes, indicating a lack of involvement of CDK7 in the induction and function of the heat-induced genes. The results taken together suggest the existence of heat-shock-specific CTD phosphorylation in living cells. This phosphorylation is resistant to DRB treatment, suggesting that not only phosphorylation but also transcription of heat-shock genes is DRB resistant and that CDK7 in heat shock cells is not associated with TFIIH.

Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes.

PubMed

Dembowski, Jill A; DeLuca, Neal A

2015-05-01

Much of the HSV-1 life cycle is carried out in the cell nucleus, including the expression, replication, repair, and packaging of viral genomes. Viral proteins, as well as cellular factors, play essential roles in these processes. Isolation of proteins on nascent DNA (iPOND) was developed to label and purify cellular replication forks. We adapted aspects of this method to label viral genomes to both image, and purify replicating HSV-1 genomes for the identification of associated proteins. Many viral and cellular factors were enriched on viral genomes, including factors that mediate DNA replication, repair, chromatin remodeling, transcription, and RNA processing. As infection proceeded, packaging and structural components were enriched to a greater extent. Among the more abundant proteins that copurified with genomes were the viral transcription factor ICP4 and the replication protein ICP8. Furthermore, all seven viral replication proteins were enriched on viral genomes, along with cellular PCNA and topoisomerases, while other cellular replication proteins were not detected. The chromatin-remodeling complexes present on viral genomes included the INO80, SWI/SNF, NURD, and FACT complexes, which may prevent chromatinization of the genome. Consistent with this conclusion, histones were not readily recovered with purified viral genomes, and imaging studies revealed an underrepresentation of histones on viral genomes. RNA polymerase II, the mediator complex, TFIID, TFIIH, and several other transcriptional activators and repressors were also affinity purified with viral DNA. The presence of INO80, NURD, SWI/SNF, mediator, TFIID, and TFIIH components is consistent with previous studies in which these complexes copurified with ICP4. Therefore, ICP4 is likely involved in the recruitment of these key cellular chromatin remodeling and transcription factors to viral genomes. Taken together, iPOND is a valuable method for the study of viral genome dynamics during infection and

Dynamics of the Extended String-Like Interaction of TFIIE with the p62 Subunit of TFIIH.

PubMed

Okuda, Masahiko; Higo, Junichi; Komatsu, Tadashi; Konuma, Tsuyoshi; Sugase, Kenji; Nishimura, Yoshifumi

2016-09-06

General transcription factor II E (TFIIE) contains an acid-rich region (residues 378-393) in its α-subunit, comprising 13 acidic and two hydrophobic (Phe387 and Val390) residues. Upon binding to the p62 subunit of TFIIH, the acidic region adopts an extended string-like structure on the basic groove of the pleckstrin homology domain (PHD) of p62, and inserts Phe387 and Val390 into two shallow pockets in the groove. Here, we have examined the dynamics of this interaction by NMR and molecular dynamics (MD) simulations. Although alanine substitution of Phe387 and/or Val390 greatly reduced binding to PHD, the binding mode of the mutants was similar to that of the wild-type, as judged by the chemical-shift changes of the PHD. NMR relaxation dispersion profiles of the interaction exhibited large amplitudes for residues in the C-terminal half-string in the acidic region (Phe387, Glu388, Val390, Ala391, and Asp392), indicating a two-site binding mode: one corresponding to the final complex structure, and one to an off-pathway minor complex. To probe the off-pathway complex structure, an atomically detailed free-energy landscape of the binding mode was computed by all-atom multicanonical MD. The most thermodynamically stable cluster corresponded to the final complex structure. One of the next stable clusters was the off-pathway structure cluster, showing the reversed orientation of the C-terminal half-string on the PHD groove, as compared with the final structure. MD calculations elucidated that the C-terminal half-acidic-string forms encounter complexes mainly around the positive groove region with nearly two different orientations of the string, parallel and antiparallel to the final structure. Interestingly, the most encountered complexes exhibit a parallel-like orientation, suggesting that the string has a tendency to bind around the groove in the proper orientation with the aid of Phe387 and/or Val390 to proceed smoothly to the final complex structure. Copyright �

Migraine headache in patients with idiopathic intracranial hypertension.

PubMed

Sina, Farzad; Razmeh, Saeed; Habibzadeh, Neda; Zavari, Arefeh; Nabovvati, Mona

2017-08-29

Migraine is a neurological disorder that afflicts many people in the world and can cause severe disability during the attacks. The pathophysiology of migraine is complex and not fully understood. It seems that migraine is common in idiopathic intracranial hypertension (IIH). However, the association between migraine headache and IIH is still unclear. The present study was conducted to assess the prevalence of migraine headache and associated factors in IIH patients. In this cross-sectional study, a total of 68 patients diagnosed with IIH underwent a medical history interview and a neurological examination. The diagnosis of migraine was based on the four diagnostic criteria of the International Classification of Headache Disorders 3rd edition. Forty-five patients (63.2%) met the diagnostic criteria of migraine headache. There was no significant difference between patients with and without migraine headache in respect of their age, gender, body mass. This study revealed high prevalence of migraine headache in IIH patients; appropriate treatment can reduce their headache and prevent unnecessary treatments for IIH.

Migraine headache in patients with idiopathic intracranial hypertension

PubMed Central

Sina, Farzad; Razmeh, Saeed; Habibzadeh, Neda; Zavari, Arefeh; Nabovvati, Mona

2017-01-01

Migraine is a neurological disorder that afflicts many people in the world and can cause severe disability during the attacks. The pathophysiology of migraine is complex and not fully understood. It seems that migraine is common in idiopathic intracranial hypertension (IIH). However, the association between migraine headache and IIH is still unclear. The present study was conducted to assess the prevalence of migraine headache and associated factors in IIH patients. In this cross-sectional study, a total of 68 patients diagnosed with IIH underwent a medical history interview and a neurological examination. The diagnosis of migraine was based on the four diagnostic criteria of the International Classification of Headache Disorders 3rd edition. Forty-five patients (63.2%) met the diagnostic criteria of migraine headache. There was no significant difference between patients with and without migraine headache in respect of their age, gender, body mass. This study revealed high prevalence of migraine headache in IIH patients; appropriate treatment can reduce their headache and prevent unnecessary treatments for IIH. PMID:29071043

Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure?

PubMed

Higgins, J Nicholas P; Pickard, John D; Lever, Andrew M L

2017-08-01

Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each - fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations? We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome. We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Over-drainage and persistent shunt-dependency in patients with idiopathic intracranial hypertension treated with shunts and bariatric surgery.

PubMed

Roth, Jonathan; Constantini, Shlomi; Kesler, Anat

2015-01-01

Idiopathic intracranial hypertension (IIH) may lead to visual impairment. Shunt surgery is indicated for refractory IIH-related symptoms that persist despite medical treatment, or those presenting with significant visual decline. Obesity is a risk factor for IIH; a reduction in weight has been shown to improve papilledema. Bariatric surgery (BS) has been suggested for treating IIH associated with morbid obesity. In this study, we describe a high rate of over-drainage (OD) seen in patients following shunts and BS. The study cohort includes 13 patients with IIH that underwent shunt surgery for treatment of the IIH-related symptoms. Six patients underwent BS in addition to the shunt surgery (but not concomitantly). Seven patients had only shunt surgeries with no BS. Data were collected retrospectively. BS effectively led to weight reduction (body mass index decreasing from 43 ± 4 to 28 ± 5). Patients undergoing BS had 1-6 (2.5 ± 1.9) shunt revisions for OD following BS, as opposed to 0-3 (1.4 ± 1.1) revisions prior to BS over similar time spans (statistically insignificant difference), and 0-6 (1.6 ± 2.5) revisions among the non-BS patients over a longer time span (statistically insignificant difference). Two patients in the BS group underwent shunt externalization and closure; however, they proved to be shunt-dependent. Patients with IIH that undergo shunt surgery and BS (not concomitantly) may suffer from OD symptoms, necessitating multiple shunt revisions, and valve upgrades. Despite BS being a valid primary treatment for some patients with IIH, among shunted patients, BS may not lead to resolution of IIH-related symptoms and patients may remain shunt-dependent.

A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence

PubMed Central

Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R.; Kehn-Hall, Kylene; Omichinski, James G.

2015-01-01

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH. PMID:25918396

A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

PubMed

Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

2015-05-12

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World.

PubMed

Rosenblatt, Amir; Klein, Ainat; Roemer, Ségolène; Borruat, François-Xavier; Meira, Dália; Silva, Marta; Gökçay, Figen; Çelebisoy, Neşe; Kesler, Anat

2016-09-01

Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder.

Generation of DNA single-strand displacement by compromised nucleotide excision repair

PubMed Central

Godon, Camille; Mourgues, Sophie; Nonnekens, Julie; Mourcet, Amandine; Coin, Fréderic; Vermeulen, Wim; Mari, Pierre-Olivier; Giglia-Mari, Giuseppina

2012-01-01

Nucleotide excision repair (NER) is a precisely coordinated process essential to avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we investigate the mechanistic details and effects of the NER machinery when it is compromised by a pathologically significant mutation in a subunit of the repair/transcription factor TFIIH, namely XPD. In contrast to previous studies, we find that no single- or double-strand DNA breaks are produced at early time points after UV irradiation of cells bearing a specific XPD mutation, despite the presence of a clear histone H2AX phosphorylation (γH2AX) signal in the UV-exposed areas. We show that the observed γH2AX signal can be explained by the presence of longer single-strand gaps possibly generated by strand displacement. Our in vivo measurements also indicate a strongly reduced TFIIH-XPG binding that could promote single-strand displacement at the site of UV lesions. This finding not only highlights the crucial role of XPG's interactions with TFIIH for proper NER, but also sheds new light on how a faulty DNA repair process can induce extreme genomic instability in human patients. PMID:22863773

Occurrence of serious injury in real-world side impacts of vehicles with good side-impact protection ratings.

PubMed

Brumbelow, Matthew L; Mueller, Becky C; Arbelaez, Raul A

2015-01-01

The Insurance Institute for Highway Safety (IIHS) introduced its side impact consumer information test program in 2003. Since that time, side airbags and structural improvements have been implemented across the fleet and the proportion of good ratings has increased to 93% of 2012-2014 model year vehicles. Research has shown that drivers of good-rated vehicles are 70% less likely to die in a left-side crash than drivers of poor-rated vehicles. Despite these improvements, side impact fatalities accounted for about one quarter of passenger vehicle occupant fatalities in 2012. This study is a detailed analysis of real-world cases with serious injury resulting from side crashes of vehicles with good ratings in the IIHS side impact test. NASS-CDS and Crash Injury Research and Engineering Network (CIREN) were queried for occupants of good-rated vehicles who sustained an Abbreviated Injury Scale (AIS) ≥ 3 injury in a side-impact crash. The resulting 110 cases were categorized by impact configuration and other factors that contributed to injury. Patterns of impact configuration, restraint performance, and occupant injury were identified and discussed in the context of potential upgrades to the current IIHS side impact test. Three quarters of the injured occupants were involved in near-side impacts. For these occupants, the most common factors contributing to injury were crash severities greater than the IIHS test, inadequate side-airbag performance, and lack of side-airbag coverage for the injured body region. In the cases where an airbag was present but did not prevent the injury, occupants were often exposed to loading centered farther forward on the vehicle than in the IIHS test. Around 40% of the far-side occupants were injured from contact with the struck-side interior structure, and almost all of these cases were more severe than the IIHS test. The remaining far-side occupants were mostly elderly and sustained injury from the center console, instrument panel, or

A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy.

PubMed Central

Weeda, G; Eveno, E; Donker, I; Vermeulen, W; Chevallier-Lagente, O; Taïeb, A; Stary, A; Hoeijmakers, J H; Mezzina, M; Sarasin, A

1997-01-01

Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is associated with TTD. Virtually all photosensitive TTD patients have a deficiency in the nucleotide excision repair (NER) of UV-induced DNA damage that is indistinguishable from that of xeroderma pigmentosum (XP) complementation group D (XP-D) patients. DNA repair defects in XP-D are associated with two additional, quite different diseases; XP, a sun-sensitive and cancer-prone repair disorder, and Cockayne syndrome (CS), a photosensitive condition characterized by physical and mental retardation and wizened facial appearance. One photosensitive TTD case constitutes a new repair-deficient complementation group, TTD-A. Remarkably, both TTD-A and XP-D defects are associated with subunits of TFIIH, a basal transcription factor with a second function in DNA repair. Thus, mutations in TFIIH components may, on top of a repair defect, also cause transcriptional insufficiency, which may explain part of the non-XP clinical features of TTD. Besides XPD and TTDA, the XPB gene product is also part of TFIIH. To date, three patients with the remarkable conjunction of XP and CS but not TTD have been assigned to XP complementation group B (XP-B). Here we present the characterization of the NER defect in two mild TTD patients (TTD6VI and TTD4VI) and confirm the assignment to X-PB. The causative mutation was found to be a single base substitution resulting in a missense mutation (T119P) in a region of the XPB protein completely conserved in yeast, Drosophila, mouse, and man. These findings define a third TTD complementation group, extend the clinical heterogeneity associated with XP-B, stress the exclusive relationship between TTD and mutations in subunits of repair/transcription factor TFIIH, and strongly

Long-term Response of Cerebrospinal Fluid Pressure in Patients with Idiopathic Intracranial Hypertension - A Prospective Observational Study.

PubMed

Gafoor, V Abdul; Smita, B; Jose, James

2017-01-01

Idiopathic intracranial hypertension (IIH) is increased intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) contents, in the absence of an intracranial mass, hydrocephalus, or other identifiable causes. The current knowledge of the treatment outcome of IIH is limited, and the data on the natural history of this entity are scant. The objective of the study is to study the treatment response of IIH by serially measuring the CSF opening pressure and to delineate the factors influencing the same. A prospective observational study in a cohort of fifty patients with IIH in whom CSF opening pressure was serially measured at pre-specified intervals. The mean CSF opening pressure at baseline was 302.4 ± 51.69 mm of H 2 O (range: 220-410). Even though a higher body mass index (BMI) showed a trend toward a higher CSF opening pressure, the association was not significant ( P = 0.168). However, the age of the patient had a significant negative correlation with the CSF pressure ( P = 0.006). The maximum reduction in CSF pressure occurred in the first 3 months of treatment, and thereafter it plateaued. Remission was attained in 12 (24%) patients. BMI had the strongest association with remission ( P = 0.001). In patients with IIH, treatment response is strongly related to BMI. However, patients with normal BMI are also shown to relapse and hence should have continuous, long-term follow-up. The reduction in CSF pressure attained in the first 3 months could reflect the long-term response to treatment.

Improving of lipid productivity of the oleaginous microalgae Chlorella pyrenoidosa via atmospheric and room temperature plasma (ARTP).

PubMed

Cao, Song; Zhou, Xu; Jin, Wenbiao; Wang, Feng; Tu, Renjie; Han, Songfang; Chen, Hongyi; Chen, Chuan; Xie, Guo-Jun; Ma, Fang

2017-11-01

In this study, an efficient screening program was established with ARTP. Five strains from oleaginous microalgae Chlorella pyrenoidosa were screened from mutant library after mutagenizing by ARTP. Among them, the optimal mutant strain was named as II-H6. In the BG11 medium, the OD 680 of II-H6 in stationary phase were increased by 32.08% than the original strain. Meanwhile, compared with the original strain, the dry weight and lipid productivity of II-H6 were increased by 22.07% and 16.85%, respectively. II-H6 showed a good genetic stability in BG11 medium and the optimum growth temperature and pH were 33°C and 9.0. 18S gene fragment length of II-H6 strain were 1886bp. Analysis of the gene fragment showed that the II-H6 strain had a close relationship to the original strain, and it belonged to the mutation within the genus Chlorella. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative observational study on the clinical presentation, intracranial volume measurements, and intracranial pressure scores in patients with either Chiari malformation Type I or idiopathic intracranial hypertension.

PubMed

Frič, Radek; Eide, Per Kristian

2017-04-01

OBJECTIVE Several lines of evidence suggest common pathophysiological mechanisms in Chiari malformation Type I (CMI) and idiopathic intracranial hypertension (IIH). It has been hypothesized that tonsillar ectopy, a typical finding in CMI, is the result of elevated intracranial pressure (ICP) combined with a developmentally small posterior cranial fossa (PCF). To explore this hypothesis, the authors specifically investigated whether ICP is comparable in CMI and IIH and whether intracranial volumes (ICVs) are different in patients with CMI and IIH, which could explain the tonsillar ectopy in CMI. The authors also examined whether the symptom profile is comparable in these 2 patient groups. METHODS The authors identified all CMI and IIH patients who had undergone overnight diagnostic ICP monitoring during the period from 2002 to 2014 and reviewed their clinical records and radiological examinations. Ventricular CSF volume (VV), PCF volume (PCFV), and total ICV were calculated from initial MRI studies by using volumetric software. The static and pulsatile ICP scores during overnight monitoring were analyzed. Furthermore, the authors included a reference (REF) group consisting of patients who had undergone ICP monitoring due to suspected idiopathic normal-pressure hydrocephalus or chronic daily headache and showed normal pressure values. RESULTS Sixty-six patients with CMI and 41 with IIH were identified, with comparable demographics noted in both groups. The occurrence of some symptoms (headache, nausea, and/or vomiting) was comparable between the cohorts. Dizziness and gait ataxia were significantly more common in patients with CMI, whereas visual symptoms, diplopia, and tinnitus were significantly more frequent in patients with IIH. The cranial volume measurements (VV, PCFV, and ICV) of the CMI and IIH patients were similar. Notably, 7.3% of the IIH patients had tonsillar descent qualifying for diagnosis of CMI (that is, > 5 mm). The extent of tonsillar ectopy was

The Melanopsin-Mediated Pupillary Light Response Is Not Changed in Patients with Newly Diagnosed Idiopathic Intracranial Hypertension.

PubMed

Ba-Ali, Shakoor; Jensen, Rigmor Højland; Larsen, Line Sofie; Lund-Andersen, Henrik; Hamann, Steffen

2018-04-01

Previously, it has been reported that melanopsin-mediated pupillary light response (PLR), measured with pupillometry, is reduced in patients with idiopathic intracranial hypertension (IIH), indicating the clinical utility of the tool in the diagnosis of IIH. In the current study, the authors aimed to measure the PLR in 13 treatment-naive patients with new-onset IIH and 13 healthy controls. In contrast to the previous report, which was based on patients with longstanding IIH ( n = 13), the authors found no significant difference in the melanopsin-mediated PLR ( p = 0.48).

Both XPD alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients

PubMed Central

Ueda, Takahiro; Compe, Emmanuel; Catez, Philippe; Kraemer, Kenneth H.

2009-01-01

Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP). Many XP patients are compound heterozygotes with a “causative” XPD point mutation R683W and different second mutant alleles, considered “null alleles.” However, there is marked clinical heterogeneity (including presence or absence of skin cancers or neurological degeneration) in these XPD/R683W patients, thus suggesting a contribution of the second allele. Here, we report XP patients carrying XPD/R683W and a second XPD allele either XPD/Q452X, /I455del, or /199insPP. We performed a systematic study of the effect of these XPD mutations on several enzymatic functions of TFIIH and found that each mutation exhibited unique biochemical properties. Although all the mutations inhibited the nucleotide excision repair (NER) by disturbing the XPD helicase function, each of them disrupted specific molecular steps during transcription: XPD/Q452X hindered the transactivation process, XPD/I455del disturbed RNA polymerase II phosphorylation, and XPD/199insPP inhibited kinase activity of the cdk7 subunit of TFIIH. The broad range and severity of clinical features in XP patients arise from a broad set of deficiencies in NER and transcription that result from the combination of mutations found on both XPD alleles. PMID:19934020

Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension.

PubMed

Lochner, Piergiorgio; Brio, Francesco; Zedde, Maria Luisa; Sanguigni, Sandro; Coppo, Lorenzo; Nardone, Raffaele; Naldi, Andrea; Sola, Daniele; Stolz, Erwin

2016-06-02

Transorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH. Twenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured. ONSD values were significantly higher in patients (6.50 ± 0.67) than controls (5.73 ± 0.66; p < 0.0001). No differences were found in OND values between patients (2.99 ± 0.26) and controls (2.93 ± 0.41; p = 0.574). No correlation was demonstrated between ONSD and CSF opening pressure (r = 0,086) (p = 0.73). No difference in frequency of IJVVI between patients (11/42 valves, 26 %) and controls (9/42, 21 %) was observed (p = 0.777). Increased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH. Not applicable. Observational, non-interventional study.

TAFII-independent activation mediated by human TBP in the presence of the positive cofactor PC4.

PubMed Central

Wu, S Y; Kershnar, E; Chiang, C M

1998-01-01

TFIID is a multiprotein complex comprised of the TATA-binding protein (TBP) and an array of TBP-associated factors (TAFIIs). Whereas TBP is sufficient for basal transcription in conjunction with other general transcription factors and RNA polymerase II, TAFIIs are additionally required for activator-dependent transcription in mammalian cell-free transcription systems. However, recent in vivo studies carried out in yeast suggest that TAFIIs are not globally required for activator function. The discrepancy between in vivo yeast studies and in vitro mammalian cell-free systems remains to be resolved. In this study, we describe a mammalian cell-free transcription system reconstituted with only recombinant proteins and epitope-tagged multiprotein complexes. Transcriptional activation can be recapitulated in this highly purified in vitro transcription system in the absence of TAFIIs. This TBP-mediated activation is not induced by human mediator, another transcriptional coactivator complex potentially implicated in activator response. In contrast, general transcription factors TFIIH and TFIIA play a significant role in TBP-mediated activation, which can be detected in vitro with Gal4 fusion proteins containing various transcriptional activation domains. Our data, therefore, suggest that TFIIH and TFIIA can mediate activator function in the absence of TAFIIs. PMID:9687514

Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats.

PubMed

Jensen, Vivi F H; Molck, Anne-Marie; Soeborg, Henrik; Nowak, Jette; Chapman, Melissa; Lykkesfeldt, Jens; Bogh, Ingrid B

2018-01-01

Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery period in some of the animals. Sciatic, plantar nerves and thigh muscle were examined histopathologically after four or eight weeks of infusion and after the recovery period. IIH resulted in high incidence of axonal degeneration in sciatic nerves and low incidence in plantar nerves indicating proximo-distal progression of the neuropathy. The neuropathy progressed in severity (sciatic nerve) and incidence (sciatic and plantar nerve) with the duration of IIH. The myopathy consisted of groups of angular atrophic myofibres which resembled histopathologic changes classically seen after denervation of skeletal muscle, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses proximo-distally, that severity and incidence increase with duration of the hypoglycaemia and that these changes are partially reversible within four weeks. Furthermore, IIH-induced myopathy is most likely secondary to the neuropathy. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Utility of Intracranial Pressure Monitoring for Diagnosis of Idiopathic Intracranial Hypertension in the Absence of Papilledema.

PubMed

Bridges, Kelly J; Raslan, Ahmed M

2018-03-01

Idiopathic intracranial hypertension (IIH) is characterized by headaches, visual obscurations, and papilledema, and the diagnosis involves lumbar puncture (LP) with an elevated opening pressure (OP) ≥20 cm H 2 0. When papilledema is absent, the diagnosis becomes less clear. Some physicians have argued that the absence of papilledema rules out IIH, whereas others maintain that elevated OP is sufficient for diagnosis. The authors performed a single-institution 4-year retrospective analysis of patients who underwent invasive intracranial pressure (ICP) monitoring for presumed IIH. A total of 22 patients were reviewed, and 13 had classic symptoms of IIH, documented elevated OP, and absence of papilledema; 5/13 (38%) patients had proven intracranial hypertension as shown by invasive ICP monitoring, whereas 8/13 (62%) had normal ICP. With the use of current diagnostic algorithms of clinical presentation and elevated OP, over half of patients without papilledema in our series would be falsely diagnosed with IIH, which could result in unnecessary medical and surgical intervention. Thus, elevated OP as determined by LP is insufficient to diagnose IIH. On the other hand, the absence of papilledema does not rule out intracranial hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

PubMed Central

Schlingmann, Karl P.; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A.M.; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J.; Rust, Stephan; Forster, Ian C.; Hernando, Nati; Jones, Glenville; Wagner, Carsten A.

2016-01-01

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

Air-to-Air Target Acquisition: Factors and Means of Improvement.

DTIC Science & Technology

1980-03-01

and an atmospheric modelo B t - Bb VISTARAQ C - b derived from input quantities and an B atmospheric model Bt Bb RAE/BAC C B derived from input...seair ’ h task in a !static, fielId. I" Osi c r r, I’lut ion is, dependi- ent upon the angle of’ t hr vi:i x is, -ft wh iih -wilil1y is measured and th

A case of idiopathic intracranial hypertension associated with PCOS.

PubMed

Lee, Y J; Jeong, J E; Joo, J K; Lee, K S

2015-01-01

Idiopathic intracranial hypertension (IIH) is a rare neurologic disorder. It is also known as pseudotumor cerebri. The incidence of IIH is one to two per 100,000 population annually. The higher incidence is in obese women from 15 to 44 years. The main symptoms are headache and visual loss. It mostly affects women of childbearing age who are overweight or obese. There are many theories of pathogenesis of IIH, but precise pathogenesis is unknown. One of the causes of IIH is intracranial venous sinus thrombosis. It can cause increased cerebrospinal fluid (CSF) pressure by obstruction of venous outflow and blocking of CSF absorption. In polycystic ovary syndrome (PCOS) patients, thrombogenic tendency is increased due to increased aromatization of testosterone to estradiol which could induce estrogen-mediated thrombophilia. The authors present a 14-year-old girl with PCOS stigma who presented with a severe headache and papilledema. These symptoms were not improved by standard medical therapy of IIH and PCOS, but improved after laparoscopic ovarian drilling. The authors report it with a review of the literature.

A feasibility of single-incision laparoscopic percutaneous extraperitoneal closure for treatment of incarcerated inguinal hernia in children: our preliminary outcome and review of the literature.

PubMed

Murase, Naruhiko; Uchida, Hiroo; Seki, Takashi; Hiramatsu, Kiyoshi

2016-02-01

The purpose of this study is to examine the feasibility of single-incision laparoscopic percutaneous extraperitoneal closure (LPEC) for incarcerated inguinal hernia (IIH) repair. 6 single-incision LPEC procedures were performed for IIH repair and 60 procedures were performed for reducible inguinal hernia (RIH) in the same period of time in one hospital. The laparoscope and one pair of grasping forceps were placed through the same umbilical incision. In IIH repair, the herniated organ was gently pulled using the grasping forceps with external manual pressure. If it was difficult to reduce the herniated organ with one pair of forceps, another pair of forceps were inserted through a multi-channel port without extending the umbilical incidion. Using the LPEC needle, the hernia orifice was closed extraperitoneally. We performed a retrospective analysis to compare the outcomes of single-incision LPEC for IIH repair or reducible inguinal hernia. All procedures were completed by single-incision without open conversion. A multi-channel port with another pair of forceps was needed in three cases. The operation time and the length of stay were significantly longer with IIH repair than with RIH repair. There were no major complications and there was no evidence of early recurrence in any patient. In conclusion, single-incision LPEC with a multi-channel port is feasible and safe for IIH repair.

Pediatric idiopathic intracranial hypertension - Is the fixed threshold value of elevated LP opening pressure set too high?

PubMed

Gerstl, Lucia; Schoppe, Nikola; Albers, Lucia; Ertl-Wagner, Birgit; Alperin, Noam; Ehrt, Oliver; Pomschar, Andreas; Landgraf, Mirjam N; Heinen, Florian

2017-11-01

Idiopathic intracranial hypertension (IIH) in children is a rare condition of unknown etiology and various clinical presentations. The primary aim of this study was to evaluate if our pediatric IIH study group fulfilled the revised diagnostic criteria for IIH published in 2013, particularly with regard to clinical presentation and threshold value of an elevated lumbar puncture opening pressure. Additionally we investigated the potential utilization of MR-based and fundoscopic methods of estimating intracranial pressure for improved diagnosis. Clinical data were collected retrospectively from twelve pediatric patients diagnosed with IIH between 2008 and 2012 and revised diagnostic criteria were applied. Comparison with non-invasive methods for measuring intracranial pressure, MRI-based measurement (MR-ICP) and venous ophthalmodynamometry was performed. Only four of the twelve children (33%) fulfilled the revised diagnostic criteria for a definite diagnosis of IIH. Regarding noninvasive methods, MR-ICP (n = 6) showed a significantly higher mean of intracranial pressure compared to a healthy age- and sex-matched control group (p = 0.0043). Venous ophthalmodynamometry (n = 4) showed comparable results to invasive lumbar puncture. The revised diagnostic criteria for IIH may be too strict especially in children without papilledema. MR-ICP and venous ophthalmodynamometry are promising complementary procedures for monitoring disease progression and response to treatment. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Idiopathic intracranial hypertension: a comparison between French and North-American white patients.

PubMed

Mrejen, S; Vignal, C; Bruce, B B; Gineys, R; Audren, F; Preechawat, P; Gaudric, A; Gout, O; Newman, N J; Vighetto, A; Bousser, M-G; Biousse, V

2009-01-01

To compare French and American white patients with idiopathic intracranial hypertension (IIH), and to determine prognostic factors associated with visual loss. Medical records of all consecutive white patients with definite IIH seen between 2001 and 2006 in three French tertiary care medical centers and one American tertiary medical center were reviewed. Demographics, associated clinical features, and visual function at presentation and follow-up were collected. French white patients were compared to American white patients. One hundred and thirty-four patients (66 French, 68 American) were included. American patients were 8.7 times more likely than French patients to have visual acuity 20/60 or worse or visual field constriction (95% CI: 2.1-36.1, p=0.0001). American patients were treated more aggressively than French patients. French patients were older (31 vs. 28 years, p=0.02) and more likely to have anemia (20 vs. 2%, p<0.001). American patients had a longer duration of symptoms prior to diagnosis (12 vs. 4 weeks, p=0.01) and longer follow-up than French patients (26 vs. 11 months, p=0.001). Multivariable analysis found that nationality was an independent risk factor for visual loss. French and American patients did not differ regarding gender proportion, frequency of obesity, sleep apnea, endocrine diseases, or systemic hypertension. Cerebrospinal fluid (CSF) opening pressures were similar in both groups. American patients with IIH had worse visual outcomes than French patients despite more aggressive treatment. These differences are not explained by differences in previously known risk factors.

Pediatric Idiopathic Intracranial Hypertension

PubMed Central

Sheldon, Claire A.; Paley, Grace L.; Xiao, Rui; Kesler, Anat; Eyal, Ori; Ko, Melissa W.; Boisvert, Chantal J.; Avery, Robert A.; Salpietro, Vincenzo; Phillips, Paul H.; Heidary, Gena; McCormack, Shana E.; Liu, Grant T.

2017-01-01

Purpose To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). Design Retrospective, international, multisite study. Participants Pediatric patients (2–18 years of age at diagnosis) with IIH. Main Outcome Measures Body mass index (BMI), height, and weight Z-scores; sexual maturation. Methods Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuroophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. Results Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson’s correlation coefficient, 0.50; 95% confidence interval [CI], 0.30–0.66; P < 0.001; n = 72), and in girls, a weak association was noted (Pearson’s correlation coefficient, 0.34; 95% CI, 0.20–0.47; P < 0.001; n = 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (n = 57/233). Prepubertal participants (n = 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (n = 45; 1.92±0.60), but this result did not reach statistical significance (P = 0.09). Conclusions With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight

Idiopathic Intracranial Hypertension After Surgical Treatment of Cushing Disease: Case Report and Review of Management Strategies.

PubMed

Wagner, Jeffrey; Fleseriu, Cara M; Ibrahim, Aly; Cetas, Justin S

2016-12-01

Idiopathic intracranial hypertension (IIH) in patients with Cushing disease (CD), after treatment, is rarely described, in adults. The cause is believed to be multifactorial, potentially related to a relative decrease in cortisol after surgical resection or medical treatment of a corticotroph pituitary adenoma. We investigate our center's CD database (140 surgically and 60 medically [primary or adjunct] treated patients) for cases of IIH, describe our center's experience with symptomatic IIH, and review treatment strategies in adults with CD after transsphenoidal resection. We present the case of a 22-year-old woman who presented with worsening headache, nausea, vomiting, blurry vision, diplopia, visual loss, and facial numbness 14 weeks after surgical resection of adrenocorticotropic hormone-positive pituitary adenoma. Her CD had been in remission since surgery, with subsequent adrenal insufficiency (AI), which was initially treated with supraphysiologic glucocorticoid replacement, tapered down to physiologic doses at the time the IIH symptoms developed. Symptomatic IIH is rare in adult patients but can be severe and result in permanent vision loss. A high index of suspicion should be maintained and a fundus examination is necessary to exclude papilledema, whenever there are suggestive symptoms that initially may overlap with AI. It is possible that some cases of mild IIH are misdiagnosed as GC withdrawal or AI; however, further studies are needed. Treatment consists of reinitiation of higher steroid doses together with acetazolamide with or without cerebrospinal fluid diversion and the priority is to preserve vision and reverse any visual loss. Published by Elsevier Inc.

Crash test ratings and real-world frontal crash outcomes: a CIREN study.

PubMed

Ryb, Gabriel E; Burch, Cynthia; Kerns, Timothy; Dischinger, Patricia C; Ho, Shiu

2010-05-01

To establish whether the Insurance Institute for Highway Safety (IIHS) offset crash test ratings are linked to different mortality rates in real world frontal crashes. The study used Crash Injury Research Engineering Network drivers of age older than 15 years who were involved in frontal crashes. The Crash Injury Research Engineering Network is a convenience sample of persons injured in crashes with at least one Abbreviated Injury Scale score of 3+ injury or two Abbreviated Injury Scale score of 2+ injuries who were either treated at a Level I trauma center or died. Cases were grouped by IIHS crash test ratings (i.e., good, acceptable, marginal, poor, and not rated). Those rated marginal were excluded because of their small numbers. Mortality rates experienced by these ratings-based groups were compared using the Mantel-Haenszel chi test. Multiple logistic regression models were built to adjust for confounders (i.e., occupant, vehicular, and crash factors). A total of 1,226 cases were distributed within not rated (59%), poor (12%), average (16%), and good (14%) categories. Those rated good and average experienced a lower unadjusted mortality rate. After adjustment by confounders, those in vehicles rated good experienced a lower risk of death (adjusted OR 0.38 [0.16-0.90]) than those in vehicles rated poor. There was no significant effect for "acceptable" rating. Other factors influencing the occurrence of death were age, DeltaV >or=70 km/h, high body mass index, and lack of restraint use. After adjusting for occupant, vehicular, and crash factors, drivers of vehicles rated good by the IIHS experienced a lower risk of death in frontal crashes.

Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin

PubMed Central

Ziani, Salim; Nagy, Zita; Alekseev, Sergey; Soutoglou, Evi; Egly, Jean-Marc

2014-01-01

In nucleotide excision repair (NER), damage recognition by XPC-hHR23b is described as a critical step in the formation of the preincision complex (PInC) further composed of TFIIH, XPA, RPA, XPG, and ERCC1-XPF. To obtain new molecular insights into the assembly of the PInC, we analyzed its formation independently of DNA damage by using the lactose operator/repressor reporter system. We observed a sequential and ordered self-assembly of the PInC operating upon immobilization of individual NER factors on undamaged chromatin and mimicking that functioning on a bona fide NER substrate. We also revealed that the recruitment of the TFIIH subunit TTDA, involved in trichothiodystrophy group A disorder (TTD-A), was key in the completion of the PInC. TTDA recruits XPA through its first 15 amino acids, depleted in some TTD-A patients. More generally, these results show that proteins forming large nuclear complexes can be recruited sequentially on chromatin in the absence of their natural DNA target and with no reciprocity in their recruitment. PMID:25154395

Quantitative imaging biomarkers for dural sinus patterns in idiopathic intracranial hypertension.

PubMed

Zur, Dinah; Anconina, Reut; Kesler, Anat; Lublinsky, Svetlana; Toledano, Ronen; Shelef, Ilan

2017-02-01

To quantitatively characterize transverse dural sinuses (TS) on magnetic resonance venography (MRV) in patients with idiopathic intracranial hypertension (IIH), compared to healthy controls, using a computer assisted detection (CAD) method. We retrospectively analyzed MRV studies of 38 IIH patients and 30 controls, matched by age and gender. Data analysis was performed using a specially developed Matlab algorithm for vessel cross-sectional analysis. The cross-sectional area and shape measurements were evaluated in patients and controls. Mean, minimal, and maximal cross-sectional areas as well as volumetric parameters of the right and left transverse sinuses were significantly smaller in IIH patients than in controls ( p  < .005 for all). Idiopathic intracranial hypertension patients showed a narrowed segment in both TS, clustering near the junction with the sigmoid sinus. In 36% (right TS) and 43% (left TS), the stenosis extended to >50% of the entire length of the TS, i.e. the TS was hypoplastic. Narrower vessels tended to have a more triangular shape than did wider vessels. Using CAD we precisely quantified TS stenosis and its severity in IIH patients by cross-sectional and volumetric analysis. This method can be used as an exact tool for investigating mechanisms of IIH development and response to treatment.

Idiopathic intracranial hypertension: ongoing clinical challenges and future prospects

PubMed Central

Julayanont, Parunyou; Karukote, Amputch; Ruthirago, Doungporn; Panikkath, Deepa; Panikkath, Ragesh

2016-01-01

Idiopathic intracranial hypertension (IIH) is an uncommon disorder characterized by increased intracranial pressure without radiological or laboratory evidence of intracranial pathology except empty sella turcica, optic nerve sheath with filled out cerebrospinal fluid spaces, and smooth-walled nonflow-related venous sinus stenosis or collapse. This condition typically affects obese women. The incidence of IIH is increasing with the rising prevalence of obesity. Persistent headache is the most common symptom. Visual impairment is a serious complication that may not be recognized by the patients. This paper reviews clinical manifestations, diagnostic challenges, and current treatments of IIH in adults. Various imaging modalities have been studied on their validity for detection of IIH and papilledema. This review also includes new studies on medical, surgical, and interventional management of this condition. Acetazolamide and topiramate are the only two medications that have been studied in randomized controlled trials about their efficacy in treatment of IIH. In patients who have severe visual impairment or progressive visual deterioration despite medical management, surgical or interventional treatment may be considered. The efficacy and complications of cerebrospinal fluid diversion, optic nerve sheath fenestration, and endovascular venous stenting reported in the last 3 decades have been summarized in this review. Finally, the prospective aspects of biomarkers and treatments are proposed for future research. PMID:26929666

Idiopathic Intracranial Hypertension in Monozygotic Female Twins: Intracranial Pressure Dynamics and Treatment Outcome.

PubMed

Polemikos, Manolis; Heissler, Hans E; Hermann, Elvis J; Krauss, Joachim K

2017-05-01

Familial cases of idiopathic intracranial hypertension (IIH) are exceedingly rare, and its occurrence in monozygotic twins has not been reported previously. We report monozygotic female twins who developed IIH, one at age 25 years and the other at age 28 years. Continuous intracranial pressure (ICP) monitoring confirmed elevated ICP as measured initially by lumbar puncture. In both cases, successful treatment with resolution of papilledema and symptoms relief was achieved after ventriculoperitoneal shunting. This report documents the first case of IIH in monozygotic twins and the associated changes in ICP dynamics. Interestingly, almost equivalent alterations in ICP dynamics were found in the 2 patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort.

PubMed

Sheldon, Claire A; Paley, Grace L; Xiao, Rui; Kesler, Anat; Eyal, Ori; Ko, Melissa W; Boisvert, Chantal J; Avery, Robert A; Salpietro, Vincenzo; Phillips, Paul H; Heidary, Gena; McCormack, Shana E; Liu, Grant T

2016-11-01

To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). Retrospective, international, multisite study. Pediatric patients (2-18 years of age at diagnosis) with IIH. Body mass index (BMI), height, and weight Z-scores; sexual maturation. Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuro-ophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson's correlation coefficient, 0.50; 95% confidence interval [CI], 0.30-0.66; P < 0.001; n = 72), and in girls, a weak association was noted (Pearson's correlation coefficient, 0.34; 95% CI, 0.20-0.47; P < 0.001; n = 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (n = 57/233). Prepubertal participants (n = 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (n = 45; 1.92±0.60), but this result did not reach statistical significance (P = 0.09). With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight or obese, and a late adolescent group that is mostly obese. Data also suggest

Changes in weight, papilledema, headache, visual field, and life status in response to diet and metformin in women with idiopathic intracranial hypertension with and without concurrent polycystic ovary syndrome or hyperinsulinemia.

PubMed

Glueck, Charles J; Golnik, Karl C; Aregawi, Dawit; Goldenberg, Naila; Sieve, Luann; Wang, Ping

2006-11-01

The authors hypothesized that a metformin (MET)-diet would improve symptoms of idiopathic intracranial hypertension (IIH) in women who also had polycystic ovary syndrome (PCOS) or hyperinsulinemia without PCOS. Changes in weight, papilledema, headache, visual fields, and overall life status were prospectively assessed in response to 6 to 14 months on 2.25 g/day MET-diet or diet alone in 36 women with IIH, 23 with PCOS, selected by baseline body mass index (BMI) > or = 25, and no previous surgery for IIH. Overall life status was graded using a self-reported 1-5 scale (1 = well, normal activities; 2 = unwell, usual activities; 3 = poor, usual activities; 4 = poor, no usual activities; 5 = totally disabled). Conventional treatment for IIH was maintained unchanged during MET-diet intervention. The diet was hypocaloric (1500 calories/day), high protein (26% of calories), and low carbohydrate (44%). Of the 23 women with PCOS, 20 received MET-diet and 3 diet only (could not tolerate MET). Of the 13 women without PCOS, 7 were hyperinsulinemic and received MET-diet and 6 received diet alone. The 3 treatment groups (diet only [n = 9], PCOS-MET-diet [n = 20], and hyperinsulinemia-MET-diet [n = 7]) did not differ by median entry BMI (33.3, 37.6, and 35.7 kg/m(2)) or by duration of treatment (10.2, 11.4, and 10.9 months). Median percent weight loss was greatest in the PCOS-MET group (7.7%, P = 0.0015), was 3.3% in the diet only group, and 2.4% (P = 0.04) in the hyperinsulinemia-MET group. Papilledema significantly improved in the diet-alone group from 100% at baseline to 13% (P = 0.03), and in the PCOS-MET group from 95% to 30% (P = 0.002). If headache persisted on therapy, it was less intense-less frequent (P = 0.03) in the diet-only group and in the PCOS-MET group (P = 0.04). As many women with IIH have PCOS, and because weight loss is central to IIH treatment, diet-MET is a novel approach to treat IIH in women with concurrent PCOS or hyperinsulinemia without PCOS.

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

PubMed Central

Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, Imre; Ye, Tao; Tora, Làszlò

2014-01-01

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation. PMID:25058334

Incidence and predictors of dural venous sinus pressure gradient in idiopathic intracranial hypertension and non-idiopathic intracranial hypertension headache patients: results from 164 cerebral venograms.

PubMed

Levitt, Michael R; Hlubek, Randall J; Moon, Karam; Kalani, M Yashar S; Nakaji, Peter; Smith, Kris A; Little, Andrew S; Knievel, Kerry; Chan, Jane W; McDougall, Cameron G; Albuquerque, Felipe C

2017-02-01

OBJECTIVE Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported. METHODS The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71-14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02-0.44). CONCLUSIONS CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

The rem Mutations in the ATP-Binding Groove of the Rad3/XPD Helicase Lead to Xeroderma pigmentosum-Cockayne Syndrome-Like Phenotypes

PubMed Central

Montelone, Beth A.; Aguilera, Andrés

2014-01-01

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease. PMID:25500814

The rem mutations in the ATP-binding groove of the Rad3/XPD helicase lead to Xeroderma pigmentosum-Cockayne syndrome-like phenotypes.

PubMed

Herrera-Moyano, Emilia; Moriel-Carretero, María; Montelone, Beth A; Aguilera, Andrés

2014-12-01

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

Differentiation Driven Changes in the Dynamic Organization of Basal Transcription Initiation

PubMed Central

Giglia-Mari, Giuseppina; Mourgues, Sophie; Nonnekens, Julie; Andrieux, Lise O.; de Wit, Jan; Miquel, Catherine; Wijgers, Nils; Maas, Alex; Fousteri, Maria; Hoeijmakers, Jan H. J.; Vermeulen, Wim

2009-01-01

Studies based on cell-free systems and on in vitro–cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion. This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent. Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs. This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies. PMID:19841728

Clinical value of the neutrophil/lymphocyte ratio in diagnosing adult strangulated inguinal hernia.

PubMed

Zhou, Huanhao; Ruan, Xiaojiao; Shao, Xia; Huang, Xiaming; Fang, Guan; Zheng, Xiaofeng

2016-12-01

Diagnosis of incarcerated inguinal hernia (IIH) is not difficult, but currently, there are no diagnostic criteria that can be used to differentiate it from strangulated inguinal hernia (SIH). This research aimed to evaluate the clinical value of the neutrophil/lymphocyte ratio (NLR) in diagnosing SIH. We retrospectively analyzed 263 patients with IIH who had undergone emergency operation. The patients were divided into two groups according to IIH severity: group A, patients with pure IIH validated during operation as having no bowel ischemia; group B, patients with SIH validated during operation as having obvious bowel ischemia, including bowel necrosis. We statistically evaluated the relation between several clinical features and SIH. The accuracy of different indices was then evaluated and compared using receiver operating characteristic (ROC) curve analyses, and the corresponding cutoff values were calculated. Univariate analysis showed eight clinical features that were significantly different between the two groups. They were then subjected to multivariate analysis, which showed that the NLR, type of hernia, and incarcerated organ were significantly related to SIH. ROC curve analysis showed that the NLR had the largest area under the ROC curve. Among the different clinical features, the NLR appears to be the best index in diagnosing SIH. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Treatment for incarcerated indirect hernia with "Cross-Internal Ring" inguinal oblique incision in children.

PubMed

Yan, Xue-Qiang; Yang, Jun; Zheng, Nan-Nan; Kuang, Hou-Fang; Duan, Xu-Fei; Bian, Hong-Qiang

2017-01-01

This study aims to evaluate the utility of the "Cross-Internal Ring" inguinal oblique incision for the surgical treatment of incarcerated indirect hernia (IIH) complicated with severe abdominal distension. Patients of IIH complicated with severe abdominal distension were reviewed retrospectively. All patients received operation through the "Cross-Internal Ring" inguinal oblique incision. There were totally 13 patients were included, male to female ratio was 9-4. The time for patients to resume oral feeding varying from 2 to 5 days after operation, no complications include delayed intestinal perforation, intra-abdominal abscess, and incision infection happened. Average postoperative hospital stay was 5.2 days. All cases were followed up for 6-18 months. No recurrence or iatrogenic cryptorchidism happened. "Cross-Internal Ring" inguinal oblique incision is a simple, safe, and reliable surgical method to treat pediatric IIH complicated with severe abdominal distension.

The xeroderma pigmentosum group B protein ERCC3 produced in the baculovirus system exhibits DNA helicase activity.

PubMed Central

Ma, L; Siemssen, E D; Noteborn, H M; van der Eb, A J

1994-01-01

The XPB/ERCC3 gene corrects the nucleotide excision-repair defect in the human hereditary disease xeroderma pigmentosum group B and encodes the largest subunit of the basal transcription factor BTF2/TFIIH. The primary sequence of the XPB/ERCC3 protein features the hallmarks of seven helicase motifs found in many known and putative helicases or helicase-related proteins. Recently, the multiprotein BTF2/TFIIH complex has been found to be associated with DNA helicase activity. To explore the properties and functions of XPB/ERCC3, we have used the baculovirus/insect-cell expression system to produce recombinant protein. We report here the construction and analysis of recombinant baculovirus expressing XPB/ERCC3. The XPB/ERCC3 protein is synthesized at a relatively high level in baculovirus-infected insect cells. While the majority of XPB/ERCC3 end up in the insoluble fraction of insect cell lysates, a minor fraction of recombinant protein is present in soluble form which can be purified under native conditions. We have found that a DNA helicase activity is associated with the purified XPB/ERCC3 protein, suggesting that XPB/ERCC3 may function as a DNA helicase in local unwinding of DNA template both in the context of transcription and nucleotide excision repair. Images PMID:7937133

The tympanic membrane displacement test and tinnitus: preliminary report on clinical observations, applications, and implications.

PubMed

Shulman, Abraham; Goldstein, Barbara; Marchbanks, Robert J

2012-01-01

The tympanic membrane displacement test (TMDT) is an attempt to record intracranial pressure (ICP) reflective of an intracranial pulse pressure amplitude wave (IPPA) transmitted to the inner ear and tympanic membrane with a probe placed into the external ear canal. Twelve tinnitus patients, divided into two groups, who were resistant to attempts to achieve tinnitus control or relief were selected for the TMDT. The group 1 TMDT recordings were obtained on one session test date, and group 2 (n = 6) recordings were obtained sequentially on different session test dates. Patient selection with the medical audiologic tinnitus patient protocol (MATPP) identified all to have a nonpulsatile, predominantly central-type severe disabling subjective idiopathic tinnitus (SIT) resistant to attempts for tinnitus relief with instrumentation or medication. Associated complaints in all selected SIT patients included persistent ear blockage in the SIT ear, normal middle-ear function, controlled secondary endolymphatic hydrops in the SIT ear, sensorineural hearing loss of high frequency, hyperacusis, occasional vertigo, and central nervous system complaints of headache, head pressure, and cognitive interference in memory and/or speech expression. Clinical concern is for the presence of an increased ICP reflecting an idiopathic intracranial hypertension (IIH) which, if not identified and treated, may be a factor influencing the clinical course of this particular cohort of SIT patients, highlighted by persistent ear blockage and associated complaints as described. We set out to accomplish a number of goals: (1) To identify abnormal intracranial pulse pressure (IPPA ICP) with the extracranial TMD in a preselected particular cohort of SIT patients clinically suspected (by use of the MATPP) to have an abnormal ICP (i.e., IIH); (2) to identify the abnormal IPPA ICP as a positive indicator for IIH and as a factor - not an etiology - influencing the clinical course of SIT in a preselected

Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25-(OH)2 D3 in Affected Patients.

PubMed

Kaufmann, Martin; Morse, Nicole; Molloy, Billy Joe; Cooper, Donald P; Schlingmann, Karl Peter; Molin, Arnaud; Kottler, Marie Laure; Gallagher, J Christopher; Armas, Laura; Jones, Glenville

2017-07-01

CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D 3 :24,25-(OH) 2 D 3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D 3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH) 2 D 3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH) 2 D 3 peak on LC-MS/MS. We employed an extended 20-min run time on LC-MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25-OH-D levels. We identified 25,26-(OH) 2 D 3 as a contaminant of the 24,25-(OH) 2 D 3 peak. In normals, the concentration of 24,25-(OH) 2 D 3 greatly exceeds 25,26-(OH) 2 D 3 ; however, 25,26-(OH) 2 D 3 becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25-(OH) 2 D 3 levels are low when CYP24A1 function is compromised. Mean R in 30 IIH-CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25-(OH) 2 D 3 levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25-(OH) 2 D 3 from 25,26-(OH) 2 D 3 produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25-(OH) 2 D 3 in IIH patients appears to be

Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

PubMed

Bateman, Grant A; Lechner-Scott, Jeannette; Copping, Ross; Moeskops, Christopher; Yap, Swee Leong

2017-07-06

There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. To further explore these mechanisms, we measured the superior sagittal sinus (SSS) cross-sectional area 3 cm above the torcular using T2 images in 20 MS, 10 spontaneous intracranial hypotension (SIH), 21 hydrocephalus and 20 idiopathic intracranial hypertension (IIH) patients and compared with 20 matched controls. The SSS area was reduced by 25% in hydrocephalus (p = 0.0008), increased by 22% (p = 0.037) in SIH and unchanged in IIH compared to matched controls. In MS there was a 16% increase in SSS area (p = 0.01).The findings suggest that changes in SSS cross-sectional are common between MS and SIH patients, while in hydrocephalus and IIH these are different.

Surgical repair of incarcerated inguinal hernia in children: laparoscopic or open?

PubMed

Nah, S A; Giacomello, L; Eaton, S; de Coppi, P; Curry, J I; Drake, D P; Kiely, E M; Pierro, A

2011-01-01

The management of Incarcerated Inguinal Hernia (IIH) in children is challenging and may be associated with complications. We aimed to compare the outcomes of laparoscopic vs. open repair of IIH. With institutional ethical approval (09SG13), we reviewed the notes of 63 consecutive children who were admitted to a single hospital with the diagnosis of IIH between 2000 and 2008. Data are reported as median (range). Groups were compared by chi-squared or t-tests as appropriate. · Open repair (n=35): There were 21 children with right and 14 with left IIH. 2 patients also had contralateral reducible inguinal hernia. Small bowel resection was required in 2 children. · Laparoscopic repair (n=28): All children had unilateral IIH (19 right sided, 9 left sided). 15 children (54%) with no clinical evidence of contralateral hernia, had contralateral patent processus vaginalis at laparoscopy, which was also repaired. The groups were similar with regard to gender, age at surgery, history of prematurity, interval between admission and surgery, and proportion of patients with successful preoperative manual reduction. However, the duration of operation was longer in the laparoscopy group (p=0.01). Time to full feeds and length of hospital stay were similar in both groups. Postoperative follow-up was 3.5 months (1-36), which was similar in both groups. 5 patients in the group undergoing open repair had serious complications: 1 vas transaction, 1 acquired undescended testis, 2 testicular atrophy and 1 recurrence. The laparoscopic group had a single recurrence. Open repair of incarcerated inguinal hernia is associated with serious complications. The laparoscopic technique appears safe, avoids the difficult dissection of an oedematous sac in the groin, allows inspection of the reduced hernia content and permits the repair of a contralateral patent processus vaginalis if present. © Georg Thieme Verlag KG Stuttgart · New York.

Pseudotumor Cerebri and Glymphatic Dysfunction.

PubMed

Bezerra, Marcio Luciano de Souza; Ferreira, Ana Carolina Andorinho de Freitas; de Oliveira-Souza, Ricardo

2017-01-01

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer's disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Pseudotumor Cerebri and Glymphatic Dysfunction

PubMed Central

Bezerra, Marcio Luciano de Souza; Ferreira, Ana Carolina Andorinho de Freitas; de Oliveira-Souza, Ricardo

2018-01-01

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer’s disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses. PMID:29387036

Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results

PubMed Central

Starke, Robert M.; Durst, Christopher R.; Crowley, R. Webster; Chalouhi, Nohra; Hasan, David M.; Dumont, Aaron S.; Jabbour, Pascal; Liu, Kenneth C.

2015-01-01

Introduction. Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. Methods. A systematic review was carried out to identify studies employing venous stenting for IIH. Results. From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4–20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5–5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7–5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8–80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1–96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0–89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5–4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4–12.4), resulting in restenting in 10 patients. Conclusion. In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH. PMID:26146651

Fulminant idiopathic intracranial hypertension and venous stasis retinopathy resulting in severe bilateral visual impairment.

PubMed

Voldman, Alexander; Durbin, Breanna; Nguyen, John; Ellis, Brian; Leys, Monique

2017-03-10

To report a complicated case of fulminant idiopathic intracranial hypertension and concomitant venous stasis retinopathy leading to postpapilledema optic atrophy. Case report. A 34-year-old morbidly obese woman with a history of idiopathic intracranial hypertension (IIH) presented with a 1-month history of bilateral vision loss, diplopia, and left eye pain after being lost to follow-up for 6 years. Fundus examination revealed florid papilledema with venous tortuosity bilaterally. Brain and orbit magnetic resonance imaging showed bilateral globe flattening, intraocular optic nerve swelling in both eyes, and no abnormality on magnetic resonance venography. After additional workup including lumbar puncture with an opening pressure of 55 cm H2O, a diagnosis of IIH was confirmed. Medical treatment with oral carbonic anhydrase inhibitors was initiated, followed by same-day bilateral optic nerve sheath decompression and ventriculoperitoneal shunt placement the following week. Fundus examination 2 months later revealed a persistent blood and thunder fundus suggestive of bilateral central retinal vein occlusions. Over the course of 6 months, both eyes displayed postpapilledema optic atrophy with light perception and hand motion vision in the right and left eyes, respectively. On Goldmann perimetry, the patient had vague limited isolated responses in both eyes to the largest target. Fulminant IIH can present with profoundly blinding complications recalcitrant to aggressive medical and surgical intervention. Central retinal vein occlusion is an uncommon blinding complication of IIH.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

DNA–DNA hybridization study of strains of Chryseobacterium, Elizabethkingia and Empedobacter and of other usually indole-producing non-fermenters of CDC groups IIc, IIe, IIh and IIi, mostly from human clinical sources, and proposals of Chryseobacterium bernardetii sp. nov., Chryseobacterium carnis sp. nov., Chryseobacterium lactis sp. nov., Chryseobacterium nakagawai sp. nov. and Chryseobacterium taklimakanense comb. nov

PubMed Central

Holmes, B.; Steigerwalt, A. G.; Nicholson, A. C.

2015-01-01

The taxonomic classification of 182 phenotypically similar isolates was evaluated using DNA–DNA hybridization and 16S rRNA gene sequence analysis. These bacterial isolates were mainly derived from clinical sources; all were Gram-negative non-fermenters and most were indoleproducing. Phenotypically, they resembled species from the genera Chryseobacterium, Elizabethkingia or Empedobacter or belonged to CDC groups IIc, IIe, IIh and IIi. Based on these analyses, four novel species are described: Chryseobacterium bernardetii sp. nov. (type strain NCTC 13530T=CCUG 60564T=CDC G229T), Chryseobacterium carnis sp. nov. (type strain NCTC 13525T=CCUG 60559T=CDC G81T), Chryseobacterium lactis sp. nov. (type strain NCTC 11390T=CCUG 60566T=CDC KC1864T) and Chryseobacterium nakagawai sp. nov. (type strain NCTC 13529T=CCUG 60563T=CDC G41T). The new combination Chryseobacterium taklimakanense comb. nov. (type strain NCTC 13490T=X-65T=CCTCC AB 208154T=NRRL B-51322T) is also proposed to accommodate the reclassified Planobacterium taklimakanense. PMID:23934253

Electrochemical Detection of Transient Cobalt Hydride Intermediates of Electrocatalytic Hydrogen Production

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

Wiedner, Eric S.; Bullock, R. Morris

2016-07-06

We report the use of variable scan rate cyclic voltammetry to detect transient CoIIIH and CoIIH intermediates of electrocatalytic H2 production by CoII(dmgBF2)2(CH3CN)2 and [CoII(PtBu2NPh2)(CH3CN)3]2+. In both cases, reduction of the CoIIIH intermediate was observed to coincide with the CoII/I couple, and the resulting CoIIH intermediate is protonated by acid to afford H2. Our studies indicate that in electrocatalytic H2 production, protonation of CoIIH is rate-limiting for CoII(dmgBF2)2(CH3CN)2, and protonation of CoI is rate-limiting for [CoII(PtBu2NPh2)(CH3CN)3]2+. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy,more » Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

PubMed

Vavaiya, Kamlesh V; Briski, Karen P

2007-10-24

While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH

Effect of venous stenting on intracranial pressure in idiopathic intracranial hypertension.

PubMed

Matloob, Samir A; Toma, Ahmed K; Thompson, Simon D; Gan, Chee L; Robertson, Fergus; Thorne, Lewis; Watkins, Laurence D

2017-08-01

Idiopathic intracranial hypertension (IIH) is characterised by an increased intracranial pressure (ICP) in the absence of any central nervous system disease or structural abnormality and by normal CSF composition. Management becomes complicated once surgical intervention is required. Venous sinus stenosis has been suggested as a possible aetiology for IIH. Venous sinus stenting has emerged as a possible interventional option. Evidence for venous sinus stenting is based on elimination of the venous pressure gradient and clinical response. There have been no studies demonstrating the immediate effect of venous stenting on ICP. Patients with a potential or already known diagnosis of IIH were investigated according to departmental protocol. ICP monitoring was performed for 24 h. When high pressures were confirmed, CT venogram and catheter venography were performed to look for venous stenosis to demonstrate a pressure gradient. If positive, venous stenting would be performed and ICP monitoring would continue for a further 24 h after deployment of the venous stent. Ten patients underwent venous sinus stenting with concomitant ICP monitoring. Nine out of ten patients displayed an immediate reduction in their ICP that was maintained at 24 h. The average reduction in mean ICP and pulsatility was significant (p = 0.003). Six out of ten patients reported a symptomatic improvement within the first 2 weeks. Venous sinus stenting results in an immediate reduction in ICP. This physiological response to venous stenting has not previously been reported. Venous stenting could offer an alternative treatment option in correctly selected patients with IIH.

Hydrogen Bonding Rescues Overpotential in Seven-Coordinated Ru Water Oxidation Catalysts

DOE PAGES

Matheu, Roc; Ertem, Mehmed Z.; Gimbert-Surinach, Carolina; ...

2017-08-15

In this paper, we describe the synthesis, structural characterization, and redox properties of two new Ru complexes containing the dianionic potentially pentadentate [2,2':6',2"-terpyridine]-6,6"-dicarboxylate (tda 2–) ligand that coordinates Ru at the equatorial plane and with additional pyridine or dmso acting as monondentate ligand in the axial positions: [Ru II(tda-κ-N 3O)(py)(dmso)], 1 II and [Ru III(tda-κ-N 3O 2)(py)(H 2O) ax] +, 2 III(H 2O) +. Complex 1 II has been characterized by single-crystal XRD in the solid state and in solution by NMR spectroscopy. The redox properties of 1 II and 2 III(H 2O) + have been thoroughly investigated by meansmore » of cyclic voltammetry and differential pulse voltammetry. Complex 2 II(H 2O) displays poor catalytic activity with regard to the oxidation of water to dioxygen, and its properties have been analyzed on the basis of foot of the wave analysis and catalytic Tafel plots. The activity of 2 II(H 2O) has been compared with related water oxidation catalysts (WOCs) previously described in the literature. Despite its moderate activity, 2 II(H 2O) constitutes the cornerstone that has triggered the rationalization of the different factors that govern overpotentials as well as efficiencies in molecular WOCs. The present work uncovers the interplay between different parameters, namely, coordination number, number of anionic groups bonded to the first-coordination sphere of the metal center, water oxidation catalysis overpotential, p K a and hydrogen bonding, and the performance of a given WOC. It thus establishes the basic principles for the design of efficient WOCs operating at low overpotentials.« less

Chiari type 1 malformation in a pseudotumour cerebri patient: is it an acquired or congenital Chiari malformation?

PubMed

Istek, Seref

2014-06-04

Chiari malformation type 1 (CM1) is a developmental abnormality of the cerebellar tonsils. Patients with CM1 commonly present with headache. Papilloedema is rarely seen in CM1. However, a 52-year-old woman presented to the hospital with a headache and her ophthalmological examination revealed bilateral papilloedema. Her cranial MRI was compatible with borderline CM1. Bilateral papilloedema and headache suggested idiopathic intracranial hypertension (IIH) as the preliminary diagnosis. IIH is a rare case in CM1. This article argues about this association and discusses as to whether it is an acquired or congenital Chiari malformation. 2014 BMJ Publishing Group Ltd.

The Drosophila melanogaster Homologue of the Xeroderma Pigmentosum D Gene Product Is Located in Euchromatic Regions and Has a Dynamic Response to UV Light-induced Lesions in Polytene Chromosomes

PubMed Central

Reynaud, Enrique; Lomelí, Hilda; Vázquez, Martha; Zurita, Mario

1999-01-01

The XPD/ERCC2/Rad3 gene is required for excision repair of UV-damaged DNA and is an important component of nucleotide excision repair. Mutations in the XPD gene generate the cancer-prone syndrome, xeroderma pigmentosum, Cockayne’s syndrome, and trichothiodystrophy. XPD has a 5′- to 3′-helicase activity and is a component of the TFIIH transcription factor, which is essential for RNA polymerase II elongation. We present here the characterization of the Drosophila melanogaster XPD gene (DmXPD). DmXPD encodes a product that is highly related to its human homologue. The DmXPD protein is ubiquitous during development. In embryos at the syncytial blastoderm stage, DmXPD is cytoplasmic. At the onset of transcription in somatic cells and during gastrulation in germ cells, DmXPD moves to the nuclei. Distribution analysis in polytene chromosomes shows that DmXPD is highly concentrated in the interbands, especially in the highly transcribed regions known as puffs. UV-light irradiation of third-instar larvae induces an increase in the signal intensity and in the number of sites where the DmXPD protein is located in polytene chromosomes, indicating that the DmXPD protein is recruited intensively in the chromosomes as a response to DNA damage. This is the first time that the response to DNA damage by UV-light irradiation can be visualized directly on the chromosomes using one of the TFIIH components. PMID:10198066

DNA-DNA hybridization study of strains of Chryseobacterium, Elizabethkingia and Empedobacter and of other usually indole-producing non-fermenters of CDC groups IIc, IIe, IIh and IIi, mostly from human clinical sources, and proposals of Chryseobacterium bernardetii sp. nov., Chryseobacterium carnis sp. nov., Chryseobacterium lactis sp. nov., Chryseobacterium nakagawai sp. nov. and Chryseobacterium taklimakanense comb. nov.

PubMed

Holmes, B; Steigerwalt, A G; Nicholson, A C

2013-12-01

The taxonomic classification of 182 phenotypically similar isolates was evaluated using DNA-DNA hybridization and 16S rRNA gene sequence analysis. These bacterial isolates were mainly derived from clinical sources; all were Gram-negative non-fermenters and most were indole-producing. Phenotypically, they resembled species from the genera Chryseobacterium, Elizabethkingia or Empedobacter or belonged to CDC groups IIc, IIe, IIh and IIi. Based on these analyses, four novel species are described: Chryseobacterium bernardetii sp. nov. (type strain NCTC 13530(T) = CCUG 60564(T) = CDC G229(T)), Chryseobacterium carnis sp. nov. (type strain NCTC 13525(T) = CCUG 60559(T) = CDC G81(T)), Chryseobacterium lactis sp. nov. (type strain NCTC 11390(T) = CCUG 60566(T) = CDC KC1864(T)) and Chryseobacterium nakagawai sp. nov. (type strain NCTC 13529(T) = CCUG 60563(T) = CDC G41(T)). The new combination Chryseobacterium taklimakanense comb. nov. (type strain NCTC 13490(T) = X-65(T) = CCTCC AB 208154(T) = NRRL B-51322(T)) is also proposed to accommodate the reclassified Planobacterium taklimakanense.

The idiopathic intracranial hypertension treatment trial: clinical profile at baseline.

PubMed

Wall, Michael; Kupersmith, Mark J; Kieburtz, Karl D; Corbett, James J; Feldon, Steven E; Friedman, Deborah I; Katz, David M; Keltner, John L; Schron, Eleanor B; McDermott, Michael P

2014-06-01

To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between -2 dB and -7 dB. All but 4 participants were women. Baseline and laboratory characteristics. The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was -3.5 (1.1) dB, (range, -2.0 to -6.4 dB) and in the best eye was -2.3 (1.1) dB (range, -5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire-25 and the Short Form-36 physical and mental health summary scales, were lower compared with population norms. The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may

A 6-month telephone-based weight loss intervention in overweight and obese subjects with idiopathic intracranial hypertension.

PubMed

Weil, Richard; Kovacs, Betty; Miller, Neil; McDermott, Michael P; Wall, Michael; Kupersmith, Mark; Pi-Sunyer, F Xavier

2016-06-01

The purpose of this paper is to measure the change in body weight after a 6-month telephone-based weight loss intervention in overweight and obese subjects with idiopathic intracranial hypertension (IIH) and mild visual loss randomized to receive either acetazolamide or placebo. One hundred sixty-five subjects with IIH, aged 29.1 ± 7.5 (mean ± SD) and BMI 39.9 + 8.3 kg/m 2 , enrolled at 38 academic and private practice sites in North America, participated in this trial. This was a randomized, double-masked, placebo-controlled trial of acetazolamide in subjects with IIH and mild visual loss. All participants received a reduced-sodium, weight-reduction diet and a 6-month telephone-based weight loss intervention. Six-month changes from baseline in body weight, perimetric mean deviation as assessed by automated perimetry and quality of life using the National Eye Institute Visual Function Questionnaire 25 and the 36-item Short Form Health Survey were measured. Mean percent weight change at 6 months was -5.9% ± 6.7% of initial body weight overall, -3.5% ± 5.9% in the placebo group and -7.8% ± 6.8% in the acetazolamide group. Weight change was not associated with changes in either mean deviation or quality of life scores. Patients with IIH and mild visual loss assigned to either acetazolamide or placebo, all of whom received a 6-month telephone-based weight loss intervention, lost an average of 5.9% of initial body weight, consistent with NHLBI guidelines of 5% to 10% of body weight loss for clinically significant health benefit.

Characteristics of the Injury Environment in Far-Side Crashes

PubMed Central

Digges, K.; Gabler, H; Mohan, P.; Alonso, B.

2005-01-01

The population of occupants in far-side crashes that are documented in the US National database (NASS/CDS) was studied. The annual number of front seat occupants with serious or fatal injuries in far-side planar and rollover crashes was 17,194. The crash environment that produces serious and fatal injuries to belted front seat occupants in planar far-side crashes was investigated in detail. It was found that both the change in velocity and extent of damage were important factors that relate to crash severity. The median severity for crashes with serious or fatal injuries was a lateral delta-V of 28 kph and an extent of damage of CDC 3.6. Vehicle-to-vehicle impacts were simulated by finite element models to determine the intrusion characteristics associated with the median crash condition. These simulations indicated that the side damage caused by the IIHS barrier was representative of the damage in crashes that produce serious injuries in far-side crashes. Occupant simulations of the IIHS barrier crash at 28 kph showed that existing dummies lack biofidelity in upper body motion. The analysis suggested test conditions for studying far-side countermeasures and supported earlier studies that showed the need for an improved dummy to evaluate safety performance in the far-side crash environment. PMID:16179148

A 6‐month telephone‐based weight loss intervention in overweight and obese subjects with idiopathic intracranial hypertension

PubMed Central

Kovacs, Betty; Miller, Neil; McDermott, Michael P.; Wall, Michael; Kupersmith, Mark; Pi‐Sunyer, F. Xavier

2016-01-01

Summary Objectives The purpose of this paper is to measure the change in body weight after a 6‐month telephone‐based weight loss intervention in overweight and obese subjects with idiopathic intracranial hypertension (IIH) and mild visual loss randomized to receive either acetazolamide or placebo. Methods One hundred sixty‐five subjects with IIH, aged 29.1 ± 7.5 (mean ± SD) and BMI 39.9 + 8.3 kg/m2, enrolled at 38 academic and private practice sites in North America, participated in this trial. This was a randomized, double‐masked, placebo‐controlled trial of acetazolamide in subjects with IIH and mild visual loss. All participants received a reduced‐sodium, weight‐reduction diet and a 6‐month telephone‐based weight loss intervention. Six‐month changes from baseline in body weight, perimetric mean deviation as assessed by automated perimetry and quality of life using the National Eye Institute Visual Function Questionnaire 25 and the 36‐item Short Form Health Survey were measured. Results Mean percent weight change at 6 months was −5.9% ± 6.7% of initial body weight overall, −3.5% ± 5.9% in the placebo group and −7.8% ± 6.8% in the acetazolamide group. Weight change was not associated with changes in either mean deviation or quality of life scores. Conclusion Patients with IIH and mild visual loss assigned to either acetazolamide or placebo, all of whom received a 6‐month telephone‐based weight loss intervention, lost an average of 5.9% of initial body weight, consistent with NHLBI guidelines of 5% to 10% of body weight loss for clinically significant health benefit. PMID:29071096

The syndrome of pseudotumour cerebri and idiopathic intracranial hypertension.

PubMed

Fraser, Clare; Plant, Gordon T

2011-02-01

Idiopathic intracranial hypertension (IIH) is a condition in which raised intracranial pressure is associated with a high body mass index, and in those societies in which the prevalence of obesity is increasing the disorder is of increasing importance. It is one cause of the syndrome of pseudotumour cerebri but the cause and the link with a rise in body weight are not understood. Furthermore the treatment of the more severe, sight-threatening cases is controversial. A major theme in recent years has been an attempt to identify the underlying mechanism of IIH. Some theories - such as the dural sinus stenosis theory - seem to ignore the relationship with weight gain; others have proposed a direct link between obesity and raised intracranial pressure through a specific fat distribution in the body; others through the production of lipokines; and yet others have suggested a converse causation with raised intracranial pressure giving rise to obesity. Uncontrolled case series continue to demonstrate the success of interventions such as cerebrospinal fluid diversion procedures, venous sinus stenting and bariatric surgery but there are no level 1 clinical trials. Interest in IIH is increasing and currently generating numerous studies but there is no consensus view on either cause or management.

ON THE CONNECTION BETWEEN PROPAGATING SOLAR CORONAL DISTURBANCES AND CHROMOSPHERIC FOOTPOINTS

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

Bryans, P.; McIntosh, S. W.; Moortel, I. De

2016-09-20

The Interface Region Imaging Spectrograph ( IRIS ) provides an unparalleled opportunity to explore the (thermal) interface between the chromosphere, transition region, and the coronal plasma observed by the Atmospheric Imaging Assembly (AIA) of the Solar Dynamics Observatory ( SDO ). The SDO /AIA observations of coronal loop footpoints show strong recurring upward propagating signals—“propagating coronal disturbances” (PCDs) with apparent speeds of the order of 100–120 km s{sup −1}. That signal has a clear signature in the slit-jaw images of IRIS in addition to identifiable spectral signatures and diagnostics in the Mg iih (2803 Å) line. In analyzing the Mgmore » iih line, we are able to observe the presence of magnetoacoustic shock waves that are also present in the vicinity of the coronal loop footpoints. We see there is enough of a correspondence between the shock propagation in Mg iih, the evolution of the Si iv line profiles, and the PCD evolution to indicate that these waves are an important ingredient for PCDs. In addition, the strong flows in the jet-like features in the IRIS Si iv slit-jaw images are also associated with PCDs, such that waves and flows both appear to be contributing to the signals observed at the footpoints of PCDs.« less

Apparent Trend of the Iron Abundance in NGC 3201: The Same Outcome with Different Data

NASA Astrophysics Data System (ADS)

Kravtsov, Valery V.

2017-08-01

We further study the unusual trend we found at statistically significant levels in some globular clusters, including NGC 3201: a decreasing iron abundance in red giants toward the cluster centers. We first show that recently published new estimates of iron abundance in the cluster reproduce this trend, in spite of the authors’ statement about no metallicity spread due to a low scatter achieved in the [Fe II/H] ratio. The mean of [Fe II/H] within R˜ 2\\prime from the cluster center is lower, by Δ[Fe II/H] = 0.05 ± 0.02 dex, than in the outer region, in agreement with our original estimate for a much larger sample size within R≈ 9\\prime . We found that an older data set traces the trend to a much larger radial distance, comparable with the cluster tidal radius, at Δ[Fe/H] ˜ 0.2 dex, due to higher metallicity of distant stars. We conclude the trend is reproduced by independent data sets and find that it is accompanied by both a notable same-sign trend of oxygen abundance that can vary by up to Δ[O/Fe] ˜ 0.3 dex within R≈ 9\\prime and an opposite-sign trend of sodium abundance.

Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database.

PubMed

Darendeliler, Feyza; Karagiannis, Georgios; Wilton, Patrick

2007-01-01

Several uncommon adverse effects may be related to growth hormone (GH) treatment. Three potential side effects, headache, idiopathic intracranial hypertension (IIH) and slipped capital femoral epiphysis (SCFE), will be discussed. Data from 57,968 children in the KIGS (Pfizer International Growth Study database) were analyzed to determine the effects of recombinant human GH (Genotropin) on these side effects. The diagnostic groups were idiopathic GH deficiency (IGHD) (n = 27,690), congenital GHD (CGHD) (n = 2,547), craniopharyngioma (n = 1,155), cranial tumours (n = 2,203), Turner syndrome (TS) (n = 6,092), idiopathic short stature (ISS) (n = 5,286), small for gestational age (SGA) (n = 2,973), chronic renal insufficiency (CRI) (n = 1,753) and Prader-Willi syndrome (PWS) (n = 1,368). Total incidence (per 100,000 treatment years) of headache was 793.5 (n = 569). The incidence was significantly higher in the groups of patients with craniopharyngiomas, CGHD and cranial tumours than in the other diagnostic groups (p < 0.05 for all). IIH occurred in 41 children resulting in a total incidence (per 100,000 treatment years) of 27.7. The incidence (per 100,000 treatment years) was significantly lower in patients with IGHD (12.2) than in those with TS (56.4) (p = 0.0004), CGHD (54.5) (p = 0.0064), PWS (68.3) (p = 0.0263) and CRI (147.8) (p < 0.001). No cases of IIH were reported in the ISS group of patients. The median duration from onset of GH therapy to IIH ranged from 0.01 to 1.3 years in various diagnostic groups. SCFE was observed in a total of 52 children resulting in a total incidence (per 100,000 treatment years) of 73.4. The incidence (per 100,000 treatment years) was significantly lower in patients with IGHD (18.3) and in those children with ISS (14.5) than in the TS (84.5), cranial tumours (86.1) and craniopharyngioma groups (120.5) (p < 0.05 for all). No cases of SCFE were reported in the SGA and PWS groups. The median duration from onset of GH therapy to SCFE

The Idiopathic Intracranial Hypertension Treatment Trial

PubMed Central

Wall, Michael; Kupersmith, Mark J.; Kieburtz, Karl D.; Corbett, James J.; Feldon, Steven E.; Friedman, Deborah I.; Katz, David M.; Keltner, John L.; Schron, Eleanor B.; McDermott, Michael P.

2015-01-01

IMPORTANCE To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. OBJECTIVE To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. DESIGN, SETTING, AND PARTICIPANTS We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between −2 dB and −7 dB. All but 4 participants were women. MAIN OUTCOMES AND MEASURES Baseline and laboratory characteristics. RESULTS The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was −3.5 (1.1) dB, (range, −2.0 to −6.4 dB) and in the best eye was −2.3 (1.1) dB (range, −5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire–25 and the Short Form–36 physical and mental health summary scales, were lower compared with population norms. CONCLUSIONS AND RELEVANCE The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show

A coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs RARα to target promoters

PubMed Central

Bruck, Nathalie; Vitoux, Dominique; Ferry, Christine; Duong, Vanessa; Bauer, Annie; de Thé, Hughes; Rochette-Egly, Cécile

2009-01-01

The nuclear retinoic acid (RA) receptor alpha (RARα) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RARα target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RARα at S369 located in the ligand-binding domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates histone H3 at S10. Finally, the phosphorylation cascade initiated by MSK1 controls the recruitment of RARα/TFIIH complexes to response elements and subsequently RARα target gene activation. Cancer cells characterized by a deregulated p38MAPK/MSK1 pathway, do not respond to RA, outlining the essential contribution of the RA-triggered phosphorylation cascade in RA signalling. PMID:19078967

XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

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

Fan, L.; Fuss, J.O.; Cheng, Q.J.

2009-05-18

Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicasemore » activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.« less

XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

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

Tainer, John; Fan, Li; Fuss, Jill O.

2008-06-02

Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicasemore » activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.« less

Localization of ultra-low frequency waves in multi-ion plasmas of the planetary magnetosphere

DOE PAGES

Kim, Eun -Hwa; Johnson, Jay R.; Lee, Dong -Hun

2015-01-01

By adopting a 2D time-dependent wave code, we investigate how mode-converted waves at the Ion-Ion Hybrid (IIH) resonance and compressional waves propagate in 2D density structures with a wide range of field-aligned wavenumbers to background magnetic fields. The simulation results show that the mode-converted waves have continuous bands across the field line consistent with previous numerical studies. These waves also have harmonic structures in frequency domain and are localized in the field-aligned heavy ion density well. Lastly, our results thus emphasize the importance of a field-aligned heavy ion density structure for ultra-low frequency wave propagation, and suggest that IIH wavesmore » can be localized in different locations along the field line.« less

Advanced Life Analysis Methods. Volume 3. Experimental Evaluation of Crack Growth Analysis Methods for Attachment Lugs

DTIC Science & Technology

1984-09-17

hole at an angle to the radial direction. No 6t.ress intensity factors were developed for a non -radial crack. To circumvent non -radial growth, for which...Structural Lugs 10 6.00 TETM TESX, MARI LOCKHEED L𔃼.0 GRUP IIhA AND 2Rii * 2~~~~.0 .RUPINI .01 .05 1 .2 .5. 9 99PROABLTY F*ý,r 1-40 4oprsno R ato nTs rga... controlled and systematically varied. In the fifth column of the table it is shown whether or not the pin is lubricated during testing. Loading directions

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

PubMed Central

Coin, Frédéric; Frit, Philippe; Viollet, Benoit; Salles, Bernard; Egly, Jean-Marc

1998-01-01

DNA damage recognition by basal transcription factors follows different mechanisms. Using transcription-competition, nitrocellulose filter binding, and DNase I footprinting assays, we show that, although the general transcription factor TFIIH is able to target any kind of lesion which can be repaired by the nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more selective in damage recognition. Only genotoxic agents which are able to induce kinked DNA structures similar to the one for the TATA box in its TBP complex are recognized. Indeed, DNase I footprinting patterns reveal that TBP protects equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at position −29 of the noncoding strand) of the adenovirus major late promoter and from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. Together, our results may partially explain differences in transcription inhibition rates following DNA damage. PMID:9632775

Laparoscopic repair of incarcerated inguinal hernia. A safe and effective procedure to adopt in children.

PubMed

Esposito, C; Turial, S; Alicchio, F; Enders, J; Castagnetti, M; Krause, K; Settimi, A; Schier, F

2013-04-01

The purpose of our retrospective study was to describe the efficacy and the advantages of laparoscopic approach to treat incarcerated inguinal hernia (IIH) in pediatric patients. In a 2-year period, 601 children underwent a laparoscopic inguinal hernia repair, 46 (7.6 %) of them presented an IIH. Our study will be focused on these 46 patients: 30 boys and 16 girls (age range 1 month-8 years). Twenty-one/46 hernias (45.6 %) were reduced preoperatively and then operated laparoscopically (RH), 25/46 (54.4 %) were irreducible and they were operated directly in laparoscopy (IRH). We have no conversions in our series. The length of surgery in RH group was in median 23 min and in IRH group was in median 30 min. Hospital stay was variable between 6 h and 3 days (median 36 h).With a minimum follow-up of 14 months, we had 2/46 recurrences (4.3 %). The laparoscopic approach to IIH appears easy to perform from the technical point of view. The 3 main advantages of laparoscopic approach are that all edematous tissue are surgically bypassed and the cord structures are not touched; the reduction is performed under direct visual control, and above all, an inspection of the incarcerated organ is performed at the end of procedure.

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

PubMed Central

Cutone, Antimo; Lepanto, Maria Stefania; Paesano, Rosalba; Valenti, Piera

2017-01-01

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1–2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes. PMID:28914813

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

Persistence of Repair Proteins at Unrepaired DNA Damage Distinguishes Diseases with ERCC2 (XPD) Mutations: Cancer-Prone Xeroderma Pigmentosum vs. Non-Cancer-Prone Trichothiodystrophy

PubMed Central

Boyle, Jennifer; Ueda, Takahiro; Oh, Kyu-Seon; Imoto, Kyoko; Tamura, Deborah; Jagdeo, Jared; Khan, Sikandar G.; Nadem, Carine; DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free. Unlike XP cells, TTD cells have a nearly normal rate of removal of UV-induced 6-4 photoproducts (6-4PP) in their DNA and low levels of the basal transcription factor, TFIIH. We examined seven XP, TTD, and XP/TTD complex patients and identified mutations in the XPD gene. We discovered large differences in nucleotide excision repair (NER) protein recruitment to sites of localized UV damage in TTD cells compared to XP or normal cells. XPC protein was rapidly localized in all cells. XPC was redistributed in TTD, and normal cells by 3 hr postirradiation, but remained localized in XP cells at 24-hr postirradiation. In XP cells recruitment of other NER proteins (XPB, XPD, XPG, XPA, and XPF) was also delayed and persisted at 24 hr (p < 0.001). In TTD cells with defects in the XPD, XPB, or GTF2H5 (TTDA) genes, in contrast, recruitment of these NER proteins was reduced compared to normals at early time points (p < 0.001) and remained low at 24 hr postirradiation. These data indicate that in XP persistence of NER proteins at sites of unrepaired DNA damage is associated with greatly increased skin cancer risk possibly by blockage of translesion DNA synthesis. In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of unrepaired photoproducts and may permit normal translesion DNA synthesis without increased skin cancer. PMID:18470933

Synthetic nebular emission from massive galaxies - I: origin of the cosmic evolution of optical emission-line ratios

NASA Astrophysics Data System (ADS)

Hirschmann, Michaela; Charlot, Stephane; Feltre, Anna; Naab, Thorsten; Choi, Ena; Ostriker, Jeremiah P.; Somerville, Rachel S.

2017-12-01

Galaxies occupy different regions of the [O III]λ5007/H β-versus-[N II]λ6584/H α emission-line ratio diagram in the distant and local Universe. We investigate the origin of this intriguing result by modelling self-consistently, for the first time, nebular emission from young stars, accreting black holes (BHs) and older, post-asymptotic giant branch (post-AGB) stellar populations in galaxy formation simulations in a full cosmological context. In post-processing, we couple new-generation nebular-emission models with high-resolution, cosmological zoom-in simulations of massive galaxies to explore which galaxy physical properties drive the redshift evolution of the optical-line ratios [O III]λ5007/H β, [N II]λ6584/H α, [S II]λλ6717, 6731/H α and [O I]λ6300/H α. The line ratios of simulated galaxies agree well with observations of both star-forming and active local Sloan Digital Sky Survey galaxies. Towards higher redshifts, at fixed galaxy stellar mass, the average [O III]/H β is predicted to increase and [N II]/H α, [S II]/H α and [O I]/H α to decrease - widely consistent with observations. At fixed stellar mass, we identify star formation history, which controls nebular emission from young stars via the ionization parameter, as the primary driver of the cosmic evolution of [O III]/H β and [N II]/H α. For [S II]/H α and [O I]/H α, this applies only to redshifts greater than z = 1.5, the evolution at lower redshift being driven in roughly equal parts by nebular emission from active galactic nuclei and post-AGB stellar populations. Instead, changes in the hardness of ionizing radiation, ionized-gas density, the prevalence of BH accretion relative to star formation and the dust-to-metal mass ratio (whose impact on the gas-phase N/O ratio we model at fixed O/H) play at most a minor role in the cosmic evolution of simulated galaxy line ratios.

Boötes-HiZELS: an optical to near-infrared survey of emission-line galaxies at z = 0.4-4.7

NASA Astrophysics Data System (ADS)

Matthee, Jorryt; Sobral, David; Best, Philip; Smail, Ian; Bian, Fuyan; Darvish, Behnam; Röttgering, Huub; Fan, Xiaohui

2017-10-01

We present a sample of ˜1000 emission-line galaxies at z = 0.4-4.7 from the ˜0.7deg2 High-z Emission-Line Survey in the Boötes field identified with a suite of six narrow-band filters at ≈0.4-2.1 μm. These galaxies have been selected on their Ly α (73), [O II] (285), H β/[O III] (387) or H α (362) emission line, and have been classified with optical to near-infrared colours. A subsample of 98 sources have reliable redshifts from multiple narrow-band (e.g. [O II]-H α) detections and/or spectroscopy. In this survey paper, we present the observations, selection and catalogues of emitters. We measure number densities of Ly α, [O II], H β/[O III] and H α and confirm strong luminosity evolution in star-forming galaxies from z ˜ 0.4 to ˜5, in agreement with previous results. To demonstrate the usefulness of dual-line emitters, we use the sample of dual [O II]-H α emitters to measure the observed [O II]/H α ratio at z = 1.47. The observed [O II]/H α ratio increases significantly from 0.40 ± 0.01 at z = 0.1 to 0.52 ± 0.05 at z = 1.47, which we attribute to either decreasing dust attenuation with redshift, or due to a bias in the (typically) fibre measurements in the local Universe that only measure the central kpc regions. At the bright end, we find that both the H α and Ly α number densities at z ≈ 2.2 deviate significantly from a Schechter form, following a power law. We show that this is driven entirely by an increasing X-ray/active galactic nucleus fraction with line luminosity, which reaches ≈100 per cent at line luminosities L ≳ 3 × 1044 erg s-1.

Difference in dummy responses in matched side impact tests of vehicles with and without side airbags.

PubMed

Viano, David C; Parenteau, Chantal S

2016-07-03

Insurance Institute for Highway Safety (IIHS) high-hooded side impacts were analyzed for matched vehicle tests with and without side airbags. The comparison provides a measure of the effectiveness of side airbags in reducing biomechanical responses for near-side occupants struck by trucks, SUVs, and vans at 50 km/h. The IIHS moving deformable barrier (MDB) uses a high-hooded barrier face. It weighs 1,500 kg and impacts the driver side perpendicular to the vehicle at 50 km/h. SID IIs dummies are placed in the driver and left second-row seats. They represent fifth percentile female occupants. IIHS tests were reviewed for matches with one test with a side airbag and another without it in 2003-2007 model year (MY) vehicles. Four side airbag systems were evaluated: (1) curtain and torso side airbags, (2) head and torso side airbag, (3) curtain side airbag, and (4) torso side airbag. There were 24 matched IIHS vehicle tests: 13 with and without a curtain and torso side airbags, 4 with and without a head and torso side airbag, 5 with and without a side curtain airbag, and 2 with and without a torso airbag. The head, chest, and pelvis responses were compared for each match and the average difference was determined across all matches for a type of side airbag. The average reduction in head injury criterion (HIC) was 68 ± 16% (P < .001) with curtain and torso side airbags compared to the HIC without side airbags. The average HIC was 296 with curtain and torso side airbags and 1,199 without them. The viscous response (VC) was reduced 54 ± 19% (P < .005) with curtain and torso side airbags. The combined acetabulum and ilium force (7 ± 15%) and pelvic acceleration (-2 ± 17%) were essentially similar in the matched tests. The head and torso side airbag reduced HIC by 42 ± 30% (P < .1) and VC by 32 ± 26% compared to vehicles without a side airbag. The average HIC was 397 with the side head and torso airbag compared to 729 without it. The curtain airbag and torso airbag

Idiopathic Intracranial Hypertension in Children and Adolescents: An Update.

PubMed

Cleves-Bayon, Catalina

2018-03-01

Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri syndrome (PTC) is a serious neurological disorder that can lead to irreversible visual loss. Predominantly a disorder affecting women in reproductive years, the pediatric population is not spared. In the past few years, the condition has been redefined, due to new accepted values for opening pressure in children and advances in neuroimaging. Emerging techniques in ophthalmology are being increasingly used to monitor disease in these patients. And, although the treatment tools have not changed in several years, important evidence for efficacy for acetazolamide finally came to light in recent years in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). This review article provides an overview on recent advances in diagnosis, evaluation and treatment of IIH. © 2017 American Headache Society.

Electronic Recorder Study

DOT National Transportation Integrated Search

1999-02-01

The Insurance Institute for Highway Safety (IIHS) petitioned the Federal Highway Administration (FHWA) in 1986 to initiate rulemaking to mandate the use of electronic recorders in all commercial motor vehicles (CMVs) required to maintain logbooks. In...

Increased Intracranial Pressure in the Setting of Enterovirus and Other Viral Meningitides.

PubMed

Beal, Jules C

2017-01-01

Increased intracranial pressure due to viral meningitis has not been widely discussed in the literature, although associations with Varicella and rarely Enterovirus have been described. Patients with increased intracranial pressure and cerebrospinal fluid analysis suggestive of a viral process are sometimes classified as having atypical idiopathic intracranial hypertension (IIH). However, a diagnosis of IIH requires normal cerebrospinal fluid, and therefore in these cases an infection with secondary intracranial hypertension may be a more likely diagnosis. Here seven patients are presented with elevated intracranial pressure and cerebrospinal fluid suggestive of viral or aseptic meningitis. Of these, 1 had Enterovirus and the remainder were diagnosed with nonspecific viral meningitis. These data suggest that viral meningitis may be associated with elevated intracranial pressure more often than is commonly recognized. Enterovirus has previously been associated with increased intracranial pressure only in rare case reports.

U.S. EPA, Pesticide Product Label, CHLORINATING TABLETS, 02/18/1989

EPA Pesticide Factsheets

2011-04-21

... "sidu.1 un ~. uinhined • t ill Iiln ACCEPTED puu • Unf~n !! .. - r: ~''!I,!;!~ I!',~~i::"ide. Furl~;"i: _, . -:J!i ',,i " •• ii,h. Act. 01 Uu .. ~.; f~r tj.~ ;'tJ· .. &l.cide ...

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle

PubMed Central

Santiago, Ammy M.; Clegg, Deborah J.; Routh, Vanessa H.

2016-01-01

Objective 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). Methods These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. Results The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. Conclusion

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.

PubMed

Santiago, Ammy M; Clegg, Deborah J; Routh, Vanessa H

2016-12-01

17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. These data suggest that physiological

Quantifying response to intracranial pressure normalization in idiopathic intracranial hypertension via dynamic neuroimaging.

PubMed

Lublinsky, Svetlana; Kesler, Anat; Friedman, Alon; Horev, Anat; Shelef, Ilan

2018-04-01

Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without a clear cause. To investigate dynamic imaging findings in IIH and their relation to mechanisms underlying intracranial pressure normalization. Prospective. Eighteen IIH patients and 30 healthy controls. T 1 -weighted, venography, fluid attenuation inversion recovery, and apparent diffusion coefficients were acquired on 1.5T scanner. The dural sinus was measured before and after lumbar puncture (LP). The degree of sinus occlusion was evaluated, based on 95% confidence intervals of controls. We studied a number of neuroimaging biomarkers associated with IIH (sinus occlusion; optic nerve; distribution of cerebrospinal fluid into the subarachnoid space, sulci and lateral ventricles (LVs); Meckel's caves; arachnoid granulation; pituitary and choroid plexus), before and after LP, using a set of specially developed quantification techniques. Relationships among various biomarkers were investigated (Pearson correlation coefficient) and linked to long-term disease outcomes (logistic regression). The t-test and the Wilcoxon rank test were used to compare between controls and before and after LP data. As a result of LP, the following were found to be in good accordance with the opening pressure: relative compression of cerebrospinal fluid (R = -0.857, P < 0.001) and brain volumes (R = -0.576, P = 0.012), LV expansion (R = 0.772, P < 0.001) and venous volume (R = 0.696, P = 0.001), enlargement of the pituitary (R = 0.640, P = 0.023), and shrinkage of subarachnoid space (R = -0.887, P < 0.001). The only parameter that had an impact on long-term prognosis was cross-sectional size of supplemental drainage veins after LP (sensitivity of 92%, specificity of 20%, and area under the curve of 0.845, P < 0.001). We present an approach for quantitative characterization of the intracranial venous system and its implementation as a diagnostic assistance

Safety Effectiveness of Stop-Sign Beacons : A Cross-Sectional Study

DOT National Transportation Integrated Search

2018-02-02

Rural intersections account for 16% of fatalities in rural areas (IIHS 2016). Rural intersection crashes are frequently a result of drivers failing to yield to the right of way. Failure to yield right-of-way (FTYROW) may be due to speeding, which ...

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Management of idiopathic intracranial hypertension with a programmable lumboperitoneal shunt: Early experience.

PubMed

Alkherayf, Fahad; Abou Al-Shaar, Hussam; Awad, Michael

2015-09-01

To evaluate the clinical outcomes and complications rate among idiopathic intracranial hypertension (IIH) patients who underwent lumboperitoneal (LP) shunt insertion with a programmable Strata valve. We retrospectively evaluated patients who underwent LP shunt with a programmable Strata valve insertion at the University of Ottawa Civic Hospital from November 2012 to June 2013. The demographic data, clinical symptoms, opening pressure, pre-operative and post-operative visual fields, neuroimaging, visual acuity, disc status, and complications were recorded and analyzed. Seven female patients with IIH underwent insertion of an LP shunt with a programmable Strata valve. The mean opening pressure was 35.8 cm H2O. The initial valve setting was 1.5, and four patients required post-operative valve pressure adjustment. All patients showed significant improvement in objective visual testing at follow-up as well as less frequent headaches. None of the patients developed intra- or post-operative complications. LP shunts with programmable Strata valve systems are a potential alternative to conventional LP and programmable ventriculoperitoneal shunt systems as well as optic nerve sheath fenestration, due to their potential in avoiding brain injury, lower failure and complication rates, lower intracranial hypotension incidence, and flexibility in adjusting valve pressure settings post-operatively evading under- and overdrainage complications. They should be considered for the management of IIH instead of early design LP systems and VP shunts. A randomized multi-center trial should be conducted to compare the efficacy of these surgical techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

U.S. EPA, Pesticide Product Label, , 06/08/1972

EPA Pesticide Factsheets

2011-04-21

... _"I" ""I,,,n r.'I"If'·~ .. to'IOll :,,' • I",n~ .. ' ~ o' " .. , f .. , ~"I c •• ·.r.It.· r r"II' 1!I .. lIt" "'; 'II rot- gUilt "Iil"'." . rut .. h",nm .. .tt- " _ iI"'''h I ... " . Ih.lt ... ...

Bariatric Surgery and the Neuro-Ophthalmologist.

PubMed

Moss, Heather E

2016-03-01

As the prevalence of obesity increases, so, too, do the prevalences of weight-related diseases and surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function. Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry, and neurosurgery literature. Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is Level IV evidence that it is associated with improvement in idiopathic intracranial hypertension (IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months after surgery, whereas B12 or copper deficiency can cause optic neuropathy in years to decades following bariatric surgery. Bariatric surgery is a potential treatment for IIH. Postoperative vitamin deficiencies may cause nystagmus, optic neuropathy, nyctalopia, and/or ophthalmoparesis weeks to years after surgery.

Relations among Academic Enablers and Academic Achievement in Children with and without High Levels of Parent-Rated Symptoms of Inattention, Impulsivity, and Hyperactivity

ERIC Educational Resources Information Center

Demaray, Michelle Kilpatrick; Jenkins, Lyndsay N.

2011-01-01

This study examined the relationships among academic enablers (i.e., engagement, interpersonal skills, motivation, study skills) and academic achievement in children with and without high levels of parent-rated symptoms of inattention, impulsivity, and hyperactivity (Symptoms of IIH Group). The study included 69 participants (29 [42%] in the IIH…

Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

PubMed

Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Magorzata; Wasko, Ryszard; Czepczynski, Rafal; Szczepanek-Parulska, Ewelina; Waligorska-Stachura, Joanna; Kurdybacha, Peter; Bereszynska, Iwona; Florek, Ewa; Stangierski, Adam; Zdanowska, Joanna; Nikisch, Elżbieta; Sowinski, Jerzy; Ruchala, Marek

2013-01-01

Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly β-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice.

PubMed

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nakamura, Takashi; Suzuki, Kenji; Nakamura, Masahiko; Ueno, Kazuyuki; Watanabe, Kenichi

2016-09-01

Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels. Copyright © 2016 Elsevier B.V. All rights reserved.

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2012 CFR

2012-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2014 CFR

2014-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2013 CFR

2013-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

U.S. EPA, Pesticide Product Label, CREOLE BRAND SUPERFINE CONDITIONED DUSTING SULFUR, 02/05/1973

EPA Pesticide Factsheets

2011-04-13

... "~, .11 ihj· 1'., .. f, I,,· ) \\ f 1'1 I' ,t) II \\Hh\\,\\TF1> '1IIf' 1)!I' \\' I'. ,\\!hl \\IIh.l-.\\ '\\lJ ()l'lIlH \\\\.lrlll'\\·1\\ ... i, fl: f: , . I (" I r.., I', r~ 'n . )' t,tf1, r ' ...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2010 CFR

2010-07-01

... paragraphs of § 63.5 as listed below. § 63.5(c) [Reserved] § 63.5(d)(1)(ii)(H) Application for approval Type... maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f)-(g) Compliance with nonopacity...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2011 CFR

2011-07-01

... paragraphs of § 63.5 as listed below. § 63.5(c) [Reserved] § 63.5(d)(1)(ii)(H) Application for approval Type... maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f)-(g) Compliance with nonopacity...

Influence of maternal stature, pregnancy age, and infant birth weight on growth during childhood in Yucatan, Mexico: a test of the intergenerational effects hypothesis.

PubMed

Varela-Silva, Maria Inês; Azcorra, Hugo; Dickinson, Federico; Bogin, Barry; Frisancho, A R

2009-01-01

In developing nations, obesity has increased dramatically in the last decade, but a high prevalence of stunting still coexists. The intergenerational influences hypothesis (IIH) is one explanation for this. We test the IIH regarding variation in maternal stature, mother's age at pregnancy, and infant birth weight in relation to risk for overweight and stunting in 206 Maya children (4-6 years old) from Mérida, Yucatan, Mexico. The Maya children are compared with growth references (Frisancho 2008: Anthropometric Standards: An Interactive Nutritional Reference of Body Size and Body Composition for Children and Adults. Ann Arbor, MI: The University of Michigan Press. 335 pp) for height, weight, and body mass index (BMI). Almost 70% of the mothers are shorter than 150 cm. Mothers' height and child's birth weight predict overweight. Children with a mother shorter than 150 cm are less than half as likely (OR = 0.44) to be overweight compared to children whose mothers are equal to or taller than 150 cm. Children with birth weights below 3,000 g are only a third as likely to be overweight (OR = 0.28) than their peers within the range of normal birth weight (3,000-3,500 g). Sex of the child, mother's height, and birth weight predict stunting. Girls are only 40% as likely as boys to be stunted. Children with a mother below 150 cm are 3.6 times more likely of being stunted. Children with birth weights below 3000 g are over 3 times more likely to be stunted relative to children with birth weights within the normal range. Mother's age at pregnancy is not a predictor of overweight or stunting. Our findings conform the IIH and with similar studies of populations undergoing nutritional/epidemiological transitions from traditional to globalized lifestyles.

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

PubMed

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

SUV rollover in single vehicle crashes and the influence of ESC and SSF.

PubMed

Kallan, Michael J; Jermakian, Jessica Steps

2008-10-01

The modern Sport Utility Vehicle (SUV) fleet continues to go through a transformation in response to the concern that they are at an increased risk of rollover. Our research objective was to look at changes in rollover rates for single vehicle crashes in the modern SUV fleet (corresponding to NCAP rollover testing model years) and the impact of electronic stability control (ESC) and lowered center of gravity. We looked at 2001-2006 NASS-GES data on a probability sample of 3,331 SUVs involved in single vehicle crashes, weighted to represent 324,149 crashes in the study population. Static Stability Factor (SSF) information from NCAP testing and ESC presence (from IIHS) were also incorporated. 20.2% of these SUVs were involved a rollover, which decreased by more than half from model year 2001 (25.3%) through 2006 (11.5%). Nearly 9% had ESC as a standard feature, including 47% in model year 2006. The majority of the late model year decline in rollover rates can be attributed to ESC presence and higher SSF. Rollover was two-thirds less likely (adjusted OR=0.33, 95% CI=0.20-0.55) in SUVs with ESC as a standard feature versus those known not to have ESC. Those SUVs with SSF > or = 1.20 were significantly less likely to rollover (adjusted OR=0.31, 95% CI=0.20-0.48). Additional significant predictors of rollover included SUV size, driver age and alcohol use. Our study builds on the previous work of NHTSA, IIHS, and others with regard to rollover risk by looking at an even wider array of late model year SUVs.

SUV Rollover in Single Vehicle Crashes and the Influence of ESC and SSF

PubMed Central

Kallan, Michael J.; Jermakian, Jessica Steps

2008-01-01

The modern Sport Utility Vehicle (SUV) fleet continues to go through a transformation in response to the concern that they are at an increased risk of rollover. Our research objective was to look at changes in rollover rates for single vehicle crashes in the modern SUV fleet (corresponding to NCAP rollover testing model years) and the impact of electronic stability control (ESC) and lowered center of gravity. We looked at 2001–2006 NASS-GES data on a probability sample of 3,331 SUVs involved in single vehicle crashes, weighted to represent 324,149 crashes in the study population. Static Stability Factor (SSF) information from NCAP testing and ESC presence (from IIHS) were also incorporated. 20.2% of these SUVs were involved a rollover, which decreased by more than half from model year 2001 (25.3%) through 2006 (11.5%). Nearly 9% had ESC as a standard feature, including 47% in model year 2006. The majority of the late model year decline in rollover rates can be attributed to ESC presence and higher SSF. Rollover was two-thirds less likely (adjusted OR=0.33, 95% CI=0.20–0.55) in SUVs with ESC as a standard feature versus those known not to have ESC. Those SUVs with SSF ≥ 1.20 were significantly less likely to rollover (adjusted OR=0.31, 95% CI=0.20–0.48). Additional significant predictors of rollover included SUV size, driver age and alcohol use. Our study builds on the previous work of NHTSA, IIHS, and others with regard to rollover risk by looking at an even wider array of late model year SUVs. PMID:19026218

Hyperthyroidism secondary to hysterosalpingography: an extremely rare complication: A case report.

PubMed

Ma, Guotao; Mao, Rui; Zhai, Haixin

2016-12-01

Hysterosalpingography (HSG), a standard procedure for the evaluation of women with infertility and repetitive pregnancy loss, is associated with complications such as uterine perforation, infection, allergic reactions, syncope, hemorrhage and shock, and pulmonary or retinal embolus. However, hyperthyroidism has not been reported as one of its complications. We report the case of a 33-year-old euthyroid woman who presented to our hospital with palpitation, hand tremor, fatigue, and excessive sweating after HSG. Thyroid function tests revealed a thyroid stimulating hormone (TSH) level of 0.012 μIU/mL (range 0.38-4.34 μIU/mL), free T4 of 2.886 ng/dL (range 0.81-1.89 ng/dL), and free T3 levels of 9.4 pg/mL (range 1.80-4.10 pg/mL), and antithyroglobulin antibody of 31.78 IU/mL (range <115 IU/mL). The triiodothyronine uptake was 3.057 ng/mL (range 0.66-1.92 ng/mL). Serum iodine (SI) and urinary iodine (UI) levels: SI of 4717.748 μg/L (range 45-90 μg/L) and UI of 18069.336 μg/L (range 26-705 μg/L). The patient was diagnosed with iodine-induced hyperthyroidism (IIH), but was not treated with antithyroid drugs. She has spontaneously recovered and is pregnant currently. This is the first reported case of overt IIH caused by HSG in a euthyroid patient without risk factors. It suggests that HSG also leads to excessive iodine absorption, which induces secondary hyperthyroidism.

Bariatric Surgery and the Neuro-Ophthalmologist

PubMed Central

Moss, Heather E.

2016-01-01

Background As the prevalence of obesity increases, so are the prevalences of weight related diseases and the incidence of surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function. Evidence acquisition Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry and neurosurgery literature. Results Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is level IV evidence that it is associated with improvement in idiopathic intracranial hypertension(IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months following surgery, B12 or copper deficiency can cause optic neuropathy in the years to decades following bariatric surgery. Conclusions Bariatric surgery may be a treatment for IIH. Postoperative vitamin deficiencies may present with nystagmus, optic neuropathy, nyctalopia and/or ophthalmoparesis weeks to years after surgery. PMID:26764529

Transcription initiation complex structures elucidate DNA opening.

PubMed

Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

2016-05-19

Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?

PubMed

Lolli, Graziano; Johnson, Louise N

2005-04-01

The Cyclin-dependent kinase (CDK) Activating Kinase (CAK) is responsible for the activating phosphorylation of CDK1, CDK2, CDK4 and CDK6 and regulation of the cell cycle. The kinase is composed of three subunits: CDK7, Cyclin H and MAT1 (ménage a trois). Together with six other subunits, CAK is also part of the general transcription factor TFIIH where it is involved in promoter clearance and progression of transcription from the preinitiation to the initiation stage. CAK is required for cell cycle progression, which suggests that CDK7 could be a target for cancer therapy. However its role in transcription and its ubiquitous presence raise sensible concerns about possible toxicity of its inhibitors. The recently determined structure of CDK7 allows the design of inhibitors with differential specificity for the different CDKs. We review the role of CAK in different biological processes and evaluate the biological evidence for CDK7 as a possible pharmacological target.

MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-catenin Signaling Transcripts by Recruiting CDK7 and RNA Methyltransferase

PubMed Central

Posternak, Valeriya; Ung, Matthew H.; Cheng, Chao; Cole, Michael D.

2016-01-01

MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/β-catenin signaling. Elevated mRNA cap methylation of Wnt signaling transcripts in response to MYC leads to augmented translational capacity, elevated protein levels, and enhanced Wnt signaling activity. Mechanistic evidence indicates that MYC promotes recruitment of RNA methyltransferase (RNMT) to Wnt signaling gene promoters by enhancing phosphorylation of serine 5 on the RNA Polymerase II Carboxy-Terminal Domain, mediated in part through an interaction between the TIP60 acetyltransferase complex and TFIIH. Implications MYC enhances mRNA cap methylation above and beyond transcriptional induction. PMID:27899423

75 FR 71012 - Description of Office, Procedures, and Public Information

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-22

... examples of ``special services'' for which additional fees may be charged. In 12 CFR 1101.4(b)(5)(ii)(H... providing a right to administratively appeal the denial of a request for a waiver or reduction of fees. In... request; (2) The reasons for the determination; (3) If the response is a denial of an initial request or...

U.S. EPA, Pesticide Product Label, DIAZINON 4 SPRAY, 10/04/1993

EPA Pesticide Factsheets

2011-04-21

... iIiHf III lill ~lflilf IIH ; Ii f ti' '11-III'n! 1]1 Ihfl JIlL III illi'l f 111"1 ,1111 III ILl Iltll! II', ~tlf II JII! ,11111 ' I'i, t $'1 it I Itit ,.11 jilt! if II! W!JIIU, JI I i II t J IL If '"' : If 5.:0 ...

U.S. EPA, Pesticide Product Label, HILO FLEA AND TICK SPRAY II, 09/12/1991

EPA Pesticide Factsheets

2011-04-14

... "r mit" wlll'lI 1l1'I'Ivlnll pI"I"h • .-I. AI"w 1"·lIlr.1 "1111,,,"' I" Ih"'''"llhlv .h·V 101'1".1' "" I "R. R"mllVl' .1t'1" 11111' hi ... ". ... ll\\lllt hi,' iU, lIIH"'n~l iO\\l~ 'lf~1 ~nn. ...

Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial.

PubMed

Wall, Michael; McDermott, Michael P; Kieburtz, Karl D; Corbett, James J; Feldon, Steven E; Friedman, Deborah I; Katz, David M; Keltner, John L; Schron, Eleanor B; Kupersmith, Mark J

Acetazolamide is commonly used to treat idiopathic intracranial hypertension (IIH), but there is insufficient information to establish an evidence base for its use. To determine whether acetazolamide is beneficial in improving vision when added to a low-sodium weight reduction diet in patients with IIH and mild visual loss. Multicenter, randomized, double-masked, placebo-controlled study of acetazolamide in 165 participants with IIH and mild visual loss who received a low-sodium weight-reduction diet. Participants were enrolled at 38 academic and private practice sites in North America from March 2010 to November 2012 and followed up for 6 months (last visit in June 2013). All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation (PMD) between -2 dB and -7 dB. The mean age was 29 years and all but 4 participants were women. Low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or matching placebo for 6 months. The planned primary outcome variable was the change in PMD from baseline to month 6 in the most affected eye, as measured by Humphrey Field Analyzer. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss. Secondary outcome variables included changes in papilledema grade, quality of life (Visual Function Questionnaire 25 [VFQ-25] and 36-Item Short Form Health Survey), headache disability, and weight at month 6. The mean improvement in PMD was greater with acetazolamide (1.43 dB, from -3.53 dB at baseline to -2.10 dB at month 6; n = 86) than with placebo (0.71 dB, from -3.53 dB to -2.82 dB; n = 79); the difference was 0.71 dB (95% CI, 0 to 1.43 dB; P = .050). Mean improvements in papilledema grade (acetazolamide: -1.31, from 2.76 to 1.45; placebo: -0.61, from 2.76 to 2.15; treatment effect, -0.70; 95% CI, -0.99 to -0.41; P�

Fifty shades of gradients: does the pressure gradient in venous sinus stenting for idiopathic intracranial hypertension matter? A systematic review.

PubMed

McDougall, Cameron M; Ban, Vin Shen; Beecher, Jeffrey; Pride, Lee; Welch, Babu G

2018-03-02

OBJECTIVE The role of venous sinus stenting (VSS) for idiopathic intracranial hypertension (IIH) is not well understood. The aim of this systematic review is to attempt to identify subsets of patients with IIH who will benefit from VSS based on the pressure gradients of their venous sinus stenosis. METHODS MEDLINE/PubMed was searched for studies reporting venous pressure gradients across the stenotic segment of the venous sinus, pre- and post-stent pressure gradients, and clinical outcomes after VSS. Findings are reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS From 32 eligible studies, a total of 186 patients were included in the analysis. Patients who had favorable outcomes had higher mean pressure gradients (22.8 ± 11.5 mm Hg vs 17.4 ± 8.0 mm Hg, p = 0.033) and higher changes in pressure gradients after stent placement (19.4 ± 10.0 mm Hg vs 12.0 ± 6.0 mm Hg, p = 0.006) compared with those with unfavorable outcomes. The post-stent pressure gradients between the 2 groups were not significantly different (2.8 ± 4.0 mm Hg vs 2.7 ± 2.0 mm Hg, p = 0.934). In a multivariate stepwise logistic regression controlling for age, sex, body mass index, CSF opening pressure, pre-stent pressure gradient, and post-stent pressure gradient, the change in pressure gradient with stent placement was found to be an independent predictor of favorable outcome (p = 0.028). Using a pressure gradient of 21 as a cutoff, 81/86 (94.2%) of patients with a gradient > 21 achieved favorable outcomes, compared with 82/100 (82.0%) of patients with a gradient ≤ 21 (p = 0.022). CONCLUSIONS There appears to be a relationship between the pressure gradient of venous sinus stenosis and the success of VSS in IIH. A randomized controlled trial would help elucidate this relationship and potentially guide patient selection.

XPD-dependent activation of apoptosis in response to triplex-induced DNA damage

PubMed Central

Kaushik Tiwari, Meetu; Rogers, Faye A.

2013-01-01

DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of γH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with γH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation. PMID:23913414

Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation.

PubMed

He, Qing-Li; Minn, Il; Wang, Qiaoling; Xu, Peng; Head, Sarah A; Datan, Emmanuel; Yu, Biao; Pomper, Martin G; Liu, Jun O

2016-09-19

Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymerase II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity in vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Real-time observation of the initiation of RNA polymerase II transcription.

PubMed

Fazal, Furqan M; Meng, Cong A; Murakami, Kenji; Kornberg, Roger D; Block, Steven M

2015-09-10

Biochemical and structural studies have shown that the initiation of RNA polymerase II transcription proceeds in the following stages: assembly of the polymerase with general transcription factors and promoter DNA in a 'closed' preinitiation complex (PIC); unwinding of about 15 base pairs of the promoter DNA to form an 'open' complex; scanning downstream to a transcription start site; synthesis of a short transcript, thought to be about 10 nucleotides long; and promoter escape. Here we have assembled a 32-protein, 1.5-megadalton PIC derived from Saccharomyces cerevisiae, and observe subsequent initiation processes in real time with optical tweezers. Contrary to expectation, scanning driven by the transcription factor IIH involved the rapid opening of an extended transcription bubble, averaging 85 base pairs, accompanied by the synthesis of a transcript up to the entire length of the extended bubble, followed by promoter escape. PICs that failed to achieve promoter escape nevertheless formed open complexes and extended bubbles, which collapsed back to closed or open complexes, resulting in repeated futile scanning.

40 CFR 52.2465 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 2FSD, and pre-dryer 3FSD from Part IV, Rule EX-4, Section 4.41(i) until December 15, 1981, submitted on...) Appendix K (7) Appendix N (8) Appendix P (9) Appendix R I., II.B., II.D., II.E., II.F., II.G., II.H., II.I...) Amendments to Part I, Subpart 1.01 (Certain Terms Defined) and to Part IV, Section 4.52 (former Section 4.705...

Toxicological Effects during and following Persistent Insulin-Induced Hypoglycaemia in Healthy Euglycaemic Rats.

PubMed

Jensen, Vivi F H; Mølck, Anne-Marie; Berthelsen, Line O; Alifrangis, Lene; Andersen, Lene; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-07-01

New insulin analogues with a longer duration of action and a 'peakless' pharmacokinetic profile have been developed to improve efficacy, safety and convenience for patients with diabetes. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In this study, we investigated the effects of persistent IIH and their reversibility in euglycaemic rats. Histopathological changes in insulin-infused animals included partly reversible axonal and reversible myofibre degeneration in peripheral nerve and skeletal muscle tissue, respectively, as well as reversible pancreatic islet atrophy and partly reversible increase in unilocular adipocytes in brown adipose tissue. Additionally, results suggested increased gluconeogenesis. The observed hyperphagia, the pancreatic, peripheral nerve and skeletal muscle changes were considered related to the hypoglycaemia. Cessation of insulin infusion resulted in transient hyperglycaemia, decreased food consumption and body-weight loss before returning to control levels. The implications for the interpretation of non-clinical studies with long-acting insulin analogues are discussed. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

A comparison of the effects of oral glutamine dipeptide, glutamine, and alanine on blood amino acid availability in rats submitted to insulin-induced hypoglycemia.

PubMed

Minguetti-Câmara, Vania C; Marques, Any de C R; Schiavon, Fabiana P M; Vilela, Vanessa R; Bruschi, Marcos L; Bazotte, Roberto Barbosa

2014-10-21

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.

Identification of Poly(ADP-Ribose) Polymerase as a Transcriptional Coactivator of the Human T-Cell Leukemia Virus Type 1 Tax Protein

PubMed Central

Anderson, Mark G.; Scoggin, Kirsten E. S.; Simbulan-Rosenthal, Cynthia M.; Steadman, Jennifer A.

2000-01-01

Human T-cell leukemia virus type 1 (HTLV-1) encodes a transcriptional activator, Tax, whose activity is believed to contribute significantly to cellular transformation. Tax stimulates transcription from the proviral promoter as well as from promoters for a variety of cellular genes. The mechanism through which Tax communicates to the general transcription factors and RNA polymerase II has not been completely determined. We investigated whether Tax could function directly through the general transcription factors and RNA polymerase II or if other intermediary factors or coactivators were required. Our results show that a system consisting of purified recombinant TFIIA, TFIIB, TFIIE, TFIIF, CREB, and Tax, along with highly purified RNA polymerase II, affinity-purified epitope-tagged TFIID, and semipurified TFIIH, supports basal transcription of the HTLV-1 promoter but is not responsive to Tax. Two additional activities were required for Tax to stimulate transcription. We demonstrate that one of these activities is poly(ADP-ribose) polymerase (PARP), a molecule that has been previously identified to be the transcriptional coactivator PC1. PARP functions as a coactivator in our assays at molar concentrations approximately equal to those of the DNA and equal to or less than those of the transcription factors in the assay. We further demonstrate that PARP stimulates Tax-activated transcription in vivo, demonstrating that this biochemical approach has functionally identified a novel target for the retroviral transcriptional activator Tax. PMID:10666246

A Study of Terrain Reductions, Density Anomalies and Geophysical Inversion Methods in Gravity Field Modelling

DTIC Science & Technology

1984-04-01

5.15) where a is a positive constant and 11 IIH the Hilbert space norm associated with the chosen covariance function K. The constant a is arbitrary...Density Anomalies 14 5. Unknown Densities - Geophysical Inversion 16 6. Density Modelling Using Rectangular Prisms 24 6.1 Space Domain 24 6.2 Frequency...theory: to calculate the gravity potential and its derivatives in space due to 6 • given density distributions. When the prime interest is in "external

Domain Decomposition with Local Mesh Refinement.

DTIC Science & Technology

1989-08-01

smoothi coefficients, or non-smooth solui ioni,. We eiriplov fromn 1 to 1024 tiles on problems containing irp to 161K (degrees of freedom. Though io... methodology survives such compromises and is even sequentially advantageous in many problems. The domain decomposition algorithms we employ (sertiun 3...iog( I + !J2 it - g i Ol Qunit squiare 1 he (,mai oive i> Hie outward normal. lfie sevoh iih exam pie, from [1. 27] has a smoothi solution, but rapidlY

Laparoscopic surgery in the treatment of incarcerated indirect inguinal hernia in children.

PubMed

Yin, Yiyu; Zhang, Hongwei; Zhang, Xiang; Sun, Fang; Zou, Huaxin; Cao, Hui; Wen, Cheng

2016-12-01

We aimed to explore the feasibility and the safety of the laparoscopic surgery for incarcerated indirect inguinal hernia (IIH) in children. From January 2012 to December 2014, 64 children were enrolled into this study. All 64 patients received laparoscopic surgery and we reviewed their perioperative and postoperative follow-up studies. In addition, we enrolled 60 cases of children who received traditional surgery of IIH administered through minimally invasive surgery as the control group. Results from the present study showed that the mean operation time for the laparoscopic group was 41.5 min (range, 15-80 min) which was significantly shorter than the control group. Nine cases developed incarcerated intestine necrosis, expanded umbilical incision and parallel resection anastomosis. They received laparoscopic hernia sac high ligation. Only 5 cases developed scrotum edema after the surgery. The postoperative length of the stay ranged from 2 to 7 days (average, 3.2). The postoperative follow-up was from 6 months to 1 year and no relapse or secondary testicular atrophy was observed in the laparoscopic group. The operation time, incidence of postoperative complications and length of stay in the laparoscopic group were decreased compared to the control group, and differences were statistically significant (P<0.05). In conclusion, laparoscopic surgery treatment for incarcerated inguinal hernia is safe and feasible and produced better results compared with the alternative.

Localization of alpha-dystroglycan on the podocyte: from top to toe.

PubMed

Vogtländer, Nils P J; Dijkman, Henry; Bakker, Marinka A H; Campbell, Kevin P; van der Vlag, Johan; Berden, Jo H M

2005-11-01

alpha-Dystroglycan (DG) is a negatively charged membrane-associated glycoprotein that links the cytoskeleton to the extracellular matrix. Previously, we described that alpha-DG covers the whole podocyte cell membrane in the rat. However, our finding was challenged by the description of a strictly basolateral localization in human kidney biopsies, using a different antibody against alpha-DG. Therefore, we studied the exact localization of glomerular alpha-DG by using these two antibodies in both species. The studies were performed by using monoclonal antibodies (MoAbs) IIH6 and VIA4.1 in immunofluorescence, confocal microscopy, and immunoelectron microscopy on both rat and human kidney sections, as well as on cultured mouse podocytes. The apical localization of alpha-DG on podocytes was more dominant than the basolateral localization. The basolateral staining with MoAb VIA4.1 was more pronounced than that of MoAb IIH6. With both MoAbs, the staining in rat kidneys was more prominent, in comparison to human kidneys. We conclude that alpha-DG is expressed at both the basolateral and apical sides of the podocyte. This localization suggests that alpha-DG plays a dual role in the maintenance of the unique architecture of podocytes by its binding to the glomerular basement membrane, and in the maintenance of the integrity of the filtration slit, respectively.

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins.

PubMed

Ly, Hoai J; Ikegami, Tetsuro

2016-07-02

Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

The head module of Mediator directs activation of preloaded RNAPII in vivo.

PubMed

Lee, Sarah K; Chen, Xu; Huang, Liangqun; Stargell, Laurie A

2013-12-01

The successful synthesis of a transcript by RNA polymerase II (RNAPII) is a multistage process with distinct rate-limiting steps that can vary depending on the particular gene. A growing number of genes in a variety of organisms are regulated at steps after the recruitment of RNAPII. The best-characterized Saccharomyces cerevisiae gene regulated in this manner is CYC1. This gene has high occupancy of RNAPII under non-inducing conditions, defining it as a poised gene. Here, we find that subunits of the head module of Mediator, Med18 and Med20, and Med19 are required for activation of transcription at the CYC1 promoter in response to environmental cues. These subunits of Mediator are required at the preloaded promoter for normal levels of recruitment and activity of the general transcription factor TFIIH. Strikingly, these Mediator components are dispensable for activation by the same activator at a different gene, which lacks a preloaded polymerase in the promoter region. Based on these results and other studies, we speculate that Mediator plays an essential role in triggering an inactive polymerase at CYC1 into a productively elongating form.

A Neutron Radiography System for Field Use

DTIC Science & Technology

1989-06-01

provoked a major renewal of interest in neutron radiography because it promises to bring neutron radiography to the workplace , a convenience provided...II I~F I C II i IiH i ii MTL TR 89-52 I-AD A NEUTRON RADIOGRAPHY SYSTEM N FOR FIELD USE e~m JOHN J. ANTAL and ALFRED S. MAROTTA, and LOUIS J. FARESE...COVERED A NEUTRON RADIOGRAPHY SYSTEM FOR FIELD USE Final Report 6. PERFORMING OR1. REPORT NUMBER 7. AUTHOR(s) S. CONTRACT OR GRANT NUMBER(s) John J

Metallurgical Characterization of the Interfaces and the Damping Mechanisms in Metal Matrix Composites.

DTIC Science & Technology

1986-09-30

Il.g. Honors, Awards - none II.h. Participants :Mr. Asok Ray ; Graduate Student working towards his Ph.D. Thesis. Advisor: Dr. V.K. Kinra at Texas A&M...Presentations ll.d.1 Invited Presentation at Topical or Scientific/Technical Society Conferences i) A.K. Ray , V.K. Kinra, S.P. Rawal and M.S. Misra...FC16 ii) S.P. Rawal, J.H. Armstrong, M.S. Misra, A.K. Ray and V.K. Kinra, "Damping Measurements of Gr/AI Composites", Symposium on Dynamic Behavior of

Analysis of crash parameters and driver characteristics associated with lower limb injury.

PubMed

Ye, Xin; Poplin, Gerald; Bose, Dipan; Forbes, Aaron; Hurwitz, Shepard; Shaw, Greg; Crandall, Jeff

2015-10-01

This study aims to investigate changes in frequency, risk, and patterns of lower limb injuries due to vehicle and occupant parameters as a function of vehicle model year. From the National Automotive Sampling System-Crashworthiness Data System, 10,988 observations were sampled and analyzed, representing 4.7 million belted drivers involved in frontal crashes for the years 1998-2010. A logistic regression model was developed to understand the association of sustaining knee and below knee lower limb injuries of moderate or greater severity with motor vehicle crash characteristics such as vehicle type and model years, toepan and instrument panel intrusions in addition to the occupant's age, gender, height and weight. Toepan intrusion greater than 2cm was significantly associated with an increased likelihood of injury (odds ratio: 9.10, 95% confidence interval 1.82-45.42). Females sustained a higher likelihood of distal lower limb injuries (OR: 6.83, 1.56-29.93) as compared to males. Increased mass of the driver was also found to have a positive association with injury (OR: 1.04, 1.02-1.06), while age and height were not associated with injury likelihood. Relative to passenger cars, vans exhibited a protective effect against sustaining lower limb injury (OR: 0.24, 0.07-0.78), whereas no association was shown for light trucks (OR: 1.31, 0.69-2.49) or SUVs (OR: 0.76, 0.28-2.02). To examine whether current crash testing results are representative of real-world NASS-CDS findings, data from frontal offset crash tests performed by the Insurance Institute for Highway Safety (IIHS) were examined. IIHS data indicated a decreasing trend in vehicle foot well and toepan intrusion, foot accelerations, tibia axial forces and tibia index in relation to increasing vehicle model year between the year 1995 and 2013. Over 90% of vehicles received the highest IIHS rating, with steady improvement from the upper and lower tibia index, tibia axial force and the resultant foot acceleration

The SAMI Galaxy Survey: spatially resolving the main sequence of star formation

NASA Astrophysics Data System (ADS)

Medling, Anne M.; Cortese, Luca; Croom, Scott M.; Green, Andrew W.; Groves, Brent; Hampton, Elise; Ho, I.-Ting; Davies, Luke J. M.; Kewley, Lisa J.; Moffett, Amanda J.; Schaefer, Adam L.; Taylor, Edward; Zafar, Tayyaba; Bekki, Kenji; Bland-Hawthorn, Joss; Bloom, Jessica V.; Brough, Sarah; Bryant, Julia J.; Catinella, Barbara; Cecil, Gerald; Colless, Matthew; Couch, Warrick J.; Drinkwater, Michael J.; Driver, Simon P.; Federrath, Christoph; Foster, Caroline; Goldstein, Gregory; Goodwin, Michael; Hopkins, Andrew; Lawrence, J. S.; Leslie, Sarah K.; Lewis, Geraint F.; Lorente, Nuria P. F.; Owers, Matt S.; McDermid, Richard; Richards, Samuel N.; Sharp, Robert; Scott, Nicholas; Sweet, Sarah M.; Taranu, Dan S.; Tescari, Edoardo; Tonini, Chiara; van de Sande, Jesse; Walcher, C. Jakob; Wright, Angus

2018-04-01

We present the ˜800 star formation rate maps for the Sydney-AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey based on H α emission maps, corrected for dust attenuation via the Balmer decrement, that are included in the SAMI Public Data Release 1. We mask out spaxels contaminated by non-stellar emission using the [O III]/H β, [N II]/H α, [S II]/H α, and [O I]/H α line ratios. Using these maps, we examine the global and resolved star-forming main sequences of SAMI galaxies as a function of morphology, environmental density, and stellar mass. Galaxies further below the star-forming main sequence are more likely to have flatter star formation profiles. Early-type galaxies split into two populations with similar stellar masses and central stellar mass surface densities. The main-sequence population has centrally concentrated star formation similar to late-type galaxies, while galaxies >3σ below the main sequence show significantly reduced star formation most strikingly in the nuclear regions. The split populations support a two-step quenching mechanism, wherein halo mass first cuts off the gas supply and remaining gas continues to form stars until the local stellar mass surface density can stabilize the reduced remaining fuel against further star formation. Across all morphologies, galaxies in denser environments show a decreased specific star formation rate from the outside in, supporting an environmental cause for quenching, such as ram-pressure stripping or galaxy interactions.

Out-of-equilibrium dynamics of photoexcited spin-state concentration waves

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

Marino, Andrea; Buron-Le Cointe, M.; Lorenc, M.

2015-01-28

The spin crossover compound [Fe IIH 2L 2-Me][PF 6]2 presents a two-step phase transition. In the intermediate phase, a spin state concentration wave (SSCW) appears resulting from a symmetry breaking (cell doubling) associated with a long-range order of alternating high and low spin molecular states. Lastly, by combining time-resolved optical and X-ray diffraction measurements on a single crystal, we study how such a system responds to femtosecond laser excitation and we follow in real time the erasing and rewriting of the SSCW

Development of Ultrasonic Modeling Techniques for the Study of Crustal Inhomogeneities.

DTIC Science & Technology

1983-08-01

layer material consisted of Carnauba wax and silica powder. A 2% (by weight) amount of beeswax was added to the middle layer material to reduce the...t 4i ci 0 ci ( a) Yn 4 J 41 E940 G) -4 C iiH U’ c W -1 >. a~ u 00 hard carnauba wax dominate the Rayleiqh velocity to a Ireat extent; the RzvlIqh...and tested to evaluate our seismic ultrasonic modeling technique. A 2.3 mm thick layer composed of the carnauba wax mixture was deposited on a

Hazardous Waste Technical Assistance Survey, Fairchild AFB, Washington

DTIC Science & Technology

1988-09-01

disposal is primarI"f the-: !--3,,Psp iih; o-1’ shoe -S gc-nearLig .na waste. Waste generators keep ;ogs on the ar-oL(0!, and.c types of ;D~:sc ino ili-jced...to the sanitary sewer. All paint waste skimmed off the top of the water is placed into a 55-gallon drum along with any sludge removed from the bottom...responsible for inspecting aircraft and aircraft parts for structural flaws using magnetic particle inspection and dye penetrant inspection. The magnetic

Identification or Development of Chemical Analysis Methods for Plants and Animal Tissues

DTIC Science & Technology

1981-01-01

Report No. DRXTH-TE-CR-80086 [E EMWSTEEACISITE - IDENTIFICATION OR DEVELOPMENT OF CHEMICAL ANALYSISI METHODS FOR PLANTS AND ANIMAL TISSUES D l...86i 4TITLE (ansdo"t) TYPE or" P 4. Iih~iti.)Final epwt. )9 A4,417 ~, Identlifiation or Development of Chemical I-g 9 O d 18 Analysis Methods for Plants...n TN oT sacmpihdo in. wEr DContinng er adetcsr aid Iuent bybopkmertda lo aeo 1.5th 1/s deeipta24ndectr Tritrotasolsoepae d andT Boloia Matrc,, 1473

The Mediator complex and transcription regulation

PubMed Central

Poss, Zachary C.; Ebmeier, Christopher C.

2013-01-01

The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

Optical frequency stabilization in infrared region using improved dual feed-back loop

NASA Astrophysics Data System (ADS)

Ružička, B.; Číp, O.; Lazar, J.

2007-03-01

Modern technologies such as DWDM (Dense Wavelength Division Multiplex) need precise stability of laser frequencies. According to this fact, requirements of new etalons of optical frequencies in the telecommunication band is rapidly growing. Lasers working in near infrared telecommunication band (1500-1600 nm) can be stabilized to 12C IIH II or 13C IIH II (acetylene) gas absorption lines. The acetylene gas absorption has been widely studied and accepted by international bodies of standardization as a primary wavelength reference in the near infrared band around 1550 nm. Our aim was to design and develop a compact fibre optics laser system generating coherent light in near-IR band with high frequency stability (at least 1.10 -8). This system should become a base for realization of a primary frequency standard for optical communications in the Czech Republic. Such an etalon will be needed for calibration of wavelengthmeters and spectral analysers for DWDM communication systems. We are co-operating with CMI (Czech Metrology Institute) on this project. We present stabilized laser system based on a single frequency DFB (Distributed Feedback) laser diode with a narrow spectral profile. The laser is pre-stabilized by means of the FM-spectroscopy on a passive resonator. Thanks to a fast feed-back loop we are able to improve spectral characteristics of the laser. The laser frequency is locked by a relatively slow second feed-back loop on an absorption line of acetylene vapour which is sealed in a cell under the optimised pressure.

Near-IR laser frequency standard stabilized using FM-spectroscopy

NASA Astrophysics Data System (ADS)

Ružička, Bohdan; Číp, Ondřej; Lazar, Josef

2006-02-01

At the present time fiber-optics and optical communication are in rapid progress. Modern technologies such as DWDM (Dense Wavelength Division Multiplex) need precise stability of laser frequencies. According to this fact, requirements of new etalons of optical frequencies in the telecommunication band is rapidly growing. Lasers working in near infrared telecommunication band (1500-1600 nm) can be stabilized to 12C IIH II or 13C IIH II (acetylene) gas absorption lines. The acetylene gas absorption has been widely studied and accepted by international bodies of standardization as a primary wavelength reference in the near infrared band around 1550nm. Our aim was to design and develop a compact fibre optics laser system generating coherent light in near-JR band with high frequency stability (at least 1.10 -8). This system should become a base for realization of a primary frequency standard for optical communications in the Czech Republic. Such an etalon will be needed for calibration of wavelength-meters and spectral analysers for DWDM communication systems. We are co-operating with CMI (Czech Metrology Institute) on this project. We present stabilized laser system based on a single frequency DFB (Distributed Feedback) laser diode with a narrow spectral profile. The laser is pre-stabilized by means of the FM-spectroscopy on a passive resonator. Thanks to a fast feed-back loop we are able to improve spectral characteristics of the laser. The laser frequency is locked by a relatively slow second feed-back loop on an absorption line of acetylene vapour which is sealed in a cell under the optimised pressure.

Computational Modeling of Cephalad Fluid Shift for Application to Microgravity-Induced Visual Impairment

NASA Technical Reports Server (NTRS)

Nelson, Emily S.; Best, Lauren M.; Myers, Jerry G.; Mulugeta, Lealem

2013-01-01

An improved understanding of spaceflight-induced ocular pathology, including the loss of visual acuity, globe flattening, optic disk edema and distension of the optic nerve and optic nerve sheath, is of keen interest to space medicine. Cephalad fluid shift causes a profoundly altered distribution of fluid within the compartments of the head and body, and may indirectly generate phenomena that are biomechanically relevant to visual function, such as choroidal engorgement, compromised drainage of blood and cerebrospinal fluid (CSF), and altered translaminar pressure gradient posterior to the eye. The experimental body of evidence with respect to the consequences of fluid shift has not yet been able to provide a definitive picture of the sequence of events. On earth, elevated intracranial pressure (ICP) is associated with idiopathic intracranial hypertension (IIH), which can produce ocular pathologies that look similar to those seen in some astronauts returning from long-duration flight. However, the clinically observable features of the Visual Impairment and Intracranial Pressure (VIIP) syndrome in space and IIH on earth are not entirely consistent. Moreover, there are at present no experimental measurements of ICP in microgravity. By its very nature, physiological measurements in spaceflight are sparse, and the space environment does not lend itself to well-controlled experiments. In the absence of such data, numerical modeling can play a role in the investigation of biomechanical causal pathways that are suspected of involvement in VIIP. In this work, we describe the conceptual framework for modeling the altered compartmental fluid distribution that represents an equilibrium fluid distribution resulting from the loss of hydrostatic pressure gradient.

The Field Relevance of NHTSA's Oblique Research Moving Deformable Barrier Tests.

PubMed

Prasad, Priya; Dalmotas, Dainius; German, Alan

2014-11-01

A small overlap frontal crash test has been recently introduced by the Insurance Institute for Highway Safety in its frontal rating scheme. Another small overlap frontal crash test is under development by the National Highway Traffic Safety Administration (NHTSA). Whereas the IIHS test is conducted against a fixed rigid barrier, the NHTSA test is conducted with a moving deformable barrier that overlaps 35% of the vehicle being tested and the angle between the longitudinal axis of the barrier and the longitudinal axis of the test vehicle is 15 degrees. The field relevance of the IIHS test has been the subject of a paper by Prasad et al. (2014). The current study is aimed at examining the field relevance of the NHTSA test. The field relevance is indicated by the frequency of occurrence of real world crashes that are simulated by the test conditions, the proportion of serious-to-fatal real world injuries explained by the test condition, and rates of serious injury to the head, chest and other body regions in the real world crashes resembling the test condition. The database examined for real world crashes is NASS. Results of the study indicate that 1.4% of all frontal 11-to-1 o'clock crashes are simulated by the test conditions that account for 2.4% to 4.5% of all frontal serious-to-fatal (MAIS3+F) injuries. Injury rates of the head and the chest are substantially lower in far-side than in near-side frontal impacts. Crash test ATD rotational responses of the head in the tests overpredict the real world risk of serious-to-fatal brain injuries.

Quantitative analysis of multi-component gas mixture based on AOTF-NIR spectroscopy

NASA Astrophysics Data System (ADS)

Hao, Huimin; Zhang, Yong; Liu, Junhua

2007-12-01

Near Infrared (NIR) spectroscopy analysis technology has attracted many eyes and has wide application in many domains in recent years because of its remarkable advantages. But the NIR spectrometer can only be used for liquid and solid analysis by now. In this paper, a new quantitative analysis method of gas mixture by using new generation NIR spectrometer is explored. To collect the NIR spectra of gas mixtures, a vacuumable gas cell was designed and assembled to Luminar 5030-731 Acousto-Optic Tunable Filter (AOTF)-NIR spectrometer. Standard gas samples of methane (CH 4), ethane (C IIH 6) and propane (C 3H 8) are diluted with super pure nitrogen via precision volumetric gas flow controllers to obtain gas mixture samples of different concentrations dynamically. The gas mixtures were injected into the gas cell and the spectra of wavelength between 1100nm-2300nm were collected. The feature components extracted from gas mixture spectra by using Partial Least Squares (PLS) were used as the inputs of the Support Vector Regress Machine (SVR) to establish the quantitative analysis model. The effectiveness of the model is tested by the samples of predicting set. The prediction Root Mean Square Error (RMSE) of CH 4, C IIH 6 and C 3H 8 is respectively 1.27%, 0.89%, and 1.20% when the concentrations of component gas are over 0.5%. It shows that the AOTF-NIR spectrometer with gas cell can be used for gas mixture analysis. PLS combining with SVR has a good performance in NIR spectroscopy analysis. This paper provides the bases for extending the application of NIR spectroscopy analysis to gas detection.

Head Trajectories of Restrained Child Dummy in Sled Tests Over 56 kph Delta-V

PubMed Central

Hauschild, Hans W.

2000-01-01

Child restraint devices (CRDs) have been used for many years to protect children in automotive crashes. The following data was collected to find out whether current restraints would be able to pass more stringent dynamic testing at higher changes in velocity (delta-v), such as the NHTSA NCAP program or the IIHS offset barrier test, and to look at one possible misuse mode. Three basic types of CRDs were sled tested at a delta-v between 57.5 & 61.4 kph (35.7 & 38.1 mph). Data from each test are presented and compared. Comparisons are made between each seat’s sled test results and various countries’ standards. PMID:11558089

Forced Draft Blowers, Duct Work For

DTIC Science & Technology

1935-06-01

il l~!! · ;Jp iiH X j H ~ rt ’l ~t;Jn; J!1 ’’ild .at~ rfl: 1:;!( ~rLtf {: PJ : tf1 :~ff:’n’’ !lh1~rt ~1~ · ., , •.. ’ , l,l·,tr t’t’t,m,;l ~ ·rr. I I...Jii ~ ~ ~~~~·htt tt ill· IQ\\u ·· ~t ~ lrt 111 t{~ ifub!ilL 0ii :trtW!,ff.’ : · tj tf1 -l-!1 ’ ·• ll·ld~Htf ’II ’t 1 lrl lll ld u [ 1 · ~ :,· l~ltl

XERODERMA PIGMENTOSUM, TRICHOTHIODYSTROPHY AND COCKAYNE SYNDROME: A COMPLEX GENOTYPE-PHENOTYPE RELATIONSHIP

PubMed Central

Kraemer, Kenneth H.; Patronas, Nicholas J.; Schiffmann, Raphael; Brooks, Brian P.; Tamura, Deborah; DiGiovanna, John J.

2008-01-01

Patients with the rare genetic disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) have defects in DNA nucleotide excision repair (NER). The NER pathway involves at least 28 genes. Three NER genes are also part of the basal transcription factor, TFIIH. Mutations in 11 NER genes have been associated with clinical diseases with at least 8 overlapping phenotypes. The clinical features of these patients have some similarities and but also have marked differences. NER is involved in protection against sunlight induced DNA damage. While XP patients have 1000-fold increase in susceptibility to skin cancer, TTD and CS patients have normal skin cancer risk. Several of the genes involved in NER also affect somatic growth and development. Some patients have short stature and immature sexual development. TTD patients have sulfur deficient brittle hair. Progressive sensorineural deafness is an early feature of XP and CS. Many of these clinical diseases are associated with developmental delay and progressive neurological degeneration. The main neuropathology of XP is a primary neuronal degeneration. In contrast, CS and TTD patients have reduced myelination of the brain. These complex neurological abnormalities are not related to sunlight exposure but may be caused by developmental defects as well as faulty repair of DNA damage to neuronal cells induced by oxidative metabolism or other endogenous processes. PMID:17276014

Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic Intracranial Hypertension Treatment Trial.

PubMed

Friedman, Deborah I; Quiros, Peter A; Subramanian, Prem S; Mejico, Luis J; Gao, Shan; McDermott, Michael; Wall, Michael

2017-09-01

character, disabling, and associated with poorer quality of life in our cohort of patients with mild visual impairment. The lack of correlation between headache disability and cerebrospinal fluid (CSF) pressure at baseline and at the end of the randomized phase of the study implies that headache in IIH may be related to factors other than intracranial hypertension, and that specific headache treatment is needed in addition to therapies directed at lowering CSF pressure. © 2017 American Headache Society.

Cerebrospinal fluid (CSF) shunting and ventriculocisternostomy (ETV) in 400 pediatric patients. Shifts in understanding, diagnostics, case-mix, and surgical management during half a century.

PubMed

Paulsen, A Henriette; Due-Tønnessen, Bernt J; Lundar, Tryggve; Lindegaard, Karl-Fredrik

2017-02-01

To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009-2013. This represents our current practice. Our previously reported cohorts of shunted children 1967-1970 (n = 128) and 1985-1988 (n = 138) served as backgrounds for comparison. In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009-2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.

PubMed

Lu, Huasong; Yu, Dan; Hansen, Anders S; Ganguly, Sourav; Liu, Rongdiao; Heckert, Alec; Darzacq, Xavier; Zhou, Qiang

2018-06-01

Hyperphosphorylation of the C-terminal domain (CTD) of the RPB1 subunit of human RNA polymerase (Pol) II is essential for transcriptional elongation and mRNA processing 1-3 . The CTD contains 52 heptapeptide repeats of the consensus sequence YSPTSPS. The highly repetitive nature and abundant possible phosphorylation sites of the CTD exert special constraints on the kinases that catalyse its hyperphosphorylation. Positive transcription elongation factor b (P-TEFb)-which consists of CDK9 and cyclin T1-is known to hyperphosphorylate the CTD and negative elongation factors to stimulate Pol II elongation 1,4,5 . The sequence determinant on P-TEFb that facilitates this action is currently unknown. Here we identify a histidine-rich domain in cyclin T1 that promotes the hyperphosphorylation of the CTD and stimulation of transcription by CDK9. The histidine-rich domain markedly enhances the binding of P-TEFb to the CTD and functional engagement with target genes in cells. In addition to cyclin T1, at least one other kinase-DYRK1A 6 -also uses a histidine-rich domain to target and hyperphosphorylate the CTD. As a low-complexity domain, the histidine-rich domain also promotes the formation of phase-separated liquid droplets in vitro, and the localization of P-TEFb to nuclear speckles that display dynamic liquid properties and are sensitive to the disruption of weak hydrophobic interactions. The CTD-which in isolation does not phase separate, despite being a low-complexity domain-is trapped within the cyclin T1 droplets, and this process is enhanced upon pre-phosphorylation by CDK7 of transcription initiation factor TFIIH 1-3 . By using multivalent interactions to create a phase-separated functional compartment, the histidine-rich domain in kinases targets the CTD into this environment to ensure hyperphosphorylation and efficient elongation of Pol II.

VizieR Online Data Catalog: Radial velocities of HD 133131A and HD 133131B (Teske+, 2016)

NASA Astrophysics Data System (ADS)

Teske, J. K.; Shectman, S. A.; Vogt, S. S.; Diaz, M.; Butler, R. P.; Crane, J. D.; Thompson, I. B.; Arriagada, P.

2017-05-01

The radial velocity observations of HD133131A and B are part of the large Magellan Planet Search Program, which began in 2002 and is surveying a sample of ~500 of the nearest stars (<100pc). The survey was started with observations from the Magellan Inamori Kyocera Echelle (MIKE) echelle spectrograph, mounted for a limited time on the Magellan I (Baade), but mostly on Magellan II (Clay), 6.5m telescopes at Las Campanas Observatory. In 2010, the survey switched to using the Carnegie Planet Finder Spectrograph (PFS), a temperature-controlled high-resolution echelle spectrograph built for precision radial velocity observations, on Magellan II. Only HD133131A observations from MIKE are included here. Using a 0.35*5'' slit, MIKE provides spectra with R~70000 in the blue and ~50000 in the red and covers 3900-6200Å. Only the red MIKE orders are used for radial velocity determination, while the blue orders provide coverage of the CaIIH and K lines for monitoring stellar activity. The MIKE observations of HD133131A span 2003 June to 2009 July, with total exposure times ranging from 150 to 600s, depending on observing conditions. Both HD133131A and B were observed with PFS, the former observations ranging from 2010 February to 2015 September, and the latter from 2010 August to 2015 September. PFS has a more limited wavelength range than MIKE (3880-6680Å), but still covers the entire iodine wavelength region, CaIIH and K, and Hα. We use a 0.5*2.5'' slit for target observations, providing R~80000 in the iodine region. The total exposure times for the A component range from 285 to 720s, and for the B component range from 282 to 800s. (6 data files).

The ratio of neutral hydrogen to neutral helium in the local interstellar medium

NASA Astrophysics Data System (ADS)

Green, James Carswell

The results are described from a sounding rocket borne EUV spectrometer that was designed and built. This instrument operated from 400 to 1150A with a spectral resolution of approx. 15A. The instrument effective area was about 1 sq cm. The instrument was successfully launched, and observed the nearby DA white dwarf G191-B2B. From this observation, it was determined that the stellar effective temperature is 61,000 + or -4000 to 6000K, and the ratio of helium to hydrogen in the stellar photosphere is 1.0 + or -0.68 to 2.2 x 10-4. Additionally, the neutral column densities of helium and hydrogen were measured to the star. The neutral helium column density was determined from the first observation of the interstellar absorption edge at 504A. The ratio of neutral helium to neutral hydrogen constrains the mean ionization of the warm gas along the line of sight to G191-B2B. The fractional ionization of hydrogen (H II/H) is approx. less than 20 percent, unless significant helium ionization is present as well. The scenario where the fractional ionization of hydrogen is high (H II/H) approx. less than 40 percent and the helium is neutral is ruled out with 99 percent certainty. This result is consistent with some recent theoretical calculations. Using these results, a self-consistent model of the local interstellar medium along the line of sight to G191-B2B is developed. In addition, an unexpected emission feature at 584A was detected in this observation with a high level of significance. Possible sources of this emission are examined, including the companion K dwarf G191-B2A, and an emission nebula near or around G191-B2B.

TAF10 and TAF10b partially redundant roles during Drosophila melanogaster morphogenesis.

PubMed

Pahi, Z; Borsos, B N; Vedelek, B; Shidlovskii, Y V; Georgieva, S G; Boros, I M; Pankotai, T

2017-01-01

Transcription of eukaryotic genes requires the cooperative action of the RNA polymerase complex, the general transcription factors (TFIIB, TFIID, TFIIE, TFIIF and TFIIH) and chromatin modifiers. The TFIID complex contributes to transcriptional activation by several mechanisms and has a subunit with associated histone acetyltransferase (HAT) activity. The histone modifier SAGA complex has both HAT and deubiquitylase (DUB) activities. TFIID and SAGA share several TBP-associated factors (TAFs), but not their HAT subunit. Recently, several duplicated TAF proteins have been identified in higher eukaryotes, but their functional diversity has been so far poorly characterized. Here, we report the functional similarities and differences of TAF10 and TAF10b, the two TAF10 orthologs of Drosophila melanogaster. Results from in silico modeling suggest that dTAF10 and dTAF10b have similar secondary structures characterized by the presence of a histone-fold domain. Additionally, dTAF10 and dTAF10b share interaction partners and show similar expression patterns in neuronal tissues. Nonetheless, dTAF10 and dTAF10b seem to have partly distinct functions. To investigate their roles, we generated dTaf10-dTaf10b double-mutants and rescued the mutant flies with transgenes, which allowed the translation of either dTAF10 or dTAF10b protein. We found that the loss of dTAF10b resulted in pupal lethality, while animals lacking dTAF10 were able to form puparium. dTaf10 mutant adults showed distorted eye morphology. During DNA repair, dTAF10 and dTAF10b act redundantly, suggesting that these proteins have distinct but partially overlapping functions.

Cdk7 mediates RPB1-driven mRNA synthesis in Toxoplasma gondii

PubMed Central

Deshmukh, Abhijit S.; Mitra, Pallabi; Maruthi, Mulaka

2016-01-01

Cyclin-dependent kinase 7 in conjunction with CyclinH and Mat1 activates cell cycle CDKs and is a part of the general transcription factor TFIIH. Role of Cdk7 is well characterized in model eukaryotes however its relevance in protozoan parasites has not been investigated. This important regulator of key processes warrants closer examination particularly in this parasite given its unique cell cycle progression and flexible mode of replication. We report functional characterization of TgCdk7 and its partners TgCyclinH and TgMat1. Recombinant Cdk7 displays kinase activity upon binding its cyclin partner and this activity is further enhanced in presence of Mat1. The activated kinase phosphorylates C-terminal domain of TgRPB1 suggesting its role in parasite transcription. Therefore, the function of Cdk7 in CTD phosphorylation and RPB1 mediated transcription was investigated using Cdk7 inhibitor. Unphosphorylated CTD binds promoter DNA while phosphorylation by Cdk7 triggers its dissociation from DNA with implications for transcription initiation. Inhibition of Cdk7 in the parasite led to strong reduction in Serine 5 phosphorylation of TgRPB1-CTD at the promoters of constitutively expressed actin1 and sag1 genes with concomitant reduction of both nascent RNA synthesis and 5′-capped transcripts. Therefore, we provide compelling evidence for crucial role of TgCdk7 kinase activity in mRNA synthesis. PMID:27759017

AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

PubMed Central

Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

2015-01-01

AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

PubMed

Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

2017-09-01

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

Architecture of the RNA polymerase II-Mediator core initiation complex.

PubMed

Plaschka, C; Larivière, L; Wenzeck, L; Seizl, M; Hemann, M; Tegunov, D; Petrotchenko, E V; Borchers, C H; Baumeister, W; Herzog, F; Villa, E; Cramer, P

2015-02-19

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.

Mediator Undergoes a Compositional Change during Transcriptional Activation.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2016-11-03

Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase module associates strongly with the enhancer, but not with the core promoter, and it dissociates from the enhancer upon depletion of the TFIIH kinase. Severing the kinase module from Mediator by removing the connecting subunit Med13 does not affect Mediator association at the core promoter but increases occupancy at enhancers. Thus, Mediator undergoes a compositional change in which the kinase module, recruited via Mediator to the enhancer, dissociates from Mediator to permit association with Pol II and the PIC. As such, Mediator acts as a dynamic bridge between the enhancer and core promoter. Copyright © 2016 Elsevier Inc. All rights reserved.

Near-atomic resolution visualization of human transcription promoter opening

PubMed Central

He, Yuan; Yan, Chunli; Fang, Jie; Inouye, Carla; Tjian, Robert; Ivanov, Ivaylo; Nogales, Eva

2016-01-01

In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA–RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB. PMID:27193682

Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

NASA Technical Reports Server (NTRS)

Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

2014-01-01

A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

Structural Design Strategies for Improved Small Overlap Crashworthiness Performance.

PubMed

Mueller, Becky C; Brethwaite, Andrew S; Zuby, David S; Nolan, Joseph M

2014-11-01

In 2012, the Insurance Institute for Highway Safety (IIHS) began a 64 km/h small overlap frontal crash test consumer information test program. Thirteen automakers already have redesigned models to improve test performance. One or more distinct strategies are evident in these redesigns: reinforcement of the occupant compartment, use of energy-absorbing fender structures, and the addition of engagement structures to induce vehicle lateral translation. Each strategy influences vehicle kinematics, posing additional challenges for the restraint systems. The objective of this two-part study was to examine how vehicles were modified to improve small overlap test performance and then to examine how these modifications affect dummy response and restraint system performance. Among eight models tested before and after design changes, occupant compartment intrusion reductions ranged from 6 cm to 45 cm, with the highest reductions observed in models with the largest number of modifications. All redesigns included additional occupant compartment reinforcement, one-third added structures to engage the barrier, and two modified a shotgun load path. Designs with engagement structures produced greater glance-off from the barrier and exhibited lower delta Vs but experienced more lateral outboard motion of the dummy. Designs with heavy reinforcement of the occupant compartment had higher vehicle accelerations and delta V. In three cases, these apparent trade-offs were not well addressed by concurrent changes in restraint systems and resulted in increased injury risk compared with the original tests. Among the 36 models tested after design changes, the extent of design changes correlated to structural performance. Half of the vehicles with the lowest intrusion levels incorporated aspects of all three design strategies. Vehicle kinematics and dummy and restraint system characteristics were similar to those observed in the before/after pairs. Different combinations of structural

Near-Infrared [Fe II] and H2 Study of the Galactic Supernova Remnants

NASA Astrophysics Data System (ADS)

Lee, Yong-Hyun; Koo, Bon-Chul; Lee, Jae-Joon; Jaffe, Daniel T.; Burton, Michael G.; Ryder, Stuart D.

2018-01-01

We have searched for near-infrared (NIR) [Fe II] (1.644 μm) and H2 1-0 S(1) (2.122 μm) emission features associated with Galactic supernova remnants (SNRs) using the narrow-band imaging surveys UWIFE / UWISH2 (UKIRT Widefield Infrared Survey for [Fe II] / H2). Both surveys cover about 180 square degrees of the first Galactic quadrant (7° < l < 65° -1.3° < b < +1.3°), and a total of 79 SNRs are falling in the survey area. We have found 19 [Fe II]- and 19 H2-emitting SNRs, giving a detection rate of 24%. Eleven SNRs show both emission features. Some of the SNRs show bright, complex, and interesting structures that have never been reported in previous studies. The brightest SNR in the both emission is W49B, contributing ~70% of the total [Fe II] luminosity of the detected SNRs. The total [Fe II] luminosity, however, is considerably less than what we would expect from the SN rate of our Galaxy.Among the SNRs showing both [Fe II] and H2 emission lines, some SNRs show the “[Fe II]-H2 reversal” phenomenon, i.e., the H2 emission features are detected outside the [Fe II] emission boundary. We carried out high resolution (R~40,000) NIR H- and K-band spectroscopy of the five SNRs showing the [Fe II]-H2 reversal (G11.2-0.3, KES 73, W44, 3C 396, W49B) using IGRINS (Immersion GRating INfrared Spectrograph). Various ro-vibrational H2 lines have been detected, which are used to derive the kinematic distances to the SNRs and to investigate the origin of the H2 emission. The detected H2 lines show broad line width (> 10 km s-1) and line flux ratios of thermal excitation. We discuss the origin of the extended H2 emission features beyond the the [Fe II] emission boundary.

Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

NASA Technical Reports Server (NTRS)

Zanello, S. B.; Stevens, B.; Calvillo, E.; Tang, R.; Gutierrez Flores, B.; Hu, L.; Skog, J.; Bershad, E.

2016-01-01

While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for

A probabilistic approach to emission-line galaxy classification

NASA Astrophysics Data System (ADS)

de Souza, R. S.; Dantas, M. L. L.; Costa-Duarte, M. V.; Feigelson, E. D.; Killedar, M.; Lablanche, P.-Y.; Vilalta, R.; Krone-Martins, A.; Beck, R.; Gieseke, F.

2017-12-01

We invoke a Gaussian mixture model (GMM) to jointly analyse two traditional emission-line classification schemes of galaxy ionization sources: the Baldwin-Phillips-Terlevich (BPT) and WH α versus [N II]/H α (WHAN) diagrams, using spectroscopic data from the Sloan Digital Sky Survey Data Release 7 and SEAGal/STARLIGHT data sets. We apply a GMM to empirically define classes of galaxies in a three-dimensional space spanned by the log [O III]/H β, log [N II]/H α and log EW(H α) optical parameters. The best-fitting GMM based on several statistical criteria suggests a solution around four Gaussian components (GCs), which are capable to explain up to 97 per cent of the data variance. Using elements of information theory, we compare each GC to their respective astronomical counterpart. GC1 and GC4 are associated with star-forming galaxies, suggesting the need to define a new starburst subgroup. GC2 is associated with BPT's active galactic nuclei (AGN) class and WHAN's weak AGN class. GC3 is associated with BPT's composite class and WHAN's strong AGN class. Conversely, there is no statistical evidence - based on four GCs - for the existence of a Seyfert/low-ionization nuclear emission-line region (LINER) dichotomy in our sample. Notwithstanding, the inclusion of an additional GC5 unravels it. The GC5 appears associated with the LINER and passive galaxies on the BPT and WHAN diagrams, respectively. This indicates that if the Seyfert/LINER dichotomy is there, it does not account significantly to the global data variance and may be overlooked by standard metrics of goodness of fit. Subtleties aside, we demonstrate the potential of our methodology to recover/unravel different objects inside the wilderness of astronomical data sets, without lacking the ability to convey physically interpretable results. The probabilistic classifications from the GMM analysis are publicly available within the COINtoolbox at https://cointoolbox.github.io/GMM_Catalogue/.

The histone modifications governing TFF1 transcription mediated by estrogen receptor.

PubMed

Li, Yanyan; Sun, Luyang; Zhang, Yu; Wang, Dandan; Wang, Feng; Liang, Jing; Gui, Bin; Shang, Yongfeng

2011-04-22

Transcription regulation by histone modifications is a major contributing factor to the structural and functional diversity in biology. These modifications are encrypted as histone codes or histone languages and function to establish and maintain heritable epigenetic codes that define the identity and the fate of the cell. Despite recent advances revealing numerous histone modifications associated with transcription regulation, how such modifications dictate the process of transcription is not fully understood. Here we describe spatial and temporal analyses of the histone modifications that are introduced during estrogen receptor α (ERα)-activated transcription. We demonstrated that aborting RNA polymerase II caused a disruption of the histone modifications that are associated with transcription elongation but had a minimal effect on modifications deposited during transcription initiation. We also found that the histone H3S10 phosphorylation mark is catalyzed by mitogen- and stress-activated protein kinase 1 (MSK1) and is recognized by a 14-3-3ζ/14-3-3ε heterodimer through its interaction with H3K4 trimethyltransferase SMYD3 and the p52 subunit of TFIIH. We showed that H3S10 phosphorylation is a prerequisite for H3K4 trimethylation. In addition, we demonstrated that SET8/PR-Set7/KMT5A is required for ERα-regulated transcription and its catalyzed H4K20 monomethylation is implicated in both transcription initiation and elongation. Our experiments provide a relatively comprehensive analysis of histone modifications associated with ERα-regulated transcription and define the biological meaning of several key components of the histone code that governs ERα-regulated transcription.

XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes.

PubMed Central

van der Spek, P J; Eker, A; Rademakers, S; Visser, C; Sugasawa, K; Masutani, C; Hanaoka, F; Bootsma, D; Hoeijmakers, J H

1996-01-01

The xeroderma pigmentosum syndrome complementation group C (XP-C) is due to a defect in the global genome repair subpathway of nucleotide excision repair (NER). The XPC protein is complexed with HHR23B, one of the two human homologs of the yeast NER protein, RAD23 (Masutani at al. (1994) EMBO J. 8, 1831-1843). Using heparin chromatography, gel filtration and native gel electrophoresis we demonstrate that the majority of HHR23B is in a free, non-complexed form, and that a minor fraction is tightly associated with XPC. In contrast, we cannot detect any bound HHR23A. Thus the HHR23 proteins may have an additional function independent of XPC. The fractionation behaviour suggests that the non-bound forms of the HHR23 proteins are not necessary for the core of the NER reaction. Although both HHR23 proteins share a high level of overall homology, they migrate very differently on native gels, pointing to a difference in conformation. Gel filtration suggests the XPC-HHR23B heterodimer resides in a high MW complex. However, immunodepletion studies starting from repair-competent Manley extracts fall to reveal a stable association of a significant fraction of the HHR23 proteins or the XPC-HHR23B complex with the basal transcription/repair factor TFIIH, or with the ERCC1 repair complex. Consistent with a function in repair or DNA/chromatin metabolism, immunofluorescence studies show all XPC, HHR23B and (the free) HHR23A to reside in the nucleus. PMID:8692695

Prospective Observational Study of Ocular Health in ISS Crews - The Ocular Health Study

NASA Technical Reports Server (NTRS)

Otto, C.; Barr, Y.; Platts, S.; Ploutz-Snyder, R.; Sargsyan, A.; Alexander, D.; Riascos, R.; Gibson, C.; Patel, N.

2015-01-01

The Visual Impairment Intracranial Pressure (VIIP) syndrome is currently NASA's number one human space flight risk. The syndrome, which is related to microgravity exposure, manifests with changes in visual acuity (hyperopic shifts, scotomas), changes in eye structure (optic disc edema, choroidal folds, cotton wool spots, globe flattening, and dilated optic nerve sheaths), and in some cases with documented increased intracranial pressure (ICP) postflight. While the eye appears to be the main affected end organ of this syndrome, the ocular effects are thought to be related to underlying changes in the vascular system and the central nervous system. The leading hypotheses for the development of VIIP involve microgravity-induced head-ward fluid shifts along with a loss of gravity-assisted drainage of venous blood from the brain, leading to cephalic congestion, decreased CSF resorption and increased ICP. Since 70% of ISS crewmembers have manifested clinical signs or symptoms of the VIIP syndrome, it is assumed that the majority have some degree of ICP elevation in-flight compared to the ground. Prolonged elevations of ICP can cause long-term reduced visual acuity and loss of peripheral visual fields, and have been reported to cause mild cognitive impairment in the analog terrestrial population of Idiopathic Intracranial Hypertension (IIH). These potentially irreversible health consequences underscore the importance of identifying the factors that lead to this syndrome and mitigating them.

The Visual Impairment Intracranial Pressure Syndrome in Long Duration NASA Astronauts: An Integrated Approach

NASA Technical Reports Server (NTRS)

Otto, C. A.; Norsk, P.; Shelhamer, M. J.; Davis, J. R.

2015-01-01

The Visual Impairment Intracranial Pressure (VIIP) syndrome is currently NASA's number one human space flight risk. The syndrome, which is related to microgravity exposure, manifests with changes in visual acuity (hyperopic shifts, scotomas), changes in eye structure (optic disc edema, choroidal folds, cotton wool spots, globe flattening, and distended optic nerve sheaths). In some cases, elevated cerebrospinal fluid pressure has been documented postflight reflecting increased intracranial pressure (ICP). While the eye appears to be the main affected end organ of this syndrome, the ocular affects are thought to be related to the effect of cephalad fluid shift on the vascular system and the central nervous system. The leading hypotheses for the development of VIIP involve microgravity induced head-ward fluid shifts along with a loss of gravity-assisted drainage of venous blood from the brain, both leading to cephalic congestion and increased ICP. Although not all crewmembers have manifested clinical signs or symptoms of the VIIP syndrome, it is assumed that all astronauts exposed to microgravity have some degree of ICP elevation in-flight. Prolonged elevations of ICP can cause long-term reduced visual acuity and loss of peripheral visual fields, and has been reported to cause mild cognitive impairment in the analog terrestrial population of Idiopathic Intracranial Hypertension (IIH). These potentially irreversible health consequences underscore the importance of identifying the factors that lead to this syndrome and mitigating them.

(Docket A-93-02) Category II-H: Public Comments Received in Response to the ANPR Dated November 15, 1996

EPA Pesticide Factsheets

This Index lists public comments received in response to the ANPR dated November 15, 1996 related to the decision to certify that DOE had met the compliance criteria established by EPA in 40 CFR Part 194 and 40 CFR Part 191.

Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill.

PubMed Central

Chung, K S; Madar, D A; Goldsmith, J C; Kingdon, H S; Roberts, H R

1978-01-01

Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules. Images PMID:711853

The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments.

PubMed Central

Goldsmith, G H; Saito, H; Ratnoff, O S

1978-01-01

Activation of plasminogen through surface-mediated reactions is well recognized. In the presence of kaolin, purified Hageman factor (Factor XII) changed plasminogen to plasmin, as assayed upon a synthetic amide substrate and by fibrinolysis. Kinetic studies suggested an enzymatic action of Hageman factor upon its substrate, plasminogen. Hageman factor fragments, at a protein concentration equivalent to whole Hageman factor, activated plasminogen to a lesser extent. These protein preparations were not contaminated with other agents implicated in surface-mediated fibrinolysis. Diisopropyl fluorophosphate treatment of plasminogen did not inhibit its activation by Hageman factor. These studies indicate that Hageman factor has a hitherto unsuspected function, the direct activation of plasminogen. PMID:659637

Human U2 snRNA Genes Exhibit a Persistently Open Transcriptional State and Promoter Disassembly at Metaphase▿

PubMed Central

Pavelitz, Thomas; Bailey, Arnold D.; Elco, Christopher P.; Weiner, Alan M.

2008-01-01

In mammals, small multigene families generate spliceosomal U snRNAs that are nearly as abundant as rRNA. Using the tandemly repeated human U2 genes as a model, we show by footprinting with DNase I and permanganate that nearly all sequences between the enhancer-like distal sequence element and the initiation site are protected during interphase whereas the upstream half of the U2 snRNA coding region is exposed. We also show by chromatin immunoprecipitation that the SNAPc complex, which binds the TATA-like proximal sequence element, is removed at metaphase but remains bound under conditions that induce locus-specific metaphase fragility of the U2 genes, such as loss of CSB, BRCA1, or BRCA2 function, treatment with actinomycin D, or overexpression of the tetrameric p53 C terminus. We propose that the U2 snRNA promoter establishes a persistently open state to facilitate rapid reinitiation and perhaps also to bypass TFIIH-dependent promoter melting; this open state would then be disassembled to allow metaphase chromatin condensation. PMID:18378697

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3

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

Vermeulen, W.; Kleijer, W.J.; Bootsma, D.

1994-02-01

The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with the remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in themore » vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here the authors report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of >40 years. Analysis of the frequency of hprt[sup [minus

Factors affecting construction performance: exploratory factor analysis

NASA Astrophysics Data System (ADS)

Soewin, E.; Chinda, T.

2018-04-01

The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

Current Status of the Application of Intracranial Venous Sinus Stenting

PubMed Central

Xu, Kan; Yu, Tiecheng; Yuan, Yongjie; Yu, Jinlu

2015-01-01

The intracranial venous sinus is an important component of vascular disease. Many diseases involve the venous sinus and are accompanied by venous sinus stenosis (VSS), which leads to increased venous pressure and high intracranial pressure. Recent research has focused on stenting as a treatment for VSS related to these diseases. However, a systematic understanding of venous sinus stenting (VS-Stenting) is lacking. Herein, the literature on idiopathic intracranial hypertension (IIH), venous pulsatile tinnitus, sinus thrombosis, high draining venous pressure in dural arteriovenous fistula (AVF) and arteriovenous malformation (AVM), and tumor-caused VSS was reviewed and analyzed to summarize experiences with VS-Stenting as a treatment. The literature review showed that satisfactory therapeutic effects can be achieved through stent angioplasty. Thus, the present study suggests that selective stent release in the venous sinus can effectively treat these diseases and provide new possibilities for treating intracranial vascular disease. PMID:26516306

An Expanding H I Photodissociated Region Associated with the Compact H II Region G213.880-11.837 in the GGD 14 Complex

NASA Astrophysics Data System (ADS)

Gómez, Y.; Garay, G.; Rodríguez-Rico, C. A.; Neria, C.; Rodríguez, L. F.; Escalante, V.; Lizano, S.; Lebrón, M.

2010-10-01

We present high angular and spectral resolution H I 21 cm line observations toward the cometary-shaped compact H II region G213.880-11.837 in the GGD 14 complex. The kinematics and morphology of the photodissociated region, traced by the H I line emission, reveal that the neutral gas is part of an expanding flow. The kinematics of the H I gas along the major axis of G213.880-11.837 shows that the emission is very extended toward the SE direction, reaching local standard of rest (LSR) radial velocities in the tail of about 14 km s-1. The ambient LSR radial velocity of the molecular gas is 11.5 km s-1, which suggests a champagne flow of the H I gas. This is the second (after G111.61+0.37) cometary H II/H I region known.

FACTORS INFLUENCING THE DESIGN OF BIOACCUMULATION FACTOR AND BIOTA-SEDIMENT ACCUMULATION FACTOR FIELD STUDIES

EPA Science Inventory

A series of modeling simulations were performed to develop an understanding of the underlying factors and principles involved in developing field sampling designs for measuring bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs. These simulations reveal...

Impact Factor? Shmimpact Factor!

PubMed Central

2007-01-01

The journal impact factor is a measure of the citability of articles published in that journal—the more citations generated, the more important that article is considered to be, and as a consequence the prestige of the journal is enhanced. The impact factor is not without controversy, and it can be manipulated. It no longer dominates the choices of journals to search for information. Online search engines, such as PubMed, can locate articles of interest in seconds across journals regardless of high or low impact factors. Editors desiring to increase their influence will need to focus on a fast and friendly submission and review process, early online and speedy print publication, and encourage the rapid turnaround of high-quality peer reviews. Authors desiring to have their results known to the world have never had it so good—the internet permits anyone with computer access to find the author's work. PMID:20806031

FACTORS INFLUENCING THE DESIGN OF BIOACCUMULATION FACTOR AND BIOTA-SEDIMENT ACCUMULATION FACTOR FIELD STUDIES

EPA Science Inventory

General guidance for designing field studies to measure bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs) is not available. To develop such guidance, a series of modeling simulations were performed to evaluate the underlying factors and principles th...

Factor IX assay

MedlinePlus

... factor assay; Serum factor IX; Hemophilic factor B; Plasma thromboplastin component; PTC ... BJ. Factor IX (Christmas factor, hemophilic factor B, plasma thromboplastin component, PTC) - blood. In: Chernecky CC, Berger ...

Determining the Number of Factors in P-Technique Factor Analysis

ERIC Educational Resources Information Center

Lo, Lawrence L.; Molenaar, Peter C. M.; Rovine, Michael

2017-01-01

Determining the number of factors is a critical first step in exploratory factor analysis. Although various criteria and methods for determining the number of factors have been evaluated in the usual between-subjects R-technique factor analysis, there is still question of how these methods perform in within-subjects P-technique factor analysis. A…

KIAA1530 Protein Is Recruited by Cockayne Syndrome Complementation Group Protein A (CSA) to Participate in Transcription-coupled Repair (TCR)

PubMed Central

Fei, Jia; Chen, Junjie

2012-01-01

Transcription-coupled repair (TCR) is the major pathway involved in the removal of UV-induced photolesions from the transcribed strand of active genes. Two Cockayne syndrome (CS) complementation group proteins, CSA and CSB, are important for TCR repair. The molecular mechanisms by which CS proteins regulate TCR remain elusive. Here, we report the characterization of KIAA1530, an evolutionarily conserved protein that participates in this pathway through its interaction with CSA and the TFIIH complex. We found that UV irradiation led to the recruitment of KIAA1530 onto chromatin in a CSA-dependent manner. Cells lacking KIAA1530 were highly sensitive to UV irradiation and displayed deficiency in TCR. In addition, KIAA1530 depletion abrogated stability of the CSB protein following UV irradiation. More excitingly, we found that a unique CSA mutant (W361C), which was previously identified in a patient with UVsS syndrome, showed defective KIAA1530 binding and resulted in a failure of recruiting KIAA1530 and stabilizing CSB after UV treatment. Together, our data not only reveal that KIAA1530 is an important player in TCR but also lead to a better understanding of the molecular mechanism underlying UVsS syndrome. PMID:22902626

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

PubMed

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

PubMed

Opgenorth, A; Nation, N; Graham, K; McFadden, G

1993-02-01

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Pseudotumor cerebri (toxic effect of the "magic bullet").

PubMed

Alemayehu, W

1995-10-01

A 10 year-old female patient presented to the outpatient unit of the ophthalmology department of Menelik II Hospital with complaints of inward deviation of the left eye, of three weeks' duration. The patient was on a mega dose of vitamin A 200,000 I.U. (the "magic bullet") daily for two months prior to the onset of the present illness. Physical examination revealed left sixth nerve palsy and bilateral papilloedema in an alert and oriented patient without localizing neurologic findings. The cerebrospinal fluid pressure ( > 250 mm water) was increased and skull X-ray findings were suggestive of increased intracranial pressure (IIP). This case meets the modified Dandy criteria except that a highly likely cause, hypervitaminosis A, is associated. Therefore, a diagnosis of Idiopathic Intracranial Hypertension (IIH) or Pseudotumor Cerebri was made. This disorder and its management is discussed and literature reviewed. The serious and potentially blinding toxic effect of Vitamin A, if consumed in excessive amounts, is emphasized.

Sequence and Analysis of the Genome of the Pathogenic Yeast Candida orthopsilosis

PubMed Central

Riccombeni, Alessandro; Vidanes, Genevieve; Proux-Wéra, Estelle; Wolfe, Kenneth H.; Butler, Geraldine

2012-01-01

Candida orthopsilosis is closely related to the fungal pathogen Candida parapsilosis. However, whereas C. parapsilosis is a major cause of disease in immunosuppressed individuals and in premature neonates, C. orthopsilosis is more rarely associated with infection. We sequenced the C. orthopsilosis genome to facilitate the identification of genes associated with virulence. Here, we report the de novo assembly and annotation of the genome of a Type 2 isolate of C. orthopsilosis. The sequence was obtained by combining data from next generation sequencing (454 Life Sciences and Illumina) with paired-end Sanger reads from a fosmid library. The final assembly contains 12.6 Mb on 8 chromosomes. The genome was annotated using an automated pipeline based on comparative analysis of genomes of Candida species, together with manual identification of introns. We identified 5700 protein-coding genes in C. orthopsilosis, of which 5570 have an ortholog in C. parapsilosis. The time of divergence between C. orthopsilosis and C. parapsilosis is estimated to be twice as great as that between Candida albicans and Candida dubliniensis. There has been an expansion of the Hyr/Iff family of cell wall genes and the JEN family of monocarboxylic transporters in C. parapsilosis relative to C. orthopsilosis. We identified one gene from a Maltose/Galactoside O-acetyltransferase family that originated by horizontal gene transfer from a bacterium to the common ancestor of C. orthopsilosis and C. parapsilosis. We report that TFB3, a component of the general transcription factor TFIIH, undergoes alternative splicing by intron retention in multiple Candida species. We also show that an intein in the vacuolar ATPase gene VMA1 is present in C. orthopsilosis but not C. parapsilosis, and has a patchy distribution in Candida species. Our results suggest that the difference in virulence between C. parapsilosis and C. orthopsilosis may be associated with expansion of gene families. PMID:22563396

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II

A novel XPD mutation in a compound heterozygote; the mutation in the second allele is present in three homozygous patients with mild sun sensitivity.

PubMed

Falik-Zaccai, Tzipora C; Erel-Segal, Reut; Horev, Liran; Bitterman-Deutsch, Ora; Koka, Sivan; Chaim, Sara; Keren, Zohar; Kalfon, Limor; Gross, Bella; Segal, Zvi; Orgal, Shlomi; Shoval, Yishay; Slor, Hanoch; Spivak, Graciela; Hanawalt, Philip C

2012-08-01

The XPD protein plays a pivotal role in basal transcription and in nucleotide excision repair (NER) as one of the ten known components of the transcription factor TFIIH. Mutations in XPD can result in the DNA repair-deficient diseases xeroderma pigmentosum (XP), trichothiodystrophy (TTD), cerebro-oculo-facial-skeletal syndrome, and in combined phenotypes such as XP/Cockayne syndrome and XP/TTD. We describe here an 18-year-old individual with mild sun sensitivity, no neurological abnormalities and no tumors, who carries a p.R683Q mutation in one allele, and the novel p.R616Q mutation in the other allele of the XPD gene. We also describe four patients from one family, homozygous for the identical p.R683Q mutation in XPD, who exhibit mild skin pigmentation and loss of tendon reflexes. Three homozygous patients presented with late-onset skin tumors, and two with features of premature aging and moderate cognitive decline. Cells from the compound heterozygous individual and from one of the patients homozygous for p.R683Q exhibited similar responses to UV irradiation: reduced viability and defective overall removal of UV-induced cyclobutane pyrimidine dimers, implying deficient global genomic NER. Cells from the compound heterozygous subject also failed to recover RNA synthesis after UV, indicating defective transcription-coupled NER. Mutations affecting codon 616 in XPD generally result in functionally null proteins; we hypothesize that the phenotype of the heterozygous patient results solely from expression of the p.R683Q allele. This study illustrates the importance of detailed follow up with sun sensitive individuals, to ensure appropriate prophylaxis and to understand the mechanistic basis of the implicated hereditary disease. Copyright © 2012 Wiley Periodicals, Inc.

Factor VII assay

MedlinePlus

Stable factor; Proconvertin; Autoprothrombin I ... be caused by an abnormally low level of factor VII. ... Decreased factor VII activity may be related to: Deficiency of factor VII Disorder in which the proteins that control ...

Factor V assay

MedlinePlus

Labile factor; Proaccelerin; Ac-globulin ... be caused by an abnormally low level of factor V. ... Decreased factor V activity may be related to: Deficiency of factor V Disorder in which the proteins that control ...

Factor Rotation and Standard Errors in Exploratory Factor Analysis

ERIC Educational Resources Information Center

Zhang, Guangjian; Preacher, Kristopher J.

2015-01-01

In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

A single factor underlies the metabolic syndrome: a confirmatory factor analysis.

PubMed

Pladevall, Manel; Singal, Bonita; Williams, L Keoki; Brotons, Carlos; Guyer, Heidi; Sadurni, Josep; Falces, Carles; Serrano-Rios, Manuel; Gabriel, Rafael; Shaw, Jonathan E; Zimmet, Paul Z; Haffner, Steven

2006-01-01

Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.

External Factors, Internal Factors and Self-Directed Learning Readiness

ERIC Educational Resources Information Center

Ramli, Nurjannah; Muljono, Pudji; Afendi, Farit M.

2018-01-01

There are many factors which affect the level of self-directed learning readiness. This study aims to investigate the relationship between external factors, internal factors and self-directed learning readiness. This study was carried out by using a census method for fourth year students of medical program of Tadulako University. Data were…

[Coagulation factor VII levels in uremic patients and theirs influence factors].

PubMed

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

Factor XII (Hageman factor) deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Factoring in Factor VIII With Acute Ischemic Stroke.

PubMed

Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

2015-10-01

There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

Analysis of vehicle classification data, including monthly and seasonal ADT factors, hourly distribution factors, and lane distribution factors

DOT National Transportation Integrated Search

1998-11-01

This report documents the development of monthly and seasonal average daily traffic (ADT) factors for performing estimating AADTs. It appears that seasonal factors can estimate AADT as well as monthly factors, and it is recommended that seasonal fact...

Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

PubMed

Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

2017-03-01

The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch

Sociodemographic factors associated with multiple cardiovascular risk factors among Malaysian adults.

PubMed

Ghazali, Sumarni Mohd; Seman, Zamtira; Cheong, Kee Chee; Hock, Lim Kuang; Manickam, Mala; Kuay, Lim Kuang; Yusoff, Ahmad Faudzi; Mustafa, Feisul Idzwan; Mustafa, Amal Nasir

2015-01-31

To determine the prevalence and sociodemographic correlates of multiple risk factors for cardiovascular disease (CVD) among Malaysian adults. We analysed data on 1044 men and 1528 women, aged 24-64 years, participants in the Non Communicable Disease Surveillance 2005/2006, a nationally representative, population-based, cross-sectional study. Prevalence of obesity, high blood pressure, dyslipidaemia, hyperglycemia, physical inactivity, smoking, risky drinking, low vegetable and fruit intake were determined and multivariable logistic regression was used to identify sociodemographic factors associated with having ≥3 of these cardiovascular disease risk factors. The response rate was 84.6% (2572/3040). Overall, 68.4% (95% CI: 63.2, 73.1) had at least three risk factors. Among men, older age and Indian ethnicity were independently associated with having ≥3 CVD risk factors; while among women, older age, low education, and housewives were more likely to have ≥3 CVD risk factors. The prevalence of cardiovascular risk factors clustering among Malaysian adults is high, raising concerns that cardiovascular disease incidence will rise steeply in the near future if no immediate preventive measures are taken. The current national health education and promotion programmes pertaining to modifiable risk factors can be further improved by taking into account the sociodemographic variation in CVD risk factors clustering.

Using Bayes factors for multi-factor, biometric authentication

NASA Astrophysics Data System (ADS)

Giffin, A.; Skufca, J. D.; Lao, P. A.

2015-01-01

Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

PubMed

Anan, K; Morisaki, T; Katano, M; Ikubo, A; Kitsuki, H; Uchiyama, A; Kuroki, S; Tanaka, M; Torisu, M

1996-03-01

Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution

PubMed Central

Paget, Mark S.

2015-01-01

Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor. PMID:26131973

Intrinsic factor

MedlinePlus

Intrinsic factor is a protein that helps your intestines absorb vitamin B12. It is made by cells in the ... Intrinsic factor is a protein that helps your body absorb vitamin B12. Vitamin B12 is needed for red blood ...

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

PubMed

Price, Bertram; MacNicoll, Michael

2015-05-01

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. © 2015 Society for Risk Analysis.

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

PubMed

Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

2017-05-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Media composition: growth factors.

PubMed

Hegde, Aparna; Behr, Barry

2012-01-01

Despite the fact that the fundamental principle underlying the most common method of culture media constitution is that of mimicking the natural environment of the preimplantation embryo, one major difference that remains between current embryo culture media and in vivo conditions is the absence of growth factors in vitro. Numerous growth factors are known to be present in the in vivo environment of human and nonhuman preimplantation embryos, often with peak concentrations corresponding to when fertilization and preimplantation embryo growth would occur. Although these growth factors are found in very small concentrations, they have a profound effect on tissue growth and differentiation through attachment to factor-specific receptors on cell surfaces. Receptors for many different growth factors have also been detected in human preimplantation embryos. Preimplantation embryos themselves express many growth factors. The growth factors and receptors are metabolically costly to produce, and thus their presence in the environment of the preimplantation embryo and in the embryo respectively strongly implies that embryos are designed to encounter and respond to the corresponding factors. Studies of embryo coculture also indirectly suggest that growth factors can improve in vitro development. Several animal and human studies attest to a probable beneficial effect of addition of growth factors to culture media. However, there is still ambiguity regarding the exact role of growth factors in embryonic development, the optimal dose of growth factors to be added to culture media, the combinatorial effect and endocrine of growth factors in embryonic development.

EVALUATING THE IMPORTANCE OF FACTORS IN ANY GIVEN ORDER OF FACTORING.

PubMed

Humphreys, L G; Tucker, L R; Dachler, P

1970-04-01

A methodology has been described and illustrated for obtaining an evaluation of the importance of the factors in a particular order of factoring that does not require faotoring beyond that order. For example, one can estimate the intercorrelations of the original measures with the perturbations of the first-order factor held constant or, the reverse, estimate the contribution to the intercorrelations of the originral measures from the first-order factors alone. Similar operations are possible at higher orders.

Heart disease - risk factors

MedlinePlus

Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

Factors influencing wound dehiscence.

PubMed

Riou, J P; Cohen, J R; Johnson, H

1992-03-01

Thirty-one abdominal fascial wound dehiscences occurred in 2,761 patients undergoing major abdominal surgery during a 5-year period (1%). Twenty-two specific local and systemic risk factors were analyzed and compared with the risk factors of a control group of 38 patients undergoing similar procedures without dehiscence. Through multivariate analysis, each factor was assessed as an independent statistical variable. Significant factors (p less than 0.05) were found to include age over 65, wound infection, pulmonary disease, hemodynamic instability, and ostomies in the incision. Additional systemic risk factors that were found to be significant included hypoproteinemia, systemic infection, obesity, uremia, hyperalimentation, malignancy, ascites, steroid use, and hypertension. Risk factors not found to be important independent variables included sex, type of incision, type of closure, foreign body in the wound, anemia, jaundice, and diabetes. When dehiscence and control groups were combined, 30% of patients with at least five significant risk factors developed dehiscence, and all the patients with more than eight risk factors developed a wound dehiscence. There was an overall mortality of 29%, which was directly related to the number of significant risk factors. The co-existence of 9 risk factors portended death in one third of the patients, and all the patients with more than 10 risk factors died.

General Factors of the Korean Exposure Factors Handbook

PubMed Central

Kim, So-Yeon; Kim, Sun-Ja; Lee, Kyung-Eun; Cheong, Hae-Kwan; Kim, Eun-Hye; Choi, Kyung-Ho; Kim, Young-Hee

2014-01-01

Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion. PMID:24570802

Block LU factorization

NASA Technical Reports Server (NTRS)

Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

1992-01-01

Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors.

PubMed

Rubio, Roman G; Adamis, Anthony P

2016-01-01

Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases. © 2016 S. Karger AG, Basel.

Application of information-theoretic measures to quantitative analysis of immunofluorescent microscope imaging.

PubMed

Shutin, Dmitriy; Zlobinskaya, Olga

2010-02-01

The goal of this contribution is to apply model-based information-theoretic measures to the quantification of relative differences between immunofluorescent signals. Several models for approximating the empirical fluorescence intensity distributions are considered, namely Gaussian, Gamma, Beta, and kernel densities. As a distance measure the Hellinger distance and the Kullback-Leibler divergence are considered. For the Gaussian, Gamma, and Beta models the closed-form expressions for evaluating the distance as a function of the model parameters are obtained. The advantages of the proposed quantification framework as compared to simple mean-based approaches are analyzed with numerical simulations. Two biological experiments are also considered. The first is the functional analysis of the p8 subunit of the TFIIH complex responsible for a rare hereditary multi-system disorder--trichothiodystrophy group A (TTD-A). In the second experiment the proposed methods are applied to assess the UV-induced DNA lesion repair rate. A good agreement between our in vivo results and those obtained with an alternative in vitro measurement is established. We believe that the computational simplicity and the effectiveness of the proposed quantification procedure will make it very attractive for different analysis tasks in functional proteomics, as well as in high-content screening. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Role of carbohydrate in multimeric structure of factor VIII/von Willebrand factor protein.

PubMed Central

Gralnick, H R; Williams, S B; Rick, M E

1983-01-01

The carbohydrate moiety of the factor VIII/von Willebrand (vW) factor protein is important in the expression of vW factor activity and the intravascular survival of the protein. Studies of normal human factor VIII/vW factor protein indicate that there is a requirement of a full complement of penultimate galactose for the maintenance of a normal multimeric structure. Release of penultimate galactose by beta-galactosidase or modification by galactose oxidase results in loss of the largest molecular weight multimers and increased numbers of intermediate and smaller multimers. In contrast, terminal galactose on the factor VIII/vW factor protein does not appear to play a significant role in the maintenance of the multimer organization. The abnormalities in multimeric structure and molecular size were demonstrated by NaDodSO4/polyacrylamide/agarose gel electrophoresis, NaDodSO4/glyoxyl-agarose electrophoresis, and sucrose density ultracentrifugation. These studies indicate that the penultimate galactose plays a role in the maintenance of the largest multimers of the factor VIII/vW factor protein. This may explain why, in some patients with variant forms of vW disease, a carbohydrate abnormality also may affect the multimeric structure of the plasma factor VIII/vW factor protein. Images PMID:6601805

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation

PubMed Central

Gaviglio, Angela L.; Knelson, Erik H.; Blobe, Gerard C.

2017-01-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor–like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.—Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. PMID:28174207

The pattern space factor and quality factor of cylindrical source antennas

NASA Astrophysics Data System (ADS)

Jarem, John M.

1982-09-01

For the first time the quality factor of cylindrical source antennas is derived by a plane wave expansion. The evanescent energy (and therefore the quality factor) as defined by a plane wave expansion is shown to be different from Collin and Rothschild's [IEEE Trans. Antennas Propagation AP-12, 23 (1964)] quality factor.

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics.

PubMed

Rho, Mi Jung; Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Jung, Dong Jin; Kim, Dai-Jin; Choi, In Young

2017-12-27

Background : Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods : Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results : The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions : These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment.

Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

PubMed

Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

2017-01-01

Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

ISS Payload Human Factors

NASA Technical Reports Server (NTRS)

Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

2016-01-01

The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

Constructivism, Factoring, and Beliefs.

ERIC Educational Resources Information Center

Rauff, James V.

1994-01-01

Discusses errors made by remedial intermediate algebra students in factoring polynomials in light of student definitions of factoring. Found certain beliefs about factoring to logically imply many of the errors made. Suggests that belief-based teaching can be successful in teaching factoring. (16 references) (Author/MKR)

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics

PubMed Central

Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Kim, Dai-Jin; Choi, In Young

2017-01-01

Background: Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods: Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results: The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions: These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment. PMID:29280953

Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery.

PubMed

Livnat, Tami; Shenkman, Boris; Spectre, Galia; Tamarin, Ilia; Dardik, Rima; Israeli, Amnon; Rivkind, Avraham; Shabtai, Moshe; Marinowitz, Uri; Salomon, Ophira

2012-07-01

Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal. Patients with 2-10% factor VII vary between asymptomatic to severe life threatening haemorrhages behaviour. Recombinant factor VIIa (rFVIIa) is the most common replacement therapy for congenital factor VII deficiency. However, unlike haemophilia patients for whom treatment protocols are straight forward, in asymptomatic factor VII deficiency patients it is still debatable. In this study, we demonstrate that a single and very low dose of recombinant factor VIIa enabled asymptomatic patients with factor VII deficiency to go through major surgery safely. This suggestion was also supported by thrombin generation, as well as by thromboelastometry.

Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

NASA Technical Reports Server (NTRS)

Cromwell, Ronita L.; Zanello, S. B.; Yarbough, P. O.; Tabbi, G.; Vizzeri, G.

2012-01-01

Reports of astronauts' visual changes have raised concern about ocular health during long-duration spaceflight. Some of these findings include globe flattening with hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, it is hypothesized that, in predisposed individuals, hypertension in the brain may follow cephalad fluid shifts during spaceflight. This possible mechanism of ocular changes may also apply to analogous cases of idiopathic intracranial hypertension (IIH) or pseudotumor cerebri on Earth patients. Head-down t ilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. Previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP) but the conditions of bed rest varied among experiments, making it difficult to compare data and draw conclusions. For these reasons, vision evaluation of bed rest subjects was implemented for NASA bed rest studies since 2010, in an attempt to monitor vision health in subjects subjected to bed rest. Vision monitoring is thus currently performed in all NASA-conducted bed rest campaigns

The Manifestation of Vortical and Secondary Flow in the Cerebral Venous Outflow Tract: An In Vivo MR Velocimetry Study

PubMed Central

Kefayati, Sarah; Amans, Matthew; Faraji, Farshid; Ballweber, Megan; Kao, Evan; Ahn, Sinyeob; Meisel, Karl; Halbach, Van; Saloner, David

2016-01-01

Aberrations in flow in the cerebral venous outflow tract (CVOT) have been implicated as the cause of several pathologic conditions including idiopathic intracranial hypertension (IIH), multiple sclerosis (MS), and pulsatile tinnitus (PT). The advent of 4D Flow magnetic resonance imaging (4D-Flow MRI) has recently allowed researchers to evaluate blood flow patterns in the arterial structures with great success. We utilized similar imaging techniques and found several distinct flow characteristics in the CVOT of subjects with and without lumenal irregularities. We present the flow patterns of 8 out of 38 subjects who have varying heights of the internal jugular bulb and varying lumenal irregularities including stenosis and diverticulum. In the internal jugular vein (IJV) with an elevated jugular bulb (JB), 4DFlow MRI revealed a characteristic spiral flow that was dependent on the level of JB elevation. Vortical flow was also observed in the diverticula of the venous sinuses and IJV. The diversity of flow complexity in the CVOT illustrates the potential importance of hemodynamic investigations in elucidating venous pathologies. PMID:27894675

Testicular Ischemia Caused by Incarcerated Inguinal Hernia in Infants: Incidence, Conservative treatment procedure, and Follow-up.

PubMed

Ozdamar, Mustafa Yasar; Karakus, Osman Zeki

2017-07-02

Testicular ischemia and necrosis, especially in the infant age, may result from incarcerated inguinal hernia. Duration of ischemia is a significant factor for the affected testicle. We aimed to present a case series on the conservative management in the testicular ischemia caused by incarcerated inguinal hernia. Inguinal hernia repairs performed in between March 2009 and December 2014 were investigated retrospectively. Patients' characteristics, hernia side, incarceration, testicular ischemia and complications were recorded. Color Doppler ultrasonography was performed in the incarcerated inguinal hernia patients preoperatively and was repeated on 3 and 7 days and then at 1, 3 and 6 months postoperatively. The testicle sizes, volumes, and arterial flow patterns of them were recorded at the same time. Total 785 inguinal hernias were treated in 738 male patients, ranging from 18 days to 16 years. From all male patients, 44 (5.9%) had the IIH. There were 16 (36.3%) irreducible hernias in 44 incarcerated hernia patients. Of these 16, testicular ischemia was determined in 9 (56.2%) infants with the irreducible incarcerated hernia. Orchidopexyprocedure was performed in these patients. Testicular atrophy was occurred in two patients (22.2%). In the others, testicular volumes and perfusions were normal during follow-up (mean 8.3 ± 2.2 months). Testicular ischemia resulting from incarcerated inguinal hernia may be treated conservatively without orchiectomy for the ischemic testicle and testicular ischemia may be followed with color Doppler ultrasound for atleast 6 months. The inguinal hernia repair in infants should be subject to urgent surgery rather than elective surgery. So, the testicular ischemia in infants with the inguinal hernia will be an avoidable complication.

Oversimplifying quantum factoring.

PubMed

Smolin, John A; Smith, Graeme; Vargo, Alexander

2013-07-11

Shor's quantum factoring algorithm exponentially outperforms known classical methods. Previous experimental implementations have used simplifications dependent on knowing the factors in advance. However, as we show here, all composite numbers admit simplification of the algorithm to a circuit equivalent to flipping coins. The difficulty of a particular experiment therefore depends on the level of simplification chosen, not the size of the number factored. Valid implementations should not make use of the answer sought.

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

PubMed

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

Factor Structure of the Penn State Worry Questionnaire: Examination of a Method Factor

ERIC Educational Resources Information Center

Hazlett-Stevens, Holly; Ullman, Jodie B.; Craske, Michelle G.

2004-01-01

The Penn State Worry Questionnaire (PSWQ) was originally designed as a unifactorial measure of pathological trait worry. However, recent studies supported a two-factor solution with positively worded items loading on the first factor and reverse-scored items loading on a second factor. The current study compared this two-factor model to a negative…

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

PubMed Central

Terasaki, Kaori; Ramirez, Sydney I.; Makino, Shinji

2016-01-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

PubMed

Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

2016-10-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice

What Are Rare Clotting Factor Deficiencies?

MedlinePlus

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Bayesian Exploratory Factor Analysis

PubMed Central

Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

2014-01-01

This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements. PMID:25431517

Risk Factors for Scleroderma

MedlinePlus

... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

Side Impact Regulatory Trends, Crash Environment and Injury Risk in the USA.

PubMed

Prasad, Priya; Dalmotas, Dainius; Chouinard, Aline

2015-11-01

Light duty vehicles in the US are designed to meet and exceed regulatory standards, self-imposed industry agreements and safety rating tests conducted by NHTSA and IIHS. The evolution of side impact regulation in the US from 1973 to 2015 is discussed in the paper along with two key industry agreements in 2003 affecting design of restraint systems and structures for side impact protection. A combination of all the above influences shows that vehicles in the US are being designed to more demanding and comprehensive requirements than in any other region of the world. The crash environment in the US related to side impacts was defined based on data in the nationally representative crash database NASS. Crash environment factors, including the distribution of cars, light trucks and vans (LTV's), and medium-to-heavy vehicles (MHV's) in the fleet, and the frequency of their interactions with one another in side impacts, were considered. Other factors like, crash severity in terms of closing velocity between two vehicles involved in crash, gender and age of involved drivers in two-vehicle and single vehicle crashes, were also examined. Injury risks in side impacts to drivers and passengers were determined in various circumstances such as near-side, far-side, and single vehicle crashes as a function of crash severity, in terms of estimated closing speed or lateral delta-V. Also injury risks in different pairs of striking and struck cars and LTV's, were estimated. A logistic regression model for studying injury risks in two vehicle crashes was developed. The risk factors included in the model include case and striking vehicles, consisting of cars, SUV's, vans, and pickup trucks, delta-V, damage extent, occupant proximity to the impact side, age and gender of the occupant, and belt use. Results show that car occupants make up the vast majority of serious-to-fatally injured occupants. Injury rates of car occupants in two-vehicle collision are highest when the car is struck by a

Coagulation Factor Tests

MedlinePlus

... your coagulation factors. Coagulation factors are known by Roman numerals (I, II VIII, etc.) or by name ( ... need this test if you have a family history of bleeding disorders. Most bleeding disorders are inherited . ...

IVI human factors strategy

DOT National Transportation Integrated Search

1999-11-01

This document focuses on human factors research that supports the Intelligent Vehicle Initiative (IVI). The status of the problem areas within categories used often by the human factors community to organize human factors process is discussed. A simi...

Factor Analysis and Counseling Research

ERIC Educational Resources Information Center

Weiss, David J.

1970-01-01

Topics discussed include factor analysis versus cluster analysis, analysis of Q correlation matrices, ipsativity and factor analysis, and tests for the significance of a correlation matrix prior to application of factor analytic techniques. Techniques for factor extraction discussed include principal components, canonical factor analysis, alpha…

FACTOR FINDER CD-ROM

EPA Science Inventory

The Factor Finder CD-ROM is a user-friendly, searchable tool used to locate exposure factors and sociodemographic data for user-defined populations. Factor Finder improves the exposure assessors and risk assessors (etc.) ability to efficiently locate exposure-related informatio...

Human Factors Job Aid

DOT National Transportation Integrated Search

1996-12-09

The purpose of this Human Factors Job Aid is to serve as a desk reference for : human factors integration during system acquisition. The first chapter contains : an overview of the FAA human factors process in system acquisitions. The : remaining eig...

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

PubMed

Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

Women's Career Success: A Factor Analytic Study of Contributing Factors.

ERIC Educational Resources Information Center

Gaskill, LuAnn Ricketts

1991-01-01

A survey of 466 women employed in retailing received 205 responses identifying (1) factors influencing the success and advancement of women in retailing and (2) how those factors differ for women in upper versus middle positions. Upper-level executives placed more importance on ambition and abilities; midlevel executives credited opportunity and…

Critical Success Factors for E-Learning Acceptance: Confirmatory Factor Models

ERIC Educational Resources Information Center

Selim, Hassan M.

2007-01-01

E-learning, one of the tools emerged from information technology, has been integrated in many university programs. There are several factors that need to be considered while developing or implementing university curriculums that offer e-learning based courses. This paper is intended to specify e-learning critical success factors (CSFs) as…

Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.

PubMed Central

Danilenko, D. M.; Ring, B. D.; Tarpley, J. E.; Morris, B.; Van, G. Y.; Morawiecki, A.; Callahan, W.; Goldenberg, M.; Hershenson, S.; Pierce, G. F.

1995-01-01

The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for

Causes and risk factors for male-factor infertility in Nigeria: a review.

PubMed

Abarikwu, Sunny O

2013-12-01

In recent times there has been a decline in the semen quality of young healthy men worldwide, with similar findings being reported in Nigeria. Although little is known about what is responsible for the decline in male sperm count worldwide, significant associations have been reported between impaired semen quality including sperm count, motility as well as morphology and exposures to heavy metals such as cadmium and lead, mycotoxins such as aflatoxins, pesticides, industrial chemicals and endocrine factors. In Nigeria, the problem is further compounded by a variety of factors such as sexually transmitted infections, genito-urinary tract infections/inflammations and deficiencies of dietary antioxidant nutrients, thereby increasing male-factor contribution to infertility in the population. In this article, we analyze data from different sources and present evidence of the possible etiology and risk factors for male-factor infertility in Nigeria.

Environmental Factors in Autism

PubMed Central

Grabrucker, Andreas M.

2013-01-01

Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed. PMID:23346059

On the Likelihood Ratio Test for the Number of Factors in Exploratory Factor Analysis

ERIC Educational Resources Information Center

Hayashi, Kentaro; Bentler, Peter M.; Yuan, Ke-Hai

2007-01-01

In the exploratory factor analysis, when the number of factors exceeds the true number of factors, the likelihood ratio test statistic no longer follows the chi-square distribution due to a problem of rank deficiency and nonidentifiability of model parameters. As a result, decisions regarding the number of factors may be incorrect. Several…

Taking the Error Term of the Factor Model into Account: The Factor Score Predictor Interval

ERIC Educational Resources Information Center

Beauducel, Andre

2013-01-01

The problem of factor score indeterminacy implies that the factor and the error scores cannot be completely disentangled in the factor model. It is therefore proposed to compute Harman's factor score predictor that contains an additive combination of factor and error variance. This additive combination is discussed in the framework of classical…

Analyzing the risk factors influencing surgical site infections: the site of environmental factors.

PubMed

Alfonso-Sanchez, Jose L; Martinez, Isabel M; Martín-Moreno, Jose M; González, Ricardo S; Botía, Francisco

2017-06-01

Addressing surgical site infection (SSI) is accomplished, in part, through studies that attempt to clarify the nature of many essential factors in the control of SSI. We sought to examine the link between multiple risk factors, including environmental factors, and SSI for prevention management. We conducted a longitudinal prospective study to identify SSIs in all patients who underwent interventions in 2014 in 8 selected hospitals on the Mediterranean coast of Spain. Risk factors related to the operating theatre included level of fungi and bacterial contamination, temperature and humidity, air renewal and differential air pressure. Patient-related variables included age, sex, comorbidity, nutrition level and transfusion. Other factors were antibiotic prophylaxis, electric versus manual shaving, American Society of Anaesthesiologists physical status classification, type of intervention, duration of the intervention and preoperative stay. Superficial SSI was most often associated with environmental factors, such as environmental contamination by fungi (from 2 colony-forming units) and bacteria as well as surface contamination. When there was no contamination in the operating room, no SSI was detected. Factors that determined deep and organ/space SSI were more often associated with patient characteristics (age, sex, transfusion, nasogastric feeding and nutrition, as measured by the level of albumin in the blood), type of intervention and preoperative stay. Antibiotic prophylaxis and shaving with electric razor were protective factors for both types of infection, whereas the duration of the intervention and the classification of the intervention as "dirty" were shared risk factors. Our results suggest the importance of environmental and surface contamination control to prevent SSI.

Psychosocial job factors and biological cardiovascular risk factors in Mexican workers.

PubMed

Garcia-Rojas, Isabel Judith; Choi, BongKyoo; Krause, Niklas

2015-03-01

Psychosocial job factors (PJF) have been implicated in the development of cardiovascular disease. The paucity of data from developing economies including Mexico hampers the development of worksite intervention efforts in those regions. This cross-sectional study of 2,330 Mexican workers assessed PJF (job strain [JS], social support [SS], and job insecurity [JI]) and biological cardiovascular disease risk factors [CVDRF] by questionnaire and on-site physical examinations. Alternative formulations of the JS scales were developed based on factor analysis and literature review. Associations between both traditional and alternative job factor scales with CVDRF were examined in multiple regression models, adjusting for physical workload, and socio-demographic factors. Alternative formulations of the job demand and control scales resulted in substantial changes in effect sizes or statistical significance when compared with the original scales. JS and JI showed hypothesized associations with most CVDRF, but they were inversely associated with diastolic blood pressure and some adiposity measures. SS was mainly protective against CVDRF. Among Mexican workers, alternative PJF scales predicted health outcomes better than traditional scales, and psychosocial stressors were associated with most CVDRF. © 2015 Wiley Periodicals, Inc.

Using Horn's Parallel Analysis Method in Exploratory Factor Analysis for Determining the Number of Factors

ERIC Educational Resources Information Center

Çokluk, Ömay; Koçak, Duygu

2016-01-01

In this study, the number of factors obtained from parallel analysis, a method used for determining the number of factors in exploratory factor analysis, was compared to that of the factors obtained from eigenvalue and scree plot--two traditional methods for determining the number of factors--in terms of consistency. Parallel analysis is based on…

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

PubMed Central

O'Brien, D P; Giles, A R; Tate, K M; Vehar, G A

1988-01-01

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated. Images PMID:3134399

Multi-factor authentication using quantum communication

DOEpatents

Hughes, Richard John; Peterson, Charles Glen; Thrasher, James T.; Nordholt, Jane E.; Yard, Jon T.; Newell, Raymond Thorson; Somma, Rolando D.

2018-02-06

Multi-factor authentication using quantum communication ("QC") includes stages for enrollment and identification. For example, a user enrolls for multi-factor authentication that uses QC with a trusted authority. The trusted authority transmits device factor information associated with a user device (such as a hash function) and user factor information associated with the user (such as an encrypted version of a user password). The user device receives and stores the device factor information and user factor information. For multi-factor authentication that uses QC, the user device retrieves its stored device factor information and user factor information, then transmits the user factor information to the trusted authority, which also retrieves its stored device factor information. The user device and trusted authority use the device factor information and user factor information (more specifically, information such as a user password that is the basis of the user factor information) in multi-factor authentication that uses QC.

Model of a ternary complex between activated factor VII, tissue factor and factor IX.

PubMed

Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

2002-07-01

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

TauFactor: An open-source application for calculating tortuosity factors from tomographic data

NASA Astrophysics Data System (ADS)

Cooper, S. J.; Bertei, A.; Shearing, P. R.; Kilner, J. A.; Brandon, N. P.

TauFactor is a MatLab application for efficiently calculating the tortuosity factor, as well as volume fractions, surface areas and triple phase boundary densities, from image based microstructural data. The tortuosity factor quantifies the apparent decrease in diffusive transport resulting from convolutions of the flow paths through porous media. TauFactor was originally developed to improve the understanding of electrode microstructures for batteries and fuel cells; however, the tortuosity factor has been of interest to a wide range of disciplines for over a century, including geoscience, biology and optics. It is still common practice to use correlations, such as that developed by Bruggeman, to approximate the tortuosity factor, but in recent years the increasing availability of 3D imaging techniques has spurred interest in calculating this quantity more directly. This tool provides a fast and accurate computational platform applicable to the big datasets (>108 voxels) typical of modern tomography, without requiring high computational power.

Risk factors for stress fractures.

PubMed

Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

1999-08-01

Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

Graduated driver licensing for reducing motor vehicle crashes among young drivers.

PubMed

Russell, Kelly F; Vandermeer, Ben; Hartling, Lisa

2011-10-05

Graduated driver licensing (GDL) has been proposed as a means of reducing crash rates among novice drivers by gradually introducing them to higher risk driving situations. To examine the effectiveness of GDL in reducing crash rates among young drivers. Studies were identified through searching MEDLINE, EMBASE, CINAHL, Healthstar, Web of Science, NTIS Bibliographic Database, TRIS Online, SIGLE, the World Wide Web, conference proceedings, consultation with experts and reference lists in relevant published literature. The searches were conducted from the time of inception to May 2009, and the Cochrane Injuries Group conducted an updated search of the TRANSPORT database in September 2009. Studies were included if: 1) they compared outcomes pre- and post-implementation of a GDL program within the same jurisdiction, 2) comparisons were made between jurisdictions with and without GDL, or 3) both. Studies had to report at least one objective, quantified outcome. Results were not pooled due to substantial heterogeneity. Percentage change was calculated for each year after the intervention, using one year prior to the intervention as baseline. Results were adjusted by internal controls. Analyses were stratified by denominators (population, licensed drivers). Results were calculated for the different crash types and presented for 16 year-olds alone as well as all teenage drivers. We included 34 studies evaluating 21 GDL programs and 2 analyses of >40 US states. GDL programs were implemented in the US (n=16), Canada (n=3), New Zealand (n=1), and Australia (n=1) and varied in their restrictions during the intermediate stage. Based on the Insurance Institute for Highway Safety (IIHS) classification, eleven programs were good, four were fair, five were marginal, one was poor and two could not be assessed. Reductions in crash rates were seen in all jurisdictions and for all crash types. Among 16 year-old drivers, the median decrease in per population adjusted overall crash rates

WRKY transcription factors.

PubMed

Rushton, Paul J; Somssich, Imre E; Ringler, Patricia; Shen, Qingxi J

2010-05-01

WRKY transcription factors are one of the largest families of transcriptional regulators in plants and form integral parts of signalling webs that modulate many plant processes. Here, we review recent significant progress in WRKY transcription factor research. New findings illustrate that WRKY proteins often act as repressors as well as activators, and that members of the family play roles in both the repression and de-repression of important plant processes. Furthermore, it is becoming clear that a single WRKY transcription factor might be involved in regulating several seemingly disparate processes. Mechanisms of signalling and transcriptional regulation are being dissected, uncovering WRKY protein functions via interactions with a diverse array of protein partners, including MAP kinases, MAP kinase kinases, 14-3-3 proteins, calmodulin, histone deacetylases, resistance proteins and other WRKY transcription factors. WRKY genes exhibit extensive autoregulation and cross-regulation that facilitates transcriptional reprogramming in a dynamic web with built-in redundancy. 2010 Elsevier Ltd. All rights reserved.

Threshold factorization redux

NASA Astrophysics Data System (ADS)

Chay, Junegone; Kim, Chul

2018-05-01

We reanalyze the factorization theorems for the Drell-Yan process and for deep inelastic scattering near threshold, as constructed in the framework of the soft-collinear effective theory (SCET), from a new, consistent perspective. In order to formulate the factorization near threshold in SCET, we should include an additional degree of freedom with small energy, collinear to the beam direction. The corresponding collinear-soft mode is included to describe the parton distribution function (PDF) near threshold. The soft function is modified by subtracting the contribution of the collinear-soft modes in order to avoid double counting on the overlap region. As a result, the proper soft function becomes infrared finite, and all the factorized parts are free of rapidity divergence. Furthermore, the separation of the relevant scales in each factorized part becomes manifest. We apply the same idea to the dihadron production in e+e- annihilation near threshold, and show that the resultant soft function is also free of infrared and rapidity divergences.

Aerospace Human Factors

NASA Technical Reports Server (NTRS)

Jordan, Kevin

1999-01-01

The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

Is the Factor Observed in Investigations on the Item-Position Effect Actually the Difficulty Factor?

PubMed

Schweizer, Karl; Troche, Stefan

2018-02-01

In confirmatory factor analysis quite similar models of measurement serve the detection of the difficulty factor and the factor due to the item-position effect. The item-position effect refers to the increasing dependency among the responses to successively presented items of a test whereas the difficulty factor is ascribed to the wide range of item difficulties. The similarity of the models of measurement hampers the dissociation of these factors. Since the item-position effect should theoretically be independent of the item difficulties, the statistical ex post manipulation of the difficulties should enable the discrimination of the two types of factors. This method was investigated in two studies. In the first study, Advanced Progressive Matrices (APM) data of 300 participants were investigated. As expected, the factor thought to be due to the item-position effect was observed. In the second study, using data simulated to show the major characteristics of the APM data, the wide range of items with various difficulties was set to zero to reduce the likelihood of detecting the difficulty factor. Despite this reduction, however, the factor now identified as item-position factor, was observed in virtually all simulated datasets.

Factors, fiction and endothelium-derived hyperpolarizing factor.

PubMed

Sandow, Shaun L

2004-09-01

1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium-dependent vasodilatory mechanism is characterized as the hyperpolarization-mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so-called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact-mediated mechanism. 2. Most evidence supports the concept that 'EDHF' activity is dependent on contact-mediated mechanisms. This involves the transfer of an endothelium-derived electrical current, as an endothelium-derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less-than-optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature. 4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the

The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents

PubMed Central

McMillin, Carl R.; Saito, Hidehiko; Ratnoff, Oscar D.; Walton, Alan G.

1974-01-01

Hageman factor (factor XII) is activated by exposure to surfaces such as glass or by solutions of certain compounds, notably ellagic acid. Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy. The spectrum of unactivated Hageman factor in aqueous solutions suggests that its conformation is mainly aperiodic. Various perturbants altered the conformation of Hageman factor in differing ways, demonstrating the sensitivity of Hageman factor to its environment. After activation of Hageman factor with solutions of ellagic acid, a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues, along with other minor changes in the peptide spectral region. Some of these changes are similar to changes that occurred upon partial neutralization of the basic residues at alkali pH. Activation of Hageman factor by adsorption to quartz surfaces (in an aqueous environment) also produced changes similar to those in the ellagic acid-activated Hageman factor, including the negative ellipticity in the tyrosine region. These observations suggest that the activation process may be related to a change in status of some of the basic amino acid residues, coupled with a specific change in the environment of some tyrosine residues. The importance of these changes during the activation process remains to be determined. The sensitivity of Hageman factor to its environment is consistent with the view that the initiation of clotting by exposure of plasma to appropriate agents is brought about by alterations in the conformation of Hageman factor that occur in the apparent absence of Fletcher factor or other recognized clotting factors. Images PMID:4373492

Testing alternative factor models of PTSD and the robustness of the dysphoria factor.

PubMed

Elklit, Ask; Armour, Cherie; Shevlin, Mark

2010-01-01

This study first aimed to examine the structure of self-reported posttraumatic stress disorder (PTSD) symptoms using three different samples. The second aim of the paper was to test the robustness of the factor analytic model when depression scores were controlled for. Based on previous factor analytic findings and the DSM-IV formulation, six confirmatory factor models were specified and estimated that reflected different symptom clusters. The best fitting model was subsequently re-fitted to the data after including a depression variable. The analyses were based on responses from 973 participants across three samples. Sample 1 consisted of 633 parents who were members of 'The National Association of Infant Death' and who had lost a child. Sample 2 consisted of 227 victims of rape, who completed a questionnaire within 4 weeks of the rape. Each respondent had been in contact with the Centre for Rape Victims (CRV) at the Aarhus University Hospital, Denmark. Sample 3 consisted of 113 refugees resident in Denmark. All participants had been referred to a treatment centre which focused on rehabilitating refugees through treatment for psychosocial integration problems (RRCF: Rehabliterings og Revliderings Centre for Flygtninge). In total 500 participants received a diagnosis of PTSD/sub-clinical PTSD (Sample 1, N=214; 2, N=176; 3, N=110). A correlated four-factor model with re-experiencing, avoidance, dysphoria, and arousal factors provided the best fit to the sample data. The average attenuation in the factor loadings was highest for the dysphoria factor (M=-.26, SD=.11) compared to the re-experiencing (M=-.14, SD=.18), avoidance (M=-.10, SD=.21), and arousal (M=-.09, SD=.13) factors. With regards to the best fitting factor model these results concur with previous research findings using different trauma populations but do not reflect the current DSM-IV symptom groupings. The attenuation of dysphoria factor loadings suggests that dysphoria is a non-specific component of

[Pathological gambling: risk factors].

PubMed

Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

2011-09-01

In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

PubMed

de Moerloose, P; Schved, J-F; Nugent, D

2016-07-01

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

[Environmental factors of longevity].

PubMed

Christen, Yves

2003-03-01

A PROBABLE ROLE: The great increase in life expectancy over the past decades and too short a time lapse for any major genetic mutations to intervene, are arguments in favour of the intervention of environmental factors in longevity. A FAIRLY LONG LIST: Various environmental factors can be envisaged: prenatal environment, pollution, radiation and oncogenic agents, notably tobacco, food (quantitatively and qualitatively), medicinal products, stress, education and socio-professional life style, isolation, number of children and sexual activity, sports and exercising, etc. It is highly likely that all these factors, or at least some of them, have a real effect on longevity, although this is difficult to demonstrate directly. A COMBINED EFFECT: The basic idea of this paper is that these environmental factors should be seen as agents, the effects of which would be combined with those of genetic factors, considered as agents of radically different nature. We suggest that, in order to have any real effect, these environmental factors have to work on the same cell mechanisms as those that affect the genetic process, notably the mechanisms related to oxidative stress and genetic expression.

The Development of the General Factor of Psychopathology 'p Factor' Through Childhood and Adolescence.

PubMed

Murray, Aja Louise; Eisner, Manuel; Ribeaud, Denis

2016-11-01

Recent studies have suggested that the structure of psychopathology may be usefully represented in terms of a general factor of psychopathology (p-factor) capturing variance common to a broad range of symptoms transcending diagnostic domains in addition to specific factors capturing variance common to smaller subsets of more closely related symptoms. Little is known about how the general co-morbidity captured by this p-factor develops and whether general co-morbidity increases or decreases over childhood and adolescence. We evaluated two competing hypotheses: 1) dynamic mutualism which predicts growth in general co-morbidity and associated p-factor strength over time and 2) p-differentiation which predicts that manifestations of liabilities towards psychopathology become increasingly specific over time. Data came from the Zurich Project on the Social Development of Children and Youths (z-proso), a longitudinal study of a normative sample (approx. 50 % male) measured at 8 time points from ages 7 to 15. We operationalised general co-morbidity as p-factor strength in a bi-factor model and used omega hierarchical to track how this changed over development. In contrast to the predictions of both dynamic mutualism and p-differentiation, p-factor strength remained relatively constant over the studied period suggesting that such processes do not govern the interplay between psychopathological symptoms during this phase of development. Future research should focus on earlier phases of development and on factors that maintain the consistency of symptom-general covariation across this period.

Exposure Factors Handbook Chapter 19

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 4

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 6

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 2

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 9

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 11

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 14

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 1

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 15

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 12

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 5

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 18

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 3

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 8

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 10

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 13

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 17

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 16

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Exposure Factors Handbook Chapter 7

EPA Pesticide Factsheets

Exposure Factors Handbook: 2011 Edition. The Exposure Factors Handbook provides information on various physiological and behavioral factors commonly used in assessing exposure to environmental chemicals.

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

PubMed Central

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C.; Nogales, Eva; Taatjes, Dylan J.

2011-01-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator–pol II interface is not well-characterized, whereas attempts to structurally define the Mediator–pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator–pol II–TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator–pol II–TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator–pol II–TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator–CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator–pol II complexes lacking TFIIF reveal that TFIIF plays a key role in

Voice disorders in teachers: occupational risk factors and psycho-emotional factors.

PubMed

van Houtte, Evelyne; Claeys, Sofie; Wuyts, Floris; van Lierde, Kristiane

2012-10-01

Teaching is a high-risk occupation for developing voice disorders. The purpose of this study was to investigate previously described vocal risk factors as well as to identify new risk factors related to both the personal life of the teacher (fluid intake, voice-demanding activities, family history of voice disorders, and children at home) and to environmental factors (temperature changes, chalk use, presence of curtains, carpet, or air-conditioning, acoustics in the classroom, and noise in and outside the classroom). The study group comprised 994 teachers (response rate 46.6%). All participants completed a questionnaire. Chi-square tests and logistic regression analyses were performed. A total of 51.2% (509/994) of the teachers presented with voice disorders. Women reported more voice disorders compared to men (56.4% versus 40.4%, P < 0.001). Vocal risk factors were a family history of voice disorders (P = 0.005), temperature changes in the classroom (P = 0.017), the number of pupils per classroom (P = 0.001), and noise level inside the classroom (P = 0.001). Teachers with voice disorders presented a higher level of psychological distress (P < 0.001) compared to teachers without voice problems. Voice disorders are frequent among teachers, especially in female teachers. The results of this study emphasize that multiple factors are involved in the development of voice disorders.

Exposure Factors Resources: Contrasting EPA’s Exposure Factors Handbook with International Sources (Journal Article)

EPA Science Inventory

Efforts to compile and standardize exposure human factors have resulted in the development of a variety of resources available to the scientific community. For example, the U.S. EPA developed the Exposure Factors Handbook and Child-specific Exposure Factors Handbook to promote c...

Factor Retention in Exploratory Factor Analysis: A Comparison of Alternative Methods.

ERIC Educational Resources Information Center

Mumford, Karen R.; Ferron, John M.; Hines, Constance V.; Hogarty, Kristine Y.; Kromrey, Jeffery D.

This study compared the effectiveness of 10 methods of determining the number of factors to retain in exploratory common factor analysis. The 10 methods included the Kaiser rule and a modified Kaiser criterion, 3 variations of parallel analysis, 4 regression-based variations of the scree procedure, and the minimum average partial procedure. The…

Is the Factor Observed in Investigations on the Item-Position Effect Actually the Difficulty Factor?

ERIC Educational Resources Information Center

Schweizer, Karl; Troche, Stefan

2018-01-01

In confirmatory factor analysis quite similar models of measurement serve the detection of the difficulty factor and the factor due to the item-position effect. The item-position effect refers to the increasing dependency among the responses to successively presented items of a test whereas the difficulty factor is ascribed to the wide range of…

Factors Affecting Medical Service Quality.

PubMed

Mosadeghrad, Ali Mohammad

2014-02-01

A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians. Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran. Individual, organizational and environmental factors enhance or inhibit the quality of medical services. Quality of medical services depends on the personal factors of the physician and patient, and factors pertaining to the healthcare setting and the broader environment. Differences in internal and external factors such as availability of resources, patient cooperation and collaboration among providers affect the quality of medical services and patient outcomes. Supportive leadership, proper planning, education and training and effective management of resources and processes improve the quality of medical services. This article contributes to healthcare theory and practice by developing a conceptual framework for understanding factors that influence medical services quality.

Depressive Symptoms in Chinese Elementary School Children: Child Social-Cognitive Factors and Parenting Factors

ERIC Educational Resources Information Center

Chan, Siu Mui; Oi Poon, Scarlet Fung

2016-01-01

This study examined child cognitive-behavioural factors and parenting factors related to childhood depressive symptoms. Results indicate that positive and negative attributional styles were protective and vulnerable factors of depression symptoms, respectively, and the attribution-depression link was mediated by self-esteem and coping responses.…

Five Describing Factors of Dyslexia.

PubMed

Tamboer, Peter; Vorst, Harrie C M; Oort, Frans J

2016-09-01

Two subtypes of dyslexia (phonological, visual) have been under debate in various studies. However, the number of symptoms of dyslexia described in the literature exceeds the number of subtypes, and underlying relations remain unclear. We investigated underlying cognitive features of dyslexia with exploratory and confirmatory factor analyses. A sample of 446 students (63 with dyslexia) completed a large test battery and a large questionnaire. Five factors were found in both the test battery and the questionnaire. These 10 factors loaded on 5 latent factors (spelling, phonology, short-term memory, rhyme/confusion, and whole-word processing/complexity), which explained 60% of total variance. Three analyses supported the validity of these factors. A confirmatory factor analysis fit with a solution of five factors (RMSEA = .03). Those with dyslexia differed from those without dyslexia on all factors. A combination of five factors provided reliable predictions of dyslexia and nondyslexia (accuracy >90%). We also looked for factorial deficits on an individual level to construct subtypes of dyslexia, but found varying profiles. We concluded that a multiple cognitive deficit model of dyslexia is supported, whereas the existence of subtypes remains unclear. We discussed the results in relation to advanced compensation strategies of students, measures of intelligence, and various correlations within groups of those with and without dyslexia. © Hammill Institute on Disabilities 2014.

Dental Students' Perceptions of Risk Factors for Musculoskeletal Disorders: Adapting the Job Factors Questionnaire for Dentistry.

PubMed

Presoto, Cristina D; Wajngarten, Danielle; Domingos, Patrícia A S; Campos, Juliana A D B; Garcia, Patrícia P N S

2018-01-01

The aims of this study were to adapt the Job Factors Questionnaire to the field of dentistry, evaluate its psychometric properties, evaluate dental students' perceptions of work/study risk factors for musculoskeletal disorders, and determine the influence of gender and academic level on those perceptions. All 580 students enrolled in two Brazilian dental schools in 2015 were invited to participate in the study. A three-factor structure (Repetitiveness, Work Posture, and External Factors) was tested through confirmatory factor analysis. Convergent validity was estimated using the average variance extracted (AVE), discriminant validity was based on the correlational analysis of the factors, and reliability was assessed. A causal model was created using structural equation modeling to evaluate the influence of gender and academic level on students' perceptions. A total of 480 students completed the questionnaire for an 83% response rate. The responding students' average age was 21.6 years (SD=2.98), and 74.8% were women. Higher scores were observed on the Work Posture factor items. The refined model presented proper fit to the studied sample. Convergent validity was compromised only for External Factors (AVE=0.47), and discriminant validity was compromised for Work Posture and External Factors (r 2 =0.69). Reliability was adequate. Academic level did not have a significant impact on the factors, but the women students exhibited greater perception. Overall, the adaptation resulted in a useful instrument for assessing perceptions of risk factors for musculoskeletal disorders. Gender was found to significantly influence all three factors, with women showing greater perception of the risk factors.

A DEIM Induced CUR Factorization

DTIC Science & Technology

2015-09-18

CUR approximate matrix factorization based on the Discrete Empirical Interpolation Method (DEIM). For a given matrix A, such a factorization provides a...CUR approximations based on leverage scores. 1 Introduction This work presents a new CUR matrix factorization based upon the Discrete Empirical...SUPPLEMENTARY NOTES 14. ABSTRACT We derive a CUR approximate matrix factorization based on the Discrete Empirical Interpolation Method (DEIM). For a given

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation

PubMed Central

Gao, Wei-wei; Xiao, Rong-quan; Peng, Bing-ling; Xu, Huan-teng; Shen, Hai-feng; Huang, Ming-feng; Shi, Tao-tao; Yi, Jia; Zhang, Wen-juan; Wu, Xiao-nan; Gao, Xiang; Lin, Xiang-zhi; Dorrestein, Pieter C.; Rosenfeld, Michael G.; Liu, Wen

2015-01-01

Although “histone” methyltransferases and demethylases are well established to regulate transcriptional programs and to use nonhistone proteins as substrates, their possible roles in regulation of heat-shock proteins in the nucleus have not been investigated. Here, we report that a highly conserved arginine residue, R469, in HSP70 (heat-shock protein of 70 kDa) proteins, an evolutionarily conserved protein family of ATP-dependent molecular chaperone, was monomethylated (me1), at least partially, by coactivator-associated arginine methyltransferase 1/protein arginine methyltransferase 4 (CARM1/PRMT4) and demethylated by jumonji-domain–containing 6 (JMJD6), both in vitro and in cultured cells. Functional studies revealed that HSP70 could directly regulate retinoid acid (RA)-induced retinoid acid receptor β2 (RARβ2) gene transcription through its binding to chromatin, with R469me1 being essential in this process. HSP70’s function in gene transcriptional regulation appears to be distinct from its protein chaperon activity. R469me1 was shown to mediate the interaction between HSP70 and TFIIH, which involves in RNA polymerase II phosphorylation and thus transcriptional initiation. Our findings expand the repertoire of nonhistone substrates targeted by PRMT4 and JMJD6, and reveal a new function of HSP70 proteins in gene transcription at the chromatin level aside from its classic role in protein folding and quality control. PMID:26080448

Recursive inverse factorization.

PubMed

Rubensson, Emanuel H; Bock, Nicolas; Holmström, Erik; Niklasson, Anders M N

2008-03-14

A recursive algorithm for the inverse factorization S(-1)=ZZ(*) of Hermitian positive definite matrices S is proposed. The inverse factorization is based on iterative refinement [A.M.N. Niklasson, Phys. Rev. B 70, 193102 (2004)] combined with a recursive decomposition of S. As the computational kernel is matrix-matrix multiplication, the algorithm can be parallelized and the computational effort increases linearly with system size for systems with sufficiently sparse matrices. Recent advances in network theory are used to find appropriate recursive decompositions. We show that optimization of the so-called network modularity results in an improved partitioning compared to other approaches. In particular, when the recursive inverse factorization is applied to overlap matrices of irregularly structured three-dimensional molecules.

Developmental expression patterns of candidate co-factors for vertebrate Six family transcription factors

PubMed Central

Neilson, Karen M.; Pignoni, Francesca; Yan, Bo; Moody, Sally A.

2010-01-01

Six family transcription factors play important roles in craniofacial development. Their transcriptional activity can be modified by co-factor proteins. Two Six genes and one co-factor gene (Eya1) are involved in the human Branchio-otic (BO) and Branchio-otic-renal (BOR) syndromes. However, mutations in Six and Eya genes only account for about half of these patients. To discover potential new causative genes, we searched the Xenopus genome for orthologues of Drosophila co-factor proteins that interact with the fly Six-related factor, SO. We identified 33 Xenopus genes with high sequence identity to 20 of the 25 fly SO-interacting proteins. We provide the developmental expression patterns of the Xenopus orthologues for 11 of the fly genes, and demonstrate that all are expressed in developing craniofacial tissues with at least partial overlap with Six1/Six2. We speculate that these genes may function as Six-interacting partners with important roles in vertebrate craniofacial development and perhaps congenital syndromes. PMID:21089078

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

PubMed

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

Salivary Gland Cancer: Risk Factors

MedlinePlus

... Cancer: Risk Factors Request Permissions Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net Editorial Board , ... To see other pages, use the menu. A risk factor is anything that increases a person’s chance ...

Phylogenetic Factor Analysis.

PubMed

Tolkoff, Max R; Alfaro, Michael E; Baele, Guy; Lemey, Philippe; Suchard, Marc A

2018-05-01

Phylogenetic comparative methods explore the relationships between quantitative traits adjusting for shared evolutionary history. This adjustment often occurs through a Brownian diffusion process along the branches of the phylogeny that generates model residuals or the traits themselves. For high-dimensional traits, inferring all pair-wise correlations within the multivariate diffusion is limiting. To circumvent this problem, we propose phylogenetic factor analysis (PFA) that assumes a small unknown number of independent evolutionary factors arise along the phylogeny and these factors generate clusters of dependent traits. Set in a Bayesian framework, PFA provides measures of uncertainty on the factor number and groupings, combines both continuous and discrete traits, integrates over missing measurements and incorporates phylogenetic uncertainty with the help of molecular sequences. We develop Gibbs samplers based on dynamic programming to estimate the PFA posterior distribution, over 3-fold faster than for multivariate diffusion and a further order-of-magnitude more efficiently in the presence of latent traits. We further propose a novel marginal likelihood estimator for previously impractical models with discrete data and find that PFA also provides a better fit than multivariate diffusion in evolutionary questions in columbine flower development, placental reproduction transitions and triggerfish fin morphometry.

[Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

PubMed

Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

2014-01-01

Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

Extension Procedures for Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Nagy, Gabriel; Brunner, Martin; Lüdtke, Oliver; Greiff, Samuel

2017-01-01

We present factor extension procedures for confirmatory factor analysis that provide estimates of the relations of common and unique factors with external variables that do not undergo factor analysis. We present identification strategies that build upon restrictions of the pattern of correlations between unique factors and external variables. The…

Cognitive style as a factor in accounting students' perceptions of career-choice factors.

PubMed

Gul, F; Huang, A; Subramaniam, N

1992-12-01

Since prior studies of individuals' perceptions of career-choice factors have not considered the effect of cognitive styles of subjects, this study, using 68 accounting students, investigated the mediating effects of the field dependent-independent cognitive dimension on perceptions of the importance of career-choice factors. The results, in general, show that cognitive style affected individuals' perceptions of career-choice factors, suggesting that future studies of individuals' perceptions should take into account individual cognitive differences.

Factor V leiden is a risk factor for myocardial infarction in young Turkish men.

PubMed

Hobikoglu, Gultekin F; Akyuz, Umit; Akyuz, Filiz; Ozer, Orhan; Güney, Dilvin; Narin, Ahmet; Unaltuna, Nihan

2004-12-01

Factor V Leiden is the most common known hereditary abnormality of the clotting system which leads to a reduced anticoagulant effect of activated protein C (APC resistance). FactorV Leiden has been shown to be the most frequent inherited thrombophilic disorder in patients with idiopathic venous thromboembolism. The relationship between this genetic abnormality and myocardial infarction is still unresolved. The aim of this study was to investigate whether factor V Leiden is a risk factor for myocardial infarction in young Turkish men or not. We compared 42 patients who had a diagnosis of acute MI and were younger than 40 years (35.6+/-4.8 years) with 66 healthy, age and sex-matched control subjects. Blood samples from the patients and the controls were analysed for the factor V Leiden mutation by DNA analysis, using polimerase chain reaction. Factor V Leiden mutation was found in 10 of 42 (23.8%) patients with myocardial infarction and 6 of 66 (9%) control subjects (p < 0.001). The odds ratio for MI was 3.1. (CI 95% 1.0-8.9) The results of this study suggest that the presence of factorV Leiden increases the risk of Ml in young Turkish men. ( Acta Cardiol 2004; 59(6): 594-597)

[Predictive factors of anxiety disorders].

PubMed

Domschke, K

2014-10-01

Anxiety disorders are among the most frequent mental disorders in Europe (12-month prevalence 14%) and impose a high socioeconomic burden. The pathogenesis of anxiety disorders is complex with an interaction of biological, environmental and psychosocial factors contributing to the overall disease risk (diathesis-stress model). In this article, risk factors for anxiety disorders will be presented on several levels, e.g. genetic factors, environmental factors, gene-environment interactions, epigenetic mechanisms, neuronal networks ("brain fear circuit"), psychophysiological factors (e.g. startle response and CO2 sensitivity) and dimensional/subclinical phenotypes of anxiety (e.g. anxiety sensitivity and behavioral inhibition), and critically discussed regarding their potential predictive value. The identification of factors predictive of anxiety disorders will possibly allow for effective preventive measures or early treatment interventions, respectively, and reduce the individual patient's suffering as well as the overall socioeconomic burden of anxiety disorders.

Beyond Collinear Factorization

NASA Astrophysics Data System (ADS)

Neill, Duff

2017-01-01

Collinear factorization is the basis of many collider observables, and is one of the most highly tested bedrocks of QCD. And yet, it reveals a very limited picture of the nucleon, and the internal dynamics of the partons bound within. I will attempt to elucidate what observables do not fall into a naive collinear factorization framework, what sorts of pictures that have been proposed to replace it in these observables, and what one can learn about the nucleon. Time permitting, I will cover new developments in Soft Collinear Effective Field Theory that allow one to discuss and calculate both collinear factorization and spectator interactions on a first principles basis, hopefully paving the way to investigate the whole coherent structure of the nucleon, not just a single lucky parton involved in the hard interaction.

New multiplex real-time PCR approach to detect gene mutations for spinal muscular atrophy.

PubMed

Liu, Zhidai; Zhang, Penghui; He, Xiaoyan; Liu, Shan; Tang, Shi; Zhang, Rong; Wang, Xinbin; Tan, Junjie; Peng, Bin; Jiang, Li; Hong, Siqi; Zou, Lin

2016-08-17

Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation. The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR. The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA. The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells.

PubMed

Vélez-Cruz, Renier; Zadorin, Anton S; Coin, Frédéric; Egly, Jean-Marc

2013-01-15

Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D/CS cells displayed a gross transcriptional dysregulation compared with "pure" XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D/CS that cannot be explained by a DNA repair defect.

Active medium gain study of electric-discharge oxygen-iodine laser

NASA Astrophysics Data System (ADS)

Kolobyanin, Yuriy; Adamenkov, Yuriy; Vyskubenko, Boris; Goryachev, Leonid; Ilyin, Sergey; Kalashnik, Anatoliy; Rakhimova, Tatiana; Rogozhnikov, Georgiy

2007-05-01

The paper reports on experimental studies of the active medium gain in supersonic electric-discharge oxygen-iodine laser (DOIL) based on traveling mw discharge. The measurements have included: absolute concentration, yield, and energy efficiency of production of SO in pure oxygen and oxygen-helium mixes at an oxygen partial pressure 3 to 15 Torr. For the gas flow to get rid of atomic oxygen, both heterogeneous mercury oxide coatings of the tube walls and homogeneous additives to the work mix, such as nitrogen oxide, have been used. The active medium of DOIL was formed using a nozzle array of the type of ejector sized as 10*50 mm2. The singlet oxygen-helium mix was supplied through three rows of sonic cylindrical nozzles, while the iodine-carrier gas mix - through two rows of supersonic conical nozzles with a half-opening angle of 10°(arc). The gas-phase iodine was produced in a quartz cell filled with iodine crystals. Room-temperature iodine vapors were picked up with a carrier gas (nitrogen or helium) and thus delivered into the nozzle array. The active medium was investigated by the high-resolution laser diode spectroscopy approach that used the laser type Vortex 6025 purchased from New Focus, Inc. The laser medium gain factor was determined by the intra-cavity approach having a sensitivity about 1*10 -6 cm -1. The static temperature of the medium was determined from the measurements of gain half-width. The gain of the active medium of electric-discharge OIL has been investigated. The DOIL in use was operating on a mix composed as O II:He=1:1 at a total pressure of 6 Torr and flowrate - about 1 mmol/s. With helium as an iodine carrier gas at a flowrate ~3 mmol/s, we have recorded a positive gain in the DOIL medium.

Brain Tumor Risk Factors

MedlinePlus

... Factors Brain Tumor Statistics ABTA Publications Brain Tumor Dictionary Upcoming Webinars Anytime Learning Brain Tumor Educational Presentations ... Factors Brain Tumor Statistics ABTA Publications Brain Tumor Dictionary Upcoming Webinars Anytime Learning Brain Tumor Educational Presentations ...

Factor H-related proteins.

PubMed

Józsi, Mihály; Meri, Seppo

2014-01-01

Factor H-related proteins (CFHRs) are plasma glycoproteins related in structure and antigenicity to each other and to the complement inhibitory protein factor H. Such proteins are found in most mammals but their number and domain composition vary. This chapter summarizes our current knowledge on the human factor H-related proteins. In contrast to factor H, they have no strong complement inhibitory activity, although for some of them regulatory or complement modulatory activity has been reported. A common feature of CFHRs is that they bind to the C3b component of complement. Novel links between CFHRs and various diseases (C3 glomerulopathies, atypical hemolytic uremic syndrome and age-related macular degeneration) have been revealed in recent years, but we are still far from understanding their biological function.

Factors Affecting Wound Healing

PubMed Central

Guo, S.; DiPietro, L.A.

2010-01-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

New microbial growth factor

NASA Technical Reports Server (NTRS)

Bok, S. H.; Casida, L. E., Jr.

1977-01-01

A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

Factors affecting wound healing.

PubMed

Guo, S; Dipietro, L A

2010-03-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds.

Quantification of Emission Factor Uncertainty

EPA Science Inventory

Emissions factors are important for estimating and characterizing emissions from sources of air pollution. There is no quantitative indication of uncertainty for these emission factors, most factors do not have an adequate data set to compute uncertainty, and it is very difficult...

Risk Factor Assessment Branch (RFAB)

Cancer.gov

The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

Human Factors Planning Guidelines

DOT National Transportation Integrated Search

1996-01-01

To ensure human factors considerations are fully incorporated in the system : development, the Integrated Product Team (IPT) or Program Manager initiates a : Human Factors Program (HFP) that addresses the human performance and human : resource parame...

Clothing factors and vaginitis.

PubMed

Heidrich, F E; Berg, A O; Bergman, J J

1984-10-01

Associations of clothing factors and vulvovaginal symptoms, signs, and microbiology were sought in 203 women seeking care at a university family medicine clinic. Clothing factors studied were use of panty hose, underwear for sleep, cotton lining panels, and pants vs skirts. Women wearing and not wearing panty hose had similar rates of vaginitis symptoms and signs, but yeast vaginitis was about three times more common among wearers. Relationships of other clothing factors to vaginitis were not found. Nonspecific vaginitis was not found to be related to clothing.

Factors affecting sign retroreflectivity

DOT National Transportation Integrated Search

2001-01-01

This study was undertaken to better understand the factors that may affect road sign retroreflectivity, specifically age and physical orientation. A better understanding of these factors could provide guidance to ODOT in managing its inventory of roa...

Intrinsic-extrinsic factors in sport motivation.

PubMed

Pedersen, Darhl M

2002-10-01

Participants were 83 students (36 men and 47 women). 10 intrinsic-extrinsic factors involved in sport motivation were obtained. The factors were generated from items obtained from the participants rather than items from the experimenter. This was done to avoid the possible influence of preconceptions on the part of the experimenter regarding what the final dimensions may be. Obtained motivational factors were Social Reinforcement, Fringe Benefits, Fame and Fortune, External Forces, Proving Oneself, Social Benefits, Mental Enrichment, Expression of Self, Sense of Accomplishment, and Self-enhancement. Each factor was referred to an intrinsic-extrinsic dimension to describe its relative position on that dimension. The order of the factors as listed indicates increasing intrinsic motivation. i.e., the first four factors were rated in the extrinsic range, whereas the remaining six were rated to be in the intrinsic range. Next, the participants rated the extent to which each of the various factors was involved in their decision to participate in sport activities. The pattern of use of the motivational factors was the same for both sexes except that men indicated greater use of the Fringe Benefits factor. Overall, the more intrinsic a sport motivation factor was rated, the more likely it was to be rated as a factor in actual sport participation.

Multi-factor authentication

DOEpatents

Hamlet, Jason R; Pierson, Lyndon G

2014-10-21

Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.

PubMed

Lefkowitz, J B; Monroe, D M; Kasper, C K; Roberts, H R

1993-07-01

A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.

Risk factors for osteoarthritis and contributing factors to current arthritic pain in South Korean older adults.

PubMed

Lee, Kyoung Min; Chung, Chin Youb; Sung, Ki Hyuk; Lee, Seung Yeol; Won, Sung Hun; Kim, Tae Gyun; Choi, Young; Kwon, Soon Sun; Kim, Yeon Ho; Park, Moon Seok

2015-01-01

Although previous studies have focused on risk factors for osteoarthritis, there is some debate on this issue. Furthermore, associated factors with arthritic symptom (arthralgia) have not been sufficiently investigated, despite its clinical importance in the management of osteoarthritis. This study was performed to examine the risk factors for osteoarthritis and the contributing factors to current arthritic pain in older adults. The Fourth Korean National Health and Nutrition Examination Surveys was conducted in 2009. Therein, 720 males and 1008 females aged 65 years and older were included. Comprehensive data on habitual, socioeconomic, medical, nutritional, and psychological factors were collected along with the presence of osteoarthritis and arthritic pain. After univariate analysis, binary logistic regression analysis was performed to identify risk factors for osteoarthritis and contributing factors to current arthritic pain. Age (p=0.005), female gender (p<0.001), higher body mass index (BMI) (p<0.001), and osteoporosis (p<0.001) were significant risk factors for osteoarthritis, while higher education level (p=0.025) was a protective factor for osteoarthritis. Higher BMI (p=0.047), lack of weekly moderate intensity activity (p<0.001), and unfavorable subjective health status (p<0.001) were significant factors contributing to current arthritic pain among subjects with osteoarthritis. Both osteoarthritis and current arthritic pain adversely affected health related quality of life. Higher BMI, lack of weekly moderate intensity activity, and unfavorable subjective health status were significant factors contributing to current arthritic pain. More attention needs to be paid to psychiatric effects on osteoarthritis and joint related pain.

Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum-free cultures of human hepatocytes.

PubMed

Runge, D M; Runge, D; Dorko, K; Pisarov, L A; Leckel, K; Kostrubsky, V E; Thomas, D; Strom, S C; Michalopoulos, G K

1999-02-01

Serum-free primary cultures of hepatocytes are a useful tool to study factors triggering hepatocyte proliferation and regeneration. We have developed a chemically defined serum-free system that allows human hepatocyte proliferation in the presence of epidermal growth factor and hepatocyte growth factor. DNA synthesis and accumulation were determined by [3H]thymidine incorporation and fluorometry, respectively. Western blot analyses and co-immunoprecipitations were used to investigate the association of proteins involved in epidermal growth factor and hepatocyte growth factor activation and signaling: epidermal growth factor receptor, hepatocyte growth factor receptor (MET), urokinase-type plasminogen activator and its receptor, and a member of the signal transducer and activator of transcription family, STAT-3. Primary human hepatocytes proliferated under serum-free conditions in a chemically defined medium for up to 12 days. Epidermal growth factor-receptor and MET were present and functional, decreasing over time. MET, urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor co-precipitated to varying degrees during the culture period. STAT-3 co-precipitated with epidermal growth factor-receptor and MET to varying degrees. Proliferation of human hepatocytes can improve by modification of a chemically defined medium originally used for rat hepatocyte cultures. In these long-term cultures of human hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate growth and differentiation by interacting with their receptors and initiating downstream signaling. This involves complex formation of the receptors with other plasma membrane components for MET (urokinase-type plasminogen activator in context of its receptor) and activation of STAT-3 for both receptors.

Bootstrap Confidence Intervals for Ordinary Least Squares Factor Loadings and Correlations in Exploratory Factor Analysis

ERIC Educational Resources Information Center

Zhang, Guangjian; Preacher, Kristopher J.; Luo, Shanhong

2010-01-01

This article is concerned with using the bootstrap to assign confidence intervals for rotated factor loadings and factor correlations in ordinary least squares exploratory factor analysis. Coverage performances of "SE"-based intervals, percentile intervals, bias-corrected percentile intervals, bias-corrected accelerated percentile…

Factors that regulate embryonic gustatory development

PubMed Central

Krimm, Robin F

2007-01-01

Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP). As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF), functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-β-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and targeting of peripheral

Scalable non-negative matrix tri-factorization.

PubMed

Čopar, Andrej; Žitnik, Marinka; Zupan, Blaž

2017-01-01

Matrix factorization is a well established pattern discovery tool that has seen numerous applications in biomedical data analytics, such as gene expression co-clustering, patient stratification, and gene-disease association mining. Matrix factorization learns a latent data model that takes a data matrix and transforms it into a latent feature space enabling generalization, noise removal and feature discovery. However, factorization algorithms are numerically intensive, and hence there is a pressing challenge to scale current algorithms to work with large datasets. Our focus in this paper is matrix tri-factorization, a popular method that is not limited by the assumption of standard matrix factorization about data residing in one latent space. Matrix tri-factorization solves this by inferring a separate latent space for each dimension in a data matrix, and a latent mapping of interactions between the inferred spaces, making the approach particularly suitable for biomedical data mining. We developed a block-wise approach for latent factor learning in matrix tri-factorization. The approach partitions a data matrix into disjoint submatrices that are treated independently and fed into a parallel factorization system. An appealing property of the proposed approach is its mathematical equivalence with serial matrix tri-factorization. In a study on large biomedical datasets we show that our approach scales well on multi-processor and multi-GPU architectures. On a four-GPU system we demonstrate that our approach can be more than 100-times faster than its single-processor counterpart. A general approach for scaling non-negative matrix tri-factorization is proposed. The approach is especially useful parallel matrix factorization implemented in a multi-GPU environment. We expect the new approach will be useful in emerging procedures for latent factor analysis, notably for data integration, where many large data matrices need to be collectively factorized.

Microcircuit Cost Factors.

DTIC Science & Technology

1981-12-01

DOCUMENTATION PAGE JR INSTRUCTIONSREKT WUMETATON EBEFORE COMPLETING FORM -ACREPORT MUMMER 3 . GOVT ACCESSION NO 3 . RE1ACIPIENT’S CATALOO NUMmER RAC-TR-81-354...2-5 2.3 MC Factors Effecting Cost ............... .o.. .... 2-8 Section Three - DESCRIPTION OF MODEL COST FACTORS ........... 3 -1 3.1 MC Research...Design, Test & Evaluation (RDT&E) .......... 3 -1 3.1.1 Literature Search ....... 3 -1 3.1.2 RDT&E (RCER) . ... . . . ... .. ... .......... . 3 -1 3.2

Soil Forming Factors

Science.gov Websites

It! What is Soil? Chip Off the Old Block Soil Forming Factors Matters of Life and Death Underneath It All Wise Choices A World of Soils << 1 Soil Forming Factors 2 A Top to Bottom Guide 3 Making a Soil Monolith 4 Soil Orders 5 State Soil Monoliths 6 Where in the Soil World Are You? >> A Top to

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries.

PubMed

Alecu, I M; Zheng, Jingjing; Zhao, Yan; Truhlar, Donald G

2010-09-14

Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Factors Related to Rape Reporting Behavior in Brazil: Examining the Role of Spatio-Temporal Factors.

PubMed

Melo, Silas Nogueira de; Beauregard, Eric; Andresen, Martin A

2016-07-01

The reporting of rape to police is an important component of this crime to have the criminal justice system involved and, potentially, punish offenders. However, for a number of reasons (fear of retribution, self-blame, etc.), most rapes are not reported to police. Most often, the research investigating this phenomenon considers incident and victim factors with little attention to the spatio-temporal factors of the rape. In this study, we consider incident, victim, and spatio-temporal factors relating to rape reporting in Campinas, Brazil. Our primary research question is whether or not the spatio-temporal factors play a significant role in the reporting of rape, over and above incident and victim factors. The subjects under study are women who were admitted to the Women's Integrated Healthcare Center at the State University of Campinas, Brazil, and surveyed by a psychologist or a social worker. Rape reporting to police was measured using a dichotomous variable. Logistic regression was used to predict the probability of rape reporting based on incident, victim, and spatio-temporal factors. Although we find that incident and victim factors matter for rape reporting, spatio-temporal factors (rape/home location and whether the rape was in a private or public place) play an important role in rape reporting, similar to the literature that considers these factors. This result has significant implications for sexual violence education. Only when we know why women decide not to report a rape may we begin to work on strategies to overcome these hurdles.

Factor Analysis via Components Analysis

ERIC Educational Resources Information Center

Bentler, Peter M.; de Leeuw, Jan

2011-01-01

When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

Factor Analysis of Intern Effectiveness

ERIC Educational Resources Information Center

Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

2012-01-01

Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

Factorization method of quadratic template

NASA Astrophysics Data System (ADS)

Kotyrba, Martin

2017-07-01

Multiplication of two numbers is a one-way function in mathematics. Any attempt to distribute the outcome to its roots is called factorization. There are many methods such as Fermat's factorization, Dixońs method or quadratic sieve and GNFS, which use sophisticated techniques fast factorization. All the above methods use the same basic formula differing only in its use. This article discusses a newly designed factorization method. Effective implementation of this method in programs is not important, it only represents and clearly defines its properties.

NASA human factors programmatic overview

NASA Technical Reports Server (NTRS)

Connors, Mary M.

1992-01-01

Human factors addresses humans in their active and interactive capacities, i.e., in the mental and physical activities that they perform and in the contributions they make to achieving the goals of the mission. The overall goal of space human factors in NASA is to support the safety, productivity, and reliability of both the on-board crew and the ground support staff. Safety and reliability are fundamental requirements that human factors shares with other disciplines, while productivity represents the defining contribution of the human factors discipline.

Cardiovascular risk factors and dementia.

PubMed

Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

2008-06-01

Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

Switching single chain magnet behavior via photoinduced bidirectional metal-to-metal charge transfer† †Electronic supplementary information (ESI) available: Synthesis and physical measurement details. Crystal data in CIF format and additional figures (Fig. S1–S15). CCDC 1528877. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03401f

PubMed Central

Jiang, Wenjing; Jiao, Chengqi; Meng, Yinshan; Zhao, Liang; Liu, Qiang

2017-01-01

The preparation of single-chain magnets (SCMs) with photo-switchable bistable states is essential for the development of high-density photo-recording devices. However, the reversible switching of the SCM behavior upon light irradiation is a formidable challenge. Here we report a well-isolated double zigzag chain {[Fe(bpy)(CN)4]2[Co(phpy)2]}·2H2O (bpy = 2,2′-bipyridine, phpy = 4-phenylpyridine), which exhibits reversible redox reactions with interconversion between FeIIILS(μ-CN)CoIIHS(μ-NC)FeIIILS (LS = low-spin, HS = high-spin) and FeIIILS(μ-CN)CoIIILS(μ-NC)FeIILS linkages under alternating irradiation with 808 and 532 nm lasers. The bidirectional photo-induced metal-to-metal charge transfer results in significant changes of anisotropy and intrachain magnetic interactions, reversibly switching the SCM behavior. The on-switching SCM behavior driven by light irradiation at 808 nm could be reversibly switched off by irradiation at 532 nm. The results provide an additional and independent way to control the bistable states of SCMs by switching in the 0 → 1 → 0 sequence, with potential applications in high density storage and molecular switches. PMID:29629126

The translation factors of Drosophila melanogaster.

PubMed

Marygold, Steven J; Attrill, Helen; Lasko, Paul

2017-01-02

Synthesis of polypeptides from mRNA (translation) is a fundamental cellular process that is coordinated and catalyzed by a set of canonical 'translation factors'. Surprisingly, the translation factors of Drosophila melanogaster have not yet been systematically identified, leading to inconsistencies in their nomenclature and shortcomings in functional (Gene Ontology, GO) annotations. Here, we describe the complete set of translation factors in D. melanogaster, applying nomenclature already in widespread use in other species, and revising their functional annotation. The collection comprises 43 initiation factors, 12 elongation factors, 3 release factors and 6 recycling factors, totaling 64 of which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of notable findings and particular insights derived from Drosophila about these factors. This catalog, together with the incorporation of the improved nomenclature and GO annotation into FlyBase, will greatly facilitate access to information about the functional roles of these important proteins.

Phonological Awareness: Factors of Influence

ERIC Educational Resources Information Center

Frohlich, Linda Paulina; Petermann, Franz; Metz, Dorothee

2013-01-01

Early child development is influenced by various genetic and environmental factors. This study aims to identify factors that affect the phonological awareness of preschool and first grade children. Based on a sample of 330 German-speaking children (mean age = 6.2 years) the following domains were evaluated: Parent factors, birth and pregnancy,…

Factorization-based texture segmentation

DOE PAGES

Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

2015-06-17

This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histogramsmore » to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.« less

Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption.

PubMed

Iorio, Alfonso; Krishnan, Sangeeta; Myrén, Karl-Johan; Lethagen, Stefan; McCormick, Nora; Yermakov, Sander; Karner, Paul

2017-04-01

Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, this study compared the first extended-half-life-recombinant factor IX (rFIX) product-recombinant factor IX Fc fusion protein (rFIXFc)-with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis. This study compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection. Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p = 0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means = 42.8-74.5 IU/kg/week [93-161%], p < 0.001). Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.

Optimizing human factors in dentistry

PubMed Central

Gupta, Arpit; Ankola, Anil V.; Hebbal, Mamata

2013-01-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs. PMID:23946745

Optimizing human factors in dentistry.

PubMed

Gupta, Arpit; Ankola, Anil V; Hebbal, Mamata

2013-03-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs.

The Unfortunate Human Factor: A Selective History of Human Factors for Technical Communicators.

ERIC Educational Resources Information Center

Johnson, Robert R.

1994-01-01

Reviews moments in the history of human factors that are especially relevant to the field of technical communications. Discusses human factors research that is applicable to technical communications. Focuses on qualitative usability research, minimalism, and human activity interface design. (HB)

The sigma factors of Bacillus subtilis.

PubMed Central

Haldenwang, W G

1995-01-01

The specificity of DNA-dependent RNA polymerase for target promotes is largely due to the replaceable sigma subunit that it carries. Multiple sigma proteins, each conferring a unique promoter preference on RNA polymerase, are likely to be present in all bacteria; however, their abundance and diversity have been best characterized in Bacillus subtilis, the bacterium in which multiple sigma factors were first discovered. The 10 sigma factors thus far identified in B. subtilis directly contribute to the bacterium's ability to control gene expression. These proteins are not merely necessary for the expression of those operons whose promoters they recognize; in many instances, their appearance within the cell is sufficient to activate these operons. This review describes the discovery of each of the known B. subtilis sigma factors, their characteristics, the regulons they direct, and the complex restrictions placed on their synthesis and activities. These controls include the anticipated transcriptional regulation that modulates the expression of the sigma factor structural genes but, in the case of several of the B. subtilis sigma factors, go beyond this, adding novel posttranslational restraints on sigma factor activity. Two of the sigma factors (sigma E and sigma K) are, for example, synthesized as inactive precursor proteins. Their activities are kept in check by "pro-protein" sequences which are cleaved from the precursor molecules in response to intercellular cues. Other sigma factors (sigma B, sigma F, and sigma G) are inhibited by "anti-sigma factor" proteins that sequester them into complexes which block their ability to form RNA polymerase holoenzymes. The anti-sigma factors are, in turn, opposed by additional proteins which participate in the sigma factors' release. The devices used to control sigma factor activity in B, subtilis may prove to be as widespread as multiple sigma factors themselves, providing ways of coupling sigma factor activation to

Recovery of Weak Factor Loadings When Adding the Mean Structure in Confirmatory Factor Analysis: A Simulation Study

PubMed Central

Ximénez, Carmen

2016-01-01

This article extends previous research on the recovery of weak factor loadings in confirmatory factor analysis (CFA) by exploring the effects of adding the mean structure. This issue has not been examined in previous research. This study is based on the framework of Yung and Bentler (1999) and aims to examine the conditions that affect the recovery of weak factor loadings when the model includes the mean structure, compared to analyzing the covariance structure alone. A simulation study was conducted in which several constraints were defined for one-, two-, and three-factor models. Results show that adding the mean structure improves the recovery of weak factor loadings and reduces the asymptotic variances for the factor loadings, particularly for the models with a smaller number of factors and a small sample size. Therefore, under certain circumstances, modeling the means should be seriously considered for covariance models containing weak factor loadings. PMID:26779071

Sufficient Forecasting Using Factor Models

PubMed Central

Fan, Jianqing; Xue, Lingzhou; Yao, Jiawei

2017-01-01

We consider forecasting a single time series when there is a large number of predictors and a possible nonlinear effect. The dimensionality was first reduced via a high-dimensional (approximate) factor model implemented by the principal component analysis. Using the extracted factors, we develop a novel forecasting method called the sufficient forecasting, which provides a set of sufficient predictive indices, inferred from high-dimensional predictors, to deliver additional predictive power. The projected principal component analysis will be employed to enhance the accuracy of inferred factors when a semi-parametric (approximate) factor model is assumed. Our method is also applicable to cross-sectional sufficient regression using extracted factors. The connection between the sufficient forecasting and the deep learning architecture is explicitly stated. The sufficient forecasting correctly estimates projection indices of the underlying factors even in the presence of a nonparametric forecasting function. The proposed method extends the sufficient dimension reduction to high-dimensional regimes by condensing the cross-sectional information through factor models. We derive asymptotic properties for the estimate of the central subspace spanned by these projection directions as well as the estimates of the sufficient predictive indices. We further show that the natural method of running multiple regression of target on estimated factors yields a linear estimate that actually falls into this central subspace. Our method and theory allow the number of predictors to be larger than the number of observations. We finally demonstrate that the sufficient forecasting improves upon the linear forecasting in both simulation studies and an empirical study of forecasting macroeconomic variables. PMID:29731537

Exploratory Bi-factor Analysis: The Oblique Case.

PubMed

Jennrich, Robert I; Bentler, Peter M

2012-07-01

Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger and Swineford (Psychometrika 47:41-54, 1937). The bi-factor model has a general factor, a number of group factors, and an explicit bi-factor structure. Jennrich and Bentler (Psychometrika 76:537-549, 2011) introduced an exploratory form of bi-factor analysis that does not require one to provide an explicit bi-factor structure a priori. They use exploratory factor analysis and a bifactor rotation criterion designed to produce a rotated loading matrix that has an approximate bi-factor structure. Among other things this can be used as an aid in finding an explicit bi-factor structure for use in a confirmatory bi-factor analysis. They considered only orthogonal rotation. The purpose of this paper is to consider oblique rotation and to compare it to orthogonal rotation. Because there are many more oblique rotations of an initial loading matrix than orthogonal rotations, one expects the oblique results to approximate a bi-factor structure better than orthogonal rotations and this is indeed the case. A surprising result arises when oblique bi-factor rotation methods are applied to ideal data.

Mixture Factor Analysis for Approximating a Nonnormally Distributed Continuous Latent Factor with Continuous and Dichotomous Observed Variables

ERIC Educational Resources Information Center

Wall, Melanie M.; Guo, Jia; Amemiya, Yasuo

2012-01-01

Mixture factor analysis is examined as a means of flexibly estimating nonnormally distributed continuous latent factors in the presence of both continuous and dichotomous observed variables. A simulation study compares mixture factor analysis with normal maximum likelihood (ML) latent factor modeling. Different results emerge for continuous versus…

14 CFR 25.619 - Special factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Special factors. 25.619 Section 25.619... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.619 Special factors. The factor of safety prescribed in § 25.303 must be multiplied by the highest pertinent special factor of safety...

Job compensable factors and factor weights derived from job analysis data.

PubMed

Chi, Chia-Fen; Chang, Tin-Chang; Hsia, Ping-Ling; Song, Jen-Chieh

2007-06-01

Government data on 1,039 job titles in Taiwan were analyzed to assess possible relationships between job attributes and compensation. For each job title, 79 specific variables in six major classes (required education and experience, aptitude, interest, work temperament, physical demands, task environment) were coded to derive the statistical predictors of wage for managers, professionals, technical, clerical, service, farm, craft, operatives, and other workers. Of the 79 variables, only 23 significantly related to pay rate were subjected to a factor and multiple regression analysis for predicting monthly wages. Given the heterogeneous nature of collected job titles, a 4-factor solution (occupational knowledge and skills, human relations skills, work schedule hardships, physical hardships) explaining 43.8% of the total variance but predicting only 23.7% of the monthly pay rate was derived. On the other hand, multiple regression with 9 job analysis items (required education, professional training, professional certificate, professional experience, coordinating, leadership and directing, demand on hearing, proportion of shift working indoors, outdoors and others, rotating shift) better predicted pay and explained 32.5% of the variance. A direct comparison of factors and subfactors of job evaluation plans indicated mental effort and responsibility (accountability) had not been measured with the current job analysis data. Cross-validation of job evaluation factors and ratings with the wage rates is required to calibrate both.

Kindergarten Risk Factors, Cognitive Factors, and Teacher Judgments as Predictors of Early Reading in Dutch

ERIC Educational Resources Information Center

Gijsel, Martine A. R.; Bosman, Anna M. T.; Verhoeven, Ludo

2006-01-01

This study focused on the predictive value of risk factors, cognitive factors, and teachers' judgments in a sample of 462 kindergartners for their early reading skills and reading failure at the beginning of Grade 1. With respect to risk factors, enrollment in speech-language therapy, history of dyslexia or speech-language problems in the family,…

Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products.

PubMed

Iorio, A; Krishnan, S; Myrén, K J; Lethagen, S; McCormick, N; Yermakov, S; Karner, P

2017-05-01

Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. Results from seven studies of conventional rFVIII products (injections 2-4 times week -1 ) were compared with rFVIIIFc (injections 1.4-2.4 times week -1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg -1 week -1 (17-26%); median differences = 12.7-29.8 IU kg -1 week -1 (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc. Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections. © 2017 John Wiley & Sons Ltd.

Exploratory Bi-Factor Analysis: The Oblique Case

ERIC Educational Resources Information Center

Jennrich, Robert I.; Bentler, Peter M.

2012-01-01

Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger and Swineford ("Psychometrika" 47:41-54, 1937). The bi-factor model has a general factor, a number of group factors, and an explicit bi-factor structure. Jennrich and Bentler ("Psychometrika" 76:537-549, 2011) introduced an exploratory form of bi-factor…

14 CFR 31.43 - Fitting factor.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fitting factor. 31.43 Section 31.43... STANDARDS: MANNED FREE BALLOONS Design Construction § 31.43 Fitting factor. (a) A fitting factor of at least... structure. This factor applies to all parts of the fitting, the means of attachment, and the bearing on the...

14 CFR 23.619 - Special factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Special factors. 23.619 Section 23.619... Special factors. The factor of safety prescribed in § 23.303 must be multiplied by the highest pertinent special factors of safety prescribed in §§ 23.621 through 23.625 for each part of the structure whose...

Factors determining lumber recovery in sawmilling

Treesearch

Philip H. Steele

1984-01-01

Lumber volume recovery in sawmilling is determined by a confusing interaction of several factors. The more one knows about each individual factor, the more one can understand how the factors interact. The author identifies and discusses in detail seven factors influencing lumber recovery. Past and current research is cited, and examples are given to illustrate the...

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Worldsheet factorization for twistor-strings

NASA Astrophysics Data System (ADS)

Adamo, Tim

2014-04-01

We study the multiparticle factorization properties of two worldsheet theories which — at tree-level — describe the scattering of massless particles in four dimensions: the Berkovits-Witten twistor-string for = 4 super-Yang-Mills coupled to = 4 conformal supergravity, and the Skinner twistor-string for = 8 supergravity. By considering these string-like theories, we can study factorization at the level of the worldsheet before any Wick contractions or integrals have been performed; this is much simpler than considering the factorization properties of the amplitudes themselves. In Skinner's twistor-string this entails the addition of worldsheet gravity as well as a formalism that represents all external states in a manifestly symmetric way, which we develop explicitly at genus zero. We confirm that the scattering amplitudes of Skinner's theory, as well as the gauge theory amplitudes for the planar sector of the Berkovits-Witten theory, factorize appropriately at genus zero. In the non-planar sector, we find behavior indicative of conformal gravity in the Berkovits-Witten twistor-string. We contrast factorization in twistor-strings with the story in ordinary string theory, and also make some remarks on higher genus factorization and disconnected prescriptions.

The p Factor: One General Psychopathology Factor in the Structure of Psychiatric Disorders?

PubMed Central

Caspi, Avshalom; Houts, Renate M.; Belsky, Daniel W.; Goldman-Mellor, Sidra J.; Harrington, HonaLee; Israel, Salomon; Meier, Madeline H.; Ramrakha, Sandhya; Shalev, Idan; Poulton, Richie; Moffitt, Terrie E.

2013-01-01

Mental disorders traditionally have been viewed as distinct, episodic, and categorical conditions. This view has been challenged by evidence that many disorders are sequentially comorbid, recurrent/chronic, and exist on a continuum. Using the Dunedin Multidisciplinary Health and Development Study, we examined the structure of psychopathology, taking into account dimensionality, persistence, co-occurrence, and sequential comorbidity of mental disorders across 20 years, from adolescence to midlife. Psychiatric disorders were initially explained by three higher-order factors (Internalizing, Externalizing, and Thought Disorder) but explained even better with one General Psychopathology dimension. We have called this dimension the p factor because it conceptually parallels a familiar dimension in psychological science: the g factor of general intelligence. Higher p scores are associated with more life impairment, greater familiality, worse developmental histories, and more compromised early-life brain function. The p factor explains why it is challenging to find causes, consequences, biomarkers, and treatments with specificity to individual mental disorders. Transdiagnostic approaches may improve research. PMID:25360393

Phenotypic factor analysis of psychopathology reveals a new body-related transdiagnostic factor.

PubMed

Pezzoli, Patrizia; Antfolk, Jan; Santtila, Pekka

2017-01-01

Comorbidity challenges the notion of mental disorders as discrete categories. An increasing body of literature shows that symptoms cut across traditional diagnostic boundaries and interact in shaping the latent structure of psychopathology. Using exploratory and confirmatory factor analysis, we reveal the latent sources of covariation among nine measures of psychopathological functioning in a population-based sample of 13024 Finnish twins and their siblings. By implementing unidimensional, multidimensional, second-order, and bifactor models, we illustrate the relationships between observed variables, specific, and general latent factors. We also provide the first investigation to date of measurement invariance of the bifactor model of psychopathology across gender and age groups. Our main result is the identification of a distinct "Body" factor, alongside the previously identified Internalizing and Externalizing factors. We also report relevant cross-disorder associations, especially between body-related psychopathology and trait anger, as well as substantial sex and age differences in observed and latent means. The findings expand the meta-structure of psychopathology, with implications for empirical and clinical practice, and demonstrate shared mechanisms underlying attitudes towards nutrition, self-image, sexuality and anger, with gender- and age-specific features.

A proposal for a novel impact factor as an alternative to the JCR impact factor

PubMed Central

Yang, Zu-Guo; Zhang, Chun-Ting

2013-01-01

One disadvantage of the JCR impact factor, the most commonly used assessment tool for ranking and evaluating scientific journals, is its inability in distinguishing among different shapes of citation distribution curves, leading to unfair evaluation of journals in some cases. This paper aims to put forward an alternative impact factor (IF′) that can properly reflect citation distributions. The two impact factors are linearly and positively correlated, and have roughly the same order of magnitude. Because of the ability of IF′ in distinguishing among different shapes of citation distribution curves, IF′ may properly reflect the academic performance of a scientific journal in a way that is different from the JCR impact factor with some unique features that reward journals with highly cited papers. Therefore, it is suggested that IF′ could be used to complement the JCR impact factor. PMID:24296521

A proposal for a novel impact factor as an alternative to the JCR impact factor.

PubMed

Yang, Zu-Guo; Zhang, Chun-Ting

2013-12-03

One disadvantage of the JCR impact factor, the most commonly used assessment tool for ranking and evaluating scientific journals, is its inability in distinguishing among different shapes of citation distribution curves, leading to unfair evaluation of journals in some cases. This paper aims to put forward an alternative impact factor (IF') that can properly reflect citation distributions. The two impact factors are linearly and positively correlated, and have roughly the same order of magnitude. Because of the ability of IF' in distinguishing among different shapes of citation distribution curves, IF' may properly reflect the academic performance of a scientific journal in a way that is different from the JCR impact factor with some unique features that reward journals with highly cited papers. Therefore, it is suggested that IF' could be used to complement the JCR impact factor.

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

PubMed

Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

Factor D Enzyme

NASA Technical Reports Server (NTRS)

2004-01-01

The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

Myeloid leukemia factor

PubMed Central

Gobert, Vanessa; Haenlin, Marc; Waltzer, Lucas

2012-01-01

Even though deregulation of human MLF1, the founding member of the Myeloid Leukemia Factor family, has been associated with acute myeloid leukemia, the function and mode of action of this family of genes have remained rather mysterious. Yet, recent findings in Drosophila shed new light on their biological activity and suggest that they play an important role in hematopoiesis and leukemia, notably by regulating the stability of RUNX transcription factors, another family of conserved proteins with prominent roles in normal and malignant blood cell development. PMID:22885977

E2F1 transcription factor and its impact on growth factor and cytokine signaling.

PubMed

Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

2016-10-01

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ). Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors influencing healthcare service quality

PubMed Central

Mosadeghrad, Ali Mohammad

2014-01-01

Background: The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. Methods: Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. Results: Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. Conclusion: This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality. PMID:25114946

The Factor Structure of the English Language Development Assessment: A Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Kuriakose, Anju

2011-01-01

This study investigated the internal factor structure of the English language development Assessment (ELDA) using confirmatory factor analysis. ELDA is an English language proficiency test developed by a consortium of multiple states and is used to identify and reclassify English language learners in kindergarten to grade 12. Scores on item…

Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.

PubMed

Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G

2007-05-15

Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

PubMed

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Power factor regulation for household usage

NASA Astrophysics Data System (ADS)

Daud, Nik Ghazali Nik; Hashim, Fakroul Ridzuan; Tarmizi, Muhammad Haziq Ahmad

2018-02-01

Power factor regulator technology has recently drawn attention to the consumer and to power generation company in order for consumers to use electricity efficiently. Controlling of power factor for efficient usage can reduce the production of power in fulfilment demands hence reducing the greenhouse effect. This paper presents the design method of power factor controller for household usage. There are several methods to improve the power factor. The power factor controller used by this method is by using capacitors. Total harmonic distortion also has become a major problem for the reliability of the electrical appliances and techniques to control it will be discussed.

Genetics Home Reference: factor V deficiency

MedlinePlus

... Twitter Home Health Conditions Factor V deficiency Factor V deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor V deficiency is a rare bleeding disorder. The signs ...

Genetics Home Reference: factor X deficiency

MedlinePlus

... Twitter Home Health Conditions Factor X deficiency Factor X deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor X deficiency is a rare bleeding disorder that varies ...

Fibroblast growth factor receptors in breast cancer.

PubMed

Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

PubMed

Kjøllesdal, M K R; Ariansen, I; Mortensen, L H; Davey Smith, G; Næss, Ø

2016-12-01

To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor VIII.

PubMed

El Adib, Ahmed Ghassan; Majdi, Farah; Dilai, Mohamed Othmane; Asmouki, Hamid; Bassir, Ahlam; Harou, Karam; Soumani, Abderraouf; Younous, Said; Mahmal, Lahoucine

2014-01-01

Inherited combined factor V and factor VIII deficiency (F5F8D) is autosomal recessive transmission disorder. Epistaxis, postsurgical bleeding, and menorrhagia are the most common symptoms. The risk of miscarriage and placental abruption is consequent. We report a case of successful pregnancy in a patient with F5F8D. 20-year-old woman, born of consanguineous parents, third gestate, first parity, two miscarriages, admitted for child birth of a spontaneous pregnancy estimated at 38 weeks and was diagnosed with F5F8D. At admission, patient was hemodynamically stable, with good obstetric conditions. The biologic results showed low levels of PT (52%), factor V (7%), and factor VIII (5%), and the activated partial thromboplastin time was prolonged (68,6%). Parturient was admitted in intensive care unit, maternal and fetal monitoring was performed. Fresh frozen plasma (FFP) and factor VIII concentrates were perfused at the induction of labor. Analgesia used fentanyl titration. The delivery gave birth to a newborn male, with Apgar 10/10 and 3000 g. The puerperium was simple without any important bleeding. Laboratory tests for the newborn were acceptable. Little literature is available on this subject and there are no guidelines available concerning pregnancy; we chose to prescribe a combination of factor VIII concentrate and FFP in pre-, per- and postpartum. The same protocol was successfully used in a patient before dental extraction and prostatectomy. Vaginal delivery is possible, as our case. Management by multidisciplinary team is recommended.

Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding

PubMed Central

Verzi, Michael P.; Shin, Hyunjin; San Roman, Adrianna K.

2013-01-01

Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors. PMID:23129810

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

PubMed

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

Genetics Home Reference: factor VII deficiency

MedlinePlus

... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

General Factor of Personality Questionnaire (GFPQ): only one factor to understand personality?

PubMed

Amigó, Salvador; Caselles, Antonio; Micó, Joan C

2010-05-01

This study proposes a psychometric approach to assess the General Factor of Personality (GFP) to explain the whole personality. This approach defends the existence of one basic factor that represents the overall personality. The General Factor of Personality Questionnaire (GFPQ) is presented to measure the basic, combined trait of the complete personality. The questionnaire includes 20 items and is constituted by two scales with 10 items each one: the Extraversion Scale (ES) and the Introversion Scale (IS). The GFPQ shows adequate internal consistency and construct validity, while the relationships with the personality factors of other models and with psychopathology are as expected. It correlates positively and significantly with Extraversion (E) and Psychoticism (P), and negatively with Neuroticism (N) of Eysenck's EPQ (Eysenck Personality Questionnaire); it correlates positively and significantly with the Sensation Seeking Scaled (SSS) of Zuckerman, and is inside the expected direction with Sensitivity to Reward (SR) and Sensitivity to Punishment (SP) of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), which represent the approach and avoidance trends of behavior, respectively. It not only relates negatively with the personality disorders of the anxiety spectrum, but also with the emotional disorders in relation to anxiety and depression, and it relates positively with the antisocial personality disorder.

Rheumatoid Factor

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Immunoreactive Trypsinogen (IRT) Influenza Tests Insulin Insulin-like Growth Factor-1 ... Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, ...

FACTORING TO FIT OFF DIAGONALS.

DTIC Science & Technology

imply an upper bound on the number of factors. When applied to somatotype data, the method improved substantially on centroid solutions and indicated a reinterpretation of earlier factoring studies. (Author)

A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

NASA Astrophysics Data System (ADS)

Hoseinzade, Zohre; Mokhtari, Ahmad Reza

2017-10-01

Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

WRKY transcription factors

PubMed Central

Bakshi, Madhunita; Oelmüller, Ralf

2014-01-01

WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

FGF growth factor analogs

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2012-07-24

The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

Risk factors in school shootings.

PubMed

Verlinden, S; Hersen, M; Thomas, J

2000-01-01

Nine incidents of multiple-victim homicide in American secondary schools are examined and common risk factors are identified. The literature dealing with individual, family, social, societal, and situational risk factors for youth violence and aggression is reviewed along with existing risk assessment methods. Checklists of risk factors for serious youth violence and school violence are used in reviewing each school shooting case. Commonalties among the cases and implications for psychologists practicing in clinical and school settings are discussed.

Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals.

PubMed

Vemuri, Prashanthi; Knopman, David S; Lesnick, Timothy G; Przybelski, Scott A; Mielke, Michelle M; Graff-Radford, Jonathan; Murray, Melissa E; Roberts, Rosebud O; Vassilaki, Maria; Lowe, Val J; Machulda, Mary M; Jones, David T; Petersen, Ronald C; Jack, Clifford R

2017-06-01

While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP. To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that "exceptional agers" with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration. This cohort study conducted a prospective analysis of 942 elderly individuals (70-≥90 years) with magnetic resonance imaging and Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP by considering individuals 85 years or older to be without significant evidence of ADP. We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d-based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP. The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not

Structure-preserving and rank-revealing QR-factorizations

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

Bischof, C.H.; Hansen, P.C.

1991-11-01

The rank-revealing QR-factorization (RRQR-factorization) is a special QR-factorization that is guaranteed to reveal the numerical rank of the matrix under consideration. This makes the RRQR-factorization a useful tool in the numerical treatment of many rank-deficient problems in numerical linear algebra. In this paper, a framework is presented for the efficient implementation of RRQR algorithms, in particular, for sparse matrices. A sparse RRQR-algorithm should seek to preserve the structure and sparsity of the matrix as much as possible while retaining the ability to capture safely the numerical rank. To this end, the paper proposes to compute an initial QR-factorization using amore » restricted pivoting strategy guarded by incremental condition estimation (ICE), and then applies the algorithm suggested by Chan and Foster to this QR-factorization. The column exchange strategy used in the initial QR factorization will exploit the fact that certain column exchanges do not change the sparsity structure, and compute a sparse QR-factorization that is a good approximation of the sought-after RRQR-factorization. Due to quantities produced by ICE, the Chan/Foster RRQR algorithm can be implemented very cheaply, thus verifying that the sought-after RRQR-factorization has indeed been computed. Experimental results on a model problem show that the initial QR-factorization is indeed very likely to produce RRQR-factorization.« less

TRASYS form factor matrix normalization

NASA Technical Reports Server (NTRS)

Tsuyuki, Glenn T.

1992-01-01

A method has been developed for adjusting a TRASYS enclosure form factor matrix to unity. This approach is not limited to closed geometries, and in fact, it is primarily intended for use with open geometries. The purpose of this approach is to prevent optimistic form factors to space. In this method, nodal form factor sums are calculated within 0.05 of unity using TRASYS, although deviations as large as 0.10 may be acceptable, and then, a process is employed to distribute the difference amongst the nodes. A specific example has been analyzed with this method, and a comparison was performed with a standard approach for calculating radiation conductors. In this comparison, hot and cold case temperatures were determined. Exterior nodes exhibited temperature differences as large as 7 C and 3 C for the hot and cold cases, respectively when compared with the standard approach, while interior nodes demonstrated temperature differences from 0 C to 5 C. These results indicate that temperature predictions can be artificially biased if the form factor computation error is lumped into the individual form factors to space.

The release of immunosuppressive factor(s) in young males following exercise.

PubMed

Tian, Ye; Nie, Jinlei; Tong, Tom K; Baker, Julien S

2012-01-01

It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years) were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th-9th min post-exercise eluates (P < 0.05). Such findings suggest that intense eccentric type exercise may lead to generation of immunosuppressive factor(s) in young males.

Growth/differentiation factor-11: an evolutionary conserved growth factor in vertebrates.

PubMed

Funkenstein, Bruria; Olekh, Elena

2010-11-01

Growth and differentiation factor-11 (GDF-11) is a member of the transforming growth factor-β superfamily and is thought to be derived together with myostatin (known also as GDF-8) from an ancestral gene. In the present study, we report the isolation and characterization of GDF-11 homolog from a marine teleost, the gilthead sea bream Sparus aurata, and show that this growth factor is highly conserved throughout vertebrates. Using bioinformatics, we identified GDF-11 in Tetraodon, Takifugu, medaka, and stickleback and found that they are highly conserved at the amino acid sequence as well as gene organization. Moreover, we found conservation of syntenic relationships among vertebrates in the GDF-11 locus. Transcripts for GDF-11 can be found in eggs and early embryos, albeit at low levels, while in post-hatching larvae expression levels are high and decreases as development progresses, suggesting that GDF-11 might have a role during early development of fish as found in tetrapods and zebrafish. Finally, GDF-11 is expressed in various tissues in the adult fish including muscle, brain, and eye.

Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

PubMed

LaBonte, Michelle L

2014-09-01

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Remarks on KERMA Factors in ACE files

NASA Astrophysics Data System (ADS)

Konno, C.; Ochiai, K.; Takakura, K.; Sato, S.

2014-04-01

Some neutron KERMA factors in ACE files are negative and extremely large if nuclear data libraries do not keep energy-balance. The status of neutron KERMA factors in the official ACE file of ENDF/B-VII.1 is examined. As a result, it is found out that neutron KERMA factors of nuclei more than 200 in ENDF/B-VII.1 have some problems. Effects of the inadequate KERMA factor are also investigated, which are large for neutron heat while those are small for total (neutron + gamma) heat. Users who use only neutron KERMA factors should check if the factors are adequate or not before they use the factors.

Review of critical factors for SEA implementation

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

Zhang Jie, E-mail: jasmine@plan.aau.dk; Christensen, Per; Kornov, Lone

The implementation process involved in translating Strategic Environmental Assessment (SEA) intention into action is vital to an effective SEA. Many factors influence implementation and thus the effectiveness of an SEA. Empirical studies have identified and documented some factors influencing the implementation of an SEA. This research is fragmented, however, and it is still not clear what are the most critical factors of effective SEA performance, and how these relate to different stages of the implementation process or other contextual circumstances. The paper takes its point of departure in implementation theory. Firstly, we introduce implementation theory, and then use it inmore » practice to establish a more comprehensive model related to the stages in the implementation process. Secondly, we identify the critical factors in order to see how they are related to the different stages of SEA or are more general in character. Finally we map the different critical factors and how they influence the overall results of an SEA. Based on a literature review, we present a comprehensive picture of the critical factors and where they are found in the process. We conclude that most of the critical factors identified are of a more general character influencing the SEA process as such, while only one out of four of these factors relates to the specific stages of the SEA. Based on this mapping we can sketch a picture of the totality of critical factors. In this study 266 notions of critical factors were identified. Seen at the level of notions of critical factors, only 24% of these relate to specific stages while for 76% the critical factors are of a more general nature. These critical factors interact in complex ways and appear in different combinations in different stages of the implementation process so tracing the cause and effect is difficult. The pervasiveness of contextual and general factors also clearly suggests that there is no single way to put SEA into practice

Assessment of Human Factors

NASA Technical Reports Server (NTRS)

Mount, Frances; Foley, Tico

1999-01-01

Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

Epidemiology and risk factors of schizophrenia.

PubMed

Janoutová, Jana; Janácková, Petra; Serý, Omar; Zeman, Tomás; Ambroz, Petr; Kovalová, Martina; Varechová, Katerina; Hosák, Ladislav; Jirík, Vitezslav; Janout, Vladimír

2016-01-01

Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition.

Regulation of Transforming Growth Factor β1, Platelet-Derived Growth Factor, and Basic Fibroblast Growth Factor by Silicone Gel Sheeting in Early-Stage Scarring.

PubMed

Choi, Jaehoon; Lee, Eun Hee; Park, Sang Woo; Chang, Hak

2015-01-01

Hypertrophic scars and keloids are associated with abnormal levels of growth factors. Silicone gel sheets are effective in treating and preventing hypertrophic scars and keloids. There has been no report on the change in growth factors in the scar tissue following the use of silicone gel sheeting for scar prevention. A prospective controlled trial was performed to evaluate whether growth factors are altered by the application of a silicone gel sheet on a fresh surgical scar. Four of seven enrolled patients completed the study. Transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were investigated immunohistochemically in biopsies taken from five scars at 4 months following surgery. In both the epidermis and the dermis, the expression of TGF-β1 (P=0.042 and P=0.042) and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone gel sheet-treated scars than in the case of untreated scars. The expression of bFGF in the dermis was significantly higher in the case of silicone gel sheet-treated scars than in the case of untreated scars (P=0.042), but in the epidermis, the expression of bFGF showed no significant difference between the groups (P=0.655). The levels of TGF-β1, PDGF, and bFGF are altered by the silicone gel sheet treatment, which might be one of the mechanisms of action in scar prevention.

Causal Indicators Can Help to Interpret Factors

ERIC Educational Resources Information Center

Bentler, Peter M.

2016-01-01

The latent factor in a causal indicator model is no more than the latent factor of the factor part of the model. However, if the causal indicator variables are well-understood and help to improve the prediction of individuals' factor scores, they can help to interpret the meaning of the latent factor. Aguirre-Urreta, Rönkkö, and Marakas (2016)…

Human Factors in Aeronautics at NASA

NASA Technical Reports Server (NTRS)

Mogford, Richard

2016-01-01

This is a briefing to a regularly meeting DoD group called the Human Systems Community of Interest: Mission Effectiveness. I was asked to address human factors in aeronautics at NASA. (Exploration (space) human factors has apparently already been covered.) The briefing describes human factors organizations at NASA Ames and Langley. It then summarizes some aeronautics tasks that involve the application of human factors in the development of specific tools and capabilities. The tasks covered include aircrew checklists, dispatch operations, Playbook, Dynamic Weather Routes, Traffic Aware Strategic Aircrew Requests, and Airplane State Awareness and Prediction Technologies. I mention that most of our aeronautics work involves human factors as embedded in development tasks rather than basic research.

Modifiable risk factors for migraine progression.

PubMed

Bigal, Marcelo E; Lipton, Richard B

2006-10-01

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

Air Emissions Factors and Quantification

EPA Pesticide Factsheets

Emissions factors are used in developing air emissions inventories for air quality management decisions and in developing emissions control strategies. This area provides technical information on and support for the use of emissions factors.

7 CFR 652.39 - Mitigating factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Mitigating factors. 652.39 Section 652.39 Agriculture... factors. In considering whether to decertify, the period of decertification, and scope of decertification, the deciding official will take into consideration any mitigating factors. Examples of mitigating...

75 FR 15993 - Civil Penalty Factors

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Part 1119 Civil Penalty Factors AGENCY: Consumer Product... final rule providing its interpretation of the civil penalty factors found in the Consumer Product... consider certain factors in determining the amount of any civil penalty to seek. The Commission published...

Human factors and education: evolution and contributions.

PubMed

Stone, Nancy J

2008-06-01

The major contributions of human factors to education are highlighted. Over the past 50 years, the education of human factors specialists has evolved, as well as the application of human factors and ergonomic knowledge to education. Human factors and ergonomics professional documentation and literature were reviewed to identify major events relevant to human factors education or the application of human factors to education. Human factors education has evolved from training in experimental psychology to highly specialized accredited human factors programs and a number of undergraduate programs, leading to program accreditation and the certification of professionals. In addition, human factors specialists have applied their knowledge to human factors education and, more recently, to educational systems in general. The greatest focus has been on technology such as multimedia. Others have evaluated the design of the physical environment, focusing primarily on seating. The research also often targets undergraduate or graduate education. Therefore, it has been proposed that a greater focus is needed at the K-12 educational level, especially given the advancement and implementation of technology in the classroom. Human factors and ergonomic expertise can benefit the educational system. Yet, there is a need to constantly evaluate the benefits of new technology in the classroom as well as the environmental design aspects of the educational environment while considering learners of different age groups, ethnicities, and sexes. Better application of human factors and ergonomics to the learning environment could enhance the educational experience for all learners.

Clinical factors related to schizophrenia relapse.

PubMed

Porcelli, Stefano; Bianchini, Oriana; De Girolamo, Giovanni; Aguglia, Eugenio; Crea, Luciana; Serretti, Alessandro

2016-01-01

Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

PubMed

Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

2017-05-01

We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Indonesian railway accidents--utilizing Human Factors Analysis and Classification System in determining potential contributing factors.

PubMed

Iridiastadi, Hardianto; Ikatrinasari, Zulfa Fitri

2012-01-01

The prevalence of Indonesian railway accidents has not been declining, with hundreds of fatalities reported in the past decade. As an effort to help the National Transportation Safety Committee (NTSC), this study was conducted that aimed at understanding factors that might have contributed to the accidents. Human Factors Analysis and Classification System (HFACS) was utilized for this purpose. A total of nine accident reports (provided by the Indonesian NTSC) involving fatalities were studied using the technique. Results of this study indicated 72 factors that were closely related to the accidents. Of these, roughly 22% were considered as operator acts while about 39% were related to preconditions for operator acts. Supervisory represented 14% of the factors, and the remaining (about 25%) were associated with organizational factors. It was concluded that, while train drivers indeed played an important role in the accidents, interventions solely directed toward train drivers may not be adequate. A more comprehensive approach in minimizing the accidents should be conducted that addresses all the four aspects of HFACS.

Examination of Substance Use, Risk Factors, and Protective Factors on Student Academic Test Score Performance.

PubMed

Arthur, Michael W; Brown, Eric C; Briney, John S; Hawkins, J David; Abbott, Robert D; Catalano, Richard F; Becker, Linda; Langer, Michael; Mueller, Martin T

2015-08-01

School administrators and teachers face difficult decisions about how best to use school resources to meet academic achievement goals. Many are hesitant to adopt prevention curricula that are not focused directly on academic achievement. Yet, some have hypothesized that prevention curricula can remove barriers to learning and, thus, promote achievement. We examined relationships among school levels of student substance use and risk and protective factors that predict adolescent problem behaviors and achievement test performance. Hierarchical generalized linear models were used to predict associations involving school-averaged levels of substance use and risk and protective factors and students' likelihood of meeting achievement test standards on the Washington Assessment of Student Learning, statistically controlling for demographic and economic factors known to be associated with achievement. Levels of substance use and risk/protective factors predicted the academic test score performance of students. Many of these effects remained significant even after controlling for model covariates. Implementing prevention programs that target empirically identified risk and protective factors has the potential to have a favorable effect on students' academic achievement. © 2015, American School Health Association.

Hand function evaluation: a factor analysis study.

PubMed

Jarus, T; Poremba, R

1993-05-01

The purpose of this study was to investigate hand function evaluations. Factor analysis with varimax rotation was used to assess the fundamental characteristics of the items included in the Jebsen Hand Function Test and the Smith Hand Function Evaluation. The study sample consisted of 144 subjects without disabilities and 22 subjects with Colles fracture. Results suggest a four factor solution: Factor I--pinch movement; Factor II--grasp; Factor III--target accuracy; and Factor IV--activities of daily living. These categories differentiated the subjects without Colles fracture from the subjects with Colles fracture. A hand function evaluation consisting of these four factors would be useful. Such an evaluation that can be used for current clinical purposes is provided.

Insulin-like growth factor and fibroblast growth factor expression profiles in growth-restricted fetal sheep pancreas.

PubMed

Chen, Xiaochuan; Rozance, Paul J; Hay, William W; Limesand, Sean W

2012-05-01

Placental insufficiency results in intrauterine growth restriction (IUGR), impaired fetal insulin secretion and less fetal pancreatic β-cell mass, partly due to lower β-cell proliferation rates. Insulin-like growth factors (IGFs) and fibroblast growth factors (FGFs) regulate fetal β-cell proliferation and pancreas development, along with transcription factors, such as pancreatic and duodenal homeobox 1 (PDX-1). We determined expression levels for these growth factors, their receptors and IGF binding proteins in ovine fetal pancreas and isolated islets. In the IUGR pancreas, relative mRNA expression levels of IGF-I, PDX-1, FGF7 and FGFR2IIIb were 64% (P < 0.01), 76% (P < 0.05), 76% (P < 0.05) and 52% (P < 0.01) lower, respectively, compared with control fetuses. Conversely, insulin-like growth factor binding protein 2 (IGFBP-2) mRNA and protein concentrations were 2.25- and 1.2-fold greater (P < 0.05) in the IUGR pancreas compared with controls. In isolated islets from IUGR fetuses, IGF-II and IGFBP-2 mRNA concentrations were 1.5- and 3.7-fold greater (P < 0.05), and insulin mRNA was 56% less (P < 0.05) than control islets. The growth factor expression profiles for IGF and FGF signaling pathways indicate that declines in β-cell mass are due to decreased growth factor signals for both pancreatic progenitor epithelial cell and mature β-cell replication.

40 CFR 227.15 - Factors considered.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Factors considered. 227.15 Section 227.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR... Factors considered. The need for dumping will be determined by evaluation of the following factors: (a...

Comparing Factor Structures of Adolescent Psychopathology

ERIC Educational Resources Information Center

Verona, Edelyn; Javdani, Shabnam; Sprague, Jenessa

2011-01-01

Research on the structure of adolescent psychopathology can provide information on broad factors that underlie different forms of maladjustment in youths. Multiple studies from the literature on adult populations suggest that 2 factors, Internalizing and Externalizing, meaningfully comprise the factor structure of adult psychopathology (e.g.,…

ESTIMATING UNCERTAINITIES IN FACTOR ANALYTIC MODELS

EPA Science Inventory

When interpreting results from factor analytic models as used in receptor modeling, it is important to quantify the uncertainties in those results. For example, if the presence of a species on one of the factors is necessary to interpret the factor as originating from a certain ...

Biota-Sediment Accumulation Factor Data

EPA Pesticide Factsheets

The Biota-Sediment Accumulation Factor contains approximately 20,000 biota-sediment accumulation factors (BSAFs) from 20 locations (mostly Superfund sites) for nonionic organic chemicals and pesticides. Fresh, tidal, and marine ecosystems are included in the data.

Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

NASA Technical Reports Server (NTRS)

Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

2000-01-01

Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

The regulation of trefoil factor 2 expression by the transcription factor Sp3.

PubMed

Liu, Jingjing; Wang, Xu; Cai, Yiling; Zhou, Jingping; Guleng, Bayasi; Shi, Huaxiu; Ren, Jianlin

2012-10-19

Trefoil factor family 2 (TFF2) participates in mucus stabilization and repair, apoptosis, and inflammatory responses. Previously published reports have indicated that several growth factors and basal transcription factors are associated with the expression of TFF2. However, the detailed mechanisms that regulate TFF2 expression are not fully understood. The present study was designed to assess the essential role of the transcription factor SP3 with respect to TFF2 expression. We first demonstrated that there was a negative correlation between the expression levels of SP3 and TFF2. Thus, in the examined cells, the overexpression of SP3 decreased the expression level of TFF2, whereas the inhibition of SP3 increased the expression level of TFF2. Moreover, we discovered two GC boxes in the TFF2 promoter and confirmed the specific binding of SP3 to this promoter. On the whole, this study indicated that Sp3 was a major regulator of TFF2 expression. This knowledge should contribute to our understanding of the role that is played by SP3 in the regulation of TFF2 expression. Copyright © 2012 Elsevier Inc. All rights reserved.

Crash reduction factor (CRF) update.

DOT National Transportation Integrated Search

2011-01-01

Recent research conducted by the Federal Highway Administration (FHWA) produced the Desktop Reference for : Crash Reduction Factors, FHWA Report No. FHWA-SA-07-015, published in September 2007. These crash : reduction factors are commonly used by sta...

[Evaluation of Contextual Factors in Psychosomatic Rehabilitation].

PubMed

Bülau, N I; Kessemeier, F; Petermann, F; Bassler, M; Kobelt, A

2016-12-01

Objectives: Although individualized and ICF-oriented implementation of rehabilitation treatment requires knowledge of relevant contextual factors, there is a lack of operationalized documentation and measurement tools to evaluate these factors. Therefore, an ICF-oriented semi-structured interview was designed. Methods: 20 contextual factors were externally assessed whether they negatively affected mental functioning and participation of psychosomatic patients. Additionally, psychometric scales were applied. Results: Six relevant impairing contextual factors were identified. Contextual factors significantly correlated with psychometric scales. Patients with higher contextual impairment showed significantly higher psychological stress levels. Conclusions: Anamnesis of contextual factors at the beginning of psychosomatic rehabilitation yields important information for therapy planning. Further research on contextual factors in medical rehabilitation is needed. © Georg Thieme Verlag KG Stuttgart · New York.

[Environmental risk factors for schizophrenia: a review].

PubMed

Vilain, J; Galliot, A-M; Durand-Roger, J; Leboyer, M; Llorca, P-M; Schürhoff, F; Szöke, A

2013-02-01

Evidence of variations in schizophrenia incidence rates has been found in genetically homogenous populations, depending on changes within time or space of certain environmental characteristics. The consideration of the impact of environmental risk factors in etiopathogenic studies has put the environment in the forefront of research regarding psychotic illnesses. Various environmental factors such as urbanicity, migration, cannabis, childhood traumas, infectious agents, obstetrical complications and psychosocial factors have been associated with the risk of developing schizophrenia. These risk factors can be biological, physical, psychological as well as social and may operate at different times in an individual's life (fetal period, childhood, adolescence and early adulthood). Whilst some of these factors act on an individual level, others act on a populational level, modulating the individual risk. These factors can have a direct action on the development of schizophrenia, or on the other hand act as markers for directly implicated factors that have not yet been identified. This article summarizes the current knowledge on this subject. An extensive literature search was conducted via the search engine Pubmed. Eight risk factors were selected and developed in the following paper: urbanicity (or living in an urban area), cannabis, migration (and ethnic density), obstetrical complications, seasonality of birth, infectious agents (and inflammatory responses), socio-demographic factors and childhood traumas. For each of these factors, we provide information on the importance of the risk, the vulnerability period, hypotheses made on the possible mechanisms behind the factors and the level of proof the current research offers (good, medium, or insufficient) according to the amount, type, quality and concordance of the studies at hand. Some factors, such as cannabis, are "unique" in their influence on the development of schizophrenia since it labels only one risk factor

Comparisons of Exploratory and Confirmatory Factor Analysis.

ERIC Educational Resources Information Center

Daniel, Larry G.

Historically, most researchers conducting factor analysis have used exploratory methods. However, more recently, confirmatory factor analytic methods have been developed that can directly test theory either during factor rotation using "best fit" rotation methods or during factor extraction, as with the LISREL computer programs developed…

14 CFR 29.623 - Bearing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01