Dominant optic atrophy

PubMed Central

2012-01-01

Definition of the disease Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients) or in the OPA3 gene (1% of patients). Prognosis Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. Management To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation. PMID:22776096

Does influence at work modify the relation between high occupational physical activity and risk of heart disease in women?

PubMed

Allesøe, Karen; Holtermann, Andreas; Rugulies, Reiner; Aadahl, Mette; Boyle, Eleanor; Søgaard, Karen

2017-07-01

To investigate whether influence at work modifies the association between demanding and strenuous occupational physical activity (OPA) and risk of ischaemic heart disease (IHD). A sample of 12,093 nurses aged 45-64 years from the Danish Nurse Cohort Study was followed for 20.6 years by individual linkage to incident IHD in the Danish National Patient Registry. Information on OPA, influence at work, other occupational factors and known risk factors for IHD was collected by self-report in 1993. During follow-up 869 nurses were hospitalised with incident IHD. Nurses exposed to strenuous OPA and low influence at work had a 46% increased risk of IHD [hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.02-2.09)] compared to the reference group of nurses with moderate OPA and high influence at work. Nurses exposed to strenuous OPA and high influence at work were not at an increased risk of IHD [HR 1.10 (95% CI 0.59-2.06)]. An additive hazards model showed there were 18.0 (95% CI -0.01 to 36.0) additional cases of IHD per 10,000 person years among nurses with strenuous OPA and low influence at work compared to nurses with moderate OPA and high influence at work. A detrimental additive interaction between strenuous OPA and low influence at work that could explain the additional cases of IHD among nurses with strenuous OPA and low influence at work was indicated. The findings suggest that high influence at work may buffer some of the adverse effects of strenuous OPA on risk of IHD.

Syndromic parkinsonism and dementia associated with OPA 1 missense mutations

PubMed Central

Musumeci, Olimpia; Caporali, Leonardo; Zanna, Claudia; La Morgia, Chiara; Del Dotto, Valentina; Porcelli, Anna Maria; Rugolo, Michela; Valentino, Maria Lucia; Iommarini, Luisa; Maresca, Alessandra; Barboni, Piero; Carbonelli, Michele; Trombetta, Costantino; Valente, Enza Maria; Patergnani, Simone; Giorgi, Carlotta; Pinton, Paolo; Rizzo, Giovanni; Tonon, Caterina; Lodi, Raffaele; Avoni, Patrizia; Liguori, Rocco; Baruzzi, Agostino; Toscano, Antonio; Zeviani, Massimo

2015-01-01

Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia. Methods Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements. Results Affected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase‐negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy. Interpretation The association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism. Ann Neurol 2015;78:21–38 PMID:25820230

Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

PubMed Central

Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Han, Changsu; Na, Hae Ri; Park, Hae Jeong; Kim, Jong Woo; Kim, Young Youl; Park, Moon Ho

2017-01-01

Objective Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. Methods One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). Results Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. Conclusion These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD. PMID:28096879

Giant mitochondria do not fuse and exchange their contents with normal mitochondria

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

Navratil, Marian; Terman, Alexei; Arriaga, Edgar A.

2008-01-01

Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giantmore » mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells.« less

Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis.

PubMed

Millet, Aurélie M C; Bertholet, Ambre M; Daloyau, Marlène; Reynier, Pascal; Galinier, Anne; Devin, Anne; Wissinguer, Bernd; Belenguer, Pascale; Davezac, Noélie

2016-06-01

OPA1 mutations cause protein haploinsufficiency leading to dominant optic atrophy (DOA), an incurable retinopathy with variable severity. Up to 20% of patients also develop extraocular neurological complications. The mechanisms that cause this optic atrophy or its syndromic forms are still unknown. After identifying oxidative stress in a mouse model of the pathology, we sought to determine the consequences of OPA1 dysfunction on redox homeostasis. Mitochondrial respiration, reactive oxygen species levels, antioxidant defenses, and cell death were characterized by biochemical and in situ approaches in both in vitro and in vivo models of OPA1 haploinsufficiency. A decrease in aconitase activity suggesting an increase in reactive oxygene species and an induction of antioxidant defenses was observed in cortices of a murine model as well as in OPA1 downregulated cortical neurons. This increase is associated with a decline in mitochondrial respiration in vitro. Upon exogenous oxidative stress, OPA1-depleted neurons did not further exhibit upregulated antioxidant defenses but were more sensitive to cell death. Finally, low levels of antioxidant enzymes were found in fibroblasts from patients supporting their role as modifier factors. Our study suggests that the pro-oxidative state induced by OPA1 loss may contribute to DOA pathogenesis and that differences in antioxidant defenses can explain the variability in expressivity. Furthermore, antioxidants may be used as therapy as they could prevent or delay DOA symptoms in patients.

SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome.

PubMed

Janer, Alexandre; Prudent, Julien; Paupe, Vincent; Fahiminiya, Somayyeh; Majewski, Jacek; Sgarioto, Nicolas; Des Rosiers, Christine; Forest, Anik; Lin, Zhen-Yuan; Gingras, Anne-Claude; Mitchell, Grant; McBride, Heidi M; Shoubridge, Eric A

2016-09-01

Mitochondria form a dynamic network that responds to physiological signals and metabolic stresses by altering the balance between fusion and fission. Mitochondrial fusion is orchestrated by conserved GTPases MFN1/2 and OPA1, a process coordinated in yeast by Ugo1, a mitochondrial metabolite carrier family protein. We uncovered a homozygous missense mutation in SLC25A46, the mammalian orthologue of Ugo1, in a subject with Leigh syndrome. SLC25A46 is an integral outer membrane protein that interacts with MFN2, OPA1, and the mitochondrial contact site and cristae organizing system (MICOS) complex. The subject mutation destabilizes the protein, leading to mitochondrial hyperfusion, alterations in endoplasmic reticulum (ER) morphology, impaired cellular respiration, and premature cellular senescence. The MICOS complex is disrupted in subject fibroblasts, resulting in strikingly abnormal mitochondrial architecture, with markedly shortened cristae. SLC25A46 also interacts with the ER membrane protein complex EMC, and phospholipid composition is altered in subject mitochondria. These results show that SLC25A46 plays a role in a mitochondrial/ER pathway that facilitates lipid transfer, and link altered mitochondrial dynamics to early-onset neurodegenerative disease and cell fate decisions. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Development of High-Fill-Factor Large-Aperture Micromirrors for Agile Optical Phased Arrays

DTIC Science & Technology

2010-02-28

Final Project Report Contract/Grant Title: Development of High-Fill-Factor Large-Aperture Micromirrors for Agile Optical Phased Arrays...factor (HFF) micromirror array (MMA) has been proposed, fabricated and tested. Optical-phased-array (OPA) beam steering based on the HFF MMA has also...electrically tuned to multiple 2. 1. Background High-fill-factor (HFF) micromirror arrays (MMAs) can form optical phased arrays (OPAs) for laser beam

Inhibition of TNFα-induced adhesion molecule expression by (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl,1-methyl).

PubMed

Chen, Caixia; Jin, Xin; Meng, Xianglan; Zheng, Chengwei; Shen, Yanhui; Wang, Yiqing

2011-06-25

Inflammation is a primary event in atherogenesis. Oleoylethanolamide (OEA), a naturally occurring fatty-acid ethanolamide, lowers lipid levels in liver and blood through activation of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPARα). We designed and synthesized (Z)-(S)-9-octadecenamide, N-(2-hydroxyethyl, 1-methyl) (OPA), an OEA analog. The present study investigated the effect of OPA on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVEC). OPA inhibited expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) stimulated by Tumor Necrosis Factor-α (TNF-α) via activation of PPARα. This inhibition of VCAM-1 and ICAM-1 expression decreased adhesion of monocyte-like cells to stimulated endothelial cells. These results demonstrate that OPA may have anti-inflammatory properties. Our results thus provide new insights into possible future therapeutic approaches to the treatment of atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

PubMed Central

Yu-Wai-Man, Patrick; Shankar, Suma P.; Biousse, Valérie; Miller, Neil R.; Bean, Lora J.H.; Coffee, Bradford; Hegde, Madhuri; Newman, Nancy J.

2010-01-01

Purpose Autosomal-dominant optic atrophy (DOA) is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease. About 60% of cases harbor OPA1 mutations, whereas OPA3 mutations have only been reported in two pedigrees with DOA and premature cataracts. The aim of this study was to determine the yield of OPA1 and OPA3 screening in a cohort of presumed DOA cases referred to a tertiary diagnostic laboratory. Design Retrospective case series. Participants One hundred and eighty-eight probands with bilateral optic atrophy referred for molecular genetic investigations at a tertiary diagnostic facility: 38 patients with an autosomal-dominant pattern of inheritance and 150 sporadic cases. Methods OPA1 and OPA3 genetic testing was initially performed using PCR-based sequencing methods. The presence of large-scale OPA1 and OPA3 genomic rearrangements was further assessed with a targeted comparative genomic hybridization (CGH) microarray platform. The three primary Leber hereditary optic neuropathy (LHON) mutations, m.3460G>A, m.11778G>A, and m.14484T>C, were also screened in all patients. Main Outcome Measures The proportion of patients with OPA1 and OPA3 pathogenic mutations. The clinical profile observed in molecularly confirmed DOA cases. Results We found 21 different OPA1 mutations in 27 of the 188 (14.4%) probands screened. The mutations included six novel pathogenic variants and the first reported OPA1 initiation codon mutation at c.1A>T. An OPA1 missense mutation, c.239A>G (p.Y80C), was identified in an 11-year-old African-American girl with optic atrophy and peripheral sensori-motor neuropathy in her lower limbs. The OPA1 detection rate was significantly higher among individuals with a positive family history of visual failure (50.0%) compared with sporadic cases (5.3%). The primary LHON screen was negative in our patient cohort, and additional molecular investigations did not reveal any large-scale OPA1 rearrangements or OPA3 genetic defects. The mean baseline visual acuity for our OPA1-positive group was 0.48 logarithm of the minimum angle of resolution (LogMAR) (Mean Snellen equivalent = 20/61, range = 20/20–20/400, 95% confidence interval = 20/52–20/71), and visual deterioration occurred in 54.2% of patients during follow-up. Conclusions OPA1 mutations are the most common genetic defects identified in patients with suspected DOA, whereas OPA3 mutations are very rare in isolated optic atrophy cases. PMID:21036400

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.

PubMed

López-Lluch, Guillermo

2017-03-01

Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diagnostic genetic testing for patients with bilateral optic neuropathy and comparison of clinical features according to OPA1 mutation status.

PubMed

Gaier, Eric D; Boudreault, Katherine; Nakata, Isao; Janessian, Maria; Skidd, Philip; DelBono, Elizabeth; Allen, Keri F; Pasquale, Louis R; Place, Emily; Cestari, Dean M; Stacy, Rebecca C; Rizzo, Joseph F; Wiggs, Janey L

2017-01-01

Inherited optic neuropathy is genetically heterogeneous, and genetic testing has an important role in risk assessment and counseling. The purpose of this study is to determine the prevalence and spectrum of mutations in a group of patients referred for genetic testing to a tertiary center in the United States. In addition, we compared the clinical features of patients with and without mutations in OPA1 , the gene most commonly involved in dominantly inherited optic atrophy. Clinical data and genetic testing results were reviewed for 74 unrelated, consecutive patients referred with a history of insidious, relatively symmetric, bilateral visual loss secondary to an optic neuropathy. Patients were evaluated for disease-causing variants in OPA1 , OPA3 , WFS1 , and the entire mitochondrial genome with DNA sequencing and copy number variation (CNV) testing. Pathogenic DNA variants were found in 25 cases, with the majority (24 patients) located in OPA1 . Demographics, clinical history, and clinical features for the group of patients with mutations in OPA1 were compared to those without disease-causing variants. Compared to the patients without mutations, cases with mutations in OPA1 were more likely to have a family history of optic nerve disease (p = 0.027); however, 30.4% of patients without a family history of disease also had mutations in OPA1 . OPA1 mutation carriers had less severe mean deviation and pattern standard deviation on automated visual field testing than patients with optic atrophy without mutations in OPA1 (p<0.005). Other demographic and ocular features were not statistically significantly different between the two groups, including the fraction of patients with central scotomas (42.9% of OPA1 mutation positive and 66.0% of OPA1 mutation negative). Genetic testing identified disease-causing mutations in 34% of referred cases, with the majority of these in OPA1. Patients with mutations in OPA1 were more likely to have a family history of disease; however, 30.4% of patients without a family history were also found to have an OPA1 mutation. This observation, as well as similar frequencies of central scotomas in the groups with and without mutations in OPA1 , underscores the need for genetic testing to establish an OPA1 genetic diagnosis.

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

PubMed Central

Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong

2010-01-01

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods. PMID:20808670

Efficacy of dendritic cells matured early with OK-432 (Picibanil), prostaglandin E2, and interferon-alpha as a vaccine for a hormone refractory prostate cancer cell line.

PubMed

Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong; Kim, Choung-Soo

2010-09-01

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China.

PubMed

Xiang, Yang-Lin; Zhang, Deng-Feng; Wang, Dong; Li, Yu-Ye; Yao, Yong-Gang

2015-11-01

Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. To investigate the potential involvement of OPA1 in leprosy. We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control.

PubMed

Glytsou, Christina; Calvo, Enrique; Cogliati, Sara; Mehrotra, Arpit; Anastasia, Irene; Rigoni, Giovanni; Raimondi, Andrea; Shintani, Norihito; Loureiro, Marta; Vazquez, Jesùs; Pellegrini, Luca; Enriquez, Jose Antonio; Scorrano, Luca; Soriano, Maria Eugenia

2016-12-13

The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis. Whether and how they physically and functionally interact is unclear. Here, we provide evidence that OPA1 is epistatic to MICOS in the regulation of cristae shape. Proteomic analysis identifies multiple MICOS components in native OPA1-containing high molecular weight complexes disrupted during cristae remodeling. MIC60, a core MICOS protein, physically interacts with OPA1, and together, they control cristae junction number and stability, OPA1 being epistatic to MIC60. OPA1 defines cristae width and junction diameter independently of MIC60. Our combination of proteomics, biochemistry, genetics, and electron tomography provides a unifying model for mammalian cristae biogenesis by OPA1 and MICOS. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Contribution of organized and nonorganized activity to children's motor skills and fitness.

PubMed

Hardy, Louise L; O'Hara, Blythe J; Rogers, Kris; St George, Alexis; Bauman, Adrian

2014-11-01

To examine the associations between children's organized physical activity (OPA), nonorganized physical activity (NOPA), and health-related outcomes (fundamental movement skill [FMS] fitness). Cross-sectional survey of children aged 10-16 years (N = 4273). Organized physical activity and NOPA were assessed by self-report, FMS by process-orientated criteria, and fitness by 20-m shuttle run test. Boys spent 97.5 minutes and girls 86.6 minutes in daily physical activity with the majority spent in OPA (boys, 56.3%; girls 60.5%). Organized physical activity increased with grade, whereas NOPA decreased. Organized physical activity and NOPA were associated with fitness, and OPA was consistently associated with FMS competency. Boys' fitness was associated with OPA and NOPA (adjusted odds ratio [AOR] 1.42, 95% confidence interval [CI]: 1.04, 1.94; AOR 1.26, 95% CI: 1.03, 1.54, respectively), FMS competency (side gallop leap, kick) with OPA and catch, and over-arm throw with both OPA and NOPA. Girls' fitness (AOR 2.62, 95% CI: 1.88, 3.66) and FMS competency were consistently associated with OPA. Both OPA and NOPA are important contributors to children's physical activity; however, for girls, OPA was more strongly associated with fitness and FMS competency. Our findings support the importance of providing children with opportunities to engage in daily OPA. School physical education programs are an ideal delivery vehicle for OPA and need to be central to education policy. © 2014, American School Health Association.

MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-1α.

PubMed

Xi, Ye; Feng, Dayun; Tao, Kai; Wang, Ronglin; Shi, Yajun; Qin, Huaizhou; Murphy, Michael P; Yang, Qian; Zhao, Gang

2018-05-26

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra compacta (SNc). Although mitochondrial dysfunction is the critical factor in the pathogenesis of PD, the underlying molecular mechanisms are not well understood, and as a result, effective medical interventions are lacking. Mitochondrial fission and fusion play important roles in the maintenance of mitochondrial function and cell viability. Here, we investigated the effects of MitoQ, a mitochondria-targeted antioxidant, in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo PD models. We observed that 6-OHDA enhanced mitochondrial fission by decreasing the expression of Mfn1, Mfn2 and OPA1 as well as by increasing the expression of Drp1 in the dopaminergic (DA) cell line SN4741. Notably, MitoQ treatment particularly upregulated the Mfn2 protein and mRNA levels and promoted mitochondrial fusion in the presence of 6-OHDA in a Mfn2-dependent manner. In addition, MitoQ also stabilized mitochondrial morphology and function in the presence of 6-OHDA, which further suppressed the formation of reactive oxygen species (ROS), as well as ameliorated mitochondrial fragmentation and cellular apoptosis. Moreover, the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) was attributed to the upregulation of Mfn2 induced by MitoQ. Consistent with these findings, administration of MitoQ in 6-OHDA-treated mice significantly rescued the decrease of Mfn2 expression and the loss of DA neurons in the SNc. Taken together, our findings suggest that MitoQ protects DA neurons in a 6-OHDA induced PD model by activating PGC-1α to enhance Mfn2-dependent mitochondrial fusion. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models.

PubMed

Kim, Hanna; Perentis, Rylee J; Caldwell, Guy A; Caldwell, Kim A

2018-05-10

Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respectively. Additionally, eat-3, an inner mitochondrial membrane fusion component, an OPA1 homolog, is also down regulated. These changes are associated with a metabolite-induced decline in mitochondrial membrane potential and enhanced DA neurodegeneration that is dependent on PINK-1 function. Genetic analysis also indicates an association between the cell death pathway and drp-1 following S. ven exposure. Metabolite-induced neurotoxicity can be suppressed by DA-neuron-specific RNAi knockdown of eat-3. AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) ameliorated metabolite- or PINK-1-induced neurotoxicity; however, it enhanced neurotoxicity under normal conditions. These studies underscore the critical role of mitochondrial dynamics in DA neurodegeneration. Moreover, given the largely undefined environmental components of PD etiology, these results highlight a response to an environmental factor that defines distinct mechanisms underlying a potential contributor to the progressive DA neurodegeneration observed in PD.

A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family

NASA Astrophysics Data System (ADS)

Zhang, Liping; Shi, Wei; Song, Liming; Zhang, Xiao; Cheng, Lulu; Wang, Yanfang; Ge, Xianglian; Li, Wei; Zhang, Wei; Min, Qingjie; Jin, Zi-Bing; Qu, Jia; Gu, Feng

2014-11-01

Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family.

PubMed

Zhang, Liping; Shi, Wei; Song, Liming; Zhang, Xiao; Cheng, Lulu; Wang, Yanfang; Ge, Xianglian; Li, Wei; Zhang, Wei; Min, Qingjie; Jin, Zi-Bing; Qu, Jia; Gu, Feng

2014-11-06

Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.

PubMed

Wu, Li-Hong; Chang, Hao-Chun; Ting, Pei-Ching; Wang, Danny L

2018-06-01

Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm 2 ) generated by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long- and short- OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα-induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation-induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity. © 2017 Wiley Periodicals, Inc.

A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy

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

Zhang, Juanjuan; Yuan, Yimin; Lin, Bing

2012-03-23

Highlights: Black-Right-Pointing-Pointer We report the characterization of a four-generation large Chinese family with ADOA. Black-Right-Pointing-Pointer We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. Black-Right-Pointing-Pointer We do not find any mitochondrial DNA mutations associated with optic atrophy. Black-Right-Pointing-Pointer Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- Abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressivemore » visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9 years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.« less

Spatial resolution limitation of liquid crystal spatial light modulator

NASA Astrophysics Data System (ADS)

Wang, Xinghua; Wang, Bin; McManamon, Paul F., III; Pouch, John J.; Miranda, Felix A.; Anderson, James E.; Bos, Philip J.

2004-10-01

The effect of fringing electric fields in a liquid crystal (LC) Optical Phased Array (OPA), also referred to as a spatial light modulator (SLM), is a governing factor that determines the diffraction efficiency (DE) of the LC OPA for high resolution spatial phase modulation. In this article, the fringing field effect in a high resolution LC OPA is studied by accurate modeling the DE of the LC blazed gratings by LC director simulation and Finite Difference Time Domain (FDTD) simulation. Influence factors that contribute significantly to the DE are discussed. Such results provide fundamental understanding for high resolution LC devices.

ROS as Regulators of Mitochondrial Dynamics in Neurons.

PubMed

Cid-Castro, Carolina; Hernández-Espinosa, Diego Rolando; Morán, Julio

2018-07-01

Mitochondrial dynamics is a complex process, which involves the fission and fusion of mitochondrial outer and inner membranes. These processes organize the mitochondrial size and morphology, as well as their localization throughout the cells. In the last two decades, it has become a spotlight due to their importance in the pathophysiological processes, particularly in neurological diseases. It is known that Drp1, mitofusin 1 and 2, and Opa1 constitute the core of proteins that coordinate this intricate and dynamic process. Likewise, changes in the levels of reactive oxygen species (ROS) lead to modifications in the expression and/or activity of the proteins implicated in the mitochondrial dynamics, suggesting an involvement of these molecules in the process. In this review, we discuss the role of ROS in the regulation of fusion/fission in the nervous system, as well as the involvement of mitochondrial dynamics proteins in neurodegenerative diseases.

Ontogeny of muscle bioenergetics in Adelie penguin chicks (Pygoscelis adeliae).

PubMed

Fongy, Anaïs; Romestaing, Caroline; Blanc, Coralie; Lacoste-Garanger, Nicolas; Rouanet, Jean-Louis; Raccurt, Mireille; Duchamp, Claude

2013-11-01

The ontogeny of pectoralis muscle bioenergetics was studied in growing Adélie penguin chicks during the first month after hatching and compared with adults using permeabilized fibers and isolated mitochondria. With pyruvate-malate-succinate or palmitoyl-carnitine as substrates, permeabilized fiber respiration markedly increased during chick growth (3-fold) and further rose in adults (1.4-fold). Several markers of muscle fiber oxidative activity (cytochrome oxidase, citrate synthase, hydroxyl-acyl-CoA dehydrogenase) increased 6- to 19-fold with age together with large rises in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial content (3- to 5-fold) and oxidative activities (1.5- to 2.4-fold). The proportion of IMF relative to SS mitochondria increased with chick age but markedly dropped in adults. Differences in oxidative activity between mitochondrial fractions were reduced in adults compared with hatched chicks. Extrapolation of mitochondrial to muscle respirations revealed similar figures with isolated mitochondria and permeabilized fibers with carbohydrate-derived but not with lipid-derived substrates, suggesting diffusion limitations of lipid substrates with permeabilized fibers. Two immunoreactive fusion proteins, mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), were detected by Western blots on mitochondrial extracts and their relative abundance increased with age. Muscle fiber respiration was positively related with Mfn2 and OPA1 relative abundance. Present data showed by two complementary techniques large ontogenic increases in muscle oxidative activity that may enable birds to face thermal emancipation and growth in childhood and marine life in adulthood. The concomitant rise in mitochondrial fusion protein abundance suggests a role of mitochondrial networks in the skeletal muscle processes of bioenergetics that enable penguins to overcome harsh environmental constraints.

Data fusion for food authentication. Combining rare earth elements and trace metals to discriminate "Fava Santorinis" from other yellow split peas using chemometric tools.

PubMed

Drivelos, Spiros A; Higgins, Kevin; Kalivas, John H; Haroutounian, Serkos A; Georgiou, Constantinos A

2014-12-15

"Fava Santorinis", is a protected designation of origin (PDO) yellow split pea species growing only in the island of Santorini in Greece. Due to its nutritional quality and taste, it has gained a high monetary value. Thus, it is prone to adulteration with other yellow split peas. In order to discriminate "Fava Santorinis" from other yellow split peas, four classification methods utilising rare earth elements (REEs) measured through inductively coupled plasma-mass spectrometry (ICP-MS) are studied. The four classification processes are orthogonal projection analysis (OPA), Mahalanobis distance (MD), partial least squares discriminant analysis (PLS-DA) and k nearest neighbours (KNN). Since it is known that trace elements are often useful to determine geographical origin of food products, we further quantitated for trace elements using ICP-MS. Presented in this paper are results using the four classification processes based on the fusion of the REEs data with the trace element data. Overall, the OPA method was found to perform best with up to 100% accuracy using the fused data. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1

PubMed Central

Chang, Chuang-Rung; Blackstone, Craig

2017-01-01

Mitochondria in cells comprise a tubulovesicular network shaped continuously by complementary fission and fusion events. The mammalian Drp1 protein plays a key role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in the balance between these opposing processes can occur rapidly, indicating that modifications to these proteins may regulate mitochondrial membrane dynamics. We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized. This dynamin-related GTPase undergoes a number of steps to mediate mitochondrial fission, including translocation from cytoplasm to the mitochondrial outer membrane, higher-order assembly into spirals, GTP hydrolysis associated with a conformational change and membrane deformation, and ultimately disassembly. Many of these steps may be influenced by covalent modification of Drp1. We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. PMID:20649536

Occupational physical activity, but not leisure-time physical activity increases the risk of atrial fibrillation: The Copenhagen City Heart Study.

PubMed

Skielboe, Ane K; Marott, Jacob L; Dixen, Ulrik; Friberg, Jens B; Jensen, Gorm B

2016-11-01

Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA. In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF. High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF. © The European Society of Cardiology 2016.

Macular Pigment Optical Density and Ocular Pulse Amplitude in Subjects with Different Axial Lengths and Refractive Errors.

PubMed

Czepita, Maciej; Karczewicz, Danuta; Safranow, Krzysztof; Czepita, Damian

2015-06-13

The purpose of our study was to: (1) investigate the macular pigment optical density (MPOD) and ocular pulse amplitude (OPA) in subjects with different axial lengths (AL) and refractive errors (RE); (2) determine if there is a correlation between MPOD and OPA; and (3) evaluate whether MPOD and OPA depend on intraocular pressure (IOP). This study included 140 eyes of 70 subjects - 17 men and 53 women, aged 18 to 29 years (mean: 22.5 years; SD=2.8). Every examined person underwent a thorough eye examination including: visual acuity, anterior segment and fundus examination, keratometry, auto-refractometry, and MPOD, OPA, AL, and IOP measurements. The obtained results were analyzed statistically using Statistica 10 software. P values of <0.05 were considered statistically significant. The following refractive errors were selected: emmetropia (34 eyes), hyperopia (18 eyes), low myopia (60 eyes), medium myopia (19 eyes), and high myopia (9 eyes). It has been established that the OPA increases with the rise in the spherical equivalents (SE) (Rs=+0.38, P<0.001), while the increase in AL correlates with the decrease of OPA (Rs=-0.40, P<0.001). The increase in IOP correlates with the rise in the OPA (Rs=+0.20, P<0.05). There were no significant correlations between IOP and SE or AL. (1) MPOD is not correlated with the OPA in subjects with different AL and RE; (2) OPA decreases with the rise of AL; (3) OPA decreases with the fall of the SE; and (4) OPA increases with the rise in IOP.

Demonstration of an optical phased array using electro-optic polymer phase shifters

NASA Astrophysics Data System (ADS)

Hirano, Yoshikuni; Motoyama, Yasushi; Tanaka, Katsu; Machida, Kenji; Yamada, Toshiki; Otomo, Akira; Kikuchi, Hiroshi

2018-03-01

We have been investigating an optical phased array (OPA) using electro-optic (EO) polymers in phase shifters to achieve ultrafast optical beam steering. In this paper, we describe the basic structures of the OPA using EO polymer phase shifters and show the beam steering capability of the OPA. The designed OPA has a multimode interference (MMI) beam splitter and 8-channel polymer waveguides with EO polymer phase shifters. We compare 1 × 8 MMI and cascaded 1 × 2 MMI beam splitters numerically and experimentally, and then obtain uniform intensity outputs from the 1 × 8 beam splitter. We fabricate the EO polymer OPA with a 1 × 8 MMI beam splitter to prevent intensity dispersion due to radiation loss in bending waveguides. We also evaluate the optical beam steering capability of the fabricated OPA and found a 2.7° deflection of far-field patterns when applying a voltage difference of 25 V in adjacent phase shifters.

Comparison of Ocular Pulse Amplitude Lowering Effects of Preservative-Free Tafluprost and Preservative-Free Dorzolamide-Timolol Fixed Combination Eyedrops.

PubMed

Seo, Du Ri; Ha, Seung Joo

2015-01-01

To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry. In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment. After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01). Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP.

Elevated hydrostatic pressure triggers release of OPA1 and cytochrome C, and induces apoptotic cell death in differentiated RGC-5 cells

PubMed Central

Kim, Keun-Young; Lindsey, James D.; Angert, Mila; Patel, Ankur; Scott, Ray T.; Liu, Quan; Crowston, Jonathan G.; Ellisman, Mark H.; Perkins, Guy A.; Weinreb, Robert N.

2009-01-01

Purpose This study was conducted to determine whether elevated hydrostatic pressure alters mitochondrial structure, triggers release of the dynamin-related guanosine triphosphatase (GTPase) optic atrophy type 1 (OPA1) or cytochrome C from mitochondria, alters OPA1 gene expression, and can directly induce apoptotic cell death in cultured retinal ganglion cell (RGC)-5 cells. Methods Differentiated RGC-5 cells were exposed to 30 mmHg for three days in a pressurized incubator. As a control, differentiated RGC-5 cell cultures were incubated simultaneously in a conventional incubator. Live RGC-5 cells were then labeled with MitoTracker Red and mitochondrial morphology was assessed by fluorescence microscopy. Mitochondrial structural changes were also assessed by electron microscopy and three-dimenstional (3D) electron microscope tomography. OPA1 mRNA was measured by Taqman quantitative PCR. The cellular distribution of OPA1 protein and cytochrome C was assessed by immunocytochemistry and western blot. Caspase-3 activation was examined by western blot. Apoptotic cell death was evaluated by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results Mitochondrial fission, characterized by the conversion of tubular fused mitochondria into isolated small organelles, was triggered after three days exposure to elevated hydrostatic pressure. Electron microscopy confirmed the fission and noted no changes to mitochondrial architecture, nor outer membrane rupture. Electron microscope tomography showed that elevated pressure depleted mitochondrial cristae content by fourfold. Elevated hydrostatic pressure increased OPA1 gene expression by 35±14% on day 2, but reduced expression by 36±4% on day 3. Total OPA1 protein content was not changed on day 2 or 3. However, pressure treatment induced release of OPA1 and cytochrome C from mitochondria to the cytoplasm. Elevated pressure also activated caspase-3 and induced apoptotic cell death. Conclusions Elevated hydrostatic pressure triggered mitochondrial changes including mitochondrial fission and abnormal cristae depletion, alteration of OPA1 gene expression, and release of OPA1 and cytochrome C into the cytoplasm before the onset of apoptotic cell death in differentiated RGC-5 cells. These results suggest that sustained moderate pressure elevation may directly damage RGC integrity by injuring mitochondria. PMID:19169378

Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

PubMed Central

Anderson, Stacey E.; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G.; Johnson, Victor J.; Joseph, Pius

2010-01-01

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG1. In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

Occupational physical activity and body mass index (BMI) among Canadian adults: does physical activity at work help to explain the socio-economic patterning of body weight?

PubMed

Barberio, Amanda; McLaren, Lindsay

2011-01-01

The behavioural and socio-cultural processes underlying the association between socio-economic position (SEP) and body mass index (BMI) remain unclear. Occupational physical activity (OPA) is one plausible explanatory variable that has not been previously considered. 1) To examine the association between OPA and BMI, and 2) to examine whether OPA mediates the SEP-BMI association, in a Canadian population-based sample. This cross-sectional study was based on secondary analysis of the 2008 Canadian Community Health Survey data, focusing on adults (age 25-64) working at a job or business (men, n = 1,036; women, n = 936). BMI was based on measured height and weight and we derived a novel indicator of OPA from the National Occupational Classification Career Handbook. Our analytic technique was ordinary least squares regression, adjusting for a range of socio-demographic, health and behavioural covariates. OPA was marginally associated with BMI in women, such that women with medium levels of OPA tended to be lighter than women with low levels of OPA, in adjusted models. No associations between OPA and BMI were detected for males. Baron and Kenny's (1986) three conditions for testing mediation were not satisfied, and thus we were unable to proceed with testing OPA as a mediator. Notwithstanding the small effects observed in women, overall the associations between OPA and BMI were neither clear nor strong, which could reflect conceptual and/or methodological reasons. Future research on this topic might incorporate other plausible explanatory variables (e.g., job-related psychosocial stress) and adopt a prospective design.

Direct fluorescence characterisation of a picosecond seeded optical parametric amplifier

NASA Astrophysics Data System (ADS)

Stuart, N. H.; Bigourd, D.; Hill, R. W.; Robinson, T. S.; Mecseki, K.; Patankar, S.; New, G. H. C.; Smith, R. A.

2015-02-01

The temporal intensity contrast of high-power lasers based on optical parametric amplification (OPA) can be limited by parametric fluorescence from the non-linear gain stages. Here we present a spectroscopic method for direct measurement of unwanted parametric fluorescence widely applicable from unseeded to fully seeded and saturated OPA operation. Our technique employs simultaneous spectroscopy of fluorescence photons slightly outside the seed bandwidth and strongly attenuated light at the seed central wavelength. To demonstrate its applicability we have characterised the performance of a two-stage picosecond OPA pre-amplifier with 2.8×105 gain, delivering 335 μJ pulses at 1054 nm. We show that fluorescence from a strongly seeded OPA is reduced by ~500× from the undepleted to full pump depletion regimes. We also determine the vacuum fluctuation driven noise term seeding this OPA fluorescence to be 0.7±0.4 photons ps-1 nm-1 bandwidth. The resulting shot-to-shot statistics highlights a 1.5% probability of a five-fold and 0.3% probability of a ten-fold increase of fluorescence above the average value. Finally, we show that OPA fluorescence can be limited to a few-ps pedestal with 3×10-9 temporal intensity contrast 1.3 ps ahead of an intense laser pulse, a level highly attractive for large scale chirped-pulse OPA laser systems.

Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8.

PubMed

Eckert, Gunter P; Schiborr, Christina; Hagl, Stephanie; Abdel-Kader, Reham; Müller, Walter E; Rimbach, Gerald; Frank, Jan

2013-04-01

The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological features of human brain aging in order to study their prevention by e.g. dietary factors. We thus investigated the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) as a model for the age-dependent changes in mitochondrial function in the brain. To this end, 2-months old male SAMR1 (n=10) and SAMP8 mice (n=7) were fed a Western type diet (control groups) for 5months and one group of SAMP8 mice (n=6) was fed an identical diet fortified with 500mg curcumin per kg. Dissociated brain cells and brain tissue homogenates were analyzed for malondialdehyde, heme oxygenase-1 mRNA, mitochondrial membrane potential (MMP), ATP concentrations, protein levels of mitochondrial marker proteins for mitochondrial membranes (TIMM, TOMM), the mitochondrial permeability transition pore (ANT1, VDAC1, TSPO), respiration complexes, and fission and fusion (Fis, Opa1, Mfn1, Drp1). Dissociated brain cells isolated from SAMP8 mice showed significantly reduced MMP and ATP levels, probably due to significantly diminished complex V protein expression, and increased expression of TSPO. Fission and fusion marker proteins indicate enhanced mitochondrial fission in brains of SAMP8 mice. Treatment of SAMP8 mice with curcumin improved MMP and ATP and restored mitochondrial fusion, probably by up-regulating nuclear factor PGC1α protein expression. In conclusion, SAMP8 compared to SAMR1 mice are a suitable model to study age-dependent changes in mitochondrial function and curcumin emerges as a promising nutraceutical for the prevention of neurodegenerative diseases that are accompanied or caused by mitochondrial dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inactivation of surrogate coronaviruses on hard surfaces by health care germicides.

PubMed

Hulkower, Rachel L; Casanova, Lisa M; Rutala, William A; Weber, David J; Sobsey, Mark D

2011-06-01

In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Intensity and temporal noise characteristics in femtosecond optical parametric amplifiers.

PubMed

Chen, Wei; Fan, Jintao; Ge, Aichen; Song, Huanyu; Song, Youjian; Liu, Bowen; Chai, Lu; Wang, Chingyue; Hu, Minglie

2017-12-11

We characterize the relative intensity noise (RIN) and relative timing jitter (RTJ) between the signal and pump pulses of optical parametric amplifiers (OPAs) seeded by three different seed sources. Compared to a white-light continuum (WLC) seeded- and an optical parametric generator (OPG) seeded OPA, the narrowband CW seeded OPA exhibits the lowest root-mean-square (RMS) RIN and RTJ of 0.79% and 0.32 fs, respectively, integrated from 1 kHz to the Nyquist frequency of 1.25 MHz. An improved numerical model based on a forward Maxwell equation (FME) is built to investigate the transfers of the pump and seed's noise to the resulting OPAs' intensity and temporal fluctuation. Both the experimental and numerical study indicate that the low level of noise from the narrowband CW seeded OPA is attributed to the elimination of the RIN and RTJ coupled from the noise of seed source, being one of the important contributions to RIN and timing jitter in the other two OPAs. The approach to achieve lower level of noise from this CW seeded OPA by driving it close to saturation is also discussed with the same numerical model.

Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway

PubMed Central

Fimland, Marius Steiro; Vie, Gunnhild; Holtermann, Andreas; Krokstad, Steinar; Nilsen, Tom Ivar Lund

2018-01-01

Objectives To prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension. Methods A population-based cohort study in Norway on 32 362 persons aged 20–65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs. Results During a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA. Conclusions We observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension. PMID:28698178

Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration

PubMed Central

Misko, Albert; Sasaki, Yo; Tuck, Elizabeth; Milbrandt, Jeffrey; Baloh, Robert H.

2012-01-01

Summary Alterations in mitochondrial dynamics (fission, fusion and movement) are implicated in many neurodegenerative diseases, from rare genetic disorders such as Charcot-Marie-Tooth disease, to common conditions including Alzheimer’s disease. However, the relationship between altered mitochondrial dynamics and neurodegeneration is incompletely understood. Here we show that disease associated MFN2 proteins suppressed both mitochondrial fusion and transport, and produced classic features of segmental axonal degeneration without cell body death, including neurofilament filled swellings, loss of calcium homeostasis, and accumulation of reactive oxygen species. By contrast, depletion of Opa1 suppressed mitochondrial fusion while sparing transport, and did not induce axonal degeneration. Axon degeneration induced by mutant MFN2 proteins correlated with the disruption of the proper mitochondrial positioning within axons, rather than loss of overall mitochondrial movement, or global mitochondrial dysfunction. We also found that augmenting expression of MFN1 rescued the axonal degeneration caused by MFN2 mutants, suggesting a possible therapeutic strategy for Charcot-Marie-Tooth disease. These experiments provide evidence that the ability of mitochondria to sense energy requirements and localize properly within axons is key to maintaining axonal integrity, and may be a common pathway by which disruptions in axonal transport contribute to neurodegeneration. PMID:22442078

U.S. Coast Guard 1995 oil pollution research grants publications : part 1

DOT National Transportation Integrated Search

1997-08-01

The Oil Pollution Research Grants Program was created by the Oil Pollution Act (OPA) of 1990, P.L. 101-380 (OPA 90), 33 U.S.C. 28761(c)(8) and 2761(c)(9). The OPA established a regional research program and authorized those agencies represented on th...

An evaluation of the effects of eyeball structure on ocular pulse amplitude in healthy subjects.

PubMed

Ishii, Kotaro; Mori, Mikiro; Oshika, Tetsuro

2012-12-01

To evaluate the effects of eyeball structure on ocular pulse amplitude (OPA) measured using dynamic contour tonometer (DCT). In 86 eyes of 43 healthy subjects, we measured OPA and intraocular pressure (IOP) with DCT (DCT-IOP), IOP with Goldmann applanation tonometry (GAT-IOP), central corneal thickness (CCT), corneal thickness 2 mm (2 mmCT) and 4 mm (4 mmCT) apart from the center, corneal volume within a 3.5-mm radius from the corneal center, corneal curvature, anterior chamber depth, anterior chamber volume, and axial length (AL). OPA had a significant positive correlation with GAT-IOP (Pearson's r = 0.412, p < 0.001), DCT-IOP (r = 0.350, p < 0.001), and 4 mmCT (r = 0.244, p = 0.0231), and had a significant negative correlation with AL (r = -0.268, p = 0.0122). In a multiple linear regression analysis, AL and GAT-IOP were significantly associated with OPA. OPA measured with DCT is significantly influenced by several factors, such as IOP, peripheral corneal thickness (4 mmCT), and AL.

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

PubMed

Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

2017-02-01

Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

The investigation of the interaction between piracetam and bovine serum albumin by spectroscopic methods

NASA Astrophysics Data System (ADS)

Guo, Xingjia; Han, Xiaowei; Tong, Jian; Guo, Chuang; Yang, Wenfeng; Zhu, Jifen; Fu, Bing

2010-03-01

The interaction between piracetam (OPA) with bovine serum albumin (BSA) has been thoroughly studied by fluorescence quenching technique in combination with UV-vis absorption, Fourier transform infrared (FT-IR), and circular dichroism (CD) spectroscopies under the simulative physiological conditions. The quenching of BSA fluorescence by OPA was found to be a static quenching process. The binding constants ( K a) are 3.014, 2.926, and 2.503 × 10 3 M -1 at 292, 298, and 309 K, respectively. According to the van't Hoff equation, the thermodynamic functions standard enthalpy (Δ H) and standard entropy (Δ S) for the reaction were calculated to be -74.560 kJ mol -1 and -159.380 J mol -1 K -1, which indicated that OPA binds to BSA mainly by hydrogen bonds and van der Waals interactions. The binding distance between BSA and OPA was calculated to be 4.10 nm according to the theory of FÖrster's non-radiation energy transfer. The displacement experiments confirmed that OPA could bind to the site I of BSA. Furthermore, the effects of pH and some common ions on the binding constant were also examined. And the alterations of protein secondary structure in the presence of OPA were observed by the CD and FT-IR spectra.

In situ interactions between Opalinus Clay and Low Alkali Concrete

NASA Astrophysics Data System (ADS)

Lerouge, Catherine; Gaboreau, Stéphane; Grangeon, Sylvain; Claret, Francis; Warmont, Fabienne; Jenni, Andreas; Cloet, Veerle; Mäder, Urs

2017-06-01

A five-year-old interface between a Low Alkali Concrete (LAC) formulation (CEM III/B containing 66% slag and 10% nano-silica) and Opalinus Clay (OPA) from a field experiment at Mont Terri Underground Rock Laboratory in Switzerland (Jenni et al., 2014) has been studied to decipher the textural, mineralogical and chemical changes that occurred between the two reacting materials. Reactivity between LAC concrete and OPA is found to be limited to a ∼1 mm thick highly porous (ca. 75% porosity) white crust developed on the concrete side. Quantitative mineralogical mapping of the white crust using an electron microprobe and infrared spectroscopy on the cement matrix provides evidence of a Mg-rich phase accounting for approximatively 25 wt % of the matrix associated with 11 wt % of calcite, calcium silicate hydrate (C-S-H) and other cement phases. EDX analyses and electron diffraction combined with transmission electron microscopy of the Mg-rich phase provide evidence for a tri-octahedral 2:1 phyllosilicate with mean composition: (Ca0.5±0.2) (Mg2.0±0.4, Fe0.2±0.1, Al0.5±03, □0.3±0.3) (Al0.9±0.2, Si3.1±0.2) O10 (OH)2, where □ represents vacancies in the octahedral site. Apart from this reactive contact, textural, mineralogical and chemical modifications at the contact with the LAC concrete are limited. OPA mineralogy remains largely unmodified. X-ray micro-fluorescence and EPMA mapping of major elements on the OPA side also provides evidence for a Mg-enriched 300-400 μm thick layer. The cation exchange capacity (CEC) values measured in the OPA in contact with the LAC concrete range between 153 and 175 meq kg-1 of dry OPA, close to the reference value of 170 ± 10 meq kg-1 of dry OPA (Pearson et al., 2003). Changing cation occupancies at the interface with LAC concrete are mainly marked by increased Ca, Mg and K, and decreased Na. Leaching tests performed on OPA with deionized water and at different solid to water ratios strongly suggest that Cl and SO4 have either conservative behaviour or are constrained by the solubility of a precipitated sulfate phase. The Cl and SO4 concentrations measured at 2 cm from the interface are close to concentrations of undisturbed OPA pore waters (SO4: 4.5 ± 1.5 mmol kg-1 of dry OPA; Cl: 7.5 ± 2.1 mmol kg-1of dry OPA), and increase towards the interface with the concrete. The SO4 to Cl ratio also increases towards the interface, suggesting that the increasing anion concentrations are not related to porosity variations but rather to a concentration gradient and sulfate phase precipitation near the interface.

Occupational physical activity, overweight, and mortality: a follow-up study of 47,405 Norwegian women and men.

PubMed

Graff-Iversen, Sidsel; Selmer, Randi; Sørensen, Marit; Skurtveit, Svetlana

2007-06-01

This population-based 24-year follow-up study evaluated the association of occupational physical activity (OPA) with overweight and mortality in 47,405 men and women, healthy at baseline, and reporting OPA as sedentary (reference), light, moderately heavy, or heavy. The adjusted odds ratio for overweight was slightly less than 1 for all categories of current nonsedentary work in men but increased by OPA in women. Only heavy OPA conferred a lower mortality with an adjusted rate ratio of 0.84 (95 % confidence interval, 0.76-0.92) for men and 0.69 (95 % confidence interval, 0.52-0.91) for women. This observational study, with OPA recorded in the 1970s and 1980s, suggested a slight protective effect for overweight by nonsedentary work for men and lower mortality by heavy OPA for both genders.

Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

PubMed Central

Anstoetz, Manuela; Rose, Terry J.; Clark, Malcolm W.; Yee, Lachlan H.; Raymond, Carolyn A.; Vancov, Tony

2015-01-01

A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha-1). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils. PMID:26633174

Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

PubMed

Anstoetz, Manuela; Rose, Terry J; Clark, Malcolm W; Yee, Lachlan H; Raymond, Carolyn A; Vancov, Tony

2015-01-01

A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha(-1)). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils.

Occupational and leisure-time physical activity and risk of disability pension: prospective data from the HUNT Study, Norway.

PubMed

Fimland, Marius Steiro; Vie, Gunnhild; Holtermann, Andreas; Krokstad, Steinar; Nilsen, Tom Ivar Lund

2018-01-01

To prospectively investigate the association between occupational physical activity (OPA) and disability pension due to musculoskeletal cause, mental cause or any cause. We also examined the combined association of OPA and leisure-time physical activity (LTPA) with disability pension. A population-based cohort study in Norway on 32 362 persons aged 20-65 years with questionnaire data on OPA and LTPA that were followed up for incident disability pension through the National Insurance Database. We used Cox regression to estimate adjusted HRs with 95% CIs. During a follow-up of 9.3 years, 3837 (12%) received disability pension. Compared with people with mostly sedentary work, those who performed much walking, much walking and lifting, and heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to 1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were stronger for disability pension due to musculoskeletal disorders, whereas there was no clear association between OPA and risk of disability pension due to mental disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to 1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for disability pension due to musculoskeletal disorders, versus low OPA and high LTPA. We observed a positive association between OPA and risk of disability pension due to all causes and musculoskeletal disorders, but not for mental disorders. Physical activity during leisure time reduced some, but not all of the unfavourable effect of physically demanding work on risk of disability pension. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

PubMed

Johswich, Kay O; McCaw, Shannon E; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E; Gray-Owen, Scott D

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

In Vivo Adaptation and Persistence of Neisseria meningitidis within the Nasopharyngeal Mucosa

PubMed Central

Johswich, Kay O.; McCaw, Shannon E.; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E.; Gray-Owen, Scott D.

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa. PMID:23935487

Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development.

PubMed

Deng, Qiannan; Guo, Ting; Zhou, Xiu; Xi, Yongmei; Yang, Xiaohang; Ge, Wanzhong

2016-08-01

Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila. Copyright © 2016 by the Genetics Society of America.

Prohibitin 2 Regulates the Proliferation and Lineage-Specific Differentiation of Mouse Embryonic Stem Cells in Mitochondria

PubMed Central

Komazaki, Shinji; Enomoto, Kei; Seki, Yasuhiro; Wang, Ying Ying; Ishigaki, Yohei; Ninomiya, Naoto; Noguchi, Taka-aki K.; Kokubu, Yuko; Ohnishi, Keigoh; Nakajima, Yoshiro; Kato, Kaoru; Intoh, Atsushi; Takada, Hitomi; Yamakawa, Norio; Wang, Pi-Chao; Asashima, Makoto; Kurisaki, Akira

2014-01-01

Background The pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown. Methodology/Principal Findings In this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria. Conclusions/Significance Our results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells. PMID:24709813

Effect of sub-Tenon's and peribulbar anesthesia on intraocular pressure and ocular pulse amplitude.

PubMed

Pianka, P; Weintraub-Padova, H; Lazar, M; Geyer, O

2001-08-01

To compare the effect of peribulbar and sub-Tenon's anesthesia on intraocular pressure (IOP) and ocular pulse amplitude (OPA) in the injected eye and the fellow noninjected (control) eye. Tel Aviv Medical Center, Tel Aviv, Israel. This prospective study measured IOP and OPA at baseline and 1 and 10 minutes after administration of lidocaine anesthesia in 40 consecutive adult patients having elective cataract surgery. The IOP remained stable throughout the study with both modes of anesthesia. One minute after injection of the anesthetic agent, the OPA was significantly decreased in the injected eyes in both the sub-Tenon's (24%; P < .05) and peribulbar (25%; P < .05) groups. The decrease in the OPA in the sub-Tenon's group (14%; P < .05) was detectable after 10 minutes in the control eyes. In the peribulbar anesthesia group, the OPA in the control eyes increased significantly (9%; P < .05) 1 minute after injection of the anesthetic agent, returning to preinjection levels 10 minutes after the injection. The OPA in the eyes in which lidocaine was injected decreased significantly in both the sub-Tenon's and peribulbar groups. These findings have implications for the management of patients whose ocular circulation may be compromised.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease.

PubMed

Granoff, Dan M

2009-06-24

Killing of Neisseria meningitidis can result from complement-mediated serum bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers > or =1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers > or =1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

PubMed Central

Granoff, Dan M.

2009-01-01

Killing of Neisseria meningitidis can result from complement-mediated bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers ≥1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers ≥1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease. PMID:19477054

Assay for optical determination of biogenic amines using microtiterplates

NASA Astrophysics Data System (ADS)

Nedeljko, Polona; Turel, Matejka; Lobnik, Aleksandra

2013-05-01

Direct determination of catecholamine noradreanaline (NOR) is presented using o-phthaldialdehyde (OPA) as an indicator reagent. The fluorescent assay in which OPA forms with NOR a fluorescent complex (OPA-NOR) can be monitored at neutral, physiological conditions (pH 7) and performed in microtiterplates. The determination of NOR is optimal in the concentration range from 4.0×10-7 to 1.0×10-5 M and limit of detection is 4.0×10-7 M. The OPA-NOR complex maximum intensity is reached within 5 minutes. Dopamine and adrenaline could not be determined using the same approach.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial.

PubMed

Frakking, Thuy T; Chang, Anne B; O'Grady, Kerry-Ann F; Walker-Smith, Katie; Weir, Kelly A

2013-11-07

Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of 'CFE + CA' versus 'CFE' only compared to MBS-identified OPA. Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12613000589785. PMID:24199872

Effect of quantifying peptide release on ruminal protein degradation determined using the inhibitor in vitro system.

PubMed

Colombini, S; Broderick, G A; Clayton, M K

2011-04-01

The aim of this work was to compare use of an o-phthaldialdehyde (OPA) colorimetric assay (OPA-C), which responds to both free AA and peptides, with an OPA fluorimetric assay (OPA-F), which is insensitive to peptides, to quantify rates of ruminal protein degradation in the inhibitor in vitro system using Michaelis-Menten saturation kinetics. Four protein concentrates (expeller-extracted soybean meal, ESBM; 2 solvent-extracted soybean meals, SSBM1 and SSBM2; and casein) were incubated in a ruminal in vitro system treated with hydrazine and chloramphenicol to inhibit microbial uptake of protein degradation products. Proteins were weighed to give a range of N concentrations (from 0.15 to 3 mg of N/mL of inoculum) and incubated with 10 mL of ruminal inoculum and 5 mL of buffer; fermentations were stopped after 2 h by adding trichloroacetic acid (TCA). Proteins were analyzed for buffer-soluble N and buffer extracts were treated with TCA to determine N degraded at t=0 (FD0). The TCA supernatants were analyzed for ammonia (phenol-hypochlorite assay), total AA (TAA; OPA-F), and TAA plus oligopeptides (OPA-C) by flow injection analysis. Velocity of protein degradation was computed from extent of release of 1) ammonia plus free TAA or 2) ammonia plus free TAA and peptides. Rate of degradation (kd) was quantified using nonlinear regression of the integrated Michaelis-Menten equation. The parameters Km (Michaelis constant) and kd (Vmax/Km), where Vmax=maximum velocity, were estimated directly; kd values were adjusted (Akd) for the fraction FD0 using the equation Akd=kd-FD0/2. The OPA-C assay yielded faster degradation rates due to the contribution of peptides to the fraction degraded (overall mean=0.280/h by OPA-C and 0.219/h by OPA-F). Degradation rates for SSBM samples (0.231/h and 0.181/h) and ESBM (0.086/h) obtained by the OPA-C assay were more rapid than rates reported by the National Research Council (NRC). Both assays indicated that the 2 SSBM differed in rumen-undegradable protein (RUP) content; the more slowly degraded SSBM had RUP content (35% by OPA-C) similar to that reported by the NRC. The RUP content of ESBM (42% by OPA-C) was lower than the NRC value. Preliminary studies with 4 additional protein concentrates confirmed that accounting for peptide formation increased degradation rate; however, a trend for an interaction between assay and protein source suggested that peptide release made a smaller contribution to rate for more slowly degraded proteins. The OPA-C assay is a simple and reliable method to quantify formation of small peptides. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Low-Level Laser Effect on Proliferation, Migration, and Antiapoptosis of Mesenchymal Stem Cells.

PubMed

Yin, Kan; Zhu, Rongjia; Wang, Shihua; Zhao, Robert Chunhua

2017-05-15

Mesenchymal stem cells (MSCs) have been proved to be an important element in cell-based therapy. Photobiomodulation used extremely low-level lasers (LLLs) to affect the behavior of cells. The effect mechanism of LLLs on MSCs from human remained to be discovered. In this study, cell viability was assessed using MTS assays and cell cycle was evaluated by fluorescence-activated cell sorting (FACS). The influence of LLLs on mitochondrial biogenesis (fission or fusion) and function (ATP, reactive oxygen species [ROS], nitric oxide [NO]) was evaluated by transmission electron microscope, FACS, quantitative real time polymerase chain reaction (q-PCR), and immunocytochemistry. Cell migration and cytoskeleton alteration (actin and tubulin) were evaluated using transwell assay, immunocytochemistry, enzyme-linked immunosorbent assay, and western blotting. Cell apoptosis was evaluated using FACS, immunocytochemistry, and western blotting. We investigated that certain influence of LLLs on MSCs in vitro 6 or 24 h after 1 h of LLL irradiation. The mechanism of the effects included proliferation rate increase mediated by increased S phase proportion; mitochondrial biogenesis and function alteration mediated by fusion (Mfn1, Mfn2, and Opa-1) and fission (Fis1, Drp-1, and MTP18)-related proteins, NRF1, TFAM, PGC-1a, and upregulated intracellular ROS and NO concentration; migration acceleration through the ERK1/2 and FAK pathway and upregulation of growth factors such as HGF and PDGF; and resistance to apoptosis with increased Bcl-2 and decreased Bax, or through tunneling nanotube formation between LLL-treated MSCs and 5-fluorouracil-induced apoptotic MSCs. These observations suggested that LLLs enhanced stem cell survival and therapeutic function, which could appear to be an innovative pretreatment in the application of MSCs.

Mitochondrial dynamics in mammalian health and disease.

PubMed

Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

2009-07-01

The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

Range and Panoramic Image Fusion Into a Textured Range Image for Culture Heritage Documentation

NASA Astrophysics Data System (ADS)

Bila, Z.; Reznicek, J.; Pavelka, K.

2013-07-01

This paper deals with a fusion of range and panoramic images, where the range image is acquired by a 3D laser scanner and the panoramic image is acquired with a digital still camera mounted on a panoramic head and tripod. The fused resulting dataset, called "textured range image", provides more reliable information about the investigated object for conservators and historians, than using both datasets separately. A simple example of fusion of a range and panoramic images, both obtained in St. Francis Xavier Church in town Opařany, is given here. Firstly, we describe the process of data acquisition, then the processing of both datasets into a proper format for following fusion and the process of fusion. The process of fusion can be divided into a two main parts: transformation and remapping. In the first, transformation, part, both images are related by matching similar features detected on both images with a proper detector, which results in transformation matrix enabling transformation of the range image onto a panoramic image. Then, the range data are remapped from the range image space into a panoramic image space and stored as an additional "range" channel. The process of image fusion is validated by comparing similar features extracted on both datasets.

Effects of Organized Physical Activity on Selected Health Indices among Women Older than 55 Years.

PubMed

Zmijewski, Piotr; Mazurek, Krzysztof; Kozdron, Ewa; Szczypiorski, Piotr; Frysztak, Agata

2015-01-01

The main aim of this study was to determine health benefits among women older than 55 years who participated in organized, group-based physical activity (OPA). Thirty-five women aged 65.0 ± 7.3 years volunteered for this study. The classical and nonclassical cardiovascular (CVD) risk factors were measured before and after a 2-week OPA camp in a remote location and 3 months of OPA. Self-guided physical activity was analyzed 18 months after OPA. Two-week effects included significant decreases in body mass index, waist and hip circumferences, resting systolic and diastolic blood pressure (BP) and resting heart rate, improved exercise capacity (EC), improved low-density lipoprotein and high-density lipoprotein (HDL-C), cholesterol, and other atherogenic lipid indices (ALI), and a reduction in 10-year estimated risk of death from CVD. Three-month effects included a further decrease in systolic BP, improvements in EC and HDL-C, and maintenance of lower levels of ALI, as well as lower CVD risk. The implementation of the OPA programme had a positive impact on somatic features, exercise capacity, biochemical indices, and risk for death from CVD. The presented programme can be regarded as an effective element of primary prevention of cardiovascular diseases among women older than 55 years.

Destruction of OPA from munitions demilitarization in supercritical water oxidation: kinetics of total organic carbon disappearance.

PubMed

Veriansyah, Bambang; Kim, Jae-Duck; Lee, Jong-Chol; Hong, Deasik

2006-01-01

The destruction of OPA from munitions demilitarization has been accomplished in supercritical water oxidation (SCWO) with oxygen as oxidant in an isothermal continuous-flow reactor. The experiments were conducted at a temperature of 689-887 K and a fixed pressure of 25 MPa, with a residence time that ranged from 7 s to 14 s. The destruction efficiency was measured by total organic carbon (TOC) conversion. At the reaction condition, the initial TOC concentrations of OPA were varied from 1.41 mmol/L to 19.57 mmol/L and the oxygen concentrations were varied from 15.03 mmol/L to 81.85 mmol/L. Experimental data showed that all the TOC conversions were >80% under the above experimental conditions. The kinetics of TOC disappearance, which is essential for the design, optimization, and control of reliable commercial SCWO reactor was developed by taking into account the dependence of the oxidant and TOC concentration on the reaction rate. A global TOC disappearance rates expression was regressed from the data of 38 experiments, to a 95% confidence level. The resulting activation energy was determined to be 44.01 +/- 1.52 kJ/mol, and the pre-exponential factor was (1.67 +/- 0.45) x 10(2) L(1.14) mmol(-0.14) s(-1). The reaction orders for the TOC and the oxidant were 0.98 +/- 0.01 and 0.16 +/- 0.02, respectively.

Mitochondrial dysfunction-associated OPA1 cleavage contributes to muscle degeneration: preventative effect of hydroxytyrosol acetate.

PubMed

Wang, X; Li, H; Zheng, A; Yang, L; Liu, J; Chen, C; Tang, Y; Zou, X; Li, Y; Long, J; Liu, J; Zhang, Y; Feng, Z

2014-11-13

Mitochondrial dysfunction contributes to the development of muscle disorders, including muscle wasting, muscle atrophy and degeneration. Despite the knowledge that oxidative stress closely interacts with mitochondrial dysfunction, the detailed mechanisms remain obscure. In this study, tert-butylhydroperoxide (t-BHP) was used to induce oxidative stress on differentiated C2C12 myotubes. t-BHP induced significant mitochondrial dysfunction in a time-dependent manner, accompanied by decreased myosin heavy chain (MyHC) expression at both the mRNA and protein levels. Consistently, endogenous reactive oxygen species (ROS) overproduction triggered by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), a mitochondrial oxidative phosphorylation inhibitor, was accompanied by decreased membrane potential and decreased MyHC protein content. However, the free radical scavenger N-acetyl-L-cysteine (NAC) efficiently reduced the ROS level and restored MyHC content, suggesting a close association between ROS and MyHC expression. Meanwhile, we found that both t-BHP and FCCP promoted the cleavage of optic atrophy 1 (OPA1) from the long form into short form during the early stages. In addition, the ATPase family gene 3-like 2, a mitochondrial inner membrane protease, was also markedly increased. Moreover, OPA1 knockdown in myotubes was accompanied by decreased MyHC content, whereas NAC failed to prevent FCCP-induced MyHC decrease with OPA1 knockdown, suggesting that ROS might affect MyHC content by modulating OPA1 cleavage. In addition, hydroxytyrosol acetate (HT-AC), an important compound in virgin olive oil, could significantly prevent t-BHP-induced mitochondrial membrane potential and cell viability loss in myotubes. Specifically, HT-AC inhibited t-BHP-induced OPA1 cleavage and mitochondrial morphology changes, accompanied by improvement on mitochondrial oxygen consumption capacity, ATP productive potential and activities of mitochondrial complex I, II and V. Moreover, both t-BHP- and FCCP-induced MyHC decrease was sufficiently inhibited by HT-AC. Taken together, our data provide evidence indicating that mitochondrial dysfunction-associated OPA1 cleavage may contribute to muscle degeneration, and olive oil compounds could be effective nutrients for preventing the development of muscle disorders.

Expression of Opacity Proteins Interferes with the Transmigration of Neisseria gonorrhoeae across Polarized Epithelial Cells.

PubMed

Stein, Daniel C; LeVan, Adriana; Hardy, Britney; Wang, Liang-Chun; Zimmerman, Lindsey; Song, Wenxia

2015-01-01

Neisseria gonorrhoeae (GC) establishes infection at the mucosal surface of the human genital tract, most of which is lined with polarized epithelial cells. GC can cause localized as well as disseminated infections, leading to various complications. GC constantly change their surface structures via phase and antigenic variation, which has been implicated as a means for GC to establish infection at various anatomic locations of male and female genital tracks. However, the exact contribution of each surface molecule to bacterial infectivity remains elusive due to their phase variation. Using a GC derivative that is genetically devoid of all opa genes (MS11∆Opa), this study shows that Opa expression interferes with GC transmigration across polarized human epithelial cells. MS11∆Opa transmigrates across polarized epithelial cells much faster and to a greater extent than MS11Opa+, while adhering at a similar level as MS11Opa+. When MS11Opa+, able to phase vary Opa expression, was inoculated, only those bacteria that turn off Opa expression transmigrate across the polarized epithelial monolayer. Similar to bacteria alone or co-cultured with non-polarized epithelial cells, MS11∆Opa fails to form large microcolonies at the apical surface of polarized epithelial cells. Apical inoculation of MS11Opa+, but not MS11∆Opa, induces the recruitment of the Opa host-cell receptor carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) to the apical junction and the vicinity of bacterial adherent sites. Our results suggest that Opa expression limits gonococcal ability to invade into subepithelial tissues by forming tight interactions with neighboring bacteria and by inducing CEACAM redistribution to cell junctions.

Drp-1 dependent mitochondrial fragmentation and protective autophagy in dopaminergic SH-SY5Y cells overexpressing alpha-synuclein.

PubMed

Martinez, Jimena Hebe; Alaimo, Agustina; Gorojod, Roxana Mayra; Porte Alcon, Soledad; Fuentes, Federico; Coluccio Leskow, Federico; Kotler, Mónica Lidia

2018-04-01

Parkinson's disease is a neurodegenerative movement disorder caused by the loss of dopaminergic neurons from substantia nigra. It is characterized by the accumulation of aggregated α-synuclein as the major component of the Lewy bodies. Additional common features of this disease are the mitochondrial dysfunction and the activation/inhibition of autophagy both events associated to the intracellular accumulation of α-synuclein. The mechanism by which these events contribute to neural degeneration remains unknown. In the present work we investigated the effect of α-synuclein on mitochondrial dynamics and autophagy/mitophagy in SH-SY5Y cells, an in vitro model of Parkinson disease. We demonstrated that overexpression of wild type α-synuclein causes moderated toxicity, ROS generation and mitochondrial dysfunction. In addition, α-synuclein induces the mitochondrial fragmentation on a Drp-1-dependent fashion. Overexpression of the fusion protein Opa-1 prevented both mitochondrial fragmentation and cytotoxicity. On the other hand, cells expressing α-synuclein showed activated autophagy and particularly mitophagy. Employing a genetic strategy we demonstrated that autophagy is triggered in order to protect cells from α-synuclein-induced cell death. Our results clarify the role of Opa-1 and Drp-1 in mitochondrial dynamics and cell survival, a controversial α-synuclein research issue. The findings presented point to the relevance of mitochondrial homeostasis and autophagy in the pathogenesis of PD. Better understanding of the molecular interaction between these processes could give rise to novel therapeutic methods for PD prevention and amelioration. Copyright © 2018 Elsevier Inc. All rights reserved.

Irritancy and Allergic Responses Induced by Exposure to the Indoor Air Chemical 4-Oxopentanal

PubMed Central

Anderson, Stacey E.; Franko, Jennifer; Jackson, Laurel G.; Wells, J. R.; Ham, Jason E.; Meade, B. J.

2012-01-01

Over the last two decades, there has been an increasing awareness regarding the potential impact of indoor air pollution on human health. People working in an indoor environment often experience symptoms such as eye, nose, and throat irritation. Investigations into these complaints have ascribed the effects, in part, to compounds emitted from building materials, cleaning/consumer products, and indoor chemistry. One suspect indoor air contaminant that has been identified is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the ozonolysis of squalene and several high-volume production compounds that are commonly found indoors. Following preliminary workplace sampling that identified the presence of 4-OPA, these studies examined the inflammatory and allergic responses to 4-OPA following both dermal and pulmonary exposure using a murine model. 4-OPA was tested in a combined local lymph node assay and identified to be an irritant and sensitizer. A Th1-mediated hypersensitivity response was supported by a positive response in the mouse ear swelling test. Pulmonary exposure to 4-OPA caused a significant elevation in nonspecific airway hyperreactivity, increased numbers of lung-associated lymphocytes and neutrophils, and increased interferon-γ production by lung-associated lymph nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may elicit irritant and allergic responses and may help to explain some of the adverse health effects associated with poor indoor air quality. PMID:22403157

Dynamin-Related Protein 1 and Mitochondrial Fragmentation in Neurodegenerative Diseases

PubMed Central

Reddy, P. Hemachandra; Reddy, Tejaswini P.; Manczak, Maria; Calkins, Marcus J.; Shirendeb, Ulziibat; Mao, Peizhong

2010-01-01

The purpose of this article is to review the recent developments of abnormal mitochondrial dynamics, mitochondrial fragmentation, and neuronal damage in neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. The GTPase family of proteins, including fission proteins, dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1), and fusion proteins (Mfn1, Mfn2 and Opa1) are essential to maintain mitochondrial fission and fusion balance, and to provide necessary adenosine triphosphate to neurons. Among these, Drp1 is involved in several important aspects of mitochondria, including shape, size, distribution, remodeling, and maintenance of X in mammalian cells. In addition, recent advancements in molecular, cellular, electron microscopy, and confocal imaging studies revealed that Drp1 is associated with several cellular functions, including mitochondrial and peroxisomal fragmentation, phosphorylation, SUMOylation, ubiquitination, and cell death. In the last two decades, tremendous progress has been made in researching mitochondrial dynamics, in yeast, worms, and mammalian cells; and this research has provided evidence linking Drp1 to neurodegenerative diseases. Researchers in the neurodegenerative disease field are beginning to recognize the possible involvement of Drp1 in causing mitochondrial fragmentation and abnormal mitochondrial dynamics in neurodegenerative diseases. This article summarizes research findings relating Drp1 to mitochondrial fission and fusion, in yeast, worms, and mammals. Based on findings from the Reddy laboratory and others’, we propose that mutant proteins of neurodegenerative diseases, including AD, PD, HD, and ALS, interact with Drp1, activate mitochondrial fission machinery, fragment mitochondria excessively, and impair mitochondrial transport and mitochondrial dynamics, ultimately causing mitochondrial dysfunction and neuronal damage. PMID:21145355

Reactions of hypoiodous acid with model compounds and the formation of iodoform in absence/presence of permanganate.

PubMed

Zhao, Xiaodan; Ma, Jun; von Gunten, Urs

2017-08-01

The kinetics for the reactions of hypoiodous acid (HOI) with various phenols (phenol, 4-nitrophenol, 4-hydroxybenzoic acid), 3-oxopentanedioic acid (3-OPA) and flavone were investigated in the pH range of 6.0-11.0. The apparent second order rate constants for the reactions of HOI with phenolic compounds, 3-OPA, flavone and citric acid at pH 8.0 are 10-10 7  M -1 s -1 , (4.0 ± 0.3) × 10 3  M -1 s -1 , (2.5 ± 0.2) × 10 3  M -1 s -1 and <1 M -1 s -1 , respectively. The effect of buffer type and concentration was investigated with acetate, phosphate and borate. All tested buffers promote the HOI reactions with phenols. The percentage of iodine incorporation for various (hydroxyl)phenolic compounds and two NOM extracts ranges from 5% to 98%, indicating that electrophilic aromatic substitution and/or electron transfer can occur. The extent of these reactions depends on the number and relative position of the hydroxyl moieties on the phenolic compounds. Iodoform formation rates increase with increasing pH and iodoform yields increase from 9% to 67% for pH 6.0-10.0 for the HOI/3-OPA reactions. In the permanganate/HOI/3-OPA and permanganate/iodide/3-OPA system at pH < 8.0, iodoform formation is elevated compared to the HOI/3-OPA system in absence of permanganate. For pH > 8.0, in presence of permanganate, iodoform formation is significantly inhibited and iodate formation enhanced, which is due to a faster permanganate-mediated HOI disproportionation to iodate compared to the iodination process. The production of reactive iodine in real waters containing iodide in contact with permanganate may lead to the formation of iodinated organic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons.

PubMed

Uo, Takuma; Dworzak, Jenny; Kinoshita, Chizuru; Inman, Denise M; Kinoshita, Yoshito; Horner, Philip J; Morrison, Richard S

2009-08-01

Mitochondria exist as dynamic networks that are constantly remodeled through the opposing actions of fusion and fission proteins. Changes in the expression of these proteins alter mitochondrial shape and size, and may promote or inhibit the propagation of apoptotic signals. Using mitochondrially targeted EGFP or DsRed2 to identify mitochondria, we observed a short, distinctly tubular mitochondrial morphology in postnatal cortical neurons in culture and in retinal ganglion cells in vivo, whereas longer, highly interconnected mitochondrial networks were detected in cortical astrocytes in vitro and non-neuronal cells in the retina in vivo. Differential expression patterns of fusion and fission proteins, in part, appear to determine these morphological differences as neurons expressed markedly high levels of Drp1 and OPA1 proteins compared to non-neuronal cells. This finding was corroborated using optic tissue samples. Moreover, cortical neurons expressed several splice variants of Drp1 including a neuron-specific isoform which incorporates exon 3. Knockdown or dominant-negative interference of endogenous Drp1 significantly increased mitochondrial length in both neurons and non-neuronal cells, but caused cell death only in cortical neurons. Conversely, depletion of the fusion protein, Mfn2, but not Mfn1, caused extensive mitochondrial fission and cell death. Thus, Drp1 and Mfn2 in normal cortical neurons not only regulate mitochondrial morphology, but are also required for cell survival. The present findings point to unique patterns of Drp1 expression and selective vulnerability to reduced levels of Drp1 expression/activity in neurons, and demonstrate that the regulation of mitochondrial dynamics must be tightly regulated in neurons.

Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons

PubMed Central

Uo, Takuma; Dworzak, Jenny; Kinoshita, Chizuru; Inman, Denise M.; Kinoshita, Yoshito; Horner, Philip J.; Morrison, Richard S.

2009-01-01

Mitochondria exist as dynamic networks that are constantly remodeled through the opposing actions of fusion and fission proteins. Changes in the expression of these proteins alter mitochondrial shape and size, and may promote or inhibit the propagation of apoptotic signals. Using mitochondrially targeted EGFP or DsRed2 to identify mitochondria, we observed a short, distinctly tubular mitochondrial morphology in postnatal cortical neurons in culture and in retinal ganglion cells in vivo, whereas longer, highly interconnected mitochondrial networks were detected in cortical astrocytes in vitro and non-neuronal cells in the retina in vivo. Differential expression patterns of fusion and fission proteins, in part, appear to determine these morphological differences as neurons expressed markedly high levels of Drp1 and OPA1 proteins compared to non-neuronal cells. This finding was corroborated using optic tissue samples. Moreover, cortical neurons expressed several splice variants of Drp1 including a neuron-specific isoform which incorporates exon 3. Knockdown or dominant negative interference of endogenous Drp1 significantly increased mitochondrial length in both neurons and non-neuronal cells, but caused cell death only in cortical neurons. Conversely, depletion of the fusion protein, Mfn2, but not Mfn1, caused extensive mitochondrial fission and cell death. Thus, Drp1 and Mfn2 in normal cortical neurons not only regulate mitochondrial morphology, but are also required for cell survival. The present findings point to unique patterns of Drp1 expression and selective vulnerability to reduced levels of Drp1 expression/activity in neurons, and demonstrate that the regulation of mitochondrial dynamics must be tightly regulated in neurons. PMID:19445933

Multiethnic involvement in autosomal-dominant optic atrophy in Singapore.

PubMed

Loo, J L; Singhal, S; Rukmini, A V; Tow, S; Amati-Bonneau, P; Procaccio, V; Bonneau, D; Gooley, J J; Reynier, P; Ferré, M; Milea, D

2017-03-01

PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.

Multiethnic involvement in autosomal-dominant optic atrophy in Singapore

PubMed Central

Loo, J L; Singhal, S; Rukmini, A V; Tow, S; Amati-Bonneau, P; Procaccio, V; Bonneau, D; Gooley, J J; Reynier, P; Ferré, M; Milea, D

2017-01-01

Purpose Autosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore. Patients and methods Preliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene. Results Among 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA. Conclusion We report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing ‘ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia. PMID:27858935

Frictional Properties of Opalinus Clay: Implications for Nuclear Waste Storage

NASA Astrophysics Data System (ADS)

Orellana, L. F.; Scuderi, M. M.; Collettini, C.; Violay, M.

2018-01-01

The kaolinite-bearing Opalinus Clay (OPA) is the host rock proposed in Switzerland for disposal of radioactive waste. However, the presence of tectonic faults intersecting the OPA formation put the long-term safety performance of the underground repository into question due to the possibility of earthquakes triggered by fault instability. In this paper, we study the frictional properties of the OPA shale. To do that, we have carried out biaxial direct shear experiments under conditions typical of nuclear waste storage. We have performed velocity steps (1-300 μm/s) and slide-hold-slide tests (1-3,000 s) on simulated fault gouge at different normal stresses (4-30 MPa). To establish the deformation mechanisms, we have analyzed the microstructures of the sheared samples through scanning electron microscopy. Our results show that peak (μpeak) and steady state friction (μss) range from 0.21 to 0.52 and 0.14 to 0.39, respectively, thus suggesting that OPA fault gouges are weak. The velocity dependence of friction indicates a velocity strengthening regime, with the friction rate parameter (a - b) that decreases with normal stress. Finally, the zero healing values imply a lack of restrengthening during interseismic periods. Taken together, if OPA fault reactivates, our experimental evidence favors an aseismic slip behavior, making the nucleation of earthquakes difficult, and long-term weakness, resulting in stable fault creeping over geological times. Based on the results, our study confirms the seismic safety of the OPA formation for a nuclear waste repository.

Line-of-sight measurements for the NIF Neutron Imaging System and determination of line-of-sight offsets in OPAS 90-135 images

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

Frank, Matthias; Fittinghoff, David N.; Bower, Dan E.

2011-05-13

This report describes line-of-sight (LOS) measurements for the NIF Neutron Imaging System (NIS) and a characterization of the NIS LOS relative to OPAS 90-135 that were performed during the NIS commissioning Nov. 2010 – Jan. 2011. As described here, data from those measurements were used to determine the relative offsets between the TCC position (x and y pixel coordinates in OPAS images) and the NIS LOS as functions of the OPAS focal distance. This data is needed to place the NIS pinhole array (PHA) onto the NIS LOS with high precision using OPAS imaging of alignment fiducials attached to themore » front and the back of the PHA. (A description of the PHA alignment fiducials, data from metrology performed on the fiducials and a description on how these fiducials were used to align the PHA for the first NIS imaging shot on Feb,. 17, 2011 will be summarized in an upcoming separate report. This report consists of an overview given in this document and a main body that consists of a set of viewgraphs (see Appendix 1) that were iterated and refined within the NIS team and with the Alignment Working Group and that contain more detailed information, schematics and calculations of the NIS line of sight offset from the OPAS LOS. See also Drury, “OPAS 90-135 Registration of Neutron Imaging System Line of Sight,” January 2011, NIF-5035484.« less

Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure

PubMed Central

Riba, Adam; Deres, Laszlo; Eros, Krisztian; Szabo, Aliz; Magyar, Klara; Sumegi, Balazs; Toth, Kalman; Halmosi, Robert; Szabados, Eszter

2017-01-01

In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress—induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 –the main regulators of mitochondrial fusion and fission—in our isoproterenol (ISO)–induced heart failure model, ultimately decreasing the severity of heart failure. In mitochondria, oxidative stress causes a shift toward fission which leads to mitochondrial fragmentation and cell death. Protecting mitochondria from oxidative stress, and the regulation of mitochondrial dynamics by drugs that shift the balance toward fusion, could be a novel therapeutic approach for heart failure. On the basis of our findings, we raise the possibility that DOX could be a novel therapeutic agent in the future treatment of heart failure. PMID:28384228

Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.

PubMed

Twa, Michael D; Roberts, Cynthia J; Karol, Huikai J; Mahmoud, Ashraf M; Weber, Paul A; Small, Robert H

2010-08-01

To evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP). Repeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated. The sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to greater HH measurement variability. The CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

Correlation between ocular pulse amplitude measured by dynamic contour tonometer and colour Doppler flow imaging of the arteric retrobulbar vessels.

PubMed

Marjanović, Ivan; Mijajlović, Milija; Covicković-Sternić, Nadezda; Kontić, Djordje; Hentova-Senćanić, Paraskeva; Marković, Vujica; Bozić, Marija

2011-01-01

An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. The aim of this study was to evaluate the correlation between ocular pulse amplitude (OPA), measured by Dynamic contour tonometer (DCT) and colour Doppler imaging (CDI) of the arteric retrobulbar vessels. Twenty patients older than 50 years were examined, and divided into two equal groups. The first group comprised of patients with normal tension glaucoma treated with topical antiglaucomatous therapy, and the second group included patients with ocular hypertension and glaucoma suspicious without any antiglaucomatous therapy. Ocular pulse amplitude (OPA) was measured with DCT. CDI was also performed. We measured haemodynamic parameters of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCA). Peak systolic (PSV), end-diastolic (EDV) velocities were measured, and resistance index (RI) and pulsatility index (PI) were calculated. Correlation with OPA showed indirect servitude in the RI of the ICA, RI and PI of the CRA, in the first group; and in the PSV and EDV of the ICA, in the RI and PI of the OA, EDV and RI of the CRA, and RI of the PCA, in the second group Increase of OPA was mostly followed by the increase of the parameters (PSV, EDV, RI, and PI) of the arteric retrobulbar vessels in the first group; in the second group, increase of OPA was in almost 50% of parameters followed by their decrease.

Mitochondrial fission contributes to heat-induced oxidative stress in skeletal muscle but not hyperthermia in mice.

PubMed

Yu, Tianzheng; Ferdjallah, Iman; Elenberg, Falicia; Chen, Star K; Deuster, Patricia; Chen, Yifan

2018-05-01

We have previously demonstrated in vitro that heat-induced skeletal muscle damage is associated with an increase in dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and no change in mitochondrial fusion. In this study, we investigated the in vivo effects of mitochondrial fission inhibition on heat-induced oxidative skeletal muscle injury and hyperthermic response in mice. Core body temperatures of mice pre-treated with vehicle or Mdivi-1 were recorded by radio telemetry during heat exposure. Tissue samples were obtained immediately following heat exposure. We found that heat exposure caused increased mitochondrial fragmentation and mitochondrial fission protein Drp1 expression, whereas had no effect on the mitochondrial fusion-related proteins mitofusin 1, mitofusin 2 and OPA1 in mouse gastrocnemius muscles. Two groups of mice with a similar high level of heat-induced hyperthermia were allowed to recover for at least one week and subsequently treated with Mdivi-1 and vehicle, respectively. Neither Mdivi-1 nor vehicle altered the hyperthermic responses of mice during heat exposure. However, Mdivi-1 significantly reduced mitochondrial fragmentation and Drp1, reactive oxygen species levels and apoptotic responses in mouse gastrocnemius muscles following heat exposure compared with vehicle. These results suggest that Drp1-mediated mitochondrial fission plays a role in heat-induced oxidative stress in skeletal muscle, but not in hyperthermic response in mice. Published by Elsevier Inc.

Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner.

PubMed

Halling, Jens Frey; Ringholm, Stine; Olesen, Jesper; Prats, Clara; Pilegaard, Henriette

2017-10-01

Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial network structure remain unclear. This study examined the effects of aging and exercise training on mitochondrial network structure using confocal microscopy on mitochondria-specific stains in single muscle fibers from PGC-1α KO and WT mice. Hyperfragmentation of mitochondrial networks was observed in aged relative to young animals while exercise training normalized mitochondrial network structure in WT, but not in PGC-1α KO. Mitochondrial fission protein content (FIS1 and DRP1) relative to mitochondrial content was increased with aging in both WT and PGC-1α KO mice, while exercise training lowered mitochondrial fission protein content relative to mitochondrial content only in WT. Mitochondrial fusion protein content (MFN1/2 and OPA1) was unaffected by aging and lifelong exercise training in both PGC-1α KO and WT mice. The present results provide evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac.

PubMed

den Braver, Michiel W; Vermeulen, Nico P E; Commandeur, Jan N M

2017-03-01

Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although 1 H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with 1 H NMR, but with a more than 100-fold lower detection limit for absolute quantification. Copyright © 2017. Published by Elsevier B.V.

Mutation analysis of seven known glaucoma-associated genes in Chinese patients with glaucoma.

PubMed

Huang, Xiaobo; Li, Miaoling; Guo, Xiangming; Li, Shiqiang; Xiao, Xueshan; Jia, Xiaoyun; Liu, Xing; Zhang, Qingjiong

2014-05-13

To evaluate mutations in the MYOC, WDR36, OPTN, OPA1, NTF4, CYP1B1, and LTBP2 genes in a cohort of Chinese patients with primary glaucoma. Genomic DNA was prepared from 683 unrelated patients, including 50 with primary congenital glaucoma, 104 with juvenile open-angle glaucoma (JOAG), 186 with primary open-angle glaucoma (POAG), and 343 with primary angle-closure glaucoma (PACG). Mutations in the seven genes in 257 patients (36 with JOAG, 89 with POAG, and 132 with PACG) were initially analyzed by exome sequencing and then confirmed by Sanger sequencing. In addition, Sanger sequencing was used to detect MYOC mutations in the remaining 426 patients. Exome sequencing identified 19 mutations (6 in MYOC, 9 in WDR36, 3 in OPA1, and 1 in OPTN) in 20 of 257 patients, including 4 patients with JOAG, 8 patients with POAG, and 8 patients with PACG. No mutation was detected in the other three genes. In addition, Sanger sequencing detected additional MYOC mutations in 5 of the remaining 426 patients, including 3 patients with JOAG and 2 patients with POAG. Twenty-two mutations in MYOC, WDR36, OPA1, and OPTN were detected in 25 of the 683 patients with primary glaucoma, including nine MYOC mutations in 11 patients, nine WDR36 mutations in 11 patients, three OPA1 mutations in 3 patients, and one OPTN mutation in a patient who also carried a MYOC mutation. Eight mutations in MYOC, WDR36, and OPA1 in 8 of the 343 PACG patients are of uncertain significance and need to be analyzed further. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Effect of quantifying peptide release on ruminal protein degradation determined using the inhibitor in vitro system

USDA-ARS?s Scientific Manuscript database

The aim of this work was to compare use of an o-phthaldialdehyde (OPA) colorimetric assay (OPA-C), which responds to both free AA and peptides, with an OPA fluorimetric assay (OPA-F), which is insensitive to peptides, to quantify rates of ruminal protein degradation in the inhibitor in vitro system ...

LSGermOPA, a custom OPA of 384 EST-derived SNPs for high-throughput lettuce (Lactuca sativa L.) germplasm fingerprinting

USDA-ARS?s Scientific Manuscript database

We assessed the genetic diversity and population structure among 148 cultivated lettuce (Lactuca sativa L.) accessions using the high-throughput GoldenGate assay and 384 EST (Expressed Sequence Tag)-derived SNP (single nucleotide polymorphism) markers. A custom OPA (Oligo Pool All), LSGermOPA was fo...

Broad anti-HIV activity of the Oscillatoria agardhii agglutinin homologue lectin family.

PubMed

Férir, Geoffrey; Huskens, Dana; Noppen, Sam; Koharudin, Leonardus M I; Gronenborn, Angela M; Schols, Dominique

2014-10-01

Oscillatoria agardhii agglutinin homologue (OAAH) proteins belong to a recently discovered lectin family. The founding member OAA and a designed hybrid OAAH (OPA) recognize similar but unique carbohydrate structures of Man-9, compared with other antiviral carbohydrate-binding agents (CBAs). These two newly described CBAs were evaluated for their inactivating properties on HIV replication and transmission and for their potential as microbicides. Various cellular assays were used to determine antiviral activity against wild-type and certain CBA-resistant HIV-1 strains: (i) free HIV virion infection in human T lymphoma cell lines and PBMCs; (ii) syncytium formation assay using persistently HIV-infected T cells and non-infected CD4+ T cells; (iii) DC-SIGN-mediated viral capture; and (iv) transmission to uninfected CD4+ T cells. OAA and OPA were also evaluated for their mitogenic properties and potential synergistic effects using other CBAs. OAA and OPA inhibit HIV replication, syncytium formation between HIV-1-infected and uninfected T cells, DC-SIGN-mediated HIV-1 capture and transmission to CD4+ target T cells, thereby rendering a variety of HIV-1 and HIV-2 clinical isolates non-infectious, independent of their coreceptor use. Both CBAs competitively inhibit the binding of the Manα(1-2)Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.3(2G12res), NL4.3(MVNres) and IIIB(GRFTres) strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrum hybrid agglutinin, 2G12 mAb and griffithsin (GRFT), with the exception of OPA/GRFT. OAA and OPA are unique CBAs with broad-spectrum anti-HIV activity; however, further optimization will be necessary for microbicidal application. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Milestone-compatible neurology resident assessments: A role for observable practice activities.

PubMed

Jones, Lyell K; Dimberg, Elliot L; Boes, Christopher J; Eggers, Scott D Z; Dodick, David W; Cutsforth-Gregory, Jeremy K; Leep Hunderfund, Andrea N; Capobianco, David J

2015-06-02

Beginning in 2014, US neurology residency programs were required to report each trainee's educational progression within 29 neurology Milestone competency domains. Trainee assessment systems will need to be adapted to inform these requirements. The primary aims of this study were to validate neurology resident assessment content using observable practice activities (OPAs) and to develop assessment formats easily translated to the Neurology Milestones. A modified Delphi technique was used to establish consensus perceptions of importance of 73 neurology OPAs among neurology educators and trainees at 3 neurology residency programs. A content validity score (CVS) was derived for each neurology OPA, with scores ≥4.0 determined in advance to indicate sufficient content validity. The mean CVS for all OPAs was 4.4 (range 3.5-5.0). Fifty-seven (78%) OPAs had a CVS ≥4.0, leaving 16 (22%) below the pre-established threshold for content validity. Trainees assigned a higher importance to individual OPAs (mean CVS 4.6) compared to faculty (mean 4.4, p = 0.016), but the effect size was small (η(2) = 0.10). There was no demonstrated effect of length of education experience on perceived importance of neurology OPAs (p = 0.23). Two sample resident assessment formats were developed, one using neurology OPAs alone and another using a combination of neurology OPAs and the Neurology Milestones. This study provides neurology training programs with content validity evidence for items to include in resident assessments, and sample assessment formats that directly translate to the Neurology Milestones. Length of education experience has little effect on perceptions of neurology OPA importance. © 2015 American Academy of Neurology.

A Role for 2-Methyl Pyrrole in the Browning of 4-Oxopentanal and Limonene Secondary Organic Aerosol

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

Aiona, Paige K.; Lee, Hyun Ji; Lin, Peng

“Brown Carbon” (BrC) is a type of organic particulate matter that absorbs visible and near ultraviolet radiation. Reactions of carbonyls in secondary organic aerosol (SOA) produced from limonene with ammonia (NH3) or ammonium sulfate (AS) are known to produce BrC with a distinctive absorption band at 500 nm. Although the general mechanism for this process has been proposed in previous studies, the specific molecular structures of the light-absorbing species remain unclear. This study examined the browning processes occurring in aqueous solutions of AS and 4-oxopentanal (4-OPA), which has a 1,4-dicarbonyl structural motif present in many limonene SOA compounds. The reactionmore » of 4-OPA with AS in a bulk aqueous solution produces a 2-methyl pyrrole (2-MP) intermediate, which is not a strong light absorber by itself, but can react further with carbonyl compounds leading to the eventual formation of BrC chromophores. The direct involvement of 2-MP in the browning process was demonstrated by reacting 2-MP with 4-OPA and with limonene SOA, both of which produced BrC chromophores with distinctive absorption bands at visible wavelengths. The formation of BrC in reaction of 4-OPA with AS and ammonium nitrate (AN) was found to be accelerated by evaporation of the solution suggesting an important role of the dehydration processes in BrC formation from 1,4- dicarbonyls. 4-OPA was also found to produce BrC in aqueous reactions with a broad spectrum of amino acids and amines. The results suggest that 4-OPA may be the smallest atmospherically relevant compound capable of browning by the same mechanism as limonene SOA.« less

Inhibition of poly(ADP-ribose) polymerase-1 alters expression of mitochondria-related genes in PC12 cells: relevance to mitochondrial homeostasis in neurodegenerative disorders.

PubMed

Czapski, Grzegorz A; Cieślik, Magdalena; Wencel, Przemysław L; Wójtowicz, Sylwia; Strosznajder, Robert P; Strosznajder, Joanna B

2018-02-01

Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells. Moreover, the effect of PARP-1 inhibitor (PJ34) on cells subjected to Aβ oligomers (AβO) - evoked stress was analyzed. Our data demonstrated that inhibition of PARP-1 in PC12 cells enhanced the transcription of genes for antioxidative enzymes (Sod1, Gpx1, Gpx4), activated genes regulating mitochondrial fission/fusion (Mfn1, Mfn2, Dnm1l, Opa1, Fis1), subunits of ETC complexes (mt-Nd1, Sdha, mt-Cytb) and modulated expression of several TFs, enhanced Foxo1 and decreased Nrf1, Stat6, Nfkb1. AβO elevated free radicals concentration, decreased mitochondria membrane potential (MMP) and cell viability after 24h. Gene transcription was not affected by AβO after 24h, but was significantly downregulated after 96h. In AβO stress, PJ34 exerted stimulatory effect on expression of several genes (Gpx1, Gpx4, Opa1, Mfn2, Fis1 and Sdha), decreased transcription of numerous TFs (Nrf1, Tfam, Stat3, Stat6, Trp53, Nfkb1) and prevented oxidative stress. Our results indicated that PARP-1 inhibition significantly enhanced transcription of genes involved in antioxidative defense and in regulation of mitochondria function, but was not able to ameliorate cells viability affected by Aβ. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of isovaline enantiomeric excesses in CM meteorites using liquid chromatography time of flight mass spectrometry

NASA Technical Reports Server (NTRS)

Glavin, Daniel P.; Dworkin, Jason P.

2003-01-01

The enantiomeric abundances of the alpha-dialkyl amino acid isovaline were measured in the CM2 meteorites Murchison and LEW 90500 using a new liquid chromatography-time of flight-mass spectrometry (LC-ToF-MS) technique coupled with OPA/NAC derivatization and UV fluorescence detection. Previous analyses of Murchison have shown that L-enantiomeric excesses of isovaline range from 0 to 15.2% with significant variation between meteorite fragments [1]. For this study, hot water extracts of interior fragments (> 2 cm from fusion crust) of the Murchison (USNM 6650.2, mass 6 g) and LEW 90500 (split 69, parent 1, mass 5 g) carbonaceous meteorites were analyzed. Enantiomeric excesses were measured using the single ion LC-ToF-MS trace for the OPA/NAC derivative of isovaline at d z 393.15 (Fig. 1). L-isovaline excesses in these meteorite samples ranged from 18.9 to 20.5% for Murchison and -0.5 to 3.0% for LEW 90500. The measured values for Murchison are the largest enantiomeric excesses for isovaline reported to date. The enantiomeric excesses of L-isovaline cannot be the result of interference from other C5 amino acid isomers present in the meteorites or terrestrial contamination from the landing site environments. The L-isovaline excesses in Murchison are inconsistent with the synthesis of all of the isovaline by the Strecker-cyanohydrin pathway on the CM meteorite parent body. The mechanism(s) for the formation of the enantiomeric asymmetry in isovaline in Murchison are currently unknown and it is not clear how the asymmetry of alpha-dialkyl amino acids could be transferred to the a-hydrogen protein amino acids common in all life on Earth today.

Hereditary motor and sensory neuropathy type VI with optic atrophy.

PubMed

Voo, Irene; Allf, Bryan E; Udar, Nitin; Silva-Garcia, Rosamaria; Vance, Jeffrey; Small, Kent W

2003-10-01

To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. Observational case series. A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct DNA sequencing. Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene.

The occipital place area represents the local elements of scenes

PubMed Central

Kamps, Frederik S.; Julian, Joshua B.; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D.

2016-01-01

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents in not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements – both in spatial boundary and scene content representation – while PPA and RSC represent global scene properties. PMID:26931815

The occipital place area represents the local elements of scenes.

PubMed

Kamps, Frederik S; Julian, Joshua B; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D

2016-05-15

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathology of ovine pulmonary adenocarcinoma.

PubMed

De las Heras, M; González, L; Sharp, J M

2003-01-01

Clinical, gross pathology, histopathology and electron microscopy of the ovine pulmonary adenocarcinoma (OPA, jaagsiekte) either natural or experimentally induced in sheep, goat and moufflon are described. OPA is caused by an oncogenic betaretrovirus,jaagsiekte sheep retrovirus (JSRV). Most natural cases of OPA appear in animals 1-4 years old. There is no evidence of sex or breed susceptibility. Sheep affected by OPA show an afebrile respiratory illness associated with loss of weight. A very characteristic clinical sign is moist rales caused by the accumulation of fluid in the respiratory airways which is discharged from the nostrils when the head is lowered. Gross lesions are confined to the lungs but occasionally thoracic or extrathoracic structures are also affected. Two pathologic forms of OPA are currently recognized, classical and atypical. In classical forms the neoplastic lesions occurs particularly in the cranioventral parts of all lung lobes. They are diffuse or nodular, light grey or light purple in colour. On the cut surface the tumour is moist, and frothy fluid may pour from the airways on slight pressure. Atypical forms tend to be more nodular in both early and advanced tumours. They are pearly white in colour, very hard in consistency, very well demarcated from the surrounding parenchyma and their surface is dry. Histology of the lung sections reveals the presence of several foci of epithelial cell neoplastic proliferation in both alveolar or bronchiolar regions. The tumours, derived from type II pneumocytes and Clara cells, proliferate into mostly papillary but also acinar or occasionally solid growths. The tumour generally shows a benign histological pattern but intra- and extrathoracic metastases have been detected in some cases. Several considerations suggest that the tumour should be classified as an adenocarcinoma of the lung. The histology of atypical OPA is similar to that of the classical disease, with an increase in the stromal reaction accompanying the epithelial proliferations. Pathological features of OPA induced experimentally in sheep, or of OPA in goats and moufflon are similar to those described in sheep. Detailed electron microscopy of tumour material confirms that type II pneumocytes and Clara bronchiolar epithelial cells are the origin of the neoplasia. Also included in this chapter is a description of the morphology of the viral particles associated with OPA.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease.

PubMed

Pérez, María J; Ponce, Daniela P; Osorio-Fuentealba, Cesar; Behrens, Maria I; Quintanilla, Rodrigo A

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

PubMed Central

Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

Differences between work and leisure in temporal patterns of objectively measured physical activity among blue-collar workers.

PubMed

Hallman, David M; Mathiassen, Svend Erik; Gupta, Nidhi; Korshøj, Mette; Holtermann, Andreas

2015-09-28

Leisure time physical activity (LTPA) is generally associated with favorable cardiovascular health outcomes, while occupational physical activity (OPA) shows less clear, or even opposite, cardiovascular effects. This apparent paradox is not sufficiently understood, but differences in temporal patterns of OPA and LTPA have been suggested as one explanation. Our aim was to investigate the extent to which work and leisure (non-occupational time) differ in temporal activity patterns among blue-collar workers, and to assess the modification of these patterns by age and gender. This study was conducted on a cross-sectional sample of male (n = 108) and female (n = 83) blue-collar workers, aged between 21 and 65 years. Physical activity and sedentary behavior were assessed using accelerometers (Actigraph GT3X+) worn on the thigh and trunk for four consecutive days. Temporal patterns of OPA and LTPA were retrieved using Exposure Variation Analysis (EVA), and expressed in terms of percentage of work and leisure time spent in uninterrupted periods of different durations (<1 min, 1-5 min, 5-10 min, 10-30 min, 30-60 min and > 60 min) of sitting, standing, and walking. Repeated measures ANOVA and linear regression analyses were used to test a) possible differences between OPA and LTPA in selected EVA derivatives, and b) the modification of these differences by age and gender. OPA showed a larger percentage time walking in brief (<5 min) periods [mean (SD): 33.4 % (12.2)], and less time in prolonged (>30 min) sitting [7.0 % (9.3)] than LTPA [walking 15.4 % (5.0); sitting 31.9 % (15.3)], even after adjustment for the difference between work and leisure in total time spent in each activity type. These marked differences in the temporal pattern of OPA and LTPA were modified by gender, but not age. We found that the temporal patterns of OPA and LTPA among blue-collar workers were markedly different even after adjustment for total physical activity time, and that this difference was modified by gender. We recommend using EVA derivatives in future studies striving to disentangle the apparent paradoxical cardiovascular effect of physical activity at work and during leisure.

Computational mechanisms underlying cortical responses to the affordance properties of visual scenes

PubMed Central

Epstein, Russell A.

2018-01-01

Biologically inspired deep convolutional neural networks (CNNs), trained for computer vision tasks, have been found to predict cortical responses with remarkable accuracy. However, the internal operations of these models remain poorly understood, and the factors that account for their success are unknown. Here we develop a set of techniques for using CNNs to gain insights into the computational mechanisms underlying cortical responses. We focused on responses in the occipital place area (OPA), a scene-selective region of dorsal occipitoparietal cortex. In a previous study, we showed that fMRI activation patterns in the OPA contain information about the navigational affordances of scenes; that is, information about where one can and cannot move within the immediate environment. We hypothesized that this affordance information could be extracted using a set of purely feedforward computations. To test this idea, we examined a deep CNN with a feedforward architecture that had been previously trained for scene classification. We found that responses in the CNN to scene images were highly predictive of fMRI responses in the OPA. Moreover the CNN accounted for the portion of OPA variance relating to the navigational affordances of scenes. The CNN could thus serve as an image-computable candidate model of affordance-related responses in the OPA. We then ran a series of in silico experiments on this model to gain insights into its internal operations. These analyses showed that the computation of affordance-related features relied heavily on visual information at high-spatial frequencies and cardinal orientations, both of which have previously been identified as low-level stimulus preferences of scene-selective visual cortex. These computations also exhibited a strong preference for information in the lower visual field, which is consistent with known retinotopic biases in the OPA. Visualizations of feature selectivity within the CNN suggested that affordance-based responses encoded features that define the layout of the spatial environment, such as boundary-defining junctions and large extended surfaces. Together, these results map the sensory functions of the OPA onto a fully quantitative model that provides insights into its visual computations. More broadly, they advance integrative techniques for understanding visual cortex across multiple level of analysis: from the identification of cortical sensory functions to the modeling of their underlying algorithms. PMID:29684011

Telephone Follow-Up following Office Anorectal Surgery

PubMed Central

Fallaize, Rebecca C; Tinline-Purvis, Christine; Dixon, Anthony R; Pullyblank, Anne-Marie

2008-01-01

INTRODUCTION Patients with minor anorectal conditions are frequently reviewed at an 8-week out-patient appointment (OPA). This study was designed to assess whether telephone follow-up could reduce OPA numbers whilst maintaining patient satisfaction. PATIENTS AND METHODS Over an 11-month period, 46 patients (23 male) underwent banding of haemorrhoids and 14 were prescribed medical treatment for fissure-in-ano (3 male). All were telephoned at 6 weeks and were offered an 8-week OPA if they had continuing problems. Patients were telephoned at a later date by a member of the hospital's patient panel to assess satisfaction. RESULTS Overall, 88% were contacted at 6 weeks, 60% at the first attempt; 40% required two or more attempts. Of those who underwent banding, 68% were asymptomatic, 17% requested an OPA for re-banding and 15% requested an OPA for a different problem. Of fissure patients, 25% were cured; the remainder were prescribed either second-line medical treatment (8%), anorectal physiology (42%) or surgery (25%). All avoided an OPA. Of a potential 60 OPAs, 47 were saved by telephone follow-up. None of 7 non-contactable patients accepted a written offer of an OPA. Overall, 89% of patients were contacted by the patient panel; of these patients, 93% reported a high level of satisfaction. CONCLUSIONS Telephone follow-up can reduce the number of OPAs following out-patient treatment of minor anorectal conditions whilst maintaining a high level of patient satisfaction. However, it requires considerable consultant time. This process could be developed into either a nurse-led service with booked telephone appointments or a patient-led service to a dedicated hotline. PMID:18598594

Telephone follow-up following office anorectal surgery.

PubMed

Fallaize, Rebecca C; Tinline-Purvis, Christine; Dixon, Anthony R; Pullyblank, Anne-Marie

2008-09-01

Patients with minor anorectal conditions are frequently reviewed at an 8-week out-patient appointment (OPA). This study was designed to assess whether telephone follow-up could reduce OPA numbers whilst maintaining patient satisfaction. Over an 11-month period, 46 patients (23 male) underwent banding of haemorrhoids and 14 were prescribed medical treatment for fissure-in-ano (3 male). All were telephoned at 6 weeks and were offered an 8-week OPA if they had continuing problems. Patients were telephoned at a later date by a member of the hospital's patient panel to assess satisfaction. Overall, 88% were contacted at 6 weeks, 60% at the first attempt; 40% required two or more attempts. Of those who underwent banding, 68% were asymptomatic, 17% requested an OPA for re-banding and 15% requested an OPA for a different problem. Of fissure patients, 25% were cured; the remainder were prescribed either second-line medical treatment (8%), anorectal physiology (42%) or surgery (25%). All avoided an OPA. Of a potential 60 OPAs, 47 were saved by telephone follow-up. None of 7 non-contactable patients accepted a written offer of an OPA. Overall, 89% of patients were contacted by the patient panel; of these patients, 93% reported a high level of satisfaction. Telephone follow-up can reduce the number of OPAs following out-patient treatment of minor anorectal conditions whilst maintaining a high level of patient satisfaction. However, it requires considerable consultant time. This process could be developed into either a nurse-led service with booked telephone appointments or a patient-led service to a dedicated hotline.

Mycobacterium massiliense BRA100 strain recovered from postsurgical infections: resistance to high concentrations of glutaraldehyde and alternative solutions for high level disinfection.

PubMed

Lorena, Nádia Suely de Oliveira; Pitombo, Marcos Bettini; Côrtes, Patrícia Barbur; Maya, Maria Cristina Araújo; Silva, Marlei Gomes da; Carvalho, Ana Carolina da Silva; Coelho, Fábrice Santana; Miyazaki, Neide Hiromi Tokumaru; Marques, Elizabeth Andrade; Chebabo, Alberto; Freitas, Andréa D'Avila; Lupi, Otília; Duarte, Rafael Silva

2010-10-01

To evaluate the minimum inhibitory concentration (MIC) of GTA against these microorganisms and alternative disinfectants for high-level disinfection (HLD). Reference mycobacteria and clinical M. massiliense strains were included in this study. Active cultures were submitted to susceptibility qualitative tests with GTA dilutions (ranging from 1.5% to 8%), and commercial orthophthaldehyde (OPA) and peracetic acid (PA)-based solutions, during the period of exposure as recommended by National Agency of Sanitary Surveillance for HLD. All reference and M. massiliense non-BRA100 strains, recovered from sputum, were susceptible to any GTA concentration, OPA and PA solutions. M. massiliense BRA100 strains presented MIC of 8% GTA and were susceptible to OPA and PA. M. massiliense BRA100 strain is resistant to high GTA concentrations (up to 7%), which proves that this product is non-effective against specific rapidly growing mycobacteria and should be substituted by OPA or PA-based solutions for HLD.

140 W peak power laser system tunable in the LWIR.

PubMed

Gutty, François; Grisard, Arnaud; Larat, Christian; Papillon, Dominique; Schwarz, Muriel; Gerard, Bruno; Ostendorf, Ralf; Rattunde, Marcel; Wagner, Joachim; Lallier, Eric

2017-08-07

We present a high peak power rapidly tunable laser system in the long-wave infrared comprising an external-cavity quantum cascade laser (EC-QCL) broadly tunable from 8 to 10 µm and an optical parametric amplifier (OPA) based on quasi phase-matching in orientation-patterned gallium arsenide (OP-GaAs) of fixed grating period. The nonlinear crystal is pumped by a pulsed fiber laser system to achieve efficient amplification in the OPA. Quasi phase-matching remains satisfied when the EC-QCL wavelength is swept from 8 to 10 µm with a crystal of fixed grating period through tuning the pump laser source around 2 µm. The OPA demonstrates parametric amplification from 8 µm to 10 µm and achieves output peak powers up to 140 W with spectral linewidths below 3.5 cm -1 . The beam profile quality (M 2 ) remains below 3.4 in both horizontal and vertical directions. Compared to the EC-QCL, the linewidth broadening is attributed to a coupling with the OPA.

Occupational and leisure-time physical activity and workload among construction workers – a randomized control study

PubMed Central

Karstad, K.; Søgaard, K.

2016-01-01

Background There is a lack of quantification of occupational physical activity (OPA) and leisure time physical activity (LTPA) among construction workers. Objectives To describe physical activity energy expenditure (PAEE), physical workload, and the effect of a PA-intervention among construction workers. Methods Sixty-seven Construction workers self-reported their physical activity (PA), had PA assessed directly (PAEE), and observed OPA using the tool “Posture, Activity, Tools and Handling.” The PA-intervention (Intervention; n = 29, Controls; n = 24) included 3x20-min training/week for 12 weeks. Results Baseline median OPA was 5036 MET-min/week and LTPA 2842 MET-min/week, p < 0.01. OPA directly recorded was (mean ± SE): 56.6 ± 3.2 J/kg/min and LTPA was: 35.7 ± 2.2 J/kg/min (p < 0.001). Manual material handling was performed for ≥ 25% of working time by more than 50% of the participants. Post-intervention, the training group reduced overall PAEE compared to the control group but not specifically during work. Conclusions OPA was within the maximum recommended level of 1/3 proposed in consensus guidelines but did not decrease with PA-intervention. PMID:27097799

Comparison of the efficacy of disinfectants in automated endoscope reprocessors for colonoscopes: tertiary amine compound (Sencron2®) versus ortho-phthalaldehyde (Cidex®OPA)

PubMed Central

Seo, Hyun Il; Lee, Dae Sung; Yoon, Eun Mi; Kwon, Min-Jung; Park, Hyosoon; Jung, Yoon Suk; Park, Jung Ho; Sohn, Chong Il

2016-01-01

Background/Aims To prevent the transmission of pathogens by endoscopes, following established reprocessing guidelines is critical. An ideal reprocessing step is simple, fast, and inexpensive. Here, we evaluated and compared the efficacy and safety of two disinfectants, a tertiary amine compound (TAC) and ortho-phthalaldehyde (OPA). Methods A total of 100 colonoscopes were randomly reprocessed using two same automated endoscope reprocessors, according to disinfectant. The exposure time was 10 minutes for 0.55% OPA (Cidex® OPA, Johnson & Johnson) and 5 minutes for 4% TAC (Sencron2®, Bab Gencel Pharma & Chemical Ind. Co.). Three culture samples were obtained from each colonoscope after reprocessing. Results A total of nine samples were positive among the 300 culture samples. The positive culture rate was not statistically different between the two groups (4% for OPA and 2% for TAC, P=0.501). There were no incidents related to safety during the study period. Conclusions TAC was non-inferior in terms of reprocessing efficacy to OPA and was safe to use. Therefore, TAC seems to be a good alternative disinfectant with a relatively short exposure time and is also less expensive than OPA. PMID:27175119

Occupational Physical Activity, Overweight, and Mortality: A Follow-Up Study of 47,405 Norwegian Women and Men

ERIC Educational Resources Information Center

Graff-Iversen, Sidsel; Selmer, Randi; Sorensen, Marit; Skurtveit, Svetlana

2007-01-01

This population-based 24-year follow-up study evaluated the association of occupational physical activity (OPA) with overweight and mortality in 47,405 men and women, healthy at baseline, and reporting OPA as sedentary (reference), light, moderately heavy, or heavy. The adjusted odds ratio for overweight was slightly less than 1 for all categories…

Effects of leisure-time and occupational physical activity on total mortality risk in NHANES III according to sex, ethnicity, central obesity, and age.

PubMed

Richard, Aline; Martin, Brian; Wanner, Miriam; Eichholzer, Monika; Rohrmann, Sabine

2015-02-01

Associations of physical activity with all-cause mortality seem to be quite strong, but little is known about potential effect modifiers as sex, race/ethnicity, age, and obesity. Data of the Third National Health and Nutrition Examination Survey (NHANES III), conducted 1988-1994 with mortality follow-up until 2006, were used to compare mortality risk between different levels of leisure-time physical activity (LTPA) and occupational physical activity (OPA). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). LTPA (n = 15,307) was inversely associated with all-cause mortality (HR 0.75, 95% CI 0.64-0.88 for regular vs. no LTPA). There was a statistically significant interaction with age (P = .03), with participants over 60 years of age benefitting more from regular or irregular LTPA. OPA was positively associated with all-cause mortality (HR 1.25, 95% CI 0.85-1.84 for high vs. low OPA), particularly among Mexican-Americans (HR 2.28, 95% CI 1.23-4.22); statistically significant interactions were observed for obesity and gender. LTPA clearly predicts all-cause mortality. However, associations between OPA and all-cause mortality are unclear and need further research with special regard to ethnic differences.

Analysis of amino acid composition in proteins of animal tissues and foods as pre-column o-phthaldialdehyde derivatives by HPLC with fluorescence detection.

PubMed

Dai, Zhaolai; Wu, Zhenlong; Jia, Sichao; Wu, Guoyao

2014-08-01

Studies of protein nutrition and biochemistry require reliable methods for analysis of amino acid (AA) composition in polypeptides of animal tissues and foods. Proteins are hydrolyzed by 6M HCl (110°C for 24h), 4.2M NaOH (105°C for 20 h), or proteases. Analytical techniques that require high-performance liquid chromatography (HPLC) include pre-column derivatization with 4-chloro-7-nitrobenzofurazan, 9-fluorenyl methylchloroformate, phenylisothiocyanate, naphthalene-2,3-dicarboxaldehyde, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, and o-phthaldialdehyde (OPA). OPA reacts with primary AA (except cysteine or cystine) in the presence of 2-mercaptoethanol or 3-mercaptopropionic acid to form a highly fluorescent adduct. OPA also reacts with 4-amino-1-butanol and 4-aminobutane-1,3-diol produced from oxidation of proline and 4-hydroxyproline, respectively, in the presence of chloramine-T plus sodium borohydride at 60°C, or with S-carboxymethyl-cysteine formed from cysteine and iodoacetic acid at 25°C. Fluorescence of OPA derivatives is monitored at excitation and emission wavelengths of 340 and 455 nm, respectively. Detection limits are 50 fmol for AA. This technique offers the following advantages: simple procedures for preparation of samples, reagents, and mobile-phase solutions; rapid pre-column formation of OPA-AA derivatives and their efficient separation at room temperature (e.g., 20-25°C); high sensitivity of detection; easy automation on the HPLC apparatus; few interfering side reactions; a stable chromatography baseline for accurate integration of peak areas; and rapid regeneration of guard and analytical columns. Thus, the OPA method provides a useful tool to determine AA composition in proteins of animal tissues (e.g., skeletal muscle, liver, intestine, placenta, brain, and body homogenates) and foods (e.g., milk, corn grain, meat, and soybean meal). Copyright © 2014 Elsevier B.V. All rights reserved.

Sericin improves heart and liver mitochondrial architecture in hypercholesterolaemic rats and maintains pancreatic and adrenal cell biosynthesis.

PubMed

Ampawong, Sumate; Isarangkul, Duangnate; Aramwit, Pornanong

2017-09-15

Hypercholesterolaemia is well known to be associated with mitochondrial dysfunction, subsequently leading to multiple organ failure. Similar to other natural products, sericin is a candidate for adjunctive therapy in hyperlipidaemic conditions. However, the cholesterol-lowering mechanisms of sericin are multifactorial and controversial. Here, a high-cholesterol-fed rat model with or without sericin treatment was established using a dosage of 1000mg/kg/day for 30 days. Blood lipid profiles, oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; nuclear factor erythroid 2-related factor, Nrf-2), dysmorphic mitochondria in relation to fission (dynamin-related protein-1; Drp-1) and fusion (guanosine triphosphatase mutated in dominant optic atrophy; OPA-1) markers and biosynthetic markers (aquaporin, AQP-1; tubulin-4β, Tb4B) in the pancreas and adrenal gland were evaluated. The results showed that sericin reduced blood cholesterol and increased high-density lipoprotein (HDL) by acting against oxidative stress. Hypocholesterolaemic and antioxidant conditions further preserved heart and liver mitochondrial architecture; however, this protection was not exhibited in the kidney, where a high level of renal mitophagy, indicating by LC-3 up-regulation, was presented. The steps of ultrastructural alteration of mitochondria from degenerative changes to necrosis were also demonstrated. Sericin also conserved AQP-1 and Tb4B levels in the exocrine pancreatic acinar cells and zona glomerulosa cells, which were positively correlated with serum lipase, HDL, antioxidative markers and mitochondrial integrity. The present study revealed that sericin not only has antioxidant capacity but also balances pancreatic and adrenal cell biosynthesis, especially lipase activity, which may have played an important role in improving lipid dysregulation in the hypercholesterolaemic rat model, leading to the reduction of dysmorphic mitochondria, particularly in the heart and liver. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Fan, Zhongqi; Yu, Huimei; Cui, Ni

Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels,more » increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy.« less

77 FR 55861 - Notice of Lodging of Consent Decree Under the Oil Pollution Act of 1990 (“OPA”)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF JUSTICE Notice of Lodging of Consent Decree Under the Oil Pollution Act of 1990 (``OPA'') Notice is hereby given that on September 4, 2012, a proposed Consent Decree in United States et... International under Section 1002 of OPA and Section 48-1-90 of the South Carolina Pollution Control Act, S.C...

Ground Demonstration of Planetary Gas Lidar Based on Optical Parametric Amplifier

NASA Technical Reports Server (NTRS)

Numata, Kenji; Riris, Haris; Li, Steve; Wu, Stewart; Kawa, Stephen R.; Krainak, Michael; Abshire, James

2012-01-01

We report on the development effort of a nanosecond-pulsed optical parametric amplifier (OPA) for remote trace gas measurements for Mars and Earth. The OPA output has high spectral purity and is widely tunable both at near-infrared and mid-infrared wavelengths, with an optical-optica1 conversion efficiency of up to approx 39 %. Using this laser source, we demonstrated open-path measurements of CH4 (3291 nm and 1651 nm), CO2 (1573 nm), H2O (1652 nm), and CO (4764 nm) on the ground. The simplicity, tunability. and power scalability of the OPA make it a strong candidate for general planetary lidar instruments, which will offer important information on the origins of the planet's geology, atmosphere, and potential for biology,

U.S. Coast Guard 1995 oil pollution research grants publications : part 2

DOT National Transportation Integrated Search

1997-08-01

The Oil Pollution Research Grants Program was created by the Oil Pollution Act (OPA) of 1990, P.L. 101-380 (OPA 90), 33 U.S.C. 28761(c)(8) and 2761(c)(9). The OPA established a regional research program and authorized those agencies represented on th...

Evaluation of Neisseria Gonorrhoeae Opacity (Opa) Protein Loops as Targets for Passive Vaccination and Investigation of the Role of Opa Proteins During Infection of a Female Host

DTIC Science & Technology

2009-08-24

Bourne, N., R. B. Pyles, D. I. Bernstein, and L. R. Stanberry. 2002. Modification of primary and recurrent genital herpes in guinea pigs by passive...Barratt, T. E. Hoen, and R. A. Cone. 1994. Passive immunization of the vagina protects mice against vaginal transmission of genital herpes ...and investigations into the role of Opa proteins during infection of the female genital tract. We demonstrated antibodies that target conserved Opa

In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging.

PubMed

Cao, Xu; Wang, Haiqiong; Wang, Zhao; Wang, Qingyao; Zhang, Shuang; Deng, Yuanping; Fang, Yanshan

2017-10-01

Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochondria or axonal degeneration. Further, unlike in in vitro cultured neurons, we found that mitophagy rarely occurred in intact axons in vivo, even in aged animals. Furthermore, blocking overall mitophagy by knockdown of the core autophagy genes Atg12 or Atg17 had little effect on the turnover of axonal mitochondria or axonal integrity, suggesting that mitophagy is not required for axonal maintenance; this is regardless of whether the mitophagy is PINK1-Parkin dependent or independent. In contrast, downregulation of mitochondrial fission-fusion genes caused age-dependent axonal degeneration. Moreover, Opa1 expression in the fly head was significantly decreased with age, which may underlie the accumulation of fragmented mitochondria in aged axons. Finally, we showed that adult-onset, neuronal downregulation of the fission-fusion, but not mitophagy genes, dramatically accelerated features of aging. We propose that axonal mitochondria are maintained independently of mitophagy and that mitophagy-independent mechanisms such as fission-fusion may be central to the maintenance of axonal mitochondria and neural integrity during normal aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Two-photon absorption in conjugated energetic molecule

DOE PAGES

Bjorgaard, Josiah August; Sifain, Andrew; Nelson, Tammie Renee; ...

2016-06-03

Time-dependent density functional theory (TD-DFT) is used to investigate the relationship between molecular structure and one- and two-photon absorption (OPA and TPA, respectively) properties in novel and recently synthesized conjugated energetic molecules (CEMs). The molecular structure of CEMs can be strategically altered to influence the heat of formation and oxygen balance, two factors that can contribute to the sensitivity and strength of an explosive material. OPA and TPA are sensitive to changes in molecular structure as well, influencing optical range of excitation. We find calculated vertical excitation energies in good agreement with experiment for most molecules. Peak TPA intensities aremore » significant and on the order of 102 GM. Natural transition orbitals for essential electronic states defining TPA peaks of relatively large intensity to examine the character of relevant transitions. Minor modification of molecular substituents, such as additional oxygen and other functional groups, produces significant changes in electronic structure, OPA, TPA, and improves the oxygen balance. Results show that select molecules are apt to nonlinear absorption, opening the possibility for controlled, direct optical initiation of CEMs through photochemical pathways.« less

Exploring Chemistry in Microcompartments Using Guided Droplet Collisions in a Branched Quadrupole Trap Coupled to a Single Droplet, Paper Spray Mass Spectrometer

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

Jacobs, Michael I.; Davies, James F.; Lee, Lance

Recent studies suggest that reactions in aqueous microcompartments can occur at significantly different rates than those in the bulk. Most studies have used electrospray to generate a polydisperse source of highly charged microdroplets, leading to multiple confounding factors potentially influencing reaction rates (e.g., evaporation, charge, and size). Thus, the underlying mechanism for the observed enhancement remains unclear. We present a new type of electrodynamic balance - the branched quadrupole trap (BQT) - which can be used to study reactions in microdroplets in a controlled environment. The BQT allows for condensed phase chemical reactions to be initiated by colliding droplets withmore » different reactants and levitating the merged droplet indefinitely. The performance of the BQT is characterized in several ways. Sub-millisecond mixing times as fast as ~400 μs are measured for low velocity (~0.1 m/s) collisions of droplets with <40 μm diameters. The reaction of o-phthalaldehyde (OPA) with alanine in the presence of dithiolthreitol is measured using both fluorescence spectroscopy and single droplet paper spray mass spectrometry. The bimolecular rate constant for reaction of alanine with OPA is found to be 84 ± 10 and 67 ± 6 M -1s -1 in a 30 μm radius droplet and bulk solution, respectively, which demonstrates that bimolecular reaction rate coefficients can be quantified using merged microdroplets and that merged droplets can be used to study rate enhancements due to compartmentalization. Products of the reaction of OPA with alanine are detected in single droplets using paper spray mass spectrometry. Finally, we demonstrate that single droplets with <100 pg of analyte can easily be studied using single droplet mass spectrometry.« less

Exploring Chemistry in Microcompartments Using Guided Droplet Collisions in a Branched Quadrupole Trap Coupled to a Single Droplet, Paper Spray Mass Spectrometer

DOE PAGES

Jacobs, Michael I.; Davies, James F.; Lee, Lance; ...

2017-10-19

Recent studies suggest that reactions in aqueous microcompartments can occur at significantly different rates than those in the bulk. Most studies have used electrospray to generate a polydisperse source of highly charged microdroplets, leading to multiple confounding factors potentially influencing reaction rates (e.g., evaporation, charge, and size). Thus, the underlying mechanism for the observed enhancement remains unclear. We present a new type of electrodynamic balance - the branched quadrupole trap (BQT) - which can be used to study reactions in microdroplets in a controlled environment. The BQT allows for condensed phase chemical reactions to be initiated by colliding droplets withmore » different reactants and levitating the merged droplet indefinitely. The performance of the BQT is characterized in several ways. Sub-millisecond mixing times as fast as ~400 μs are measured for low velocity (~0.1 m/s) collisions of droplets with <40 μm diameters. The reaction of o-phthalaldehyde (OPA) with alanine in the presence of dithiolthreitol is measured using both fluorescence spectroscopy and single droplet paper spray mass spectrometry. The bimolecular rate constant for reaction of alanine with OPA is found to be 84 ± 10 and 67 ± 6 M -1s -1 in a 30 μm radius droplet and bulk solution, respectively, which demonstrates that bimolecular reaction rate coefficients can be quantified using merged microdroplets and that merged droplets can be used to study rate enhancements due to compartmentalization. Products of the reaction of OPA with alanine are detected in single droplets using paper spray mass spectrometry. Finally, we demonstrate that single droplets with <100 pg of analyte can easily be studied using single droplet mass spectrometry.« less

Development, evaluation and comparison of two independent sampling and analytical methods for ortho-phthalaldehyde vapors and condensation aerosols in air† ‡

PubMed Central

2015-01-01

Two independent sampling and analytical methods for ortho-phthalaldehyde (OPA) in air have been developed, evaluated and compared (1) a reagent-coated solid sorbent HPLC-UV method and (2) an impinger-fluorescence method. In the first method, air sampling is conducted at 1.0 L min−1 with a sampler containing 350 mg of silica gel coated with 1 mg of acidified 2,4-dinitrophenylhydrazine (DNPH). After sampling, excess DNPH in ethyl acetate is added to the sampler prior to storage for 68 hours. The OPA-DNPH derivative is eluted with 4.0 mL of dimethyl sulfoxide (DMSO) for measurement by HPLC with a UV detector set at 3S5 nm. The estimated detection limit is 0.016 µg per sample or 0.067 µg m−3 (0.012 ppb) for a 240 L air sample. Recoveries of vapor spikes at levels of 1.2 to 6.2 µg were 96 to 101%. Recoveries of spikes as mixtures of vapor and condensation aerosols were 97 to 100%. In the second method, air sampling is conducted at 1.0 L mm−1 with a midget impinger containing 10 mL of DMSO solution containing N-acetyl-l-cysteine and ethylenediamine. The fluorescence reading is taken 80 min after the completion of air sampling. Since the time of taking the fluorescence reading is critical, the reading is taken with a portable fluorometer. The estimated detection limit is 0.024 µg per sample or 0.1 µg m−3 (0.018 ppb) for a 240 L air sample. Recoveries of OPA vapor spikes at levels of 1.4 to 5.0 µg per sample were 97 to 105%. Recoveries of spikes as mixtures of vapors and condensation aerosols were 95 to 99%. The collection efficiency for a mixture of vapor and condensation aerosol was 99.4%. The two methods were compared side-by-side in a generation system constructed for producing controlled atmospheres of OPA vapor in air. Average air concentrations of OPA vapor found by both methods agreed within ±10%. PMID:26346658

Tier 1 and Tier 3 eAdjudication Business Rule Validation

DTIC Science & Technology

2018-04-01

Approved for Public Distribution Defense Personnel and Security Research Center Office of People Analytics OPA-2018-038 PERSEREC-TR-18-06 April...Northrop Grumman Technology Services Leissa C. Nelson, Ph.D. Susan C. Reed Defense Personnel and Security Research Center Office of People Analytics...Defense Personnel and Security Research Center Office of People Analytics 400 Gigling Road, Seaside, CA 93955 OPA-2018-038 PERSEREC-TR-06 April

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

PubMed

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Noiseless optical amplification in quasi-phase-matched bulk lithium niobate

NASA Astrophysics Data System (ADS)

Lovering, D. J.; Levenson, J. A.; Vidakovic, P.; Webjörn, J.; Russell, P. St. J.

1996-09-01

An optical parametric amplifier (OPA) has been demonstrated in bulk, periodically poled lithium niobate and is shown to operate with a noise figure well below the classical limit. In contrast to conventional OPA's, this device uses quasi-phase matching to provide the coupling between the pump and the signal. Comparison of the measured performance with that of a theoretical model reveals that the main intrinsic contribution to the output noise is due to spatial and temporal mode mixing, which arises as a consequence of tight focusing of the incident beams. Factors that affect the performance of this amplifier are identified theoretically and their relative importance investigated for both amplification and squeezing.

Natural history of JSRV in sheep.

PubMed

Sharp, J M; DeMartini, J C

2003-01-01

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep and, rarely, goats that arises from two types of secretory epithelial cell that retain their luxury function of surfactant synthesis and secretion. It is classified as a low-grade adenocarcinoma and is viewed as a good model for epithelial neoplasia because of its morphological resemblance to the human lung tumour, bronchioloalveolar adenocarcinoma. OPA is present in most of the sheep rearing areas of the globe and, in affected flocks, tumours are present in a high proportion of sheep. OPA is associated with the ovine retrovirus, jaagsiekte sheep retrovirus (JSRV), and is transmissible only with inocula that contain JSRV. All sheep contain JSRV-related endogenous viruses, but JSRV is an exogenous virus that is associated exclusively with OPA. JSRV is detected consistently in the lung fluid, tumour and lymphoid tissues of sheep affected by both natural and experimental OPA or unaffected in-contact flockmates and never in sheep from unaffected flocks with no history of the tumour. JSRV replicates principally in the epithelial tumour cells, but also establishes a disseminated infection of several lymphoid cell types, including peripheral blood leukocytes (PBLs). Longitudinal studies in flocks with endemic OPA have revealed JSRV in PBLs before the onset of clinical OPA and even in the absence of discernible lung tumour. The prevalence of JSRV infection is 40%-80%, although only 30% of sheep appear to develop OPA lesions. A unique feature of OPA is the absence of a specific humoral immune response to JSRV, despite the highly productive infection in the lungs and the disseminated lymphoid infection. This feature is associated with reduced responsiveness to some mitogens, although the phenotypic profile of the peripheral blood remains unaltered. The reduced response is an early and sustained event during infection and may indicate that the failure of infected sheep to produce specific antibodies to JSRV is a direct consequence of infection.

Astigmatism transfer phenomena in the optical parametric amplification process

NASA Astrophysics Data System (ADS)

Li, Wenkai; Chen, Yun; Li, Yanyan; Xu, Yi; Guo, Xiaoyang; Lu, Jun; Leng, Yuxin

2017-01-01

We numerically and experimentally investigate the astigmatism transfer phenomena in femtosecond optical parametric amplification (OPA). We model the OPA process based on the coupled second-order three-wave nonlinear propagation equations. The numerical and experimental results support that the input pump pulse astigmatism can be transferred into the idler pulse but not the signal pulse, and the idler pulse astigmatism originating from spatial walk-off is less than the idler pulse astigmatism received from the pump. Thus, we can provide a clear understanding of astigmatism transfer mechanisms in the OPA process, and make better use of broadband tunable OPA sources.

Inflammatory effects induced by selected limonene oxidation products: 4-OPA, IPOH, 4-AMCH in human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines.

PubMed

Lipsa, Dorelia; Leva, Paolo; Barrero-Moreno, Josefa; Coelhan, Mehmet

2016-11-16

Limonene, a monoterpene abundantly present in most of the consumer products (due to its pleasant citrus smell), easily undergoes ozonolysis leading to several limonene oxidation products (LOPs) such as 4-acetyl-1-methylcyclohexene (4-AMCH), 4-oxopentanal (4-OPA) and 3-isopropenyl-6-oxoheptanal (IPOH). Toxicological studies have indicated that human exposure to limonene and ozone can cause adverse airway effects. However, little attention has been paid to the potential health impact of specific LOPs, in particular of IPOH, 4-OPA and 4-AMCH. This study evaluates the cytotoxic effects of the selected LOPs on human bronchial epithelial (16HBE14o-) and alveolar epithelial (A549) cell lines by generating concentration-response curves using the neutral red uptake assay and analyzing the inflammatory response with a series of cytokines/chemokines. The cellular viability was mostly reduced by 4-OPA [IC 50 =1.6mM (A549) and 1.45mM (16HBE14o-)] when compared to IPOH [IC 50 =3.5mM (A549) and 3.4mM (16HBE14o-)] and 4-AMCH [IC 50 could not be calculated]. As a result from the inflammatory response, IPOH [50μM] induced an increase of both IL-6 and IL-8 secretion in A549 (1.5-fold change) and in 16HBE14o- (2.8- and 7-fold change respectively). 4-OPA [50μM] treatment of A549 increased IL-6 (1.4-times) and IL-8 (1.3-times) levels, while in 16HBE14o- had an opposite effect. A549 treated with 4-AMCH [50μM] elevate both IL-6 and IL-8 levels by 1.2-times, while in 16HBE14o- had an opposite effect. Based on our results, lung cellular injury characterized by inflammatory cytokine release was observed for both cell lines treated with the selected chemicals at concentrations that did not affect their cellular viability. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Body mass index: different nutritional status according to WHO, OPAS and Lipschitz classifications in gastrointestinal cancer patients.

PubMed

Barao, Katia; Forones, Nora Manoukian

2012-01-01

The body mass index (BMI) is the most common marker used on diagnoses of the nutritional status. The great advantage of this index is the easy way to measure, the low cost, the good correlation with the fat mass and the association to morbidity and mortality. To compare the BMI differences according to the WHO, OPAS and Lipschitz classification. A prospective study on 352 patients with esophageal, gastric or colorectal cancer was done. The BMI was calculated and analyzed by the classification of WHO, Lipschitz and OPAS. The mean age was 62.1 ± 12.4 years and 59% of them had more than 59 years. The BMI had not difference between the genders in patients <59 years (P = 0.75), but over 59 years the BMI was higher in women (P<0.01). The percentage of undernourished was 7%, 18% and 21% (P<0.01) by WHO, Lipschitz and OPAS, respectively. The overweight/obesity was also different among the various classifications (P<0.01). Most of the patients with gastrointestinal cancer had more than 65 years. A different cut off must be used for this patients, because undernourished patients may be wrongly considered well nourished.

Objectively measured physical activity and 12-month trajectories of neck-shoulder pain in workers: A prospective study in DPHACTO.

PubMed

Hallman, David M; Birk Jørgensen, Marie; Holtermann, Andreas

2017-05-01

This study aimed to investigate the association between objectively measured physical activity at work and leisure and the intensity (mean level and time course) of neck-shoulder pain (NSP) over 12 months among male and female blue collar workers. Data were obtained from 625 blue collar workers from the Danish cohort DPHACTO. Physical activity was measured objectively at baseline using accelerometers. The percentage of time spent in physical activity (walking, climbing stairs, running and cycling) was calculated for both work and leisure time. Longitudinal data on the intensity of NSP (numerical rating scale 0-10) were collected using text messages every fourth week over 12 months. Linear mixed models were used to investigate the associations between occupational physical activity (OPA) and leisure time physical activity (LTPA) and the trajectories of the intensity of NSP, adjusted for individual, biomechanical and psychosocial factors, and baseline pain. OPA was not associated with the mean intensity of NSP over 12 months. LTPA was negatively associated with the mean intensity of NSP both among men ( B=-0.71, 95% CI -1.31 to -0.11) and women ( B=-0.85, 95% CI -1.57 to -0.13). Sex interactions on the 12-month trajectories of NSP showed that higher physical activity was associated with a slower reduction in NSP among men for OPA only ( B=0.03, 95% CI 0.01-0.05) and women for LTPA only ( B=0.05, 95% CI 0.00-0.09). We found that more time in LTPA was associated with a lower overall intensity of NSP over 12 months among blue collar workers. However, depending on sex and domain, high physical activity had an unfavourable effect on the course of NSP over 12 months.

2016 Military Investigation and Justice Experience Survey: Overview Report

DTIC Science & Technology

2017-05-01

2016 Military Investigation and Justice Experience Survey (MIJES) Overview Report Additional copies of this report may be obtained from...dtic/order.html Ask for report by DTIC # OPA Report No. 2017-003 March 2017 2016 MILITARY INVESTIGATION AND JUSTICE EXPERIENCE SURVEY (MIJES...Justice Experience Survey (MIJES) 2017 ii | OPA Acknowledgments The Office of People Analytics (OPA) is indebted to numerous people for their

Determination of ammonium ion by fluorometry or spectrophotometry after on-line derivatization with o-phthalaldehyde

NASA Technical Reports Server (NTRS)

Goyal, S. S.; Rains, D. W.; Huffaker, R. C.

1988-01-01

A fast, sensitive, simple, and highly reproducible method for routine assay of ammonium ion (NH4+) was developed by using HPLC equipment. The method is based on the reaction of NH4+ with o-phthalaldehyde (OPA) in the presence of 2-mercaptoethanol. After an on-line derivatization, the resulting NH4(+)-OPA product was quantified by using fluorometric or spectrophotometric detection. For fluorometric detection, the excitation and emission wavelengths were 410 and 470 nm, respectively. The spectrophotometric detection was made by measuring absorbance at 410 nm. Results on the effects of OPA-reagent composition and pH, reaction temperature, sample matrix, and linearity of the assay are presented. Even though it took about 2 min from the time of sample injection to the appearance of sample peak, sample injections could be overlapped at an interval of about 1 min. Thus, the actual time needed for analysis was about 1 min per assay. The method can be used in a fully automated mode by using an autosampler injector.

Ghost imaging via optical parametric amplification

NASA Astrophysics Data System (ADS)

Li, Hong-Guo; Zhang, De-Jian; Xu, De-Qin; Zhao, Qiu-Li; Wang, Sen; Wang, Hai-Bo; Xiong, Jun; Wang, Kaige

2015-10-01

We investigate theoretically and experimentally thermal light ghost imaging where the light transmitted through the object as the seed light is amplified by an optical parametric amplifier (OPA). In conventional lens imaging systems with OPA, the spectral bandwidth of OPA dominates the image resolution. Theoretically, we prove that in ghost imaging via optical parametric amplification (GIOPA) the bandwidth of OPA will not affect the image resolution. The experimental results show that for weak seed light the image quality in GIOPA is better than that of conventional ghost imaging. Our work may be valuable in remote sensing with ghost imaging technique, where the light passed through the object is weak after a long-distance propagation.

A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.

PubMed

Martin, Ola J; Lai, Ling; Soundarapandian, Mangala M; Leone, Teresa C; Zorzano, Antonio; Keller, Mark P; Attie, Alan D; Muoio, Deborah M; Kelly, Daniel P

2014-02-14

Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) α and PGC-1β, have been shown to regulate mitochondrial biogenesis in the heart at the time of birth. The function of PGC-1 coactivators in the heart after birth has been incompletely understood. Our aim was to assess the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts in mice. Conditional gene targeting was used in mice to explore the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts. Marked mitochondrial structural derangements were observed in hearts of PGC-1α/β-deficient mice during postnatal growth, including fragmentation and elongation, associated with the development of a lethal cardiomyopathy. The expression of genes involved in mitochondrial fusion (Mfn1, Opa1) and fission (Drp1, Fis1) was altered in the hearts of PGC-1α/β-deficient mice. PGC-lα was shown to directly regulate Mfn1 gene transcription by coactivating the estrogen-related receptor α on a conserved DNA element. Surprisingly, PGC-1α/β deficiency in the adult heart did not result in evidence of abnormal mitochondrial dynamics or heart failure. However, transcriptional profiling demonstrated that PGC-1 coactivators are required for high-level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial dynamics and energy transduction in the adult heart. These results reveal distinct developmental stage-specific programs involved in cardiac mitochondrial dynamics.

Number-Theory in Nuclear-Physics in Number-Theory: Non-Primality Factorization As Fission VS. Primality As Fusion; Composites' Islands of INstability: Feshbach-Resonances?

NASA Astrophysics Data System (ADS)

Siegel, Edward

2011-10-01

Numbers: primality/indivisibility/non-factorization versus compositeness/divisibility /factor-ization, often in tandem but not always, provocatively close analogy to nuclear-physics: (2 + 1)=(fusion)=3; (3+1)=(fission)=4[=2 × 2]; (4+1)=(fusion)=5; (5 +1)=(fission)=6[=2 × 3]; (6 + 1)=(fusion)=7; (7+1)=(fission)=8[= 2 × 4 = 2 × 2 × 2]; (8 + 1) =(non: fission nor fusion)= 9[=3 × 3]; then ONLY composites' Islands of fusion-INstability: 8, 9, 10; then 14, 15, 16,... Could inter-digit Feshbach-resonances exist??? Applications to: quantum-information/computing non-Shore factorization, millennium-problem Riemann-hypotheses proof as Goodkin BEC intersection with graph-theory ``short-cut'' method: Rayleigh(1870)-Polya(1922)-``Anderson'' (1958)-localization, Goldbach-conjecture, financial auditing/accounting as quantum-statistical-physics;... abound!!!

Number-Theory in Nuclear-Physics in Number-Theory: Non-Primality Factorization As Fission VS. Primality As Fusion; Composites' Islands of INstability: Feshbach-Resonances?

NASA Astrophysics Data System (ADS)

Siegel, Edward

2011-04-01

Numbers: primality/indivisibility/non-factorization versus compositeness/divisibility /factor-ization, often in tandem but not always, provocatively close analogy to nuclear-physics: (2 + 1)=(fusion)=3; (3+1)=(fission)=4[=2 x 2]; (4+1)=(fusion)=5; (5+1)=(fission)=6[=2 x 3]; (6 + 1)=(fusion)=7; (7+1)=(fission)=8[= 2 x 4 = 2 x 2 x 2]; (8 + 1) =(non: fission nor fusion)= 9[=3 x 3]; then ONLY composites' Islands of fusion-INstability: 8, 9, 10; then 14, 15, 16,... Could inter-digit Feshbach-resonances exist??? Applications to: quantum-information and computing non-Shore factorization, millennium-problem Riemann-hypotheses physics-proof as numbers/digits Goodkin Bose-Einstein Condensation intersection with graph-theory ``short-cut'' method: Rayleigh(1870)-Polya(1922)-``Anderson'' (1958)-localization, Goldbach-conjecture, financial auditing/accounting as quantum-statistical-physics;... abound!!!

2017 Workplace and Gender Relations Survey of Reserve Component Members: Overview Report

DTIC Science & Technology

2018-04-30

2017 Workplace and Gender Relations Survey of Reserve Component Members DoD Overview Report Additional copies of this report may be...www.dtic.mil/dtic/order.html Ask for report by DTIC# OPA Report No. 2018-026 April 2018 2017 Workplace and Gender Relations Survey of...OPA) 4800 Mark Center Drive, Suite 06E22, Alexandria, VA 22350-4000 OPA 2017 Workplace and Gender Relations Survey of Reserve Component Members ii

Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

PubMed

Kitao, Kyoko; Mutai, Hideki; Namba, Kazunori; Morimoto, Noriko; Nakano, Atsuko; Arimoto, Yukiko; Sugiuchi, Tomoko; Masuda, Sawako; Okamoto, Yasuhide; Morita, Noriko; Sakamoto, Hirokazu; Shintani, Tomoko; Fukuda, Satoshi; Kaga, Kimitaka; Matsunaga, Tatsuo

2018-04-23

Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs before using hearing aids. The adult AN group comprised 2 patients with OPA1 mutations, 2 with OTOF mutations, and 5 with indefinite causes. Four ears (22%) showed no change in DPOAE, 13 ears (72%) showed a decrease, and one ear (6%) showed a loss of DPOAE. Although the ratio of DPOAE decrease was higher in the adult AN group than in the pediatric AN group, the ratio of DPOAE loss was lower in the adult AN group. DPOAE was not lost in all four ears with OPA1 mutations and in all four ears with OTOF mutations in the adult group. DPOAE was decreased or lost in approximately 70% of pediatric and about 80% of adult AN patients. Eleven percent of pediatric AN patients lost DPOAEs by 1 year of age. Genetic factors were thought to have influenced the time course of DPOAEs in the pediatric AN group. In most adult AN patients, DPOAE was rarely lost regardless of the genetic cause.

Typing of mutans streptococci by arbitrarily primed polymerase chain reaction.

PubMed

Saarela, M; Hannula, J; Mättö, J; Asikainen, S; Alaluusua, S

1996-01-01

The discriminative power of the arbitrarily primed polymerase chain reaction (AP-PCR) in differentiating between Streptococcus mutans and Strep. sobrinus species, serotypes and clones was investigated. Mutans streptococcal isolates (12(7)) obtained from 65 individuals (1-10 isolates per individual) were AP-PCR typed separately with two random primers, OPA-05 and OPA-13. Bacterial cell lysates were used as a template in PCR reactions, which made AP-PCR easy and fast to perform. Eighty-one isolates from 19 individuals were also ribotyped to compare the discriminative ability of ribotyping and AP-PCR techniques. AP-PCR performed with the two primers differentiated between Strep. mutans and Strep. sobrinus isolates, but neither primer detected serotype-specific amplification products. OPA-05 distinguished two main AP-PCR patterns among Strep. mutans isolates and one main pattern among Strep. sobrinus isolates, whereas OPA-13 found one main AP-PCR pattern among Strep. mutans isolates and two main patterns among Strep. sobrinus isolates. Ribotyping and AP-PCR revealed 40 and 33 different types among 81 selected isolates, respectively. Both techniques detected intra-individual heterogeneity in 16 out of 19 participants. The results indicate that AP-PCR has good discriminative ability in differentiating between mutans streptococcal clones and that the technique is suitable for epidemiological studies on mutans streptococci.

Loss of Mitofusin 2 Promotes Endoplasmic Reticulum Stress*

PubMed Central

Ngoh, Gladys A.; Papanicolaou, Kyriakos N.; Walsh, Kenneth

2012-01-01

The outer mitochondrial membrane GTPase mitofusin 2 (Mfn2) is known to regulate endoplasmic reticulum (ER) shape in addition to its mitochondrial fusion effects. However, its role in ER stress is unknown. We report here that induction of ER stress with either thapsigargin or tunicamycin in mouse embryonic fibroblasts leads to up-regulation of Mfn2 mRNA and protein levels with no change in the expression of the mitochondrial shaping factors Mfn1, Opa1, Drp1, and Fis1. Genetic deletion of Mfn2 but not Mfn1 in mouse embryonic fibroblasts or cardiac myocytes in mice led to an increase in the expression of the ER chaperone proteins. Genetic ablation of Mfn2 in mouse embryonic fibroblasts amplified ER stress and exacerbated ER stress-induced apoptosis. Deletion of Mfn2 delayed translational recovery through prolonged eIF2α phosphorylation associated with decreased GADD34 and p58IPK expression and elevated C/EBP homologous protein induction at late time points. These changes in the unfolded protein response were coupled to increased cell death reflected by augmented caspase 3/7 activity, lactate dehydrogenase release from cells, and an increase in propidium iodide-positive nuclei in response to thapsigargin or tunicamycin treatment. In contrast, genetic deletion of Mfn1 did not affect ER stress-mediated increase in ER chaperone synthesis or eIF2α phosphorylation. Additionally, ER stress-induced C/EBP homologous protein, GADD34, and p58IPK induction and cell death were not affected by loss of Mfn1. We conclude that Mfn2 but not Mfn1 is an ER stress-inducible protein that is required for the proper temporal sequence of the ER stress response. PMID:22511781

A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma

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

Varela, Mariana; Golder, Matthew; Archer, Fabienne

2008-02-05

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env. Most inhibitors were not effective in blocking JSRV Env-induced transformation. On the contrary, various Hsp90 inhibitors efficiently blocked JSRV transformation. This phenomenon was at least partly due to Akt degradation, which is activatedmore » in JSRV-transformed cells. Hsp90 was found expressed in tumor cells of sheep with naturally occurring OPA. In addition, Hsp90 inhibitors specifically inhibited proliferation of immortalized and moreover primary cells derived from OPA tumors. Thus, OPA could be used as a large animal model for comprehensive studies investigating the effects of Hsp90 inhibitors in lung adenocarcinoma.« less

Mitochondrial dynamics regulate melanogenesis through proteasomal degradation of MITF via ROS-ERK activation.

PubMed

Kim, Eun Sung; Park, So Jung; Goh, Myeong-Jin; Na, Yong-Joo; Jo, Doo Sin; Jo, Yoon Kyung; Shin, Ji Hyun; Choi, Eun Sun; Lee, Hae-Kwang; Kim, Ju-Yeon; Jeon, Hong Bae; Kim, Jin Cheon; Cho, Dong-Hyung

2014-11-01

Mitochondrial dynamics control mitochondrial functions as well as their morphology. However, the role of mitochondrial dynamics in melanogenesis is largely unknown. Here, we show that mitochondrial dynamics regulate melanogenesis by modulating the ROS-ERK signaling pathway. Genetic and chemical inhibition of Drp1, a mitochondrial fission protein, increased melanin production and mitochondrial elongation in melanocytes and melanoma cells. In contrast, down-regulation of OPA1, a mitochondria fusion regulator, suppressed melanogensis but induced massive mitochondrial fragmentation in hyperpigmented cells. Consistently, treatment with CCCP, a mitochondrial fission chemical inducer, also efficiently repressed melanogenesis. Furthermore, we found that ROS production and ERK phosphorylation were increased in cells with fragmented mitochondria. And inhibition of ROS or ERK suppressed the antimelanogenic effect of mitochondrial fission in α-MSH-treated cells. In addition, the activation of ROS-ERK pathway by mitochondrial fission induced phosphorylation of serine73 on MITF accelerating its proteasomal degradation. In conclusion, mitochondrial dynamics may regulate melanogenesis by modulating ROS-ERK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dicalcium phosphate (CaHPO4·2H2O) precipitation through ortho- or meta-phosphoric acid-etching: effects on the durability and nanoleakage/ultra-morphology of resin-dentine interfaces.

PubMed

Feitosa, Victor Pinheiro; Bazzocchi, Maria Giulia; Putignano, Angelo; Orsini, Giovanna; Luzi, Arlinda Luzi; Sinhoreti, Mário Alexandre Coelho; Watson, Timothy F; Sauro, Salvatore

2013-11-01

To compare the effects of two etching procedures using meta-phosphoric (MPA) or ortho-phosphoric acid (OPA) on dentine demineralisation, resin-dentine bonds durability and interface nanoleakage/ultra-morphology. Middle-dentine specimens were etched using 37% OPA (15s) or 40% MPA (60s) and submitted to infrared spectroscopy (FTIR) or ultra-morphology dye-assisted (calcium-staining) confocal microscopy (Ca-CLSM). A three-step etch-and-rinse adhesive was formulated, applied onto dentine and light-cured for 30s before composite build-up. After 24h, the dentine-bonded specimens were cut into 1mm(2) beams; half were immediately submitted to microtensile bond strength (μTBS) and half stored in DW for six months. The μTBS results were analysed with repeated-measures ANOVA and Tukey's test (p<0.05). Further teeth were bonded and prepared for interface nanoleakage/ultra-morphology confocal evaluation. FTIR and Ca-CLSM analyses showed dicalcium phosphate dihydrate (Brushite) precipitation in MPA-etched dentine and on the bottom (front of demineralisation) of the OPA-etched dentine. Statistical analysis showed similar μTBS for both etching procedures after 24h. The μTBS of specimens in OPA-group dropped significantly (p<0.05) after six month; the specimens in the MPA group showed no statistically difference (p>0.05). CLSM depicted no evident sign of nanoleakage within the resin-dentine interface of the MPA-treated specimens, while the specimens in OPA-group presented intense nanoleakage and interface degradation. The use of MPA (60s) as an alternative dentine conditioning agent in etch-and-rinse bonding procedures may be a suitable strategy to create more durable resin-dentine bonds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Determination of (alpha)-dialkylamino acids and their Enantiomers in Geological Samples by High-Performance Liquid Chromatography after Dervatization with a Chiral Adduct of (omicron)-Phthaldialdehyde

NASA Technical Reports Server (NTRS)

Zhoa, Meixun; Bada, Jeffrey L.

1995-01-01

Derivatization with (omicron)-phthaldialdehyde (OPA) and the chiral thiol N-acetyl-L-cysteine (NAC) is a convenient and sensitive technique for the HPLC detection and resolution of protein amino acid enantiomers. The kinetics of the reaction of OPA-NAC with (alpha)-dialkylamino acids was investigated. The fluorescence yield of (alpha)-dialkylamino acids was only about 10% of that of protein amino acids when the derivatization was carried out at room temperature for 1-2 min, which is the procedure generally used for protein amino acid analyses. The fluorescence yield of (alpha)-dialkylamino acids can be enhanced by up to ten-fold when the derivatization reaction time is increased to 15 min at room temperature. The OPA-NAC technique was optimized for the detection and enantiomeric resolution of a-dialkylamino acids in geological samples which contain a large excess of protein amino acids. The estimated detection limit for a-dialkylamino acids is 1-2 pmol, comparable to that for protein amino acids.

10-year trends in physical activity in the eastern Finnish adult population: relationship to socioeconomic and lifestyle characteristics.

PubMed

Marti, B; Salonen, J T; Tuomilehto, J; Puska, P

1988-01-01

In a large, community-based cardiovascular disease prevention study in Eastern Finland, independent random population samples were surveyed in 1972, 1977 and 1982. The leisure-time physical activity (LTPA), occupational physical activity (OPA), and socioeconomic and lifestyle characteristics were assessed. In men and women aged 30-59, the proportion with high LTPA increased from 1972 to 1982 by approximately one half (p less than 0.001), whereas that of high OPA decreased during the same period (p less than 0.001). In both sexes, high overall physical activity fell from 1972 to 1977 (p less than 0.001), but no more from 1977 to 1982. The proportion of entirely sedentary remained stable. Education, income and younger age showed a positive, body mass index, smoking and OPA a graded, negative association with high LTPA in 1972 and 1982. Significant (p less than 0.001) differences in 10-year trends of changes in LTPA were observed: men and women with low education or income increased LTPA more than those with high education and income. Socioeconomic factors, such as income and education, appear to have lost importance as determinants of population-wide exercise, whereas the clustering of low physical activity with overweight and smoking has increased.

Ozonolysis at vegetation surfaces. a source of acetone, 4-oxopentanal, 6-methyl-5-hepten-2-one, and geranyl acetone in the troposphere

NASA Astrophysics Data System (ADS)

Fruekilde, P.; Hjorth, J.; Jensen, N. R.; Kotzias, D.; Larsen, B.

The present study gives a possible explanation for the ubiquitous occurrence of 6-methyl-5-hepten-2-one and acetone in ambient air and reports for the first time on a widespread occurrence of geranyl acetone and 4-oxopentanal. We have conducted a series of laboratory experiments in which it is demonstrated that significant amounts of geranyl acetone, 6-methyl-5-hepten-2-one (6-MHO), 4-oxopentanal (4-OPA), and acetone are formed by the reaction of ozone with foliage of common vegetation in the Mediterranean area ( Quercus ilex>Citrus sinensis>Quercus suber>Quercus freinetto>Pinus pinea). In order to rule out biological formation, epicuticular waxes were extracted from the leaves, dispersed on glass wool and allowed to react with a flow of artificial air. Significant amounts of 6-MHO and 4-OPA were formed at ozone concentrations of 50-100 ppbv, but not at zero ozone. A number of terpenoids common in vegetation contain the structural element necessary for ozonolytic formation of 6-MHO. Two sesquiterpenes (nerolidol; farnesol), and a triterpene (squalene) selected as representative test compounds were demonstrated to be strong precursors for acetone, 4-OPA, and 6-MHO. Squalene was also a strong precursor for geranyl acetone. The atmospheric lifetime of geranyl acetone and 6-MHO is less than 1 h under typical conditions. For the present study, we have synthesized 4-OPA and investigated the kinetics of its gas-phase reaction with OH, NO 3, and O 3. A tropospheric lifetime longer than 17 h under typical conditions was calculated from the measured reaction rate constants, which explains the tropospheric occurrence of 4-OPA. It is concluded that future atmospheric chemistry investigations should included geranyl acetone, 6-MHO, and 4-OPA. In a separate experiment it was demonstrated that human skin lipid which contains squalene as a major component is a strong precursor for the four above-mentioned compounds plus nonanal and decanal. The accidental touching of material which later comes into contact with ozone can lead to strong artifact formation of these carbonyl compounds. Previously published results on these compounds must be seen in this new light.

Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity.

PubMed

Sacks, Jessica; Mulya, Anny; Fealy, Ciaran E; Huang, Hazel; Mosinski, John D; Pagadala, Mangesh R; Shimizu, Hideharu; Batayyah, Esam; Schauer, Philip R; Brethauer, Stacy A; Kirwan, John P

2018-02-01

Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding. We assessed expression of mitochondrial proteins involved in fusion, fission, mitochondrial autophagy (mitophagy) and biogenesis, as well as differences in citrate synthase activity and markers of oxidative stress. Gene expression for mitochondrial fusion genes, mitofusin 1 (Mfn1; P < 0.05), mitofusin 2 (Mfn2; P < 0.01), and optic atrophy 1 (OPA1; P < 0.05) increased following RYGB surgery. Biogenesis regulators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α; P < 0.01) and nuclear respiratory factor 1 (Nrf1; P < 0.05), also increased in the RYGB group, as well as mitophagy marker, BCL-2 interacting protein 3 (Bnip3; P < 0.01). Protein expression for Mfn1 (P < 0.001), PGC1α (P < 0.05), BNIP3 (P < 0.0001), and mitochondrial complexes I-V (P < 0.01) was also increased by RYGB, and Mfn1 expression negatively correlated with body weight, insulin resistance, and fasting plasma insulin. In the RYGB group, citrate synthase activity was increased (P < 0.02) and reactive oxygen species (ROS) was decreased compared to the Sham control group (P < 0.05), although total antioxidant capacity was unchanged between groups. These data are the first to show an association between RYGB surgery and improved markers of liver mitochondrial dynamics. These observed improvements may be related to weight loss and reduced energetic demand on the liver, which could facilitate normalization of glucose homeostasis and protect against hepatic steatosis. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Target Detection of Quantum Illumination Receiver Based on Photon-subtracted Entanglement State

NASA Astrophysics Data System (ADS)

Chi, Jiao; Liu, HongJun; Huang, Nan; Wang, ZhaoLu

2017-12-01

We theoretically propose a quantum illumination receiver based on the ideal photon-subtracted two-mode squeezed state (PSTMSS) to efficiently detect the noise-hidden target. This receiver is generated by applying an optical parametric amplifier (OPA) to the cross correlation detection. With analyzing the output performance, it is found that OPA as a preposition technology of the receiver can contribute to the PSTMSS by significantly reducing the error probability than that of the general two-mode squeezed state (TMSS). Comparing with TMSS, the signal-to-noise ratio of quantum illumination based on ideal PSTMSS and OPA is improved more than 4 dB under an optimal gain of OPA. This work may provide a potential improvement in the application of accurate target detection when two kinds of resource have the identical real squeezing parameter.

The usability of the optical parametric amplification of light for high-angular-resolution imaging and fast astrometry

NASA Astrophysics Data System (ADS)

Kurek, A. R.; Stachowski, A.; Banaszek, K.; Pollo, A.

2018-05-01

High-angular-resolution imaging is crucial for many applications in modern astronomy and astrophysics. The fundamental diffraction limit constrains the resolving power of both ground-based and spaceborne telescopes. The recent idea of a quantum telescope based on the optical parametric amplification (OPA) of light aims to bypass this limit for the imaging of extended sources by an order of magnitude or more. We present an updated scheme of an OPA-based device and a more accurate model of the signal amplification by such a device. The semiclassical model that we present predicts that the noise in such a system will form so-called light speckles as a result of light interference in the optical path. Based on this model, we analysed the efficiency of OPA in increasing the angular resolution of the imaging of extended targets and the precise localization of a distant point source. According to our new model, OPA offers a gain in resolved imaging in comparison to classical optics. For a given time-span, we found that OPA can be more efficient in localizing a single distant point source than classical telescopes.

Fine mapping of the rice Bph1 gene, which confers resistance to the brown planthopper (Nilaparvata lugens stal), and development of STS markers for marker-assisted selection.

PubMed

Cha, Young-Soon; Ji, Hyeonso; Yun, Doh-Won; Ahn, Byoung-Ohg; Lee, Myung Chul; Suh, Seok-Cheol; Lee, Chun Seok; Ahn, Eok Keun; Jeon, Yong-Hee; Jin, Il-Doo; Sohn, Jae-Keun; Koh, Hee-Jong; Eun, Moo-Young

2008-08-31

The brown planthopper (BPH) is a major insect pest in rice, and damages these plants by sucking phloem-sap and transmitting viral diseases. Many BPH resistance genes have been identified in indica varieties and wild rice accessions, but none has yet been cloned. In the present study we report fine mapping of the region containing the Bph1 locus, which enabled us to perform marker-aided selection (MAS). We used 273 F8 recombinant inbred lines (RILs) derived from a cross between Cheongcheongbyeo, an indica type variety harboring Bph1 from Mudgo, and Hwayeongbyeo, a BPH susceptible japonica variety. By random amplification of polymorphic DNA (RAPD) analysis using 656 random 10-mer primers, three RAPD markers (OPH09, OPA10 and OPA15) linked to Bph1 were identified and converted to SCAR (sequence characterized amplified region) markers. These markers were found to be contained in two BAC clones derived from chromosome 12: OPH09 on OSJNBa0011B18, and both OPA10 and OPA15 on OSJNBa0040E10. By sequence analysis of ten additional BAC clones evenly distributed between OSJNBa0011B18 and OSJNBa0040E10, we developed 15 STS markers. Of these, pBPH4 and pBPH14 flanked Bph1 at distances of 0.2 cM and 0.8 cM, respectively. The STS markers pBPH9, pBPH19, pBPH20, and pBPH21 co-segregated with Bph1. These markers were shown to be very useful for marker-assisted selection (MAS) in breeding populations of 32 F6 RILs from a cross between Andabyeo and IR71190, and 32 F5 RILs from a cross between Andabyeo and Suwon452.

Natural Resource Damages: Trustees

EPA Pesticide Factsheets

CERCLA and OPA authorize the United States, States, and Indian Tribes to act on behalf of the public as Natural Resource Trustees for natural resources under their respective trusteeship. OPA also authorizes foreign governments to act as Trustees.

OEI and OPA Issue a Joint Memorandum of Understanding (2002 Memo)

EPA Pesticide Factsheets

This MOU delineates certain interdependent functions, oversight responsibilities, and joint initiatives of the Office of Public Affairs (OPA) and the Office of Environmental Information (OEI) for the Agency's public Web site.

Association of occupational activity with joint space narrowing and osteophytosis in the medial compartment of the knee: the ROAD study (OAC5914R2).

PubMed

Muraki, S; Oka, H; Akune, T; En-yo, Y; Yoshida, M; Nakamura, K; Kawaguchi, H; Yoshimura, N

2011-07-01

We investigated the association of occupational activity with joint space narrowing and osteophytosis at the knee separately in Japanese subjects using a large-scale population-based cohort of the Research on Osteoarthritis Against Disability (ROAD). From the baseline survey of the ROAD study, 1,402 participants (512 men and 890 women) living in mountainous and seacoast communities were analyzed. Information collected included a lifetime occupational history and details of specific workplace physical activities. To estimate the severity of joint space narrowing and osteophytosis at the knee, minimum joint space width (mJSW) and osteophyte area (OPA) in the medial compartment of the knee were measured using a knee osteoarthritis (OA) computer-aided diagnosis system. For women, agricultural, forestry, and fishery workers had significantly lower mJSW values compared with clerical workers or technical experts, whereas OPA did not differ significantly among job titles in men or women. For occupational activities, kneeling and squatting were associated with lower mJSW as well as higher OPA. Walking and heavy lifting were associated with lower mJSW, but not with OPA. This cross-sectional study using a population-based cohort suggests that an occupational activity that includes kneeling and squatting appears to have a greater effect on knee OA. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Evaluation of genetic variability in micropropagated propagules of ornamental pineapple [Ananas comosus var. bracteatus (Lindley) Coppens and Leal] using RAPD markers.

PubMed

Santos, M D M; Buso, G C S; Torres, A C

2008-10-21

The objective of the present study was to evaluate the genetic variability in micropropagated plantlets of ornamental pineapple, after the fourth period of subculture. The basal culture medium consisted of MS salts, vitamins, 3% sucrose, liquid formulation, supplemented with 6-benzylaminopurine (BAP) at concentrations of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L. The addition of BAP influenced the occurrence of genetic variation revealed using random amplified polymorphic DNA (RAPD) markers. Of a total of 520 primers tested, 44 were selected and amplified; 402 monomorphic bands (97.2%) and 18 polymorphic bands (2.8%) resulted among regenerated plantlets. The polymorphic fragments were produced by 12 primers (OPA-01, OPA-20, OPB-01, OPB-19, OPC-19, OPF-13, OPL-17, OPM-13, OPP-16, OPT-07, OPV-19, and OPX-03). Among the primers that identified polymorphism, OPA-01, OPA-20, OPB-19, OPC-19, OPL-17, OPP-16, and OPX-3 each showed, one polymorphic band and OPF-13 amplified a maximum of three bands. In this study, the RAPD technique was effective in showing the occurrence of somaclonal variations that occur during the micropropagation process of ornamental pineapple cultivation in BAP-supplemented medium, and it is possible to detect the presence of genetic variation in early stages of plant development.

A misleading false-negative result using Neisseria gonorrhoeae opa MGB multiplex PCR assay in patient's rectal sample due to partial mutations of the opa gene.

PubMed

Vahidnia, Ali; van Empel, Pieter Jan; Costa, Sandra; Oud, Rob T N; van der Straaten, Tahar; Bliekendaal, Harry; Spaargaren, Joke

2015-07-01

A 53-year-old homosexual man presented at his general practitioner (GP) practice with a suspicion of sexually transmitted infection. Initial NAAT screening was performed for Chlamydia trachomatis and Neisseria gonorrhoeae. The patient was positive for Neisseria gonorrhoeae both for his urine and rectal sample. The subsequent confirmation test for Neisseria gonorrhoeae by a second laboratory was only confirmed for the urine sample and the rectal sample was negative. We report a case of a potential false-negative diagnosis of Neisseria gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample. The patient did not suffer any discomfort as diagnosis of Neisseria gonorrhoeae in his urine sample had already led to treatment by prescribing the patient with Ceftriaxone 500 mg IV dissolved in 1 ml lidocaine 2% and 4 mL saline. The patient also received a prescription for Azithromycin (2x500 mg).

Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts.

PubMed

Sin, Jon; Andres, Allen M; Taylor, David J R; Weston, Thomas; Hiraumi, Yoshimi; Stotland, Aleksandr; Kim, Brandon J; Huang, Chengqun; Doran, Kelly S; Gottlieb, Roberta A

2016-01-01

Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 [autosomal dominant]) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.

Recurrence of Lower Urinary Tract Symptoms Following Prostate Artery Embolization for Benign Hyperplasia: Single Center Experience Comparing Two Techniques

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

Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br; Moreira, Airton Mota; Harward, Sardis Honoria

PurposeTo compare recurrence of lower urinary tract symptoms (LUTS) recurrence at 12 months following original prostate artery embolization (oPAE) or “proximal embolization first, then embolize distal” (PErFecTED) PAE for benign prostatic hyperplasia (BPH).Materials and Methods105 consecutive patients older than 45 years, with prostate size greater than 30 cm{sup 3}, International Prostate Symptom Score (IPSS) ≥ 8, quality of life (QoL) index ≥ 3, and refractory status or intolerance of medical management were prospectively enrolled between June 2008 and August 2013. The study was IRB-approved, and all patients provided informed consent. Patients underwent oPAE or PErFecTED PAE and were followed for at least 12 months. Technical success was definedmore » as bilateral embolization and clinical success (non-recurrence) was defined as removal of the Foley catheter in patients with urinary retention, IPSS < 8 and QoL index < 3 at 12 months of follow-up. Nonparametric statistics were used to compare the study groups due to the size of the study population and distributions of clinical data.Results97 patients had 12-month data and were categorized as oPAE without recurrence (n = 46), oPAE with recurrence (n  = 13), PErFecTED without recurrence (n  = 36), or PErFecTED with recurrence (n  = 2). Recurrence was significantly more common in oPAE patients (χ{sup 2}, p = 0.026). Unilateral embolization was significantly associated with recurrence among patients who underwent oPAE (χ{sup 2}, p = 0.032).ConclusionsBoth oPAE and PErFecTED PAE are safe and effective methods for treatment of LUTS, but PErFecTED PAE is associated with a significantly lower rate of symptom recurrence.« less

The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.

PubMed

Chidley, Christopher; Trauger, Sunia A; Birsoy, Kıvanç; O'Shea, Erin K

2016-07-12

Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells.

International Space Station (ISS) Internal Active Thermal Control System (IATCS) New Biocide Selection, Qualification and Implementation

NASA Technical Reports Server (NTRS)

Wilson, Mark E.; Cole, Harold E.; Rector, Tony; Steele, John; Varsik, Jerry

2011-01-01

The Internal Active Thermal Control System (IATCS) aboard the International Space Station (ISS) is primarily responsible for the removal of heat loads from payload and system racks. The IATCS is a water based system which works in conjunction with the EATCS (External ATCS), an ammonia based system, which are interfaced through a heat exchanger to facilitate heat transfer. On-orbit issues associated with the aqueous coolant chemistry began to occur with unexpected increases in CO2 levels in the cabin. This caused an increase in total inorganic carbon (TIC), a reduction in coolant pH, increased corrosion, and precipitation of nickel phosphate. These chemical changes were also accompanied by the growth of heterotrophic bacteria that increased risk to the system and could potentially impact crew health and safety. Studies were conducted to select a biocide to control microbial growth in the system based on requirements for disinfection at low chemical concentration (effectiveness), solubility and stability, material compatibility, low toxicity to humans, compatibility with vehicle environmental control and life support systems (ECLSS), ease of application, rapid on-orbit measurement, and removal capability. Based on these requirements, ortho-phthalaldehyde (OPA), an aromatic dialdehyde compound, was selected for qualification testing. This paper presents the OPA qualification test results, development of hardware and methodology to safely apply OPA to the system, development of a means to remove OPA, development of a rapid colorimetric test for measurement of OPA, and the OPA on-orbit performance for controlling the growth of microorganisms in the ISS IATCS since November 3, 2007.

International Space Station (ISS) Internal Active Thermal Control System (IATCS) New Biocide Selection, Qualification and Implementation

NASA Technical Reports Server (NTRS)

Wilson, Mark E.; Cole, Harold; Rector, Tony; Steele, John; Varsik, Jerry

2010-01-01

The Internal Active Thermal Control System (IATCS) aboard the International Space Station (ISS) is primarily responsible for the removal of heat loads from payload and system racks. The IATCS is a water based system which works in conjunction with the EATCS (External ATCS), an ammonia based system, which are interfaced through a heat exchanger to facilitate heat transfer. On-orbit issues associated with the aqueous coolant chemistry began to occur with unexpected increases in CO2 levels in the cabin. This caused an increase in total inorganic carbon (TIC), a reduction in coolant pH, increased corrosion, and precipitation of nickel phosphate. These chemical changes were also accompanied by the growth of heterotrophic bacteria that increased risk to the system and could potentially impact crew health and safety. Studies were conducted to select a biocide to control microbial growth in the system based on requirements for disinfection at low chemical concentration (effectiveness), solubility and stability, material compatibility, low toxicity to humans, compatibility with vehicle environmental control and life support systems (ECLSS), ease of application, rapid on-orbit measurement, and removal capability. Based on these requirements, ortho-phthalaldehyde (OPA), an aromatic dialdehyde compound, was selected for qualification testing. This paper presents the OPA qualification test results, development of hardware and methodology to safely apply OPA to the system, development of a means to remove OPA, development of a rapid colorimetric test for measurement of OPA, and the OPA on-orbit performance for controlling the growth of microorganisms in the ISS IATCS since November 3, 2007.

Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway.

PubMed

Palomera-Avalos, V; Griñán-Ferré, C; Puigoriol-Ilamola, D; Camins, A; Sanfeliu, C; Canudas, A M; Pallàs, M

2017-04-01

Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence-accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by β-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of β-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions.

Physiotherapist agreement when visually rating movement quality during lower extremity functional screening tests.

PubMed

Whatman, Chris; Hing, Wayne; Hume, Patria

2012-05-01

To investigate physiotherapist agreement in rating movement quality during lower extremity functional tests using two visual rating methods and physiotherapists with differing clinical experience. Clinical measurement. Six healthy individuals were rated by 44 physiotherapists. These raters were in three groups (inexperienced, novice, experienced). Video recordings of all six individuals performing four lower extremity functional tests were visually rated (dichotomous or ordinal scale) using two rating methods (overall or segment) on two occasions separated by 3-4 weeks. Intra and inter-rater agreement for physiotherapists was determined using overall percentage agreement (OPA) and the first order agreement coefficient (AC1). Intra-rater agreement for overall and segment methods ranged from slight to almost perfect (OPA: 29-96%, AC1: 0.01 to 0.96). AC1 agreement was better in the experienced group (84-99% likelihood) and for dichotomous rating (97-100% likelihood). Inter-rater agreement ranged from fair to good (OPA: 45-79%; AC1: 0.22-0.71). AC1 agreement was not influenced by clinical experience but was again better using dichotomous rating. Physiotherapists' visual rating of movement quality during lower extremity functional tests resulted in slight to almost perfect intra-rater agreement and fair to good inter-rater agreement. Agreement improved with increased level of clinical experience and use of dichotomous rating. Copyright © 2011 Elsevier Ltd. All rights reserved.

Target-based coherent beam combining of an optical phased array fed by a broadband laser source

NASA Astrophysics Data System (ADS)

Hyde, Milo W., IV; McCrae, Jack E.; Tyler, Glenn A.

2017-11-01

The target-based phasing of an optical phased array (OPA) fed by a broadband master oscillator laser source is investigated. The specific scenario examined here considers an OPA phasing through atmospheric turbulence on a rough curved object. An analytical expression for the detected or received intensity is derived. Gleaned from this expression are the conditions under which target-based phasing is possible. A detailed OPA wave optics simulation is performed to validate the theoretical findings. Key aspects of the simulation set-up as well as the results are thoroughly discussed.

Orthogonal projection approach and continuous wavelet transform-feed forward neural networks for simultaneous spectrophotometric determination of some heavy metals in diet samples.

PubMed

Abbasi Tarighat, Maryam

2016-02-01

Simultaneous spectrophotometric determination of a mixture of overlapped complexes of Fe(3+), Mn(2+), Cu(2+), and Zn(2+) ions with 2-(3-hydroxy-1-phenyl-but-2-enylideneamino) pyridine-3-ol(HPEP) by orthogonal projection approach-feed forward neural network (OPA-FFNN) and continuous wavelet transform-feed forward neural network (CWT-FFNN) is discussed. Ionic complexes HPEP were formulated with varying reagent concentration, pH and time of color formation for completion of complexation reactions. It was found that, at 5.0 × 10(-4) mol L(-1) of HPEP, pH 9.5 and 10 min after mixing the complexation reactions were completed. The spectral data were analyzed using partial response plots, and identified non-linearity modeled using FFNN. Reducing the number of OPA-FFNN and CWT-FFNN inputs were simplified using dissimilarity pure spectra of OPA and selected wavelet coefficients. Once the pure dissimilarity plots ad optimal wavelet coefficients are selected, different ANN models were employed for the calculation of the final calibration models. The performance of these two approaches were tested with regard to root mean square errors of prediction (RMSE %) values, using synthetic solutions. Under the working conditions, the proposed methods were successfully applied to the simultaneous determination of metal ions in different vegetable and foodstuff samples. The results show that, OPA-FFNN and CWT-FFNN were effective in simultaneously determining Fe(3+), Mn(2+), Cu(2+), and Zn(2+) concentration. Also, concentrations of metal ions in the samples were determined by flame atomic absorption spectrometry (FAAS). The amounts of metal ions obtained by the proposed methods were in good agreement with those obtained by FAAS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of pH and application time of meta-phosphoric acid on resin-enamel and resin-dentin bonding.

PubMed

Cardenas, A F M; Siqueira, F S F; Bandeca, M C; Costa, S O; Lemos, M V S; Feitora, V P; Reis, A; Loguercio, A D; Gomes, J C

2018-02-01

To evaluate the immediate microshear resin-enamel bond strength (μSBS) and the immediate and 6-month microtensile bond strength (μTBS) and nanoleakage (NL) of the adhesive interface performed by different pHs of 40% meta-phosphoric acid (MPA) were compared with conventional 37% ortho-phosphoric acid (OPA) under different application times. Additionally, the enamel etching patterns were evaluated and the chemical/morphological changes induced by these differents groups were evaluated. One hundred and ninety-eight extracted human molars were randomly assigned into experimental groups according to the combination of independent variables: Acid [37% ortho-phosphoric acid (OPA), 40% meta-phosphoric acid (MPA) at pHs of: 0.5, 1 and 2] and Application Time [7, 15 and 30s]. Enamel-bond specimens were prepared and tested under μSBS. Resin-dentin beams were tested under μTBS tested immediately or after 6-months of water storage. Nanoleakage was evaluated using bonded-beams of each tooth/time-period. Enamel etching pattern and chemical and ultra-morphology analyses were also performed. The μSBS (MPa) data were subjected to a two-way repeated measures ANOVA (Acid vs. Application time). For μTBS, Acid vs application time vs storage time data were subjected to three-way ANOVA and Tukey's test (α = 0.05). MPA pH 0.5 showed μTBS similar to OPA, independently of the application time on enamel (p>0.05) or dentin (p>0.05). OPA provided higher nanoleakage values than MPA (p = 0.003). Significant decreases in TBS and increases in NL were only observed for OPA after 6 months (p = 0.001). An increase in the application time resulted in a more pronounced etching pattern for MPA. Chemical analysis showed that dentin demineralized by MPA depicted peaks of brushite and octacalcium phosphate. MPA exposed less collagen than OPA. However, optimal results for MPA were dependent on pH/application time. The use of 40% meta-phosphoric acid with a pH of 0.5 is an alternative acid-etching agent for dentin and enamel bonding. Furthermore, the use of MPA preserves the resin-dentin interface over a 6-months period, due to presence of brushite and octacalcium phosphate and a reduced demineralization pattern. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Total Dose Effects on Micropower Op-Amps: Bipolar and CMOS

NASA Technical Reports Server (NTRS)

Lee, C.; Johnston, A.

1998-01-01

This paper compares low-paper op-amps, OPA241 (bipolar) and OPA336 (CMOS), from Burr-Brown, MAX473 (bipolar) and MAX409 (CMOS), characterizing their total dose response with a single 2.7V power supply voltage.

Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart.

PubMed

Guo, Yongzheng; Wang, Zhen; Qin, Xinghua; Xu, Jie; Hou, Zuoxu; Yang, Hongyan; Mao, Xuechao; Xing, Wenjuan; Li, Xiaoliang; Zhang, Xing; Gao, Feng

2018-06-01

Heart failure (HF) is characterized by reduced fatty acid (FA) utilization associated with mitochondrial dysfunction. Recent evidence has shown that enhancing FA utilization may provide cardioprotection against HF. Our aim was to investigate the effects and the underlying mechanisms of cardiac FA utilization on cardiac function in response to pressure overload. Transverse aortic constriction (TAC) was used in C57 mice to establish pressure overload-induced HF. TAC mice fed on a high fat diet (HFD) exhibited increased cardiac FA utilization and improved cardiac function and survival compared with those on control diet. Such cardioprotection could also be provided by cardiac-specific overexpression of CD36. Notably, both HFD and CD36 overexpression attenuated mitochondrial fragmentation and improved mitochondrial function in the failing heart. Pressure overload decreased ATP-dependent metalloprotease (YME1L) expression and induced the proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 as a result of suppressed FA utilization. Enhancing FA utilization upregulated YME1L expression and subsequently rebalanced OPA1 processing, resulting in restoration of mitochondrial morphology in the failing heart. In addition, cardiac-specific overexpression of YME1L exerted similar cardioprotective effects against HF to those provided by HFD or CD36 overexpression. These findings demonstrate that enhancing FA utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing OPA1 processing in pressure overload-induced HF, suggesting a unique metabolic intervention approach to improving cardiac functions in HF.

Towards a petawatt-class few-cycle infrared laser system via dual-chirped optical parametric amplification.

PubMed

Fu, Yuxi; Midorikawa, Katsumi; Takahashi, Eiji J

2018-05-16

Expansion of the wavelength range for an ultrafast laser is an important ingredient for extending its range of applications. Conventionally, optical parametric amplification (OPA) has been employed to expand the laser wavelength to the infrared (IR) region. However, the achievable pulse energy and peak power have been limited to the mJ and the GW level, respectively. A major difficulty in the further energy scaling of OPA results from a lack of suitable large nonlinear crystals. Here, we circumvent this difficulty by employing a dual-chirped optical parametric amplification (DC-OPA) scheme. We successfully generate a multi-TW IR femtosecond laser pulse with an energy of 100 mJ order, which is higher than that reported in previous works. We also obtain excellent energy scaling ability, ultrashort pulses, flexiable wavelength tunability, and high-energy stability, which prove that DC-OPA is a superior method for the energy scaling of IR pulses to the 10 J/PW level.

A-DROP: A predictive model for the formation of oil particle aggregates (OPAs)

USGS Publications Warehouse

Zhao, Lin; Boufadel, Michel C.; Geng, Xiaolong; Lee, Kenneth; King, Thomas; Robinson, Brian; Fitzpatrick, Faith A.

2016-01-01

Oil–particle interactions play a major role in removal of free oil from the water column. We present a new conceptual–numerical model, A-DROP, to predict oil amount trapped in oil–particle aggregates. A new conceptual formulation of oil–particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil–particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil–particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil–particle aggregation.

A-DROP: A predictive model for the formation of oil particle aggregates (OPAs).

PubMed

Zhao, Lin; Boufadel, Michel C; Geng, Xiaolong; Lee, Kenneth; King, Thomas; Robinson, Brian; Fitzpatrick, Faith

2016-05-15

Oil-particle interactions play a major role in removal of free oil from the water column. We present a new conceptual-numerical model, A-DROP, to predict oil amount trapped in oil-particle aggregates. A new conceptual formulation of oil-particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil-particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil-particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil-particle aggregation. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Determination of fumonisins B1 and B2 in corn by high performance liquid chromatography with post-column derivatization method].

PubMed

Zhang, Xiaoxu; Xiao, Zhiyong; Zhang, Hongyan; Yang, Lili; Ma, Liyan

2012-08-01

A high performance liquid chromatography-fluorescence detection with post-column derivatization method was developed to detect fumonisin B1 (FB1) and fumonisin B2 (FB2) in corn. Several factors, such as the pH of derivatization buffer, concentration and flow rate of derivatization reagents, excitation wavelength, emission wavelength, which affected the detection of fumonisins were optimized. The separation was performed on a ZORBAX SB C18 column operated at 40 degrees C with the gradient elution by two mobile phases of 0.1 mol/L sodium dihydrogen phosphate solution (pH 3.3) and methanol at a flow rate of 0.8 mL/min. The derivatization was performed at ambient temperature. The o-phthalaldehyde (OPA) flow rate was 0.4 mL/min. The results showed that the optimum conditions were pH 10.5 of the derivatization reagent, OPA concentration at 2 g/L, and excitation wavelength of 335 nm, emission wavelength of 440 nm. The linear plots of FB1 and FB2 were obtained between 0.2 to 20 mg/L, with the correlation coefficients above 0.999 for both FB1 and FB2. The limits of detection of fumonisins B1 and B2 were 0.02 mg/kg. The mean recoveries at the three spiked levels of 0.1 - 4.0 mg/kg were 82.5% - 89.8%. This method is accurate, simple, rapid and suitable for the determination of fumonisins B1 and B2 in corn.

The importance of proximal fusion level selection for outcomes of multi-level lumbar posterolateral fusion.

PubMed

Nam, Woo Dong; Cho, Jae Hwan

2015-03-01

There are few studies about risk factors for poor outcomes from multi-level lumbar posterolateral fusion limited to three or four level lumbar posterolateral fusions. The purpose of this study was to analyze the outcomes of multi-level lumbar posterolateral fusion and to search for possible risk factors for poor surgical outcomes. We retrospectively analyzed 37 consecutive patients who underwent multi-level lumbar or lumbosacral posterolateral fusion with posterior instrumentation. The outcomes were deemed either 'good' or 'bad' based on clinical and radiological results. Many demographic and radiological factors were analyzed to examine potential risk factors for poor outcomes. Student t-test, Fisher exact test, and the chi-square test were used based on the nature of the variables. Multiple logistic regression analysis was used to exclude confounding factors. Twenty cases showed a good outcome (group A, 54.1%) and 17 cases showed a bad outcome (group B, 45.9%). The overall fusion rate was 70.3%. The revision procedures (group A: 1/20, 5.0%; group B: 4/17, 23.5%), proximal fusion to L2 (group A: 5/20, 25.0%; group B: 10/17, 58.8%), and severity of stenosis (group A: 12/19, 63.3%; group B: 3/11, 27.3%) were adopted as possible related factors to the outcome in univariate analysis. Multiple logistic regression analysis revealed that only the proximal fusion level (superior instrumented vertebra, SIV) was a significant risk factor. The cases in which SIV was L2 showed inferior outcomes than those in which SIV was L3. The odds ratio was 6.562 (95% confidence interval, 1.259 to 34.203). The overall outcome of multi-level lumbar or lumbosacral posterolateral fusion was not as high as we had hoped it would be. Whether the SIV was L2 or L3 was the only significant risk factor identified for poor outcomes in multi-level lumbar or lumbosacral posterolateral fusion in the current study. Thus, the authors recommend that proximal fusion levels be carefully determined when multi-level lumbar fusions are considered.

The Importance of Proximal Fusion Level Selection for Outcomes of Multi-Level Lumbar Posterolateral Fusion

PubMed Central

Nam, Woo Dong

2015-01-01

Background There are few studies about risk factors for poor outcomes from multi-level lumbar posterolateral fusion limited to three or four level lumbar posterolateral fusions. The purpose of this study was to analyze the outcomes of multi-level lumbar posterolateral fusion and to search for possible risk factors for poor surgical outcomes. Methods We retrospectively analyzed 37 consecutive patients who underwent multi-level lumbar or lumbosacral posterolateral fusion with posterior instrumentation. The outcomes were deemed either 'good' or 'bad' based on clinical and radiological results. Many demographic and radiological factors were analyzed to examine potential risk factors for poor outcomes. Student t-test, Fisher exact test, and the chi-square test were used based on the nature of the variables. Multiple logistic regression analysis was used to exclude confounding factors. Results Twenty cases showed a good outcome (group A, 54.1%) and 17 cases showed a bad outcome (group B, 45.9%). The overall fusion rate was 70.3%. The revision procedures (group A: 1/20, 5.0%; group B: 4/17, 23.5%), proximal fusion to L2 (group A: 5/20, 25.0%; group B: 10/17, 58.8%), and severity of stenosis (group A: 12/19, 63.3%; group B: 3/11, 27.3%) were adopted as possible related factors to the outcome in univariate analysis. Multiple logistic regression analysis revealed that only the proximal fusion level (superior instrumented vertebra, SIV) was a significant risk factor. The cases in which SIV was L2 showed inferior outcomes than those in which SIV was L3. The odds ratio was 6.562 (95% confidence interval, 1.259 to 34.203). Conclusions The overall outcome of multi-level lumbar or lumbosacral posterolateral fusion was not as high as we had hoped it would be. Whether the SIV was L2 or L3 was the only significant risk factor identified for poor outcomes in multi-level lumbar or lumbosacral posterolateral fusion in the current study. Thus, the authors recommend that proximal fusion levels be carefully determined when multi-level lumbar fusions are considered. PMID:25729522

Simulation of a current source with a Cole-Cole load for multi-frequency electrical impedance tomography.

PubMed

Aguiar Santos, Susana; Schlebusch, Thomas; Leonhardt, Steffen

2013-01-01

An accurate current source is one of the keys in the hardware of Electrical impedance Tomography systems. Limitations appear mainly at higher frequencies and for non-simple resistive loads. In this paper, we simulate an improved Howland current source with a Cole-Cole load. Simulations comparing two different op-amps (THS4021 and OPA843) were performed at 1 kHz to 1 MHz. Results show that the THS4021 performed better than the OPA843. The current source with THS4021 reaches an output impedance of 20 MΩ at 1 kHz and above 320 kΩ at 1 MHz, it provides a constant and stable output current up to 4 mA, in the complete range of frequencies, and for Cole-Cole (resistive and capacitive) load.

Comparison of Opa Locka Tower with other ATC facilities by means of a biochemical stress index.

DOT National Transportation Integrated Search

1974-12-01

Physiological and biochemical measurements of stress in 14 Opa Locka Tower (OPF) controllers indicated that the principal stressor at that facility was the heavy volume of air traffic. Controllers responded to this stressor with a large increase in u...

In-Use Evaluation of Peracetic Acid for High-Level Disinfection of Endoscopes.

PubMed

Chenjiao, Wu; Hongyan, Zhang; Qing, Gu; Xiaoqi, Zhong; Liying, Gu; Ying, Fang

2016-01-01

Many high-level disinfectants have been used for disinfection of endoscopes such as 2% glutaraldehyde (GA), 0.55% ortho-phthalaldehyde (OPA), and peracetic acid (PAA). Both GA and OPA are widely used in disinfection of endoscopes and have been previously discussed, but there is little research on the practical use of PAA as an endoscope disinfectant. An experimental model of a flexible gastrointestinal endoscope being contaminated with 9 strains of microorganism was designed. After the cleaning and disinfecting procedure was completed, we evaluated the biocidal activity (850 ppm PAA, 2% GA, and 0.55% OPA) on our flexible gastrointestinal endoscope model. We also evaluated sterilization effectiveness of PAA on other bacteria, including some antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile). The residual bacterial colony count number of the PAA-disinfected endoscope was significantly lower than that of the GA- and OPA-disinfected endoscopes. The biocidal effect and efficiency of the endoscope disinfection by PAA appeared to be better than either the GA- or OPA-disinfected endoscope. PAA has demonstrated a good sterilization effect on other bacterial species; of particular note are common antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile. The results of this study demonstrate that PAA is a fast and effective high-level disinfectant for use in the reprocessing of flexible endoscopes.

[Genetic variability and differentiation of three Russian populations of yellow potato cyst nematode Globodera rostochiensis as revealed by nuclear markers].

PubMed

Khrisanfova, G G; Kharchevnikov, D A; Popov, I O; Zinov'eva, S V; Semenova, S K

2008-05-01

Genetic variability of yellow potato cyst nematode G. rostochiensis from three Russian populations (Karelia, Vladimir oblast, and Moscow oblast) was investigated using two types of nuclear markers. Using RAPD markers identified with the help of six random primers (P-29, OPA-10, OPT-14, OPA-11, OPB-11, and OPH-20), it was possible to distinguish Karelian population from the group consisting of the populations from two adjacent regions (Moscow oblast and Vladimir oblast). Based on the combined matrix, containing 294 RAPD fragments, dendrogram of genetic differences was constructed, and the indices of genetic divergence and partition (P, H, and G(st)), as well as the gene flow indices N(m) between the nematode samples examined, were calculated. The dendrogram structure, genetic diversity indices, and variations of genetic distances between single individuals in each population from Karelia and Central Russia pointed to genetic isolation and higher genetic diversity of the nematodes from Karelia. Based on polymorphism of rDNA first intergenic spacer ITS1, attribution of all populations examined to the species G. rostochiensis was proved. Small variations of the ITS1 sequence in different geographic populations of nematodes from different regions of the species world range did not allow isolation of separate groups within the species. Possible factors (including interregional transportations of seed potato) affecting nematode population structure in Russia are discussed.

30 CFR 253.1 - What is the purpose of this part?

Code of Federal Regulations, 2011 CFR

2011-07-01

... THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 253.1 What... covered offshore facilities (COFs) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U...

Bistability in a hybrid optomechanical system: effect of a gain medium

NASA Astrophysics Data System (ADS)

Asghari Nejad, A.; Baghshahi, H. R.; Askari, H. R.

2017-11-01

In this paper, we investigate the optical bistability of a hybrid optomechanical system consisting of two coupled cavities: a bare optomechanical cavity (with an oscillating mirror at one end) and a traditional one. The traditional cavity is filled with an optical parametric amplifier (OPA), and an input pump laser is applied to it. The Hamiltonian of the system is written in a rotating frame. The dynamics of the system is driven by the quantum Langevin equations of motion. We demonstrate that the presence of an OPA can dramatically affect the type of stability of the optomechanical cavity. We show that it is possible to create a proper optical bistability for the optomechanical cavity by changing the gain coefficient of the OPA. Also, it is shown that changing the phase of the field driving the OPA has two different effects on the bistability region of the optomechanical cavity. Moreover, we show that by choosing a proper value for the detuning of the traditional cavity it is possible to observe a tristable behavior in the optomechanical cavity.

Near-Infrared Spectroscopy of Small Protonated Water Clusters

NASA Astrophysics Data System (ADS)

Wagner, J. Philipp; McDonald, David C., II; McCoy, Anne B.; Duncan, Michael A.

2017-06-01

Small protonated water clusters and their argon tagged analogues of the general formula H^{+}(H_{2}O)_{n}Ar_{m} have been generated in a pulsed electric discharge source. Clusters containing n=1-8 water molecules were mass-selected and their absorptions in the near-infrared were probed with a tunable Nd/colonYAG pumped OPA/OPA laser system in the region from 4850-7350 cm^{-1}. A doublet corresponding to overtones of the free O-H stretches of the external waters was observed around 7200 cm^{-1} that was continuously decreasing in intensity with increasing cluster size. Broad, mostly featureless absorptions were found around 5300 cm^{-1} associated with stretch/bend combinations and with the hydrogen bonded waters in the core of the clusters. Vibrational assignments were substantiated by comparison to anharmonic frequency computations via second-order vibrational perturbation theory (VPT2) at the MP2/aug-cc-pVTZ level of theory.

Number-Theory in Nuclear-Physics in Number-Theory: Non-Primality Factorization As Fission VS. Primality As Fusion; Composites' Islands of INstability: Feshbach-Resonances?

NASA Astrophysics Data System (ADS)

Smith, A.; Siegel, Edward Carl-Ludwig

2011-03-01

Numbers: primality/indivisibility/non-factorization versus compositeness/divisibility/ factorization, often in tandem but not always, provocatively close analogy to nuclear-physics: (2 + 1)=(fusion)=3; (3+1)=(fission)=4[=2 x 2]; (4+1)=(fusion)=5; (5 +1)=(fission)=6[=2 x 3]; (6 + 1)=(fusion)=7; (7+1)=(fission)=8[= 2 x 4 = 2 x 2 x 2]; (8 + 1) =(non: fission nor fusion)= 9[=3 x 3]; then ONLY composites' Islands of fusion-INstability: 8, 9, 10; then 14, 15, 16, ... Could inter-digit Feshbach-resonances exist??? Possible applications to: quantum-information/ computing non-Shore factorization, millennium-problem Riemann-hypotheses proof as Goodkin BEC intersection with graph-theory "short-cut" method: Rayleigh(1870)-Polya(1922)-"Anderson"(1958)-localization, Goldbach-conjecture, financial auditing/accounting as quantum-statistical-physics; ...abound!!! Watkins [www.secamlocal.ex.ac.uk/people/staff/mrwatkin/] "Number-Theory in Physics" many interconnections: "pure"-maths number-theory to physics including Siegel [AMS Joint Mtg.(2002)-Abs.# 973-60-124] inversion of statistics on-average digits' Newcomb(1881)-Weyl(14-16)-Benford(38)-law to reveal both the quantum and BEQS (digits = bosons = digits:"spinEless-boZos"). 1881 1885 1901 1905 1925 < 1927, altering quantum-theory history!!!

Deformation mechanisms and evolution of the microstructure of gouge in the Main Fault in Opalinus Clay in the Mont Terri rock laboratory (CH)

NASA Astrophysics Data System (ADS)

Laurich, Ben; Urai, Janos L.; Vollmer, Christian; Nussbaum, Christophe

2018-01-01

We studied gouge from an upper-crustal, low-offset reverse fault in slightly overconsolidated claystone in the Mont Terri rock laboratory (Switzerland). The laboratory is designed to evaluate the suitability of the Opalinus Clay formation (OPA) to host a repository for radioactive waste. The gouge occurs in thin bands and lenses in the fault zone; it is darker in color and less fissile than the surrounding rock. It shows a matrix-based, P-foliated microfabric bordered and truncated by micrometer-thin shear zones consisting of aligned clay grains, as shown with broad-ion-beam scanning electron microscopy (BIB-SEM) and optical microscopy. Selected area electron diffraction based on transmission electron microscopy (TEM) shows evidence for randomly oriented nanometer-sized clay particles in the gouge matrix, surrounding larger elongated phyllosilicates with a strict P foliation. For the first time for the OPA, we report the occurrence of amorphous SiO2 grains within the gouge. Gouge has lower SEM-visible porosity and almost no calcite grains compared to the undeformed OPA. We present two hypotheses to explain the origin of gouge in the Main Fault: (i) authigenic generation consisting of fluid-mediated removal of calcite from the deforming OPA during shearing and (ii) clay smear consisting of mechanical smearing of calcite-poor (yet to be identified) source layers into the fault zone. Based on our data we prefer the first or a combination of both, but more work is needed to resolve this. Microstructures indicate a range of deformation mechanisms including solution-precipitation processes and a gouge that is weaker than the OPA because of the lower fraction of hard grains. For gouge, we infer a more rate-dependent frictional rheology than suggested from laboratory experiments on the undeformed OPA.

76 FR 59731 - Draft Damage Assessment and Restoration Plan and Environmental Assessment for the M/V Cosco Busan...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... for restoring injured natural resources and compensating recreational losses resulting from the Cosco... under OPA, will pay damages to compensate the public for the injuries to natural resources and lost... accordance with the OPA, the Natural Resource Damage Assessment regulations found in the Code of Federal...

Tumor necrosis factor-{alpha} enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

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

Song, Kai; Zhu, Fei; Zhang, Han-zhong

Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-{alpha} (TNF-{alpha}) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oralmore » squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-{alpha}-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer-endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-{alpha} could enhance cancer-endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer-endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: Black-Right-Pointing-Pointer Spontaneous oral cancer-endothelial cell fusion. Black-Right-Pointing-Pointer TNF-{alpha} enhanced cell fusions. Black-Right-Pointing-Pointer VCAM-1/VLA-4 expressed in oral cancer. Black-Right-Pointing-Pointer TNF-{alpha} increased expression of VCAM-1 on endothelial cells. Black-Right-Pointing-Pointer VCAM-1/VLA-4 mediated TNF-{alpha}-enhanced cell fusions.« less

Fault Frictional Stability in a Nuclear Waste Repository

NASA Astrophysics Data System (ADS)

Orellana, Felipe; Violay, Marie; Scuderi, Marco; Collettini, Cristiano

2016-04-01

Exploitation of underground resources induces hydro-mechanical and chemical perturbations in the rock mass. In response to such disturbances, seismic events might occur, affecting the safety of the whole engineering system. The Mont Terri Rock Laboratory is an underground infrastructure devoted to the study of geological disposal of nuclear waste in Switzerland. At the site, it is intersected by large fault zones of about 0.8 - 3 m in thickness and the host rock formation is a shale rock named Opalinus Clay (OPA). The mineralogy of OPA includes a high content of phyllosilicates (50%), quartz (25%), calcite (15%), and smaller proportions of siderite and pyrite. OPA is a stiff, low permeable rock (2×10-18 m2), and its mechanical behaviour is strongly affected by the anisotropy induced by bedding planes. The evaluation of fault stability and associated fault slip behaviour (i.e. seismic vs. aseismic) is a major issue in order to ensure the long-term safety and operation of the repository. Consequently, experiments devoted to understand the frictional behaviour of OPA have been performed in the biaxial apparatus "BRAVA", recently developed at INGV. Simulated fault gouge obtained from intact OPA samples, were deformed at different normal stresses (from 4 to 30 MPa), under dry and fluid-saturated conditions. To estimate the frictional stability, the velocity-dependence of friction was evaluated during velocity steps tests (1-300 μm/s). Slide-hold-slide tests were performed (1-3000 s) to measure the amount of frictional healing. The collected data were subsequently modelled with the Ruina's slip dependent formulation of the rate and state friction constitutive equations. To understand the deformation mechanism, the microstructures of the sheared gouge were analysed. At 7 MPa normal stress and under dry conditions, the friction coefficient decreased from a peak value of μpeak,dry = 0.57 to μss,dry = 0.50. Under fluid-saturated conditions and same normal stress, the friction coefficient decreased from a peak value of μpeak,sat = 0.45 to μss,sat = 0.34. Additionally, it has been observed that the weakening distance Dw is smaller under fluid- saturated conditions (˜4 mm) compared to dry conditions (˜6 mm). Results showed a linear decrease of both peak friction and steady state friction when normal stress increases. When fluid- saturation degree of gouges is reduced, gouge samples underwent a transition from velocity strengthening to velocity weakening behaviour, thus indicating a potentially unstable frictional behaviour of the fault. Furthermore, under both saturated and dry conditions, the frictional healing rate showed a low recovery of the friction coefficient under different holding times. Our experiments indicate that the frictional behaviour of Opalinus Clay is characterized by complex processes depending upon normal stress, sliding velocity, and saturation degree of the samples. This complexity highlights the need for further experiments in order to better evaluate the seismic risk during long-term nuclear waste disposal within the OPA clay formation.

Demonstration of a 100-mJ OPO/OPA for future lidar applications and laser-induced damage threshold testing of optical components for MERLIN

NASA Astrophysics Data System (ADS)

Elsen, Florian; Livrozet, Marie; Strotkamp, Michael; Wüppen, Jochen; Jungbluth, Bernd; Kasemann, Raphael; Löhring, Jens; Meissner, Ansgar; Meyer, Rudolf; Hoffmann, Hans-Dieter; Poprawe, Reinhart

2018-02-01

In the field of atmospheric research, lidar is a powerful technology that can measure gas or aerosol concentrations, wind speed, or temperature profiles remotely. To conduct such measurements globally, spaceborne systems are advantageous. Pulse energies in the 100-mJ range are required to achieve highly accurate, longitudinal resolved measurements. Measuring concentrations of specific gases, such as CH4 or CO2, requires output wavelengths in the IR-B, which can be addressed by optical-parametric frequency conversion. An OPO/OPA frequency conversion setup was designed and built as a demonstration module to address the 1.6-μm range. The pump laser is an Nd:YAG-MOPA system, consisting of a stable oscillator and two subsequent Innoslab-based amplifier stages that deliver up to 500 mJ of output pulse energy at 100 Hz repetition frequency. The OPO is inherited from the OPO design for the CH4 lidar instrument on the French-German climate satellite methane remote-sensing lidar mission (MERLIN). To address the 100-mJ regime, the OPO output beam is amplified in a subsequent multistage OPA. With potassium titanyl phosphate as nonlinear medium, the OPO/OPA delivered more than 100 mJ of output energy at 1645 nm from 450 mJ of the pump energy and a pump pulse duration of 30 ns. This corresponds to a quantum conversion efficiency of about 25%. In addition to demonstrating optical performance for future lidar systems, this laser will be part of a laser-induced damage thresholds test facility, which will be used to qualify optical components especially for the MERLIN.

Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa

PubMed Central

Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R.

2016-01-01

Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

2017 Military Investigation and Justice Experience Survey: Overview Report

DTIC Science & Technology

2018-04-30

2016–2017 Military Investigation and Justice Experience Survey (MIJES) Overview Report Additional copies of this report may be obtained...www.dtic.mil/dtic/order.html OPA Report No. 2017-027 January 2018 2016–2017 Military Investigation and Justice Experience Survey (MIJES...Investigation and Justice Experience Survey (MIJES) ii Acknowledgments Acknowledgments The Office of People Analytics (OPA) is indebted to numerous

2017 Workplace and Gender Relations Survey of Reserve Component Members: Statistical Methodology Report

DTIC Science & Technology

2018-04-30

2017 Workplace and Gender Relations Survey of Reserve Component Members Statistical Methodology Report Additional copies of this report...Survey of Reserve Component Members Statistical Methodology Report Office of People Analytics (OPA) 4800 Mark Center Drive, Suite...RESERVE COMPONENT MEMBERS STATISTICAL METHODOLOGY REPORT Introduction The Office of People Analytics’ Center for Health and Resilience (OPA[H&R

78 FR 46339 - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of Temporary Moratoria...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...-crm-510.html . \\10\\ Department of Justice, ``Owners of Miami Home Health Companies Sentenced to Prison in $48 million Health Care Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/February/13-crm-243... Convicted in Medicare Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/March/13-crm-273.html . \\24...

13.5 nm High Harmonic Generation Driven by a Visible Noncollinear Optical Parametric Amplifier

DTIC Science & Technology

2011-11-11

compressed through a CaF2 prism pair at Brewster angle , and directed to the second OPA stage after a periscope flipping its polarization. The 90% part of...FWHM pulse duration. HHG setup The OPA pulses are sent into a vacuum chamber and focused in an Argon ( lens focal length 150 mm) or Helium (focal

The Causes of Blistering in Boat Building Materials

DTIC Science & Technology

1986-08-01

acrylate units (MET) Ethylene glycol (MET) Propylene glycol (MET) Neopentyl glycol (NET) Maleic acid or anhydride (unsaturated) (NET) lumaric acid...PROPYLENE GLYCOL OPA ORTHOPHTHALIC ACID VINYL - URETHANE BASED POLYESTER IqPG NEOPENTYL GLYCOL RESIN EG - ETHYLENE GLYCOL TMPD - 22,, - TRiMETHY...IPA Isophthalic acid WSN Low molecular weight water soluble material NPG Neopentyl glycol OPA Orthophthalio acid PG Propylene glycol MEKP Hethyl

Phonon-assisted nonlinear optical processes in ultrashort-pulse pumped optical parametric amplifiers

NASA Astrophysics Data System (ADS)

Isaienko, Oleksandr; Robel, István

2016-03-01

Optically active phonon modes in ferroelectrics such as potassium titanyl phosphate (KTP) and potassium titanyl arsenate (KTA) in the ~7-20 THz range play an important role in applications of these materials in Raman lasing and terahertz wave generation. Previous studies with picosecond pulse excitation demonstrated that the interaction of pump pulses with phonons can lead to efficient stimulated Raman scattering (SRS) accompanying optical parametric oscillation or amplification processes (OPO/OPA), and to efficient polariton-phonon scattering. In this work, we investigate the behavior of infrared OPAs employing KTP or KTA crystals when pumped with ~800-nm ultrashort pulses of duration comparable to the oscillation period of the optical phonons. We demonstrate that under conditions of coherent impulsive Raman excitation of the phonons, when the effective χ(2) nonlinearity cannot be considered instantaneous, the parametrically amplified waves (most notably, signal) undergo significant spectral modulations leading to an overall redshift of the OPA output. The pump intensity dependence of the redshifted OPA output, the temporal evolution of the parametric gain, as well as the pump spectral modulations suggest the presence of coupling between the nonlinear optical polarizations PNL of the impulsively excited phonons and those of parametrically amplified waves.

Dispersing surface-modified imogolite nanotubes in polar and non-polar solvents

NASA Astrophysics Data System (ADS)

Li, Ming; Brant, Jonathan A.

2018-02-01

Furthering the development of nanocomposite structures, namely membranes for water treatment applications, requires that methods be developed to ensure nanoparticle dispersion in polar and non-polar solvents, as both are widely used in associated synthesis techniques. Here, we report on a two-step method to graft polyvinylpyrrolidone (PVP), and a one-step method for octadecylphosphonic acid (OPA), onto the outer surfaces of imogolite nanotubes. The goal of these approaches was to improve and maintain nanotube dispersion in polymer compatible polar and non-polar solvents. The PVP coating modified the imogolite surface charge from positive to weakly negative at pH ≤ 9; the OPA made it weakly positive at acidic pH values to negative at pH ≥ 7. The PVP surface coating stabilized the nanotubes through steric hindrance in polar protic, dipolar aprotic, and chloroform. In difference to the PVP, the OPA surface coating allowed the nanotubes to be dispersed in n-hexane and chloroform, but not in the polar solvents. The lack of miscibility in the polar solvents, as well as the better dispersion in n-hexane, was attributed to the stronger hydrophobicity of the OPA polymer relative to the PVP. [Figure not available: see fulltext.

Fluorometric enzymatic assay of L-arginine

NASA Astrophysics Data System (ADS)

Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

2017-01-01

The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning.

PubMed

Kulmala, Jenni; Ngandu, Tiia; Pajala, Satu; Lehtisalo, Jenni; Levälahti, Esko; Antikainen, Riitta; Laatikainen, Tiina; Oksa, Heikki; Peltonen, Markku; Rauramaa, Rainer; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia

2016-10-01

Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning. The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants' data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning. A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24-0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27-0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22-2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14-2.69) and poorer walking speed (β = .10, P = .005). This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work.

Project-Based Learning with an Online Peer Assessment System in a Photonics Instruction for Enhancing LED Design Skills

ERIC Educational Resources Information Center

Chang, Shu-Hsuan; Wu, Tsung-Chih; Kuo, Yen-Kuang; You, Li-Chih

2012-01-01

This study proposed a novel instructional approach, a two-stage LED simulation of Project-based learning (PBL) course with online peer assessment (OPA), and explored how to apply OPA to the different structured problems in a PBL course to enhance students' professional skills in LED design as well as meta-cognitive thinking. The participants of…

Improved Performance of an Optically Pumped Mid-Infrared Acetylene-Filled Hollow-Core Fiber Laser

NASA Astrophysics Data System (ADS)

Dadashzadeh, Neda

The focus of this research is improving the pulse output energy of a mid-IR pulsed acetylene-filled Hollow-core Optical Fiber Gas LASer (HOFGLAS) system. Pump pulses and acetylene molecules interact with each other inside hollow-core photonic crystal fiber that effectively confines light and allows for strong gain. This results in lasing at 3.11 mum and 3.17 mum lines based on population inversion of acetylene molecules, which are optically pumped at rotational-vibrational overtones near 1.5 mum using 1 ns pulse duration from an optical parametric amplifier (OPA). This acetylene laser operates with no cavity mirrors because of a high gain in a single pass configuration. There are few laser sources in the mid-IR region while there are many applications for having a laser source in this range such as remote sensing, hazardous chemical detection, and breath analysis. This adds to the importance of the acetylene-filled HOFGLAS system. Some of the applications like remote sensing require high power. So, we moved toward power scaling this laser system by optimizing the laser operation through maximizing the OPA alignment to improve its modal content using longer length of fiber to increase the interaction length and improving the beam quality of the mid-IR emissions. The highest pulse energy ever obtained in the 3 microm mid-IR region from the acetylene-filled HOFGLAS after applying the improvements is reported here (1.4 muJ). Higher mid-IR pulse energies can be achieved by improving the pulse energy achievable from the OPA pump source and working with longer pulse duration to decrease the bandwidth of the OPA. This operation demonstrates many novel properties of acetylene-filled pulsed mid-IR hollow-core fiber lasers. The excellent spatial beam quality at highest power and phenomenological scaling of saturation power and efficiency with pressure that we observe point to the promise of power scaling and motivate further development of numerical models of the laser for deeper insight into these effects. M2 measurement method was used to examine spatial beam quality and it was found to be fiber-dependent. For the improved setup, M2 was investigated at several input pump powers in addition to the reproducibility checks. M 2 of 1.14 at the maximum output power motivates for beam combining to scale to higher power. The independence of efficiency on pressure is an evidence for reaching higher mid-IR power at a pressure where saturation behavior does not exist. achieving the highest mid-IR power to date, 1.4 muJ, encourages for building higher power OPA to produce high power mid-IR emissions. Taken as a whole, this laser exhibits novel behavior that motivates both numerical/theoretical investigation and further efforts to scale to higher powers.

Long-term study of ovine pulmonary adenocarcinogenesis in sheep with marginal vs. sufficient nutritional selenium supply: results from computed tomography, pathology, immunohistochemistry, JSRV-PCR and lung biochemistry.

PubMed

Humann-Ziehank, Esther; Renko, Kostja; Bruegmann, Michael L; Devi, Vemuri Rama; Hewicker-Trautwein, Marion; Andreae, Arnim; Ganter, Martin

2013-10-01

The impact of selenium (Se) in carcinogenesis is still debatable due to inconsistent results of observational studies, recent suspicion of diabetic side effects and e.g. dual roles of glutathione peroxidases (GPx). Previously, our group introduced long-term studies on lung carcinogenesis using the jaagtsiekte sheep retrovirus (JSRV) induced ovine pulmonary adenocarcinoma (OPA) as an innovative animal model. The present report describes the results of sufficient (0.2 mg Se/kg dry weight (dw)) vs. marginal (<0.05 mg Se/kg dw) nutritional Se supply on cancer progression over a two-year period in 16 animals. Computed tomography (CT) evaluation of lung cancer progression, final pathological examination, evidence of pro-viral JSRV-DNA in lung, lymph nodes and broncho-alveolar lavage cells as well as biochemical analysis of Se, GPx1 and thioredoxin reductase (TrxR) activity in lung tissue were recorded. Additionally, immunohistochemical determination of GPx1 expression in unaffected and neoplastic lung cells was implemented. The feeding regime caused significant differences in Se concentration and GPx1 activity in lung tissue between groups, whereas TrxR activity remained unaffected. JSRV was evident in broncho-alveolar lavage cells, lung tissue and lung lymph nodes. Quarterly executed CT could not demonstrate differences in lung cancer proliferation intensity. Necropsy and histopathology substantiated CT findings. Immunohistochemical analysis of GPx1 in lung tissue suggested a coherency of GPx1 immunolabelling intensity in dependence of tumour size. It was concluded that the model proved to be suitable for long-term studies of lung cancer proliferation including the impact of modifiable nutritional factors. Proliferation of OPA was unaffected by marginal vs. sufficient nutritional Se supply. Copyright © 2013 Elsevier GmbH. All rights reserved.

m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

PubMed

Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

2018-04-09

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Potential Protective Mechanism in the Cardiac Microvascular Injury.

PubMed

Li, Xiuchuan; Hou, Juanni; Du, Jin; Feng, Jian; Yang, Yi; Shen, Yang; Chen, Sha; Feng, Juan; Yang, Dachun; Li, De; Pei, Haifeng; Yang, Yongjian

2018-05-07

Cardiac microvascular injury often occurs in patients with type 2 diabetes mellitus (T2DM) who develop hyperglycemia and hyperlipidemia. However, besides reported contradictory roles in cardiac diseases, the function of TRPV1 (transient receptor potential vanilloid 1) in cardiac microvessels is not well defined. This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding. CMECs were cultured separately in mediums of normal glucose, high glucose (HG), high fatty acid (HF), and HG plus HF (HG-HF). HG-HF inhibited TRPV1 expression in CMECs, reducing cellular Ca 2+ content ([Ca 2+ ] i ). T2DM impaired cardiac function, disturbed glucose uptake, and damaged microvascular barrier, which were further aggravated by TRPV1 -/- Exposure to HG-HF, particularly in TRPV1 -/- CMECs, led to a higher level of apoptosis and a lower level of nitric oxide production in viable CMECs. HG-HF markedly enhanced generation of reactive oxygen species and nitrotyrosine, especially in the absence of TRPV1. H 2 O 2 administration reduced TRPV1 expression in CMECs. HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca 2+ ] i , whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1 -/- Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM. Collectively, T2DM leads to cardiac microvascular injury by exacerbating the vicious circle of TRPV1 blockage and reactive oxygen species overload. Long-term capsaicin can protect cardiac microvessels against T2DM via suppressing oxidative/nitrative stress mediated by TRPV1/Ca 2+ /PGC-1α/OPA1 pathway in CMECs. © 2018 American Heart Association, Inc.

PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction.

PubMed

Park, Yun Sun; Choi, Su Eun; Koh, Hyun Chul

2018-03-01

Mitochondrial dynamics and mitophagy are critical processes for regulating mitochondrial homeostasis. Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis, but the roles of PGAM5 in mitochondrial dynamics and mitophagy remain unclear. In this study, we investigated the role of PGAM5 in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced mitochondrial damage and the correlation between mitochondrial dynamics and mitophagy using SH-SY5Y cells. We found that CCCP decreased mitochondrial membrane potential, resulting in mitochondrial dysfunction. CCCP increased PGAM5, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expression of the mitochondrial fraction in a time-dependent manner. Knockdown of PGAM5 inhibited DRP1 translocation without a change in OPA1 expression in CCCP-treated cells. Furthermore, knockdown of PGAM5 and DRP1 significantly blocked the increase of PTEN-induced putative protein kinase 1 (PINK1) and Parkin expression in the mitochondrial fraction of CCCP-treated cells. Interestingly, CCCP did not alter PINK1/Parkin expression in the mitochondrial fraction of OPA1 knockdown cells. Inhibiting mitophagy by PGAM5 knockdown accelerated CCCP-induced apoptosis. CCCP treatment also results in PINK1 stabilization on the mitochondrial membrane, which subsequently increases Parkin recruitment from the cytosol to abnormal mitochondria. In addition, we found that CCCP increased the level of mitochondrial LC3II, indicating that Parkin recruitment of PINK1 is a result of mitophagy. We propose that activation of PGAM5 is associated with DRP1 recruitment and PINK1 stabilization, which contribute to the modulation of mitophagy in CCCP-treated cells with mitochondrial dysfunction. In conclusion, we demonstrated that PGAM5 regulates PINK1-Parkin-mediated mitophagy, which can exert a neuroprotective effect against CCCP-induced apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

On the Fringe Field of Wide Angle LC Optical Phased Array

NASA Technical Reports Server (NTRS)

Wang, Xighua; Wang, Bin; Bos, Philip J.; Anderson, James E.; Pouch, John; Miranda, Felix; McManamon, Paul F.

2004-01-01

For free space laser communication, light weighted large deployable optics is a critical component for the transmitter. However, such an optical element will introduce large aberrations due to the fact that the surface figure of the large optics is susceptable to deformation in the space environment. We propose to use a high-resolution liquid crystal spatial light modulator to correct for wavefront aberrations introduced by the primary optical element, and to achieve very fine beam steering and shaping at the same time. A 2-D optical phased array (OPA) antenna based on a Liquid Crystal on Silicon (LCOS) spatial light modulator is described. This device offers a combination of low cost, high resolution, high accuracy, high diffraction efficiency at video speed. To quantitatively understand the influence factor of the different design parameters, a computer simulation of the device is given by the 2-D director simulation and the Finite Difference Time domain (FDTD) simulation. For the 1-D OPA, we define the maximum steering angle to have a grating period of 8 pixel/reset scheme; as for larger steering angles than this criterion, the diffraction efficiency drops dramatically. In this case, the diffraction efficiency of 0.86 and the Strehl ratio of 0.9 are obtained in the simulation. The performance of the device in achieving high resolution wavefront correction and beam steering is also characterized experimentally.

High repetition rate tunable femtosecond pulses and broadband amplification from fiber laser pumped parametric amplifier.

PubMed

Andersen, T V; Schmidt, O; Bruchmann, C; Limpert, J; Aguergaray, C; Cormier, E; Tünnermann, A

2006-05-29

We report on the generation of high energy femtosecond pulses at 1 MHz repetition rate from a fiber laser pumped optical parametric amplifier (OPA). Nonlinear bandwidth enhancement in fibers provides the intrinsically synchronized signal for the parametric amplifier. We demonstrate large tunability extending from 700 nm to 1500 nm of femtosecond pulses with pulse energies as high as 1.2 muJ when the OPA is seeded by a supercontinuum generated in a photonic crystal fiber. Broadband amplification over more than 85 nm is achieved at a fixed wavelength. Subsequent compression in a prism sequence resulted in 46 fs pulses. With an average power of 0.5 W these pulses have a peak-power above 10 MW. In particular, the average power and pulse energy scalability of both involved concepts, the fiber laser and the parametric amplifier, will enable easy up-scaling to higher powers.

Offset-Free Gigahertz Midinfrared Frequency Comb Based on Optical Parametric Amplification in a Periodically Poled Lithium Niobate Waveguide

NASA Astrophysics Data System (ADS)

Mayer, A. S.; Phillips, C. R.; Langrock, C.; Klenner, A.; Johnson, A. R.; Luke, K.; Okawachi, Y.; Lipson, M.; Gaeta, A. L.; Fejer, M. M.; Keller, U.

2016-11-01

We report the generation of an optical-frequency comb in the midinfrared region with 1-GHz comb-line spacing and no offset with respect to absolute-zero frequency. This comb is tunable from 2.5 to 4.2 μ m and covers a critical spectral region for important environmental and industrial applications, such as molecular spectroscopy of trace gases. We obtain such a comb using a highly efficient frequency conversion of a near-infrared frequency comb. The latter is based on a compact diode-pumped semiconductor saturable absorber mirror-mode-locked ytterbium-doped calcium-aluminum gadolynate (Yb:CALGO) laser operating at 1 μ m . The frequency-conversion process is based on optical parametric amplification (OPA) in a periodically poled lithium niobate (PPLN) chip containing buried waveguides fabricated by reverse proton exchange. The laser with a repetition rate of 1 GHz is the only active element of the system. It provides the pump pulses for the OPA process as well as seed photons in the range of 1.4 - 1.8 μ m via supercontinuum generation in a silicon-nitride (Si3 N4 ) waveguide. Both the PPLN and Si3 N4 waveguides represent particularly suitable platforms for low-energy nonlinear interactions; they allow for mid-IR comb powers per comb line at the microwatt level and signal amplification levels up to 35 dB, with 2 orders of magnitude less pulse energy than reported in OPA systems using bulk devices. Based on numerical simulations, we explain how high amplification can be achieved at low energy using the interplay between mode confinement and a favorable group-velocity mismatch configuration where the mid-IR pulse moves at the same velocity as the pump.

Theoretical investigation on ratiometric two-photon fluorescent probe for Zn2+ detection based on ICT mechanism

NASA Astrophysics Data System (ADS)

Huang, Shuang; Yang, Bao-Zhu; Ren, Ai-Min

2016-06-01

OPA (one-photon absorption), TPA (two-photon absorption) and fluorescence properties of a free ligand L upon coordination with Zn2+, and the regeneration with CN- were investigated in theory. According to our research, OPA spectra of ligand L show red-shift binding with Zn2+ while blue-shift with CN-. The fluorescence spectra and TPA wavelength are shifted in the same situation as those of OPA spectra. The value of TPA cross-section decreased at first, and then increased to 1813 GM for [L-Zn(CN)4]2-. Intramolecular charge transfer (ICT) mechanism was investigated by natural bond orbital (NBO) analysis. It demonstrates that L is hopeful to be a good ratiometric fluorescent probe for zinc ion detection in solution, and it can regenerate after CN- was introduced.

Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

PubMed

Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

2010-05-21

NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

90-day Readmission After Lumbar Spinal Fusion Surgery in New York State Between 2005 and 2014: A 10-year Analysis of a Statewide Cohort.

PubMed

Baaj, Ali A; Lang, Gernot; Hsu, Wei-Chun; Avila, Mauricio J; Mao, Jialin; Sedrakyan, Art

2017-11-15

MINI: We assessed 90-day readmission and evaluated risk factors associated with readmission after lumbar spinal fusion surgery in New York State. The overall 90-day readmission rate was 24.8%. Age, sex, race, insurance, procedure, number of operated spinal levels, health service area, and comorbidities are major risk factors for 90-day readmission. Retrospective cohort study. The aim of this study was to assess 90-day readmission and evaluate risk factors associated with readmission after lumbar fusion in New York State. Readmission is becoming an important metric for quality and efficiency of health care. Readmission and its predictors following spine surgery are overall poorly understood and limited evidence is available specifically in lumbar fusion. The New York Statewide Planning and Research Cooperative System (SPARCS) was utilized to capture patients undergoing lumbar fusion from 2005 to 2014. Temporal trend of 90-day readmission was assessed using Cochran-Armitage test. Logistic regression was used to examine predictors associated with 90-day readmission. There were 86,869 patients included in this cohort study. The overall 90-day readmission rate was 24.8%. On a multivariable analysis model, age (odds ratio [OR] comparing ≥75 versus <35 years: 1.24, 95% confidence interval [CI]: 1.13-1.35), sex (OR female to male: 1.19, 95% CI: 1.15-1.23), race (OR African-American to white: 1.60, 95% CI: 1.52-1.69), insurance (OR Medicaid to Medicare: 1.42, 95% CI: 1.33-1.53), procedure (OR comparing thoracolumbar fusion, combined [International Classification of Disease, Ninth Revision, ICD-9: 81.04] to posterior lumbar interbody fusion/transforaminal lumbar spinal fusion [ICD-9: 81.08]: 2.10, 95% CI: 1.49-2.97), number of operated spinal levels (OR comparing four to eight vertebrae to two to three vertebrae: 2.39, 95% CI: 2.07-2.77), health service area ([HSA]; OR comparing Finger Lakes to New York-Pennsylvania border: 0.67, 95% CI: 0.61-0.73), and comorbidity, i.e., coronary artery disease (OR: 1.26, 95% CI: 1.19-1.33) were significantly associated with 90-day readmission. Directions of the odds ratios for these factors were consistent after stratification by procedure type. Age, sex, race, insurance, procedure, number of operated spinal levels, HSA, and comorbidities are major risk factors for 90-day readmission. Our study allows risk calculation to determine high-risk patients before undergoing spinal fusion surgery to prevent early readmission, improve quality of care, and reduce health care expenditures. 3.

Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

PubMed

Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2015-05-01

Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

Binaural pitch fusion: Comparison of normal-hearing and hearing-impaired listenersa)

PubMed Central

Reiss, Lina A. J.; Shayman, Corey S.; Walker, Emily P.; Bennett, Keri O.; Fowler, Jennifer R.; Hartling, Curtis L.; Glickman, Bess; Lasarev, Michael R.; Oh, Yonghee

2017-01-01

Binaural pitch fusion is the fusion of dichotically presented tones that evoke different pitches between the ears. In normal-hearing (NH) listeners, the frequency range over which binaural pitch fusion occurs is usually <0.2 octaves. Recently, broad fusion ranges of 1–4 octaves were demonstrated in bimodal cochlear implant users. In the current study, it was hypothesized that hearing aid (HA) users would also exhibit broad fusion. Fusion ranges were measured in both NH and hearing-impaired (HI) listeners with hearing losses ranging from mild-moderate to severe-profound, and relationships of fusion range with demographic factors and with diplacusis were examined. Fusion ranges of NH and HI listeners averaged 0.17 ± 0.13 octaves and 1.7 ± 1.5 octaves, respectively. In HI listeners, fusion ranges were positively correlated with a principal component measure of the covarying factors of young age, early age of hearing loss onset, and long durations of hearing loss and HA use, but not with hearing threshold, amplification level, or diplacusis. In NH listeners, no correlations were observed with age, hearing threshold, or diplacusis. The association of broad fusion with early onset, long duration of hearing loss suggests a possible role of long-term experience with hearing loss and amplification in the development of broad fusion. PMID:28372056

Phonon-assisted nonlinear optical processes in ultrashort-pulse pumped optical parametric amplifiers

DOE PAGES

Isaienko, Oleksandr; Robel, Istvan

2016-03-15

Optically active phonon modes in ferroelectrics such as potassium titanyl phosphate (KTP) and potassium titanyl arsenate (KTA) in the ~7–20 THz range play an important role in applications of these materials in Raman lasing and terahertz wave generation. Previous studies with picosecond pulse excitation demonstrated that the interaction of pump pulses with phonons can lead to efficient stimulated Raman scattering (SRS) accompanying optical parametric oscillation or amplification processes (OPO/OPA), and to efficient polariton-phonon scattering. In this work, we investigate the behavior of infrared OPAs employing KTP or KTA crystals when pumped with ~800-nm ultrashort pulses of duration comparable to themore » oscillation period of the optical phonons. We demonstrate that under conditions of coherent impulsive Raman excitation of the phonons, when the effective χ (2) nonlinearity cannot be considered instantaneous, the parametrically amplified waves (most notably, signal) undergo significant spectral modulations leading to an overall redshift of the OPA output. Furthermore, the pump intensity dependence of the redshifted OPA output, the temporal evolution of the parametric gain, as well as the pump spectral modulations suggest the presence of coupling between the nonlinear optical polarizations P NL of the impulsively excited phonons and those of parametrically amplified waves.« less

Time trends in physical activity from 1982 to 2012 in Finland.

PubMed

Borodulin, K; Harald, K; Jousilahti, P; Laatikainen, T; Männistö, S; Vartiainen, E

2016-01-01

The aim of this study was to examine population trends from 1982 to 2012 in Finland for leisure time physical activity (LTPA), commuting physical activity (CPA), occupational physical activity (OPA), and total physical activity. Furthermore, time trends in physical activity by educational levels and body mass index (BMI) categories were explored. Data were collected in independent cross-sectional population surveys, implemented every 5 years from 1982 to 2012. The data comprised 21,903 men and 24,311 women. Participants underwent a health examination and filled in questionnaires. Information on LTPA, CPA, and OPA was used both separately and combined to create an index of total physical activity. Between 1982 and 2012, high LTPA has increased in men (from 21% to 33%) and women (from 12% to 27%). High CPA and high OPA have decreased in men (from 17% to 12% and from 48% to 36%, respectively) and women (from 30% to 20% and from 26% to 21%, respectively). Total physical activity has remained fairly stable. Differences by education and BMI have increased, particularly for LTPA. Marked changes in physical activity have taken place over time. Differences in LTPA and OPA have grown wider across educational groups and BMI categories. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-energy infrared femtosecond pulses generated by dual-chirped optical parametric amplification.

PubMed

Fu, Yuxi; Takahashi, Eiji J; Midorikawa, Katsumi

2015-11-01

We demonstrate high-energy infrared femtosecond pulse generation by a dual-chirped optical parametric amplification (DC-OPA) scheme [Opt. Express19, 7190 (2011)]. By employing a 100 mJ pump laser, a signal pulse energy exceeding 20 mJ at a wavelength of 1.4 μm was achieved before dispersion compensation. A total output energy of 33 mJ was recorded. Under a further energy scaling condition, the signal pulse was compressed to an almost transform-limited duration of 27 fs using a fused silica prism compressor. Since the DC-OPA scheme is efficient and energy scalable, design parameters for obtaining 100 mJ level infrared pulses are presented, which are suitable as driver lasers for the energy scaling of high-order harmonic generation with sub-keV photon energy.

Optical phased array configuration for an extremely large telescope.

PubMed

Meinel, Aden Baker; Meinel, Marjorie Pettit

2004-01-20

Extremely large telescopes are currently under consideration by several groups in several countries. Extrapolation of current technology up to 30 m indicates a cost of over dollars 1 billion. Innovative concepts are being explored to find significant cost reductions. We explore the concept of an Optical Phased Array (OPA) telescope. Each element of the OPA is a separate Cassegrain telescope. Collimated beams from the array are sent via an associated set of delay lines to a central beam combiner. This array of small telescope elements offers the possibility of starting with a low-cost array of a few rings of elements, adding structure and additional Cass elements until the desired diameter telescope is attained. We address the salient features of such an extremely large telescope and cost elements relative to more conventional options.

Does Aerobic Exercise Increase 24-Hour Ambulatory Blood Pressure Among Workers With High Occupational Physical Activity?-A RCT.

PubMed

Korshøj, Mette; Krause, Niklas; Clays, Els; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas

2017-04-01

High occupational physical activity (OPA) increases cardiovascular risk and aerobic exercise has been recommended for reducing this risk. This paper investigates the effects of an aerobic exercise intervention on 24-hour ambulatory blood pressure (ABP) among cleaners with high OPA. Hundred and sixteen cleaners between 18 and 65 years were randomized. During the 4-month intervention period, the aerobic exercise group (AE) (n = 57) performed worksite aerobic exercise (2 × 30 minutes/week), while the reference group (REF) (n = 59) attended lectures. Between-group differences in 4-month ABP changes were evaluated by intention-to-treat analysis using a repeated-measure 2 × 2 multiadjusted mixed-models design. Relative to REF, 24-hour ABP significantly increased in AE: systolic 3.6 mm Hg (95% confidence interval (CI) 1.6-5.7) and diastolic 2.3 mm Hg (95% CI 0.9-3.8). Cleaners with high aerobic workload exhibited particularly high 24-hour ABP increases: systolic 6.0 mm Hg (95% CI 2.4-9.6), and diastolic 3.8 mm Hg (95% CI 1.3-6.4). Aerobic exercise increased 24-hour ABP among cleaners. This adverse effect raises questions about the safety and intended benefits of aerobic exercise, especially among workers with high OPA and a demanding aerobic workload. http://www.controlled-trials.com/ISRCTN86682076. Unique identifier ISRCTN86682076. Trial Number ISRCTN86682076. © The Author 2017. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.

The dissimilar effect of diacylglycerols on Ca(2+)-induced phosphatidylserine vesicle fusion.

PubMed Central

Sánchez-Migallón, M P; Aranda, F J; Gómez-Fernández, J C

1995-01-01

We have studied the effect of physiological concentrations of different diacylglycerols on Ca(2+)-induced fusion between phosphatidylserine vesicles. We monitored vesicle fusion as mixing of membrane lipids under conditions where the limiting factor was the aggregation and also in conditions where this aggregation was not the limiting factor. We found that diacylglycerols have a different modulating effect on the Ca(2+)-induced fusion: i) depending on their interfacial conformation, so that 1,2-isomers of diacylglycerols containing unsaturated or short saturated acyl chains stimulated fusion and their 1,3-isomers did not, and ii) depending on their specific type of bilayer interior perturbation, so that diacylglycerols containing unsaturated or short chain saturated acyl chains stimulated fusion but those containing long-chain saturated acyl chains did not. These requirements resembled those required for the diacylglycerol activation of protein kinase C, suggesting that diacylglycerol acts in both the specific activation of this enzyme and the induction of membrane fusion through the same perturbation of lipid structure. We found that polylysine affected the stimulatory role of 1,2-dioleoylglycerol differently, depending on whether aggregation was the limiting factor of fusion. When we studied the effect of very low concentrations of diacylglycerols on the bulk structural properties of phosphatidylserine, we found that they neither significantly perturbed the thermotropic transitions of phosphatidylserine nor affected the interaction of Ca2+ with the phosphate group of phosphatidylserine. The underlying mechanism of fusion between phosphatidylserine vesicles is discussed. PMID:7696508

Analysis of Snail1 function and regulation by Twist1 in palatal fusion.

PubMed

Yu, Wenli; Zhang, Yanping; Ruest, L Bruno; Svoboda, Kathy K H

2013-01-01

Palatal fusion is a tightly controlled process which comprises multiple cellular events, including cell movement and differentiation. Midline epithelial seam (MES) degradation is essential to palatal fusion. In this study, we analyzed the function of Snail1 during the degradation of the MES. We also analyzed the mechanism regulating the expression of the Snail1 gene in palatal shelves. Palatal explants treated with Snail1 siRNA did not degrade the MES and E-cadherin was not repressed leading to failure of palatal fusion. Transforming growth factor beta 3 (Tgfβ3) regulated Snail1 mRNA, as Snail1 expression decreased in response to Tgfβ3 neutralizing antibody and a PI-3 kinase (PI3K) inhibitor. Twist1, in collaboration with E2A factors, regulated the expression of Snail1. Twist1/E47 dimers bond to the Snail1 promoter to activate expression. Without E47, Twist1 repressed Snail1 expression. These results support the hypothesis that Tgfβ3 may signal through Twist1 and then Snail1 to downregulate E-cadherin expression during palatal fusion.

30 CFR 253.1 - What is the purpose of this part?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What is the purpose of this part? 253.1 Section 253.1 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL... the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

30 CFR 553.1 - What is the purpose of this part?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

30 CFR 553.1 - What is the purpose of this part?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

30 CFR 553.1 - What is the purpose of this part?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 553.1 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL SPILL FINANCIAL RESPONSIBILITY FOR OFFSHORE FACILITIES General § 553.1 What is the purpose of this part...) under Title I of the Oil Pollution Act of 1990 (OPA), as amended, 33 U.S.C. 2701 et seq. ...

2017 Workplace and Gender Relations Survey of Reserve Component Members: Tabulations of Responses

DTIC Science & Technology

2018-04-30

2017 Workplace and Gender Relations Survey of Reserve Component Members Tabulations of Responses Additional copies of this report may be...http://www.dtic.mil/dtic/order.html Ask for report by DTIC# OPA Report No. 2018-012 April 2018 2017 Workplace and Gender Relations Survey of...Alexandria, VA 22350-4000 2017 Workplace and Gender Relations Survey of Reserve Component Members ii OPA Acknowledgments The Office of People Analytics

Entanglement-seeded, dual, optical parametric amplification: Applications to quantum imaging and metrology

NASA Astrophysics Data System (ADS)

Glasser, Ryan T.; Cable, Hugo; Dowling, Jonathan P.; de Martini, Francesco; Sciarrino, Fabio; Vitelli, Chiara

2008-07-01

The study of optical parametric amplifiers (OPAs) has been successful in describing and creating nonclassical light for use in fields such as quantum metrology and quantum lithography [Agarwal , J. Opt. Soc. Am. B 24, 2 (2007)]. In this paper we present the theory of an OPA scheme utilizing an entangled state input. The scheme involves two identical OPAs seeded with the maximally path-entangled ∣N00N⟩ state (∣2,0⟩+∣0,2⟩)/2 . The stimulated amplification results in output state probability amplitudes that have a dependence on the number of photons in each mode, which differs greatly from two-mode squeezed vacuum. A large family of entangled output states are found. Specific output states allow for the heralded creation of N=4 N00N states, which may be used for quantum lithography, to write sub-Rayleigh fringe patterns, and for quantum interferometry, to achieve Heisenberg-limited phase measurement sensitivity.

Thermal effects in high average power optical parametric amplifiers.

PubMed

Rothhardt, Jan; Demmler, Stefan; Hädrich, Steffen; Peschel, Thomas; Limpert, Jens; Tünnermann, Andreas

2013-03-01

Optical parametric amplifiers (OPAs) have the reputation of being average power scalable due to the instantaneous nature of the parametric process (zero quantum defect). This Letter reveals serious challenges originating from thermal load in the nonlinear crystal caused by absorption. We investigate these thermal effects in high average power OPAs based on beta barium borate. Absorption of both pump and idler waves is identified to contribute significantly to heating of the nonlinear crystal. A temperature increase of up to 148 K with respect to the environment is observed and mechanical tensile stress up to 40 MPa is found, indicating a high risk of crystal fracture under such conditions. By restricting the idler to a wavelength range far from absorption bands and removing the crystal coating we reduce the peak temperature and the resulting temperature gradient significantly. Guidelines for further power scaling of OPAs and other nonlinear devices are given.

On the frictional (in) stability of clay-bearing faults

NASA Astrophysics Data System (ADS)

Violay, M.; Orellana, F.; Scuderi, M. M.; Collettini, C.

2016-12-01

Opalinus clay (OPA) is shale rock studied under the context of deep geological disposal by The Mont Terri Laboratory research program in Switzerland. Despite its favorable hydro-mechanical properties, the presence of a large tectonic fault system intersecting the rock formation arises questions over the long-term safety performance of a nuclear waste repository, in terms of possible leakages and the possibility of earthquakes triggered by fault instability. To study the frictional stability of OPA, we have performed velocity steps (1-300 μm/s) and slide-hold-slide tests (1-10000 s) on simulated gouge and intact samples - sheared parallel and perpendicular to foliation - at different normal stresses (4 - 30 MPa). To understand the deformation mechanisms, we have analyzed the microstructures of the sheared samples trough optical and SE microscopy. Results reported peak and steady state friction values ranging from 0.21 to 0.52 and from 0.14 to 0.39 respectively. Consistently, samples with well-developed layering showed lower friction values than gouge samples even though they have the same mineralogical composition. At all normal stresses, velocity dependence tests on gouge showed a velocity strengthening regime, whereas, intact samples developed both velocity-strengthening and velocity-weakening regimes. Finally, we have recorded near zero healing values for both intact and powdered samples at different normal stress. However, a complex evolution from negative to positive frictional healing rate, with an inflexion holding time of 300 s, has been observed. In conclusion, our data suggests that both the velocity strengthening regime and the near zero healing for the simulated gouge, are consistent with aseismic creep. We have also reported the possibility of unstable sliding outside the fault core accompanied by low capacity of contact regeneration, and low capacity to sustain future stress drops compared to evidence showed by experiments on simulated gouge. Moreover, microstructure analysis revealed different deformation patterns due to anisotropy of the material. Thus, the complex frictional behavior of OPA highlights the need for further experiments in order to better evaluate the seismic risk during long-term nuclear waste disposal within the OPA clay formation.

PAX3-FOXO1: Zooming in on an "undruggable" target.

PubMed

Wachtel, Marco; Schäfer, Beat W

2018-06-01

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

PubMed

Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

2013-12-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae

PubMed Central

Lee, Miriam; Ko, Young-Joon; Moon, Yeojin; Han, Minsoo; Kim, Hyung-Wook; Lee, Sung Haeng; Kang, KyeongJin

2015-01-01

Dynamin-like GTPases of the atlastin family are thought to mediate homotypic endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism remains largely unclear. Here, we developed a simple and quantitative in vitro assay using isolated yeast microsomes for measuring yeast atlastin Sey1p-dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE-mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p, another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on isolated microsomes, together with the lack of fusion between Sey1p proteoliposomes even with a 25-fold excess of the physiological concentration of Sey1p, suggests that Sey1p requires additional factors to support ER fusion in vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion is involved in atlastin-initiated homotypic ER fusion. PMID:26216899

Ground and Airborne Methane Measurements with an Optical Parametric Amplifier

NASA Technical Reports Server (NTRS)

Numata, Kenji

2012-01-01

We report on ground and airborne atmospheric methane measurements with a differential absorption lidar using an optical parametric amplifier (OPA). Methane is a strong greenhouse gas on Earth and its accurate global mapping is urgently needed to understand climate change. We are developing a nanosecond-pulsed OPA for remote measurements of methane from an Earth-orbiting satellite. We have successfully demonstrated the detection of methane on the ground and from an airplane at approximately 11-km altitude.

Competing collinear and noncollinear interactions in chirped quasi-phase-matched optical parametric amplifiers

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

Charbonneau-Lefort, Mathieu; Afeyan, Bedros; Fejer, M. M.

Chirped quasi-phase-matched optical parametric amplifiers (chirped QPM OPAs) are investigated experimentally. The measured collinear gain is constant over a broad bandwidth, which makes these devices attractive candidates for use in femtosecond amplifier systems. The experiment also shows that chirped QPM OPAs support noncollinear gain-guided modes. These modes can dominate the desired collinear gain and generate intense parametric fluorescence. Finally, design guidelines to mitigate these parasitic processes are discussed.

Transporting US oil imports: The impact of oil spill legislation on the tanker market. Draft final report

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

Rowland, P.J.

1992-05-01

The Oil Pollution Act of 1990 (``OPA``) and an even more problematic array of State pollution laws have raised the cost, and risk, of carrying oil into and out of the US. This report, prepared under contract to the US Department of energy`s Office of Domestic and International Policy, examines the impact of Federal and State oil spill legislation on the tanker market. It reviews the role of marine transportation in US oil supply, explores the OPA and State oil spill laws, studies reactions to OPA in the tanker and tank barge industries and in related industries such as insurancemore » and ship finance, and finally, discusses the likely developments in the years ahead. US waterborne oil imports amounted to 6.5 million B/D in 1991, three-quarters of which was crude oil. Imports will rise by almost 3 million B/D by 2000 according to US Department of energy forecasts, with most of the crude oil growth after 1995. Tanker demand will grow even faster: most of the US imports and the increased traffic to other world consuming regions will be on long-haul trades. Both the number of US port calls by tankers and the volume of offshore lightering will grow. Every aspect of the tanker industry`s behavior is affected by OPA and a variety of State pollution laws.« less

Transporting US oil imports: The impact of oil spill legislation on the tanker market

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

Rowland, P.J.

1992-05-01

The Oil Pollution Act of 1990 ( OPA'') and an even more problematic array of State pollution laws have raised the cost, and risk, of carrying oil into and out of the US. This report, prepared under contract to the US Department of energy's Office of Domestic and International Policy, examines the impact of Federal and State oil spill legislation on the tanker market. It reviews the role of marine transportation in US oil supply, explores the OPA and State oil spill laws, studies reactions to OPA in the tanker and tank barge industries and in related industries such asmore » insurance and ship finance, and finally, discusses the likely developments in the years ahead. US waterborne oil imports amounted to 6.5 million B/D in 1991, three-quarters of which was crude oil. Imports will rise by almost 3 million B/D by 2000 according to US Department of energy forecasts, with most of the crude oil growth after 1995. Tanker demand will grow even faster: most of the US imports and the increased traffic to other world consuming regions will be on long-haul trades. Both the number of US port calls by tankers and the volume of offshore lightering will grow. Every aspect of the tanker industry's behavior is affected by OPA and a variety of State pollution laws.« less

Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae.

PubMed

Walsh, S E; Maillard, J Y; Russell, A D; Hann, A C

2001-07-01

This investigation compared glutaraldehyde (GTA)-sensitive and -resistant strains of Mycobacterium chelonae and examined the effects of pretreatment of GTA-sensitive and -resistant strains of Myco. chelonae with chemical agents that interfere with cell wall synthesis. When exposed to 2% (v/v) GTA at 25 degrees C, GTA-resistant strains of Myco. chelonae dried on to glass carriers were not inactivated to any significant extent. By contrast, GTA-sensitive strains of Myco. chelonae and a strain of Myco. terrae suffered a > 6 log reduction in viability in 5 min. However, ortho-phthalaldehyde (OPA; 0.5% w/v) achieved a corresponding inactivation against two GTA-resistant strains within 5-10 and 10-20 min, respectively. Electron microscopy, using a non-aldehyde fixation process and also negative staining, failed to detect any extensive changes in GTA-sensitive and -resistant cultures exposed to GTA or OPA. Thin-layer chromatography was unsuccessful in detecting differences between GTA-resistant and -sensitive strains of Myco. chelonae. However, pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility further to OPA but not to GTA. Ortho-phthalaldehyde is an effective new biocidal agent that, at its in-use concentration, is rapidly bactericidal to non-sporulating bacteria, including GTA-sensitive and -resistant mycobacteria. Pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility to OPA but not to GTA.

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

PubMed

Tsurudome, M; Ito, Y

2000-01-01

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

Femtosecond optical parametric amplification in BBO and KTA driven by a Ti:sapphire laser for LIDT testing and diagnostic development

NASA Astrophysics Data System (ADS)

Meadows, Alexander R.; Cupal, Josef; Hříbek, Petr; Durák, Michal; Kramer, Daniel; Rus, Bedřich

2017-05-01

We present the design of a collinear femtosecond optical parametric amplification (OPA) system producing a tunable output at wavelengths between 1030 nm and 1080 nm from a Ti:Sapphire pump laser at a wavelength of 795 nm. Generation of a supercontinuum seed pulse is followed by one stage of amplification in Beta Barium Borate (BBO) and two stages of amplification in Potassium Titanyle Arsenate (KTA), resulting in a 225 μJ output pulse with a duration of 90 fs. The output of the system has been measured by self-referenced spectral interferometry to yield the complete spectrum and spectral phase of the pulse. When compared to KTP, the greater transparency of KTA in the spectral range from 3 - 4 μm allows for reduced idler absorption and enhanced gain from the OPA process when it is pumped by the fundamental frequency of a Ti:sapphire laser. In turn, the use of the Ti:sapphire fundamental at 795 nm as a pump improves the efficiency with which light can be converted to wavelengths between 1030 nm and 1080 nm and subsequently used to test components for Nd-based laser systems. This OPA system is operated at 1 kHz for diagnostic development and laser-induced damage threshold testing of optical components for the ELI-Beamlines project.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating

PubMed Central

Rogers, Jason V.; Arlow, Tim; Inkellis, Elizabeth R.; Koo, Timothy S.; Rose, Mark D.

2013-01-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide–sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway. PMID:24152736

Design of Recombinant Stem Cell Factor macrophage Colony Stimulating Factor Fusion Proteins and their Biological Activity In Vitro

NASA Astrophysics Data System (ADS)

Chen, Tao; Yang, Jie; Wang, Yuelang; Zhan, Chenyang; Zang, Yuhui; Qin, Junchuan

2005-05-01

Stem cell factor (SCF) and macrophage colony stimulating factor (M-CSF) can act in synergistic way to promote the growth of mononuclear phagocytes. SCF-M-CSF fusion proteins were designed on the computer using the Homology and Biopolymer modules of the software packages InsightII. Several existing crystal structures were used as templates to generate models of the complexes of receptor with fusion protein. The structure rationality of the fusion protein incorporated a series of flexible linker peptide was analyzed on InsightII system. Then, a suitable peptide GGGGSGGGGSGG was chosen for the fusion protein. Two recombinant SCF-M-CSF fusion proteins were generated by construction of a plasmid in which the coding regions of human SCF (1-165aa) and M-CSF (1-149aa) cDNA were connected by this linker peptide coding sequence followed by subsequent expression in insect cell. The results of Western blot and activity analysis showed that these two recombinant fusion proteins existed as a dimer with a molecular weight of 84 KD under non-reducing conditions and a monomer of 42 KD at reducing condition. The results of cell proliferation assays showed that each fusion protein induced a dose-dependent proliferative response. At equimolar concentration, SCF/M-CSF was about 20 times more potent than the standard monomeric SCF in stimulating TF-1 cell line growth, while M-CSF/SCF was 10 times of monomeric SCF. No activity difference of M-CSF/SCF or SCF/M-CSF to M-CSF (at same molar) was found in stimulating the HL-60 cell linear growth. The synergistic effect of SCF and M-CSF moieties in the fusion proteins was demonstrated by the result of clonogenic assay performed with human bone mononuclear, in which both SCF/M-CSF and M-CSF/SCF induced much higher number of CFU-M than equimolar amount of SCF or M-CSF or that of two cytokines mixture.

Domain retention in transcription factor fusion genes and its biological and clinical implications: a pan-cancer study

PubMed Central

Kim, Pora; Ballester, Leomar Y.; Zhao, Zhongming

2017-01-01

Genomic rearrangements involving transcription factors (TFs) can form fusion proteins resulting in either enhanced, weakened, or even loss of TF activity. Functional domain (FD) retention is a critical factor in the activity of transcription factor fusion genes (TFFGs). A systematic investigation of FD retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer study has not yet been completed. Here, we examined the FD retention status in 386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs that retained FDs. To measure the potential biological relevance of TFs in TFFGs, we introduced a Major Active Isofusion Index (MAII) and built a prioritized TFFG network using MAII scores and the observed frequency of fusion positive samples. Interestingly, the four TFFGs (PML-RARA, RUNX1-RUNX1T1, TMPRSS2-ERG, and SFPQ-TFE3) with the highest MAII scores showed 50 differentially expressed target genes (DETGs) in fusion-positive versus fusion-negative cancer samples. DETG analysis revealed that they were involved in tumorigenesis-related processes in each cancer type. PLAU, which encodes plasminogen activator urokinase and serves as a biomarker for tumor invasion, was found to be consistently activated in the samples with the highest MAII scores. Among the 50 DETGs, 21 were drug targetable genes. Fourteen of these 21 DETGs were expressed in acute myeloid leukemia (AML) samples. Accordingly, we constructed an AML-specific TFFG network, which included 38 DETGs in RUNX1-RUNX1T1 or PML-RARA positive samples. In summary, this study revealed several TFFGs and their potential target genes, and provided insights into the clinical implications of TFFGs. PMID:29299133

Augmentation of antitumor immunity by fusions of ethanol-treated tumor cells and dendritic cells stimulated via dual TLRs through TGF-β1 blockade and IL-12p70 production.

PubMed

Koido, Shigeo; Homma, Sadamu; Okamoto, Masato; Namiki, Yoshihisa; Takakura, Kazuki; Takahara, Akitaka; Odahara, Shunichi; Tsukinaga, Shintaro; Yukawa, Toyokazu; Mitobe, Jimi; Matsudaira, Hiroshi; Nagatsuma, Keisuke; Kajihara, Mikio; Uchiyama, Kan; Arihiro, Seiji; Imazu, Hiroo; Arakawa, Hiroshi; Kan, Shin; Hayashi, Kazumi; Komita, Hideo; Kamata, Yuko; Ito, Masaki; Hara, Eiichi; Ohkusa, Toshifumi; Gong, Jianlin; Tajiri, Hisao

2013-01-01

The therapeutic efficacy of fusion cell (FC)-based cancer vaccine generated with whole tumor cells and dendritic cells (DCs) requires the improved immunogenicity of both cells. Treatment of whole tumor cells with ethanol resulted in blockade of immune-suppressive soluble factors such as transforming growth factor (TGF)-β1, vascular endothelial growth factor, and IL-10 without decreased expression of major histocompatibility complex (MHC) class I and the MUC1 tumor-associated antigen. Moreover, the ethanol-treated tumor cells expressed "eat-me" signals such as calreticulin (CRT) on the cell surface and released immunostimulatory factors such as heat shock protein (HSP)90α and high-mobility group box 1 (HMGB1). A dual stimulation of protein-bound polysaccharides isolated from Coriolus versicolor (TLR2 agonist) and penicillin-inactivated Streptococcus pyogenes (TLR4 agonist) led human monocyte-derived DCs to produce HSP90α and multiple cytokines such as IL-12p70 and IL-10. Interestingly, incorporating ethanol-treated tumor cells and TLRs-stimulated DCs during the fusion process promoted fusion efficiency and up-regulated MHC class II molecules on a per fusion basis. Moreover, fusions of ethanol-treated tumor cells and dual TLRs-stimulated DCs (E-tumor/FCs) inhibited the production of multiple immune-suppressive soluble factors including TGF-β1 and up-regulated the production of IL-12p70 and HSP90α. Most importantly, E-tumor/FCs activated T cells capable of producing high levels of IFN-γ, resulting in augmented MUC1-specific CTL induction. Collectively, our results illustrate the synergy between ethanol-treated whole tumor cells and dual TLRs-stimulated DCs in inducing augmented CTL responses in vitro by FC preparations. The alternative system is simple and may provide a platform for adoptive immunotherapy.

Ultrafast polarisation spectroscopy of photoinduced charges in a conjugated polymer

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

Bakulin, A A; Loosdrecht, P van; Pshenichnikov, M S

2009-07-31

Tunable optical parametric generators and amplifiers (OPA), proposed and developed by Akhmanov and his colleagues, have become the working horses in exploration of dynamical processes in physics, chemistry, and biology. In this paper, we demonstrate the possibility of using ultrafast polarisation-sensitive two-colour spectroscopy, performed with a set of two OPAs, to study charge photogeneration and transport in conjugated polymers and their donor-acceptor blends. (special issue devoted to the 80th birthday of S.A. Akhmanov)

Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

PubMed

da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

2014-02-01

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions.

PubMed

Dalin, Martin G; Katabi, Nora; Persson, Marta; Lee, Ken-Wing; Makarov, Vladimir; Desrichard, Alexis; Walsh, Logan A; West, Lyndsay; Nadeem, Zaineb; Ramaswami, Deepa; Havel, Jonathan J; Kuo, Fengshen; Chadalavada, Kalyani; Nanjangud, Gouri J; Ganly, Ian; Riaz, Nadeem; Ho, Alan L; Antonescu, Cristina R; Ghossein, Ronald; Stenman, Göran; Chan, Timothy A; Morris, Luc G T

2017-10-30

Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.

The effects of local insulin application to lumbar spinal fusions in a rat model.

PubMed

Koerner, John D; Yalamanchili, Praveen; Munoz, William; Uko, Linda; Chaudhary, Saad B; Lin, Sheldon S; Vives, Michael J

2013-01-01

The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a time-released insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry. A time-released insulin implant may have similar effects when applied in a lumbar spinal fusion model. This study analyzes the effects of a local time-released insulin implant applied to the fusion bed in a rat posterolateral lumbar spinal fusion model. Our hypothesis was twofold: first, a time-released insulin implant applied to the autograft bed in a rat posterolateral lumbar fusion will increase the rate of successful fusion and second, will alter the local environment of the fusion site by increasing the levels of local growth factors. Animal model (Institutional Animal Care and Use Committee approved) using 40 adult male Sprague-Dawley rats. Forty skeletally mature Sprague-Dawley rats weighing approximately 500 g each underwent posterolateral intertransverse lumbar fusions with iliac crest autograft from L4 to L5 using a Wiltse-type approach. After exposure of the transverse processes and high-speed burr decortication, a Linplant (Linshin Canada, Inc., ON, Canada) consisting of 95% microrecrystalized palmitic acid and 5% bovine insulin (experimental group) or a sham implant consisting of only palmitic acid (control group) was implanted on the fusion bed with iliac crest autograft. As per the manufacturer, the Linplant has a release rate of 2 U/day for a minimum of 40 days. The transverse processes and autograft beds of 10 animals from the experimental and 10 from the control group were harvested at Day 4 and analyzed for growth factors. The remaining 20 spines were harvested at 8 weeks and underwent a radiographic examination, manual palpation, and microcomputed tomographic (micro-CT) examination. One of the 8-week control animals died on postoperative Day 1, likely due to anesthesia. In the groups sacrificed at Day 4, there was a significant increase in insulinlike growth factor-I (IGF-I) in the insulin treatment group compared with the controls (0.185 vs. 0.129; p=.001). No significant differences were demonstrated in the levels of transforming growth factor beta-1, platelet-derived growth factor-AB, and vascular endothelial growth factor between the groups (p=.461, .452, and .767 respectively). Based on the radiographs, 1 of 9 controls had a solid bilateral fusion mass, 2 of 9 had unilateral fusion mass, 3 of 9 had small fusion mass bilaterally, and 3 of 9 had graft resorption. The treatment group had solid bilateral fusion mass in 6 of 10 and unilateral fusion mass in 4 of 10, whereas a small bilateral fusion mass and graft resorption were not observed. The difference between the groups was significant (p=.0067). Based on manual palpation, only 1 of 9 controls was considered fused, 4 of 9 were partially fused, and 4 of 9 were not fused. In the treatment group, there were 6 of 10 fusions, 3 of 10 partial fusions, and 1 of 10 were not fused. The difference between the groups was significant (p=.0084). Based on the micro-CT, the mean bone volume of the control group was 126.7 mm(3) and 203.8 mm(3) in the insulin treatment group. The difference between the groups was significant (p=.0007). This study demonstrates the potential role of a time-released insulin implant as a bone graft enhancer using a rat posterolateral intertransverse lumbar fusion model. The insulin-treatment group had significantly higher fusion rates based on the radiographs and manual palpation and had significantly higher levels of IGF-I and significantly more bone volume on micro-CT. Copyright © 2013 Elsevier Inc. All rights reserved.

A fast and simple spectrofluorometric method for the determination of alendronate sodium in pharmaceuticals

PubMed Central

Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; de la Guardia, Miguel; Valizadeh, Hadi

2014-01-01

Introduction: Alendronate sodium enhances bone formation and increases osteoblast proliferation and maturation and leads to the inhibition of osteoblast apoptosis. Therefore, a rapid and simple spectrofluorometric method has been developed and validated for the quantitative determination of it. Methods: The procedure is based on the reaction of primary amino group of alendronate with o-phthalaldehyde (OPA) in sodium hydroxide solution. Results: The calibration graph was linear over the concentration range of 0.0-2.4 μM and limit of detection and limit of quantification of the method was 8.89 and 29 nanomolar, respectively. The enthalpy and entropy of the reaction between alendronate sodium and OPA showed that the reaction is endothermic and entropy favored (ΔH = 154.08 kJ/mol; ΔS = 567.36 J/mol K) which indicates that OPA interaction with alendronate is increased at elevated temperature. Conclusion: This simple method can be used as a practical technique for the analysis of alendronate in various samples. PMID:24790897

Bactericidal activity of glutaraldehyde-like compounds from olive products.

PubMed

Medina, Eduardo; Brenes, Manuel; García, Aranzazu; Romero, Concepción; de Castro, Antonio

2009-12-01

The bactericidal effects of several olive compounds (nonenal, oleuropein, tyrosol, the dialdehydic form of decarboxymethyl elenolic acid either free [EDA] or linked to tyrosol [TyEDA] or to hydroxytyrosol [HyEDA]), other food phenolic compounds (catechin, epicatechin, eugenol, thymol, carvacrol, and carnosic acid), and commercial disinfectants (glutaraldehyde [GTA] and ortho-phthalaldehyde [OPA]), were tested against strains of Pseudomonas fluorescens, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. It was found that the bactericidal activities of olive GTA-like compounds (EDA, HyEDA, and TyEDA) were greater than those exerted by several food phenolic substances. Surprisingly, these olive antimicrobials were as active as the synthetic biocides GTA and OPA against the four bacteria studied. Thus, it has been proposed that the bactericidal activity of the main olive antimicrobials is primarily due to their dialdehydic structure, which is similar to that of the commercial biocides GTA and OPA. Our results clearly reveal that olive GTA-like compounds possess a strong bactericidal activity even greater than that of other food phenolic compounds or synthetic biocides.

BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers

PubMed Central

Delevoye, Cédric; Romao, Maryse; Owen, David J.; Raposo, Graça

2016-01-01

Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of fusion factors to their sites of origin. Melanosomes and other lysosome-related organelles obtain cargoes from early endosomes, but the fusion machinery involved and its recycling pathway are unknown. Here, we show that the v-SNARE VAMP7 mediates fusion of melanosomes with tubular transport carriers that also carry the cargo protein TYRP1 and that require BLOC-1 for their formation. Using live-cell imaging, we identify a pathway for VAMP7 recycling from melanosomes that employs distinct tubular carriers. The recycling carriers also harbor the VAMP7-binding scaffold protein VARP and the tissue-restricted Rab GTPase RAB38. Recycling carrier formation is dependent on the RAB38 exchange factor BLOC-3. Our data suggest that VAMP7 mediates fusion of BLOC-1–dependent transport carriers with melanosomes, illuminate SNARE recycling from melanosomes as a critical BLOC-3–dependent step, and likely explain the distinct hypopigmentation phenotypes associated with BLOC-1 and BLOC-3 deficiency in Hermansky–Pudlak syndrome variants. PMID:27482051

Expression and Purification of Recombinant Human Basic Fibroblast Growth Factor Fusion Proteins and Their Uses in Human Stem Cell Culture.

PubMed

Imsoonthornruksa, Sumeth; Pruksananonda, Kamthorn; Parnpai, Rangsun; Rungsiwiwut, Ruttachuk; Ketudat-Cairns, Mariena

2015-01-01

To reduce the cost of cytokines and growth factors in stem cell research, a simple method for the production of soluble and biological active human basic fibroblast growth factor (hbFGF) fusion protein in Escherichia coli was established. Under optimal conditions, approximately 60-80 mg of >95% pure hbFGF fusion proteins (Trx-6xHis-hbFGF and 6xHis-hbFGF) were obtained from 1 liter of culture broth. The purified hbFGF proteins, both with and without the fusion tags, were biologically active, which was confirmed by their ability to stimulate proliferation of NIH3T3 cells. The fusion proteins also have the ability to support several culture passages of undifferentiated human embryonic stem cells and induce pluripotent stem cells. This paper describes a low-cost and uncomplicated method for the production and purification of biologically active hbFGF fusion proteins. © 2015 S. Karger AG, Basel.

Activity coefficients from molecular simulations using the OPAS method

NASA Astrophysics Data System (ADS)

Kohns, Maximilian; Horsch, Martin; Hasse, Hans

2017-10-01

A method for determining activity coefficients by molecular dynamics simulations is presented. It is an extension of the OPAS (osmotic pressure for the activity of the solvent) method in previous work for studying the solvent activity in electrolyte solutions. That method is extended here to study activities of all components in mixtures of molecular species. As an example, activity coefficients in liquid mixtures of water and methanol are calculated for 298.15 K and 323.15 K at 1 bar using molecular models from the literature. These dense and strongly interacting mixtures pose a significant challenge to existing methods for determining activity coefficients by molecular simulation. It is shown that the new method yields accurate results for the activity coefficients which are in agreement with results obtained with a thermodynamic integration technique. As the partial molar volumes are needed in the proposed method, the molar excess volume of the system water + methanol is also investigated.

High peak-power laser system tuneable from 8 to 10 μm

NASA Astrophysics Data System (ADS)

Gutty, François; Grisard, Arnaud; Larat, Christian; Papillon, Dominique; Schwarz, Muriel; Gérard, Bruno; Ostendorf, Ralf; Wagner, Joachim; Lallier, Eric

2017-04-01

A high peak-power rapidly tuneable laser system in the long-wave infrared is obtained using an external cavity quantum-cascade laser (EC-QCL) broadly tuneable from 8 to 10 μm and an optical parametric amplifier (OPA) based on quasi phase-matching in orientation-patterned gallium arsenide (OP-GaAs). To provide an efficient amplification, the nonlinear crystal is pumped by a pulsed fiber laser source. With a pump laser source tuneable around 2 μm, quasi phase-matching remains satisfied with a fixed grating period in the OP-GaAs crystal when the EC-QCL wavelength is swept from 8 to 10 μm. The OPA demonstrates parametric amplification from 8 to 10 μm and achieves output peak powers up to 140 W, with spectral linewidths below 3.5 cm-1 and a beam profile quality (M2) below 3.4 in both horizontal and vertical directions.

Fiber optical parametric amplifiers in optical communication systems

PubMed Central

Marhic (†), Michel E; Andrekson, Peter A; Petropoulos, Periklis; Radic, Stojan; Peucheret, Christophe; Jazayerifar, Mahmoud

2015-01-01

The prospects for using fiber optical parametric amplifiers (OPAs) in optical communication systems are reviewed. Phase-insensitive amplifiers (PIAs) and phase-sensitive amplifiers (PSAs) are considered. Low-penalty amplification at/or near 1 Tb/s has been achieved, for both wavelength- and time-division multiplexed formats. High-quality mid-span spectral inversion has been demonstrated at 0.64 Tb/s, avoiding electronic dispersion compensation. All-optical amplitude regeneration of amplitude-modulated signals has been performed, while PSAs have been used to demonstrate phase regeneration of phase-modulated signals. A PSA with 1.1-dB noise figure has been demonstrated, and preliminary wavelength-division multiplexing experiments have been performed with PSAs. 512 Gb/s have been transmitted over 6,000 km by periodic phase conjugation. Simulations indicate that PIAs could reach data rate x reach products in excess of 14,000 Tb/s × km in realistic wavelength-division multiplexed long-haul networks. Technical challenges remaining to be addressed in order for fiber OPAs to become useful for long-haul communication networks are discussed. PMID:25866588

FIRST NEW SOLAR MODELS WITH OPAS OPACITY TABLES

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

Le Pennec, M.; Turck-Chièze, S.; Salmon, S.

Stellar seismology appears more and more as a powerful tool for a better determination of the fundamental properties of solar-type stars. However, the particular case of the Sun is still challenging. For about a decade now, the helioseismic sound-speed determination has continued to disagree with the standard solar model (SSM) prediction, questioning the reliability of this model. One of the sources of uncertainty could be in the treatment of the transport of radiation from the solar core to the surface. In this Letter, we use the new OPAS opacity tables, recently available for solar modeling, to address this issue. Wemore » discuss first the peculiarities of these tables, then we quantify their impact on the solar sound-speed and density profiles using the reduced OPAS tables taken on the grids of the OPAL ones. We use the two evolution codes, Modules for Experiments in Stellar Astrophysics and Code Liégeois d’Evolution Stellaire, that led to similar conclusions in the solar radiative zone. In comparison to commonly used OPAL opacity tables, the new solar models are computed for the most recent photospheric composition with OPAS tables and present improvements to the location of the base of the convective zone and to the description of the solar radiative zone in comparison to the helioseismic observations, even if the differences in the Rosseland mean opacity do not exceed 6%. We finally carry out a comparison to a solar model computed with the OP opacity tables.« less

Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

PubMed

Zheng, Difan; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Xinghua; Cheng, Chao; Zheng, Shanbo; Li, Hang; Gong, Ranxia; Li, Yuan; Shen, Xuxia; Sun, Yihua; Chen, Haiquan

2016-04-01

We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

PubMed Central

Yonezawa, Akihito; Cavrois, Marielle; Greene, Warner C.

2005-01-01

The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope. Fusion was detected by cleavage of the fluorogenic substrate CCF2 by β-lactamase-Vpr incorporated into virions and released as a result of virion fusion. Entry and fusion induced by the Ebola virus GP occurred with much slower kinetics than with vesicular stomatitis virus G protein (VSV-G) and were blocked by depletion of membrane cholesterol and by inhibition of vesicular acidification with bafilomycin A1. These properties confirmed earlier studies and validated the assay for exploring other properties of Ebola virus GP-mediated entry and fusion. Entry and fusion of Ebola virus GP pseudotypes, but not VSV-G or HIV-1 Env pseudotypes, were impaired in the presence of the microtubule-disrupting agent nocodazole but were enhanced in the presence of the microtubule-stabilizing agent paclitaxel (Taxol). Agents that impaired microfilament function, including cytochalasin B, cytochalasin D, latrunculin A, and jasplakinolide, also inhibited Ebola virus GP-mediated entry and fusion. Together, these findings suggest that both microtubules and microfilaments may play a role in the effective trafficking of vesicles containing Ebola virions from the cell surface to the appropriate acidified vesicular compartment where fusion occurs. In terms of Ebola virus GP-mediated entry and fusion to various target cells, primary macrophages proved highly sensitive, while monocytes from the same donors displayed greatly reduced levels of entry and fusion. We further observed that tumor necrosis factor alpha, which is released by Ebola virus-infected monocytes/macrophages, enhanced Ebola virus GP-mediated entry and fusion to human umbilical vein endothelial cells. Thus, Ebola virus infection of one target cell may induce biological changes that facilitate infection of secondary target cells that play a key role in filovirus pathogenesis. Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens. PMID:15613320

Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

ERIC Educational Resources Information Center

Berry, David C.; Seitz, S. Robert

2011-01-01

The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

33 CFR 1.01-80 - FWPCA and OPA 90 delegations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vessels; with or without warrant, arrest any person who, in the Commander's presence or view, violates a... any person who, in the Commander's presence or view, violates a provision of section 311 of the FWPCA... On-Scene Coordinator by the applicable Regional Contingency Plan is delegated authority pursuant to...

28 CFR 16.79 - Exemption of Pardon Attorney System.

Code of Federal Regulations, 2010 CFR

2010-07-01

... System (JUSTICE/OPA-001) is to enable the Justice Department to prepare reports and recommendations to... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exemption of Pardon Attorney System. 16... OR INFORMATION Exemption of Records Systems Under the Privacy Act § 16.79 Exemption of Pardon...

Retrospective exploration of risk factors for L5 radiculopathy following lumbar floating fusion surgery.

PubMed

Orita, Sumihisa; Yamagata, Masatsune; Ikeda, Yoshikazu; Nakajima, Fumitake; Aoki, Yasuchika; Nakamura, Junichi; Takahashi, Kazuhisa; Suzuki, Takane; Ohtori, Seiji

2015-10-17

Lumbar floating fusion occasionally causes postoperative adjacent segment disorder (ASD) at lumbosacral level, causing L5 spinal nerve disorder by L5-S1 foraminal stenosis. The disorder is considered to be one of the major outcomes of L5-S1 ASD, which has not been evaluated yet. The present study aimed to evaluate the incidence and risk factors of postoperative L5 spinal nerve disorder after lumbar interbody fusion extending to the L5 vertebra. We evaluated 125 patients with a diagnosis of spondylolisthesis who underwent floating fusion surgery with transforaminal lumbar interbody fusion with average postoperative period of 25.2 months. The patients were regarded as symptomatic with postoperative L5 spinal nerve disorder such as radicular pain/numbness in the lower limbs and/or motor dysfunction. We estimated and compared the wedging angle (frontal view) and height (lateral view) of the lumbosacral junction in pre- and postoperative plain X-ray images and the foraminal ratio (ratio of the narrower foraminal diameter to the wider diameter in the craniocaudal direction) in the preoperative magnetic resonance image. Risk factors for the incidence of L5 spinal nerve disorder were explored using multivariate logistic regression. Eight of the 125 patients (6.4%) were categorized as symptomatic, an average of 13.3 months after surgery. The wedging angle was significantly higher, and the foraminal ratio was significantly decreased in the symptomatic group (both P < 0.05) compared to the asymptomatic group. Multivariate logistic regression analysis of possible risk factors revealed that the wedging angle, foraminal ratio, and multileveled fusion were statistically significant. Higher wedging angle and lower foraminal ratio in the lumbosacral junction were significantly predictive for the incidence of L5 nerve root disorder as well as multiple-leveled fusion. These findings indicate that lumbosacral fixation should be considered for patients with these risk factors even if they have few symptoms from the L5-S1 junction.

Towards Terawatt Sub-Cycle Long-Wave Infrared Pulses via Chirped Optical Parametric Amplification and Indirect Pulse Shaping

PubMed Central

Yin, Yanchun; Chew, Andrew; Ren, Xiaoming; Li, Jie; Wang, Yang; Wu, Yi; Chang, Zenghu

2017-01-01

We present an approach for both efficient generation and amplification of 4–12 μm pulses by tailoring the phase matching of the nonlinear crystal Zinc Germanium Phosphide (ZGP) in a narrowband-pumped optical parametric chirped pulse amplifier (OPCPA) and a broadband-pumped dual-chirped optical parametric amplifier (DC-OPA), respectively. Preliminary experimental results are obtained for generating 1.8–4.2 μm super broadband spectra, which can be used to seed both the signal of the OPCPA and the pump of the DC-OPA. The theoretical pump-to-idler conversion efficiency reaches 27% in the DC-OPA pumped by a chirped broadband Cr2+:ZnSe/ZnS laser, enabling the generation of  Terawatt-level 4–12 μm pulses with an available large-aperture ZGP. Furthermore, the 4–12 μm idler pulses can be compressed to sub-cycle pulses by compensating the tailored positive chirp of the idler pulses using the bulk compressor NaCl, and by indirectly controlling the higher-order idler phase through tuning the signal (2.4–4.0 μm) phase with a commercially available acousto-optic programmable dispersive filter (AOPDF). A similar approach is also described for generating high-energy 4–12 μm sub-cycle pulses via OPCPA pumped by a 2 μm Ho:YLF laser. PMID:28367966

One- and two-photon absorption spectra of the yellow fluorescent protein citrine: effects of intramolecular electron-vibrational coupling and intermolecular interactions

NASA Astrophysics Data System (ADS)

Chen, Fasheng; Zhao, Xinyi; Liang, WanZhen

2018-04-01

Both the vibrationally resolved and statistically averaged one-photon absorption (OPA) and two-photon absorption (TPA) spectra of the anionic form of chromophore (AC) in its micro-environment of yellow fluorescent protein (YFP) Citrine have been calculated. The result comparison has been made with those of the AC model compounds in vacuo and methanol solution, which allows us to allocate the individual contribution of the intramolecular electron-vibrational coupling, the electrostatic π-stacking interaction between Tyr203 and AC, and the interaction between AC and its micro-environment to the spectra. The results reveal that the non-Condon vibronic coupling effect is responsible for the blue shift of TPA absorption maximum compared with its OPA counterpart corresponding to S0 → S1, and that the π-stacking interaction between Tyr203 and AC alters the relative intensities of TPA maxima, which further enhances the higher-energy vibronic peaks and weakens the lowest-energy peak. The statically averaged OPA and TPA spectra calculated by quantum mechanics/molecular mechanics (QM/MM) methods based on Born-Oppenheimer molecular dynamics simulation largely deviate the experimental spectral lineshapes, which further verifies the significant contribution of non-Condon vibronic coupling effect on the spectra. The interaction of individual amino acid residue or water close to AC+Tyr203 has different effects on the spectra, which may increase/decrease the excitation energy depending on its position and electronic property.

Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.

PubMed

Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel

2017-09-12

Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd. All rights reserved.

Local protein dynamics during microvesicle exocytosis in neuroendocrine cells.

PubMed

Somasundaram, Agila; Taraska, Justin

2018-06-06

Calcium triggered exocytosis is key to many physiological processes, including neurotransmitter and hormone release by neurons and endocrine cells. Dozens of proteins regulate exocytosis, yet the temporal and spatial dynamics of these factors during vesicle fusion remain unclear. Here we use total internal reflection fluorescence microscopy to visualize local protein dynamics at single sites of exocytosis of small synaptic-like microvesicles in live cultured neuroendocrine PC12 cells. We employ two-color imaging to simultaneously observe membrane fusion (using vesicular acetylcholine transporter (VAChT) tagged to pHluorin) and the dynamics of associated proteins at the moments surrounding exocytosis. Our experiments show that many proteins, including the SNAREs syntaxin1 and VAMP2, the SNARE modulator tomosyn, and Rab proteins, are pre-clustered at fusion sites and rapidly lost at fusion. The ATPase NSF is locally recruited at fusion. Interestingly, the endocytic BAR domain-containing proteins amphiphysin1, syndapin2, and endophilins are dynamically recruited to fusion sites, and slow the loss of vesicle membrane-bound cargo from fusion sites. A similar effect on vesicle membrane protein dynamics was seen with the over-expression of the GTPases dynamin1 and dynamin2. These results suggest that proteins involved in classical clathrin-mediated endocytosis can regulate exocytosis of synaptic-like microvesicles. Our findings provide insights into the dynamics, assembly, and mechanistic roles of many key factors of exocytosis and endocytosis at single sites of microvesicle fusion in live cells.

Improvement of ablative margins by the intraoperative use of CEUS-CT/MR image fusion in hepatocellular carcinoma.

PubMed

Li, Kai; Su, Zhong-Zhen; Xu, Er-Jiao; Ju, Jin-Xiu; Meng, Xiao-Chun; Zheng, Rong-Qin

2016-04-18

To assess whether intraoperative use of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion can accurately evaluate ablative margin (AM) and guide supplementary ablation to improve AM after hepatocellular carcinoma (HCC) ablation. Ninety-eight patients with 126 HCCs designated to undergo thermal ablation treatment were enrolled in this prospective study. CEUS-CT/MR image fusion was performed intraoperatively to evaluate whether 5-mm AM was covered by the ablative area. If possible, supplementary ablation was applied at the site of inadequate AM. The CEUS image quality, the time used for CEUS-CT/MR image fusion and the success rate of image fusion were recorded. Local tumor progression (LTP) was observed during follow-up. Clinical factors including AM were examined to identify risk factors for LTP. The success rate of image fusion was 96.2% (126/131), and the duration required for image fusion was 4.9 ± 2.0 (3-13) min. The CEUS image quality was good in 36.1% (53/147) and medium in 63.9% (94/147) of the cases. By supplementary ablation, 21.8% (12/55) of lesions with inadequate AMs became adequate AMs. During follow-up, there were 5 LTPs in lesions with inadequate AMs and 1 LTP in lesions with adequate AMs. Multivariate analysis showed that AM was the only independent risk factor for LTP (hazard ratio, 9.167; 95% confidence interval, 1.070-78.571; p = 0.043). CEUS-CT/MR image fusion is feasible for intraoperative use and can serve as an accurate method to evaluate AMs and guide supplementary ablation to lower inadequate AMs.

Optical parametric amplification of arbitrarily polarized light in periodically poled LiNbO3.

PubMed

Shao, Guang-hao; Song, Xiao-shi; Xu, Fei; Lu, Yan-qing

2012-08-13

Optical parametric amplification (OPA) of arbitrarily polarized light is proposed in a multi-section periodically poled Lithium Niobate (PPLN). External electric field is applied on selected sections to induce the polarization rotation of involved lights, thus the quasi-phase matched optical parametric processes exhibit polarization insensitivity under suitable voltage. In addition to the amplified signal wave, an idler wave with the same polarization is generated simultaneously. As an example, a ~10 times OPA showing polarization independency is simulated. Applications of this technology are also discussed.

Advanced laser architectures for high power eyesafe illuminators

NASA Astrophysics Data System (ADS)

Baranova, N.; Pati, B.; Stebbins, K.; Bystryak, I.; Rayno, M.; Ezzo, K.; DePriest, C.

2018-02-01

Q-Peak has demonstrated a novel pulsed eyesafe laser architecture operating with >50 mJ pulse energies at Pulse Repetition Frequencies (PRFs) as high as 320 Hz. The design leverages an Optical Parametric Oscillator (OPO) and Optical Parametric Amplifier (OPA) geometry, which provides the unique capability for high power in a comparatively compact package, while also offering the potential for additional eyesafe power scaling. The laser consists of a Commercial Off-the-Shelf (COTS) Q-switched front-end seed laser to produce pulse-widths around 10 ns at 1.06-μm, which is then followed by a pair of Multi-Pass Amplifier (MPA) architectures (comprised of side-pumped, multi-pass Nd:YAG slabs with a compact diode-pump-array imaging system), and finally involving two sequential nonlinear optical conversion architectures for transfer into the eyesafe regime. The initial seed beam is first amplified through the MPA, and then split into parallel optical paths. An OPO provides effective nonlinear conversion on one optical path, while a second MPA further amplifies the 1.06-μm beam for use in pumping an OPA on the second optical path. These paths are then recombined prior to seeding the OPA. Each nonlinear conversion subsystem utilizes Potassium Titanyl Arsenate (KTA) for effective nonlinear conversion with lower risk to optical damage. This laser architecture efficiently produces pulse energies of >50 mJ in the eyesafe band at PRFs as high as 320 Hz, and has been designed to fit within a volume of 4,500 in3 (0.074 m3 ). We will discuss theoretical and experimental details of the nonlinear optical system for achieving higher eyesafe powers.

Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

PubMed

Lund Rasmussen, Charlotte; Nielsen, Line; Linander Henriksen, Marie; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas; Korshøj, Mette

2018-02-01

High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.

Idler-efficiency-enhanced long-wave infrared beam generation using aperiodic orientation-patterned GaAs gratings.

PubMed

Gürkan Figen, Ziya; Aytür, Orhan; Arıkan, Orhan

2016-03-20

In this paper, we design aperiodic gratings based on orientation-patterned gallium arsenide (OP-GaAs) for converting 2.1 μm pump laser radiation into long-wave infrared (8-12 μm) in an idler-efficiency-enhanced scheme. These single OP-GaAs gratings placed in an optical parametric oscillator (OPO) or an optical parametric generator (OPG) can simultaneously phase match two optical parametric amplification (OPA) processes, OPA 1 and OPA 2. We use two design methods that allow simultaneous phase matching of two arbitrary χ⁽²⁾ processes and also free adjustment of their relative strength. The first aperiodic grating design method (Method 1) relies on generating a grating structure that has domain walls located at the zeros of the summation of two cosine functions, each of which has a spatial frequency that equals one of the phase-mismatch terms of the two processes. Some of the domain walls are discarded considering the minimum domain length that is achievable in the production process. In this paper, we propose a second design method (Method 2) that relies on discretizing the crystal length with sample lengths that are much smaller than the minimum domain length and testing each sample's contribution in such a way that the sign of the nonlinearity maximizes the magnitude sum of the real and imaginary parts of the Fourier transform of the grating function at the relevant phase mismatches. Method 2 produces a similar performance as Method 1 in terms of the maximization of the height of either Fourier peak located at the relevant phase mismatch while allowing an adjustable relative height for the two peaks. To our knowledge, this is the first time that aperiodic OP-GaAs gratings have been proposed for efficient long-wave infrared beam generation based on simultaneous phase matching.

SNARE-encoding genes VdSec22 and VdSso1 mediate protein secretion required for full virulence in Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Proteins that mediate cellular and subcellular membrane fusion are key factors in vesicular trafficking in all eukaryotic cells, including the secretion and transport of plant pathogen virulence factors. In this study, we identified vesicle fusion components that included 22 soluble N-ethylmaleimide...

Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion.

PubMed

James, Declan J; Khodthong, Chuenchanok; Kowalchyk, Judith A; Martin, Thomas F J

2008-07-28

Phosphatidylinositol 4,5-bisphosphate (PI 4,5-P(2)) on the plasma membrane is essential for vesicle exocytosis but its role in membrane fusion has not been determined. Here, we quantify the concentration of PI 4,5-P(2) as approximately 6 mol% in the cytoplasmic leaflet of plasma membrane microdomains at sites of docked vesicles. At this concentration of PI 4,5-P(2) soluble NSF attachment protein receptor (SNARE)-dependent liposome fusion is inhibited. Inhibition by PI 4,5-P(2) likely results from its intrinsic positive curvature-promoting properties that inhibit formation of high negative curvature membrane fusion intermediates. Mutation of juxtamembrane basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggesting that syntaxin sequesters PI 4,5-P(2) to alleviate inhibition. To define an essential rather than inhibitory role for PI 4,5-P(2), we test a PI 4,5-P(2)-binding priming factor required for vesicle exocytosis. Ca(2+)-dependent activator protein for secretion promotes increased rates of SNARE-dependent fusion that are PI 4,5-P(2) dependent. These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion.

Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

PubMed

Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

2013-08-02

Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Workers' Compensation, Return to Work, and Lumbar Fusion for Spondylolisthesis.

PubMed

Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

2016-01-01

Lumbar fusion for spondylolisthesis is associated with consistent outcomes in the general population. However, workers' compensation is a risk factor for worse outcomes. Few studies have evaluated prognostic factors within this clinically distinct population. The goal of this study was to identify prognostic factors for return to work among patients with workers' compensation claims after fusion for spondylolisthesis. The authors used International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes to identify 686 subjects from the Ohio Bureau of Workers' Compensation who underwent fusion for spondylolisthesis from 1993 to 2013. Positive return to work status was recorded in patients who returned to work within 2 years of fusion and remained working for longer than 6 months. The criteria for return to work were met by 29.9% (n=205) of subjects. The authors used multivariate logistic regression analysis to identify prognostic factors for return to work. Negative preoperative prognostic factors for postoperative return to work included: out of work for longer than 1 year before fusion (P<.001; odds ratio [OR], 0.16); depression (P=.007; OR<0.01); long-term opioid analgesic use (P=.006; OR, 0.41); lumbar stenosis (P=.043; OR, 0.55); and legal representation (P=.042; OR, 0.63). Return to work rates associated with these factors were 9.7%, 0.0%, 10.0%, 29.2%, and 25.0%, respectively. If these subjects were excluded, the return to work rate increased to 60.4%. The 70.1% (n=481) of subjects who did not return to work had markedly worse outcomes, shown by higher medical costs, chronic opioid dependence, and higher rates of failed back syndrome, total disability, and additional surgery. Psychiatric comorbidity increased after fusion but was much higher in those who did not return to work. Future studies are needed to identify how to better facilitate return to work among similar patients with workers' compensation claims. Copyright 2016, SLACK Incorporated.

In-capillary derivatization with o-phthalaldehyde in the presence of 3-mercaptopropionic acid for the simultaneous determination of monosodium glutamate, benzoic acid, and sorbic acid in food samples via capillary electrophoresis with ultraviolet detection.

PubMed

Aung, Hnin-Pwint; Pyell, Ute

2016-06-03

For the rapid simultaneous determination of monosodium glutamate (MSG), benzoic acid (BA), and sorbic acid (SA) in canned food and other processed food samples, we developed a method that combines in-capillary derivatization with separation by capillary electrophoresis. This method employs the rapid derivatization of MSG with o-phthalaldehyde (OPA) in the presence of 3-mercaptopropionic acid (3-MPA) and enables the detection of the resulting OPA-MSG derivative and of non-derivatized BA and SA at 230nm. The composition of the background electrolyte and the parameters of derivatization and separation are as follows: 25mM borax containing 5mM OPA and 6mM 3-MPA, separation voltage 25mV, injection at 30mbar for 20s, and column temperature 25°C. Because of the high reaction rate and suitably adapted effective electrophoretic mobilities, band broadening due to the derivatization reaction at the start of the separation process is kept to a minimum. The optimized method is validated with respect to LOD, LOQ, linearity, recovery, and precision. This method can be applied to real samples such as soy, fish, oyster and sweet and sour chili sauces after application of appropriate clean-up steps. Mechanisms of zone broadening and zone focusing are discussed showing the validity of the employed theoretical approach regarding the dependence of the peak shape for OPA-MSG on the concentration of MSG in the sample. Copyright © 2016 Elsevier B.V. All rights reserved.

Risk Factors for Blood Transfusion With Primary Posterior Lumbar Fusion.

PubMed

Basques, Bryce A; Anandasivam, Nidharshan S; Webb, Matthew L; Samuel, Andre M; Lukasiewicz, Adam M; Bohl, Daniel D; Grauer, Jonathan N

2015-11-01

Retrospective cohort study. To identify factors associated with blood transfusion for primary posterior lumbar fusion surgery, and to identify associations between blood transfusion and other postoperative complications. Blood transfusion is a relatively common occurrence for patients undergoing primary posterior lumbar fusion. There is limited information available describing which patients are at increased risk for blood transfusion, and the relationship between blood transfusion and short-term postoperative outcomes is poorly characterized. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients undergoing primary posterior lumbar fusion from 2011 to 2013. Multivariate analysis was used to find associations between patient characteristics and blood transfusion, along with associations between blood transfusion and postoperative outcomes. Out of 4223 patients, 704 (16.7%) had a blood transfusion. Age 60 to 69 (relative risk [RR] 1.6), age greater than equal to 70 (RR 1.7), American Society of Anesthesiologists class greater than equal to 3 (RR 1.1), female sex (RR 1.1), pulmonary disease (RR 1.2), preoperative hematocrit less than 36.0 (RR 2.0), operative time greater than equal to 310 minutes (RR 2.9), 2 levels (RR 1.6), and 3 or more levels (RR 2.1) were independently associated with blood transfusion. Interbody fusion (RR 0.9) was associated with decreased rates of blood transfusion. Receiving a blood transfusion was significantly associated with any complication (RR 1.7), sepsis (RR 2.6), return to the operating room (RR 1.7), deep surgical site infection (RR 2.6), and pulmonary embolism (RR 5.1). Blood transfusion was also associated with an increase in postoperative length of stay of 1.4 days (P < 0.001). 1 in 6 patients received a blood transfusion while undergoing primary posterior lumbar fusion, and risk factors for these occurrences were characterized. Strategies to minimize blood loss might be considered in these patients to avoid the associated complications. 3.

Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.

PubMed

Carette, Jan E; Raaben, Matthijs; Wong, Anthony C; Herbert, Andrew S; Obernosterer, Gregor; Mulherkar, Nirupama; Kuehne, Ana I; Kranzusch, Philip J; Griffin, April M; Ruthel, Gordon; Dal Cin, Paola; Dye, John M; Whelan, Sean P; Chandran, Kartik; Brummelkamp, Thijn R

2011-08-24

Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.

The pharmacological efficacy of the anti-IL17 scFv and sTNFR1 bispecific fusion protein in inflammation mouse stimulated by LPS.

PubMed

Yang, Yongbi; Zhang, Teng; Cao, Hongxue; Yu, Dan; Zhang, Tong; Zhao, Shaojuan; Jing, Xiaohui; Song, Liying; Liu, Yunye; Che, Ruixiang; Liu, Xin; Li, Deshan; Ren, Guiping

2017-08-01

Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Recently, our study found that a bispecific fusion protein treatment can ameliorate the lung injury induced by LPS. However, the molecular mechanisms which bispecific fusion protein ameliorates acute lung injury remain unclear. In this study, we found that the bispecific fusion protein treatment inhibited the nuclear transcription of NF-κB in confocal laser scanning fluorescence microscopy, the bispecific fusion protein exert protective effects in the cell model of ALI induced by lipopolysaccharide (LPS) via inhibiting the nuclear factor κB (NF-κB) signaling pathway and mediate inflammation. Moreover, the treatment of the bispecific fusion protein show its efficacy in animal models stimulated by LPS, the results of real-time PCR and ELISA demonstrate that bispecific fusion protein treatment effectively inhibited the over-expression of inflammatory cytokines(tumor necrosis factor α, interleukin 1β and interleukin 17). In addition, LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology, which was meliorated by bispecific fusion protein treatment. Collectively, these results demonstrate that bispecific fusion protein treatment ameliorates LPS-induced ALI through reducing inflammatory cytokines and lung inflammation, which may be associated with the decreased the nuclear transcription of NF-κB. The bispecific fusion protein may be useful as a novel therapy to treat ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Objective quality assessment for multiexposure multifocus image fusion.

PubMed

Hassen, Rania; Wang, Zhou; Salama, Magdy M A

2015-09-01

There has been a growing interest in image fusion technologies, but how to objectively evaluate the quality of fused images has not been fully understood. Here, we propose a method for objective quality assessment of multiexposure multifocus image fusion based on the evaluation of three key factors of fused image quality: 1) contrast preservation; 2) sharpness; and 3) structure preservation. Subjective experiments are conducted to create an image fusion database, based on which, performance evaluation shows that the proposed fusion quality index correlates well with subjective scores, and gives a significant improvement over the existing fusion quality measures.

Optical tristability in a hybrid optomechanical system

NASA Astrophysics Data System (ADS)

Asghari Nejad, A.; Askari, H. R.; Baghshahi, H. R.

2018-05-01

In this paper, we investigate a hybrid optomechanical system consisting of two cavities, which one of them is an optomechanical cavity that includes an optical parametric amplifier (OPA) and the other is a traditional cavity which contains an atomic medium. Hamiltonian of the system is written in a rotating frame with a rotation frequency of the frequency of input field to the system. Using Heisenberg-Langevin equations of motion, the dynamics of the system is described. Applying the steady-state conditions leads to a system of equations of the mean values of the operators of the system. The stability condition of the system is satisfied numerically and behavior of optomechanical cavity is investigated in different situations to find the effect of changing of the parameters of the system on the type of its stability. We show proposed system has the capability of tristable behavior, where, the gain coefficient of OPA acts as a switch in changing the bistability of the system to a tristable manner. The building block of the tristability in this system can be figured out as the enhanced nonlinearity of the system due to the presence of OPA.

78 FR 44561 - Ortho-Phthalaldehyde; Receipt of Application for Emergency Exemption, Solicitation of Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code 311). Pesticide manufacturing (NAICS code 32532). B. What should I consider as I prepare my comments for EPA? 1. Submitting CBI... coolant additives. Non-use of OPA in the requested manner would leave NASA's International Space Station...

78 FR 20631 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Spill...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPA-2007-0584; FRL-9530-1] Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Spill Prevention, Control and Countermeasure..., Control and Countermeasures (SPCC) Plans (Renewal)'' (EPA ICR No. 0328.16, OMB Control No. 2050-0021) to...

Kinetic advantage of controlled intermediate nuclear fusion

NASA Astrophysics Data System (ADS)

Guo, Xiaoming

2012-09-01

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion very difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.

Observing relationships in Finnish adoptive families: Oulu Family Rating Scale.

PubMed

Tienari, Pekka; Wynne, Lyman C; Sorri, Anneli; Lahti, Ilpo; Moring, Juha; Nieminen, Pentti; Joukamaa, Matti; Naarala, Mikko; Seitamaa, Markku; Wahlberg, Karl-Erik; Miettunen, Jouko

2005-01-01

Adoption studies were intended to separate genetic from environmental "causal" factors. In earlier adoption studies, psychiatric diagnostic labels for the adoptive parents were used as a proxy for the multiple dimensions of the family rearing environment. In the Finnish Adoption Study, research design provided the opportunity to study directly the adoptive family rearing environment. For this purpose 33 sub-scales were selected creating what we call Oulu Family Rating Scale (OPAS, Oulun PerheArviointiSkaala). In this paper, the manual for scoring of these sub-scales is presented.

Ultra-wideband and high-gain parametric amplification in telecom wavelengths with an optimally mode-matched PPLN waveguide.

PubMed

Sua, Yong Meng; Chen, Jia-Yang; Huang, Yu-Ping

2018-06-15

We report a wideband optical parametric amplification (OPA) over 14 THz covering telecom S, C, and L bands with observed maximum parametric gain of 38.3 dB. The OPA is realized through cascaded second-harmonic generation and difference-frequency generation (cSHG-DFG) in a 2 cm periodically poled LiNbO 3 (PPLN) waveguide. With tailored cross section geometry, the waveguide is optimally mode matched for efficient cascaded nonlinear wave mixing. We also identify and study the effect of competing nonlinear processes in this cSHG-DFG configuration.

General analysis of group velocity effects in collinear optical parametric amplifiers and generators.

PubMed

Arisholm, Gunnar

2007-05-14

Group velocity mismatch (GVM) is a major concern in the design of optical parametric amplifiers (OPAs) and generators (OPGs) for pulses shorter than a few picoseconds. By simplifying the coupled propagation equations and exploiting their scaling properties, the number of free parameters for a collinear OPA is reduced to a level where the parameter space can be studied systematically by simulations. The resulting set of figures show the combinations of material parameters and pulse lengths for which high performance can be achieved, and they can serve as a basis for a design.

Intraduodenal Administration of Intact Pea Protein Effectively Reduces Food Intake in Both Lean and Obese Male Subjects

PubMed Central

Geraedts, Maartje C. P.; Troost, Freddy J.; Munsters, Marjet J. M.; Stegen, Jos H. C. H.; de Ridder, Rogier J.; Conchillo, Jose M.; Kruimel, Joanna W.; Masclee, Ad A. M.; Saris, Wim H. M.

2011-01-01

Background Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. Methods Ten lean (BMI:23.0±0.7 kg/m2) and ten obese (BMI:33.4±1.4 kg/m2) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. Results CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA. Conclusions Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity. PMID:21931864

FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.

PubMed

Wang, Rui; Wang, Lei; Li, Yuan; Hu, Haichuan; Shen, Lei; Shen, Xuxia; Pan, Yunjian; Ye, Ting; Zhang, Yang; Luo, Xiaoyang; Zhang, Yiliang; Pan, Bin; Li, Bin; Li, Hang; Zhang, Jie; Pao, William; Ji, Hongbin; Sun, Yihua; Chen, Haiquan

2014-08-01

The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions. Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected. Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095). FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation. ©2014 American Association for Cancer Research.

2016 Workplace and Gender Relations Survey of Active Duty Members: Overview Report

DTIC Science & Technology

2017-05-01

Grifka 1 Chapter 2: Survey Methodology Ms. Lisa Davis, Mr. Eric Falk, and Mr. Jeff Schneider 19 Chapter 3: Estimated Sexual Assault...assessing the gender relations environment across the Services. Study Background and Methodology Study Background The Defense Research, Surveys, and...gender discrimination. 3 Chapter 1 provides additional information on the construction of these metrics. Survey Methodology OPA conducts DoD cross

Disinfection procedures: their efficacy and effect on dimensional accuracy and surface quality of an irreversible hydrocolloid impression material.

PubMed

Rentzia, A; Coleman, D C; O'Donnell, M J; Dowling, A H; O'Sullivan, M

2011-02-01

This study investigated the antibacterial efficacy and effect of 0.55% ortho-phthalaldehyde (Cidex OPA(®)) and 0.5% sodium hypochlorite (NaOCl) on the dimensional accuracy and surface quality of gypsum casts retrieved from an irreversible hydrocolloid impression material. A simulated clinical cast and technique was developed to compare the dimensional accuracy and surface quality changes of the test gypsum casts with controls. Dimensional accuracy measurements were completed between fixed points using a travelling microscope under low angle illumination at a magnification of ×3. Surface quality changes of "smooth" and "rough" areas on the cast were evaluated by means of optical profilometry. The efficacy of the disinfection procedures against Pseudomonas aeruginosa was evaluated by determining the number of colony forming units (cfu) recovered after disinfection of alginate discs inoculated with 1×10⁶cfu for defined intervals. The dimensional accuracy of the gypsum casts was not significantly affected by the disinfection protocols. Neither disinfectant solution nor immersion time had an effect on the surface roughness of the "smooth" area on the cast, however, a significant increase in surface roughness was observed with increasing immersion time for the "rough" surface. Complete elimination of viable Pseudomonas aeruginosa cells from alginate discs was obtained after 30 and 120 s immersion in Cidex OPA(®) and NaOCl, respectively. Immersion of irreversible hydrocolloid impressions in Cidex OPA(®) for 30 s was proved to be the most effective disinfection procedure. Copyright © 2010 Elsevier Ltd. All rights reserved.

Risk factors for surgical site infections after pediatric spine operations.

PubMed

Croft, Lindsay D; Pottinger, Jean M; Chiang, Hsiu-Yin; Ziebold, Christine S; Weinstein, Stuart L; Herwaldt, Loreen A

2015-01-15

Matched case-control study. To identify modifiable risk factors for surgical site infections (SSIs) after pediatric spinal fusion. The number of SSIs after pediatric spinal fusions increased. Between July 2001 and July 2010, 22 of 598 pediatric patients who underwent spinal fusion at a university hospital acquired SSIs. Each patient with an SSI was matched with 2 controls by procedure date. Bivariable and multivariable analyses were used to identify risk factors for SSIs and outcomes of SSIs. Gram-negative organisms caused more than 50% of the SSIs. By multivariable analysis, neuromuscular scoliosis (odds ratio [OR] = 20.8; 95% confidence interval [CI], 3.1-889.5; P < 0.0001) and weight-for-age at the 95th percentile or higher (OR = 8.6; 95% CI, 1.2-124.9; P = 0.02) were preoperative factors associated with SSIs. Blood loss (OR = 1.0; 95% CI, 1.0-1.0; P = 0.039) and allografts and allografts in combination with other grafts were operative risk factors for SSIs. The final overall risk model for SSIs was weight-for-age at the 95th percentile or higher (OR = 4.0; 95% CI, 1.4-∞; P = 0.037), American Society of Anesthesiologists score 3 or more (OR = 3.8; 95% CI, 1.6-∞; P = 0.01), and prolonged operation duration (OR = 1.0/min increase; 95% CI, 1.0-1.0; P = 0.004). SSIs were associated with 2.8 days of additional postoperative length of stay (P = 0.02). Neuromuscular scoliosis was the only factor significantly associated with hospital readmission (OR = 23.6; 95% CI, 3.8-147.3; P = 0.0007). Our results suggest that pediatric patients undergoing spinal fusion might benefit from antimicrobial prophylaxis that covers gram-negative organisms. Surgical duration, graft implantation, and blood loss are potentially modifiable operative risk factors. Neuromuscular scoliosis, high weight-for-age, and American Society of Anesthesiologists scores 3 or more may help surgical teams identify patients at high risk for SSI.

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

Guo Xiaoming

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion verymore » difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.« less

Host Species Barriers to Jaagsiekte Sheep Retrovirus Replication and Carcinogenesis

PubMed Central

Martineau, Henny; De las Heras, Marcelo; Murgia, Claudio; Huang, Robert; Centorame, Patrizia; Di Francesco, Gabriella; Di Gialleonardo, Luigina; Spencer, Thomas E.; Griffiths, David J.; Palmarini, Massimo

2013-01-01

Understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. In this study, in order to further clarify the pathogenesis of OPA, we investigated whether goats are resistant to JSRV replication and carcinogenesis. We found that JSRV induces lung tumors in goats with macroscopic and histopathological features that dramatically differ from those in sheep. However, the origins of the tumor cells in the two species are identical. Interestingly, in experimentally infected lambs and goat kids, we revealed major differences in the number of virus-infected cells at early stages of infection. These differences were not related to the number of available target cells for virus infection and cell transformation or the presence of a host-specific immune response toward JSRV. Indeed, we also found that goats possess transcriptionally active endogenous retroviruses (enJSRVs) that likely influence the host immune response toward the exogenous JSRV. Overall, these results suggest that goat cells, or at least those cells targeted for viral carcinogenesis, are not permissive to virus replication but can be transformed by JSRV. PMID:23903827

Mitochondrial dysfunction in H9c2 cells during ischemia and amelioration with Tribulus terrestris L.

PubMed

Reshma, P L; Sainu, Neethu S; Mathew, Anil K; Raghu, K G

2016-05-01

The present study investigates the protective effect of partially characterized Tribulus terrestris L. fruit methanol extract against mitochondrial dysfunction in cell based (H9c2) myocardial ischemia model. To induce ischemia, the cells were maintained in an ischemic buffer (composition in mM -137 NaCl, 12 KCl, 0.5 MgCl2, 0.9 CaCl2, 20 HEPES, 20 2-deoxy-d-glucose, pH-6.2) at 37°C with 0.1% O2, 5% CO2, and 95% N2 in a hypoxia incubator for 1h. Cells were pretreated with various concentrations of T. terrestris L. fruit methanol extract (10 and 25μg/ml) and Cyclosporin A (1μM) for 24h prior to the induction of ischemia. Different parameters like lactate dehydrogenase release, total antioxidant capacity, glutathione content and antioxidant enzymes were investigated. Studies were conducted on mitochondria by analyzing alterations in mitochondrial membrane potential, integrity, and dynamics (fission and fusion proteins - Mfn1, Mfn2, OPA1, Drp1 and Fis1). Various biochemical processes in mitochondria like activity of electron transport chain (ETC) complexes, oxygen consumption and ATP production was measured. Ischemia for 1h caused a significant (p≤0.05) increase in LDH leakage, decrease in antioxidant activity and caused mitochondrial dysfunction. T. terrestris L. fruit methanol extract pretreatment was found effective in safeguarding mitochondria via its antioxidant potential, mediated through various bioactives. HPLC of T. terrestris L. fruit methanol extract revealed the presence of ferulic acid, phloridzin and diosgenin. T. terrestris L. fruit ameliorate ischemic insult in H9c2 cells by safeguarding mitochondrial function. This validates the use of T. terrestris L. against heart disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children's Oncology Group.

PubMed

Rudzinski, Erin R; Anderson, James R; Chi, Yueh-Yun; Gastier-Foster, Julie M; Astbury, Caroline; Barr, Frederic G; Skapek, Stephen X; Hawkins, Douglas S; Weigel, Brenda J; Pappo, Alberto; Meyer, William H; Arnold, Michael A; Teot, Lisa A; Parham, David M

2017-12-01

Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS-IV, which included the height of this diagnostic shift, showed both an increased number of ARMS and an increase in the proportion of fusion-negative ARMS. Following diagnostic standardization and histologic re-review of ARMS cases enrolled during this era, analysis of low-risk (D9602) and intermediate-risk (D9803) rhabdomyosarcoma (RMS) studies showed that fusion status rather than histology best predicts prognosis for patients with RMS. This analysis remains to be completed for patients with high-risk RMS. We re-reviewed cases on high-risk COG studies D9802 and ARST0431 with an enrollment diagnosis of ARMS. We compared the event-free survival (EFS) and overall survival by histology, PAX-FOXO1 fusion, and clinical risk factors (Oberlin score) for patients with metastatic RMS using the log-rank test. Histology re-review resulted in reclassification as ERMS for 12% of D9802 cases and 5% of ARST0431 cases. Fusion-negative RMS had a superior EFS to fusion-positive RMS; however, poorer outcome for metastatic RMS was most related to clinical risk factors including age, primary site, and number of metastatic sites. In contrast to low- or intermediate-risk RMS, in metastatic RMS, clinical risk factors have the most impact on patient outcome. PAX-FOXO1 fusion is more common in patients with a high Oberlin score, but fusion status is not an independent biomarker of prognosis. © 2017 Wiley Periodicals, Inc.

Chronic pre-operative opioid use is a risk factor for increased complications, resource use and costs after cervical fusion.

PubMed

Jain, Nikhil; Brock, John L; Phillips, Frank M; Weaver, Tristan; Khan, Safdar N

2018-04-27

As healthcare transitions to value-based models, there has been an increased focus on patient factors that can influence peri- and post-operative adverse events, resource use, and costs. Many studies have reported risk factors for systemic complications after cervical fusion, but none have studied chronic opioid therapy (COT) as a risk factor. To answer the following questions from a large cohort of patients who underwent primary cervical fusion for degenerative pathology: (1) What is the patient profile associated with pre-operative COT? (2) Is pre-operative COT a risk factor for 90-day systemic complications, emergency department (ED) visits, readmission, and one-year adverse events? (3) What are the risk factors and one-year adverse events related to long-term post-operative opioid use? and (4) How much did payers reimburse for management of complications and adverse events? Retrospective review of Humana commercial insurance data (2007-Q3 2015). 29,101 patients undergoing primary cervical fusion for degenerative pathology. Patients and procedures of interest were included using International Classification of Diseases (ICD) coding. Patients with opioid prescriptions for >6 months before surgery were considered as having pre-operative COT. Patients with continued opioid use till one-year after surgery were considered as long-term users. Descriptive analysis of patient cohorts has been done. Multiple-variable logistic regression analyses adjusting for approach, number of levels of surgery, discharge disposition, and comorbidities were done to answer first three study questions. Reimbursement data from insurers has been reported to answer our fourth study question. Of the entire cohort, 6,643 (22.8%) had pre-operative COT. Pre-operative COT was associated with a higher risk of 90-day wound complications (OR 1.39, 95% CI:1.16-1.66), all-cause 90-day ED visits (adjusted OR 1.22, 95% CI:1.13-1.32), and pain-related ED visits (adjusted OR 1.39, 95% CI:1.24-1.55). Patients who had pre-operative COT were more likely to receive epidural and/or facet joint injections within one-year after surgery (adjusted OR 1.68, 95% CI: 1.47-1.92). These patients were also more likely to undergo a repeat cervical fusion within a year as compared to patients who did not have pre-operative COT (adjusted OR 1.21, 95% CI: 1.01-1.43). Pre-operative COT had a higher likelihood of long-term use after surgery (adjusted OR 4.72, 95% CI:4.41-5.06). Long-term opioid use after surgery was associated with a higher risk of new-onset constipation (adjusted OR 1.34, 95% CI:1.22-1.48). The risk of complications and adverse events was not found to be significant in patients with < 3-months pre-operative opioid use or those who stopped opioids for at-least 6-weeks before surgery. The cost of additional resource use for medications, ED visits, constipation, injections and revision fusion ranged from $623-$27,360 per patient. Pre-operative opioid use among cervical fusion patients increases complication rates, post-operative opioid usage, healthcare resource utilization and costs. These risks may be reduced by restricting the duration of pre-operative opioid use or weaning off before surgery. Better understanding and management of pain in the pre-operative period with judicious use of opioids is critical to enhance outcomes after cervical fusion surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

PubMed

Murgia, Claudio; Caporale, Marco; Ceesay, Ousman; Di Francesco, Gabriella; Ferri, Nicola; Varasano, Vincenzo; de las Heras, Marcelo; Palmarini, Massimo

2011-03-01

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

Proline-coated column for the capillary electrochromatographic separation of amino acids by in-column derivatization.

PubMed

Lin, Chun-Chi; Liu, Chuen-Ying

2004-10-01

With 3-trimethoxysilylpropyl chloride as the spacer, a proline-coated capillary column was prepared for the capillary electrochromatographic (CEC) separation of amino acids by in-column derivatization. Nine standard mixtures, including aspartic acid, glutamic acid, valine, phenylalanine, alanine, isoleucine, leucine, tyrosine, and tryptophan, were injected. o-Phthalaldehyde (OPA), OPA/2-mercaptoethanol (2-ME) and OPA/N-acetylcysteine (NAC) in borate buffer were tested as the derivatizing agent. Among them, OPA (50 mM) in borate buffer (pH 9.5, 50 mM) gave the best performance. The formation of isoindole could be detected by UV detection. The sandwich-type injection was carried out in hydrostatic mode (10 cm) with the program R(10 s)S(10 s) R(10 s)W(10 min) with R, S, and W being the reagent, sample, and waiting times. Mesityl oxide, benzyl alcohol, and acetone showed some interaction with the column. A current monitoring method was used instead of the determination of the electroosmotic flow (EOF). The direction of EOF was from anode to cathode even under acidic condition lower than the pI value (6.31) of the bonded group due to some unreacted silanol groups. Some parameters including pH, nature, and concentration of the mobile phase and the effect of organic modifier with regard to the CEC separation were investigated. With the proline-coated column (75 (50) cm x 75 microm ID) the best separation was performed in phosphate buffer (pH 4.00, 100 mM) with an applied voltage of -15 kV. The established method was also compared with those precolumn derivatized prior to the separation with proline-coated column as well as with in-capillary derivatization and separation with a bare fused-silica column. Copyright 2004 WILEY-VCH Verlag GmbH & Co.

Genetic diversity of Palestine landraces of faba bean (Vicia faba) based on RAPD markers.

PubMed

Basheer-Salimia, R; Shtaya, M; Awad, M; Abdallah, J; Hamdan, Y

2013-09-03

Until now, neither phenotypic nor molecular approaches have been used to characterize the landraces of Palestine faba beans (Vicia faba). We used PCR-based RAPD markers to determine the genetic diversity and relatedness among 26 Palestinian faba bean landraces (traditional farmers' varieties) from 8 localities in the West Bank, Palestine. In tests with 37 primers, 14 generated no polymorphic bands, 12 exhibited weak and unclear products, and 11 primers produced good amplification products with high intensity and pattern stability. Ninety-four DNA fragments (loci) were detected, with an average of 8.54 loci per primer and size ranging from 160 to 1370 bp. A minimum of 4 and a maximum of 14 DNA fragments were obtained using (OPA-05 and OPA-09) and (BC-261) primers, respectively. The maximum percentage of polymorphic markers was 71.4 (BC-298) and the minimum was 50.0 (OPA-05, -09, -16). The 11 primers exhibited relatively high collective resolving power (Rp) values of 26.316, and varied from 0.154 for the OPA-09 primer to 5.236 for the BC-261, with an overall mean of 2.392. The primers BC-261, -322, and -298 were found to be the most useful RAPD primers to assess the genetic diversity of Palestinian faba beans, as they revealed relatively high Rp rates (5.236, 3.618, and 3.150, respectively). Based on the Jaccard coefficient, the genetic distance ranged from 0.358 to 0.069, with a mean of 0.213. We conclude that the RAPD technique is useful for determining genetic diversity and for developing suitable fingerprints for faba bean landraces grown in Palestine.

CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.

PubMed

James, Declan J; Kowalchyk, Judith; Daily, Neil; Petrie, Matt; Martin, Thomas F J

2009-10-13

Ca(2+)-dependent activator protein for secretion (CAPS) is an essential factor for regulated vesicle exocytosis that functions in priming reactions before Ca(2+)-triggered fusion of vesicles with the plasma membrane. However, the precise events that CAPS regulates to promote vesicle fusion are unclear. In the current work, we reconstituted CAPS function in a SNARE-dependent liposome fusion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes. The CAPS stimulation of fusion required PI(4,5)P(2) in acceptor liposomes and was independent of Ca(2+), but Ca(2+) dependence was restored by inclusion of synaptotagmin. CAPS stimulated trans-SNARE complex formation concomitant with the stimulation of full membrane fusion at physiological SNARE densities. CAPS bound syntaxin-1, and CAPS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion. The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane.

2016 Workplace and Gender Relations Survey of Active Duty Members: Statistical Methodology Report

DTIC Science & Technology

2017-03-01

2016 Workplace and Gender Relations Survey of Active Duty Members Statistical Methodology Report Additional copies of this report may be...MEMBERS: STATISTICAL METHODOLOGY REPORT Office of People Analytics (OPA) Defense Research, Surveys, and Statistics Center 4800 Mark Center Drive...20 1 2016 WORKPLACE AND GENDER RELATIONS SURVEY OF ACTIVE DUTY MEMBERS: STATISTICAL METHODOLOGY REPORT

Three Dimensionally Interconnected Silicon Nanomembranes for Optical Phased Array (OPA) and Optical True Time Delay (TTD) Applications

DTIC Science & Technology

2012-06-01

Nanophotonic Waveguides," J. Lightwave Technol. 25 (1), 151-156 (2007). [7-4] Yongbo Tang, Zhechao Wang, Lech Wosinski, Urban Westergren, and Sailing...Waveguides," Photonics Journal, IEEE 3 (2), 203-208 (2011). [8-25] Zhechao Wang, Ning Zhu, Yongbo Tang, Lech Wosinski, Daoxin Dai, and Sailing He

Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer's disease.

PubMed

Manczak, Maria; Kandimalla, Ramesh; Yin, Xiangling; Reddy, P Hemachandra

2018-04-15

The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris water maze tests, immunoblotting and immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2 and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express Swedish mutation. Mitochondrial function was assessed by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. Morris water maze and rotarod tests revealed that hippocampal learning and memory and motor learning and coordination were impaired in APP mice relative to wild-type (WT) mice. Increased levels of mitochondrial fission proteins, Drp1 and Fis1 and decreased levels of fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 and TFAM), autophagy (ATG5 and LC3BI, LC3BII), mitophagy (PINK1 and TERT), synaptic (synaptophysin and PSD95) and dendritic (MAP2) proteins were found in 12-month-old APP mice relative to age-matched non-transgenic WT mice. Golgi-cox staining analysis revealed that dendritic spines are significantly reduced. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in APP mice. These findings suggest that hippocampal accumulation of mutant APP and Aβ is responsible for abnormal mitochondrial dynamics and defective biogenesis, reduced MAP2, autophagy, mitophagy and synaptic proteins and reduced dendritic spines and hippocampal-based learning and memory impairments, and mitochondrial structural and functional changes in 12-month-old APP mice.

Mitochondria-targeted molecules MitoQ and SS31 reduce mutant huntingtin-induced mitochondrial toxicity and synaptic damage in Huntington's disease

PubMed Central

Yin, Xiangling; Manczak, Maria; Reddy, P. Hemachandra

2016-01-01

The objective of this study was to determine the protective effects of the mitochondria-targeted molecules MitoQ and SS31 in striatal neurons that stably express mutant huntingtin (Htt) (STHDhQ111/Q111) in Huntington's disease (HD). We studied mitochondrial and synaptic activities by measuring mRNA and the protein levels of mitochondrial and synaptic genes, mitochondrial function, and ultra-structural changes in MitoQ- and SS31-treated mutant Htt neurons relative to untreated mutant Htt neurons. We used gene expression analysis, biochemical methods, transmission electron microscopy (TEM) and confocal microscopy methods. In the MitoQ- and SS31-treated mutant Htt neurons, fission genes Drp1 and Fis1 were down-regulated, and fusion genes Mfn1, Mfn2 and Opa1 were up-regulated relative to untreated neurons, suggesting that mitochondria-targeted molecules reduce fission activity. Interestingly, the mitochondrial biogenesis genes PGC1α, PGC1β, Nrf1, Nrf2 and TFAM were up-regulated in MitoQ- and SS31-treated mutant Htt neurons. The synaptic genes synaptophysin and PSD95 were up-regulated, and mitochondrial function was normal in the MitoQ- and SS31-treated mutant Htt neurons. Immunoblotting findings of mitochondrial and synaptic proteins agreed with the mRNA findings. TEM studies revealed decreased numbers of structurally intact mitochondria in MitoQ- and SS31-treated mutant Htt neurons. These findings suggest that mitochondria-targeted molecules MitoQ and SS31 are protective against mutant Htt-induced mitochondrial and synaptic damage in HD neurons, and these mitochondria-targeted molecules are potential therapeutic molecules for the treatment of HD neurons. PMID:26908605

Mitochondria-targeted molecules MitoQ and SS31 reduce mutant huntingtin-induced mitochondrial toxicity and synaptic damage in Huntington's disease.

PubMed

Yin, Xiangling; Manczak, Maria; Reddy, P Hemachandra

2016-05-01

The objective of this study was to determine the protective effects of the mitochondria-targeted molecules MitoQ and SS31 in striatal neurons that stably express mutant huntingtin (Htt) (STHDhQ111/Q111) in Huntington's disease (HD). We studied mitochondrial and synaptic activities by measuring mRNA and the protein levels of mitochondrial and synaptic genes, mitochondrial function, and ultra-structural changes in MitoQ- and SS31-treated mutant Htt neurons relative to untreated mutant Htt neurons. We used gene expression analysis, biochemical methods, transmission electron microscopy (TEM) and confocal microscopy methods. In the MitoQ- and SS31-treated mutant Htt neurons, fission genes Drp1 and Fis1 were down-regulated, and fusion genes Mfn1, Mfn2 and Opa1 were up-regulated relative to untreated neurons, suggesting that mitochondria-targeted molecules reduce fission activity. Interestingly, the mitochondrial biogenesis genes PGC1α, PGC1β, Nrf1, Nrf2 and TFAM were up-regulated in MitoQ- and SS31-treated mutant Htt neurons. The synaptic genes synaptophysin and PSD95 were up-regulated, and mitochondrial function was normal in the MitoQ- and SS31-treated mutant Htt neurons. Immunoblotting findings of mitochondrial and synaptic proteins agreed with the mRNA findings. TEM studies revealed decreased numbers of structurally intact mitochondria in MitoQ- and SS31-treated mutant Htt neurons. These findings suggest that mitochondria-targeted molecules MitoQ and SS31 are protective against mutant Htt-induced mitochondrial and synaptic damage in HD neurons, and these mitochondria-targeted molecules are potential therapeutic molecules for the treatment of HD neurons. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Binaural Pitch Fusion in Bilateral Cochlear Implant Users.

PubMed

Reiss, Lina A J; Fowler, Jennifer R; Hartling, Curtis L; Oh, Yonghee

Binaural pitch fusion is the fusion of stimuli that evoke different pitches between the ears into a single auditory image. Individuals who use hearing aids or bimodal cochlear implants (CIs) experience abnormally broad binaural pitch fusion, such that sounds differing in pitch by as much as 3-4 octaves are fused across ears, leading to spectral averaging and speech perception interference. The goal of this study was to determine if adult bilateral CI users also experience broad binaural pitch fusion. Stimuli were pulse trains delivered to individual electrodes. Fusion ranges were measured using simultaneous, dichotic presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the range that fused with the reference stimulus. Bilateral CI listeners had binaural pitch fusion ranges varying from 0 to 12 mm (average 6.1 ± 3.9 mm), where 12 mm indicates fusion over all electrodes in the array. No significant correlations of fusion range were observed with any subject factors related to age, hearing loss history, or hearing device history, or with any electrode factors including interaural electrode pitch mismatch, pitch match bandwidth, or within-ear electrode discrimination abilities. Bilateral CI listeners have abnormally broad fusion, similar to hearing aid and bimodal CI listeners. This broad fusion may explain the variability of binaural benefits for speech perception in quiet and in noise in bilateral CI users.

Laparoscopic vs open approach for transverse colon cancer. A systematic review and meta-analysis of short and long term outcomes.

PubMed

Athanasiou, Christos D; Robinson, Jonathan; Yiasemidou, Marina; Lockwood, Sonia; Markides, Georgios A

2017-05-01

Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparoscopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes. Medline, Embase, Cochrane library, Scopus and Web of Knowledge databases were interrogated. Selected studies were critically appraised and the short-term morbidity and long term oncological outcomes were meta-analyzed. Sensitivity analysis according to the quality of the study, type of procedure (laparoscopic vs laparoscopically assisted) and level of lymphadenectomy was performed. Statistical heterogeneity and publication bias were also investigated. Eleven case control trials (1415 patients) were included in the study. There was no difference between the LPA and the OPA in overall survival [Hazard Ratio (HR) = 0.83 (0.56, 1.22); P = 0.34], disease free survival (p = 0.20), local recurrence (p = 0.81) or distant metastases (p = 0.24). LPA was found to have longer operative time [Weighted mean difference (WMD) = 45.00 (29.48, 60.52); P < 0.00001] with earlier establishment of oral intake [WMD = -1.68 (-1.84, -1.53); P < 0.00001] and shorter hospital stay [WMD = -2.94 (-4.27, -1.62); P = 0.0001]. No difference was found in relation to anastomotic leakage (p = 0.39), intra-abdominal abscess (p = 0.25), lymph nodes harvested (p = 0.17). LPA seems to be safe with equivalent oncological outcomes to OPA and better short term outcomes in selected patient populations. High quality Randomized control trials are required to further investigate the role of laparoscopy in transverse colon cancer. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

The strategy of fusion genes construction determines efficient expression of introduced transcription factors.

PubMed

Adamus, Tomasz; Konieczny, Paweł; Sekuła, Małgorzata; Sułkowski, Maciej; Majka, Marcin

2014-01-01

The main goal in gene therapy and biomedical research is an efficient transcription factors (TFs) delivery system. SNAIL, a zinc finger transcription factor, is strongly involved in tumor, what makes its signaling pathways an interesting research subject. The necessity of tracking activation of intracellular pathways has prompted fluorescent proteins usage as localization markers. Advanced molecular cloning techniques allow to generate fusion proteins from fluorescent markers and transcription factors. Depending on fusion strategy, the protein expression levels and nuclear transport ability are significantly different. The P2A self-cleavage motif through its cleavage ability allows two single proteins to be simultaneously expressed. The aim of this study was to compare two strategies for introducing a pair of genes using expression vector system. We have examined GFP and SNAI1 gene fusions by comprising common nucleotide polylinker (multiple cloning site) or P2A motif in between them, resulting in one fusion or two independent protein expressions respectively. In each case transgene expression levels and translation efficiency as well as nuclear localization of expressed protein have been analyzed. Our data showed that usage of P2A motif provides more effective nuclear transport of SNAIL transcription factor than conventional genes linker. At the same time the fluorescent marker spreads evenly in subcellular space.

Antibiotic Resistance In Neisseria Gonorrhoeae: Impact Of Ceftriaxone Resistance On Microbial Fitness And Potential Of Resistance Determinants To Spread During Mixed Infection

DTIC Science & Technology

2016-03-07

14 1.4d Antibacterial Drug Resistance .......................................................................... 17 1.4d1 Modification of the...Depending upon receptor engagement, Opa-mediated interactions can either activate the innate immune system via neutrophil activation or suppress the...himself was never able to develop the antibacterial mold he had discovered into a mass-produced antibiotic for human use, efforts by scientists in

Scattering and Polarization Measurements Using the PL/OPA Low Altitude Lidar

DTIC Science & Technology

1990-12-20

66 A.3.2 Application to Lidar Data .. .. .. .. .. ... ... ... .. 70 References 72 iv List of Figures 1 The Poincare ... the vcctor in the I __ plane is the degree of linear polarization (defined as [Q2 + U2 II/2 /1). The component of the vector along the K axis is the ...scattering refers to the scattering of a monochromatic electromagr1tic plane wave by a spherically shaped, homogeneous, isotropic dielectric and conducting

Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs.

PubMed

You, Jinyoung; Lee, Joohyeong; Kim, Jinyoung; Park, Junhong; Lee, Eunsong

2010-02-01

The objective of this study was to examine the effect of post-fusion treatment of somatic cell nuclear transfer (SCNT) oocytes with the proteasomal inhibitor MG132 on maturation promoting factor (MPF) activity, nuclear remodeling, embryonic development, and gene expression of cloned pig embryos. Immediately after electrofusion, SCNT oocytes were treated with MG132 and/or caffeine for 2 hr, vanadate for 0.5 hr, or vanadate for 0.5 hr followed by MG132 for 1.5 hr. Of the MG132 concentrations tested (0-5 microM), the 1 microM concentration showed a higher rate of blastocyst formation (25.9%) than 0 (14.2%), 0.5 (16.9%), and 5 microM (16.9%). Post-fusion treatment with MG132, caffeine, and both MG132 and caffeine improved blastocyst formation (22.1%, 21.4%, and 24.4%, respectively), whereas vanadate treatment inhibited blastocyst formation (6.5%) compared to the control (11.1%). When examined 2 hr after fusion and 1 hr after activation, MPF activity remained at a higher (P < 0.05) level in SCNT oocytes that were treated post-fusion with caffeine and/or MG132, but it was decreased by vanadate. The rate of oocytes showing premature chromosome condensation was not altered by MG132 but was decreased by vanadate treatment. In addition, formation of single pronuclei was increased by MG132 compared to control and vanadate treatment. MG132-treated embryos showed increased expression of POU5F1, DPPA2, DPPA3, DPPA5, and NDP52l1 genes compared to control embryos. Our results demonstrate that post-fusion treatment of SCNT oocytes with MG132 prevents MPF degradation and increases expression of transcription factors in SCNT embryos, which are necessary for normal development of SCNT embryos. (c) 2009 Wiley-Liss, Inc.

Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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

Liu, Penghao; Xie, Qihai; Wei, Tong

Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in bothmore » strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.« less

Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers.

PubMed

Scott, Kenneth A; Browning, Raymond C

2016-01-01

Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well.

Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway.

PubMed

Werner, Haim; Meisel-Sharon, Shilhav; Bruchim, Ilan

2018-02-19

The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis. Increasing evidence gathered over the past fifteen years demonstrate that this type of genomic rearrangements is common not only among pediatric and hematological malignancies, as classically thought, but may also provide a molecular and cytogenetic foundation for an ever-increasing portion of adult epithelial tumors. In this review article we provide evidence that the mechanism of action of oncogenic fusion proteins associated with both pediatric and adult malignancies involves transactivation of the IGF1R gene, with ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation. Disrupted transcription factors adopt the IGF1R signaling pathway and elicit their oncogenic activities via activation of this critical regulatory network. Combined targeting of oncogenic fusion proteins along with the IGF1R may constitute a promising therapeutic approach.

Tuning the Band Bending and Controlling the Surface Reactivity at Polar and Nonpolar Surfaces of ZnO through Phosphonic Acid Binding.

PubMed

McNeill, Alexandra R; Hyndman, Adam R; Reeves, Roger J; Downard, Alison J; Allen, Martin W

2016-11-16

ZnO is a prime candidate for future use in transparent electronics; however, development of practical materials requires attention to factors including control of its unusual surface band bending and surface reactivity. In this work, we have modified the O-polar (0001̅), Zn-polar (0001), and m-plane (101̅0) surfaces of ZnO with phosphonic acid (PA) derivatives and measured the effect on the surface band bending and surface sensitivity to atmospheric oxygen. Core level and valence band synchrotron X-ray photoemission spectroscopy was used to measure the surface band bending introduced by PA modifiers with substituents of opposite polarity dipole moment: octadecylphosphonic acid (ODPA) and 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctylphosphonic acid (F 13 OPA). Both PAs act as surface electron donors, increasing the downward band bending and the strength of the two-dimensional surface electron accumulation layer on all of the ZnO surfaces investigated. On the O-polar (0001̅) and m-plane (101̅0) surfaces, the ODPA modifier produced the largest increase in downward band bending relative to the hydroxyl-terminated unmodified surface of 0.55 and 0.35 eV, respectively. On the Zn-polar (0001) face, the F 13 OPA modifier gave the largest increase (by 0.50 eV) producing a total downward band bending of 1.00 eV, representing ∼30% of the ZnO band gap. Ultraviolet (UV) photoinduced surface wettability and photoconductivity measurements demonstrated that the PA modifiers are effective at decreasing the sensitivity of the surface toward atmospheric oxygen. Modification with PA derivatives produced a large increase in the persistence of UV-induced photoconductivity and a large reduction in UV-induced changes in surface wettability.

High-performance liquid chromatography - Ultraviolet method for the determination of total specific migration of nine ultraviolet absorbers in food simulants based on 1,1,3,3-Tetramethylguanidine and organic phase anion exchange solid phase extraction to remove glyceride.

PubMed

Wang, Jianling; Xiao, Xiaofeng; Chen, Tong; Liu, Tingfei; Tao, Huaming; He, Jun

2016-06-17

The glyceride in oil food simulant usually causes serious interferences to target analytes and leads to failure of the normal function of the RP-HPLC column. In this work, a convenient HPLC-UV method for the determination of the total specific migration of nine ultraviolet (UV) absorbers in food simulants was developed based on 1,1,3,3-tetramethylguanidine (TMG) and organic phase anion exchange (OPAE) SPE to efficiently remove glyceride in olive oil simulant. In contrast to the normal ion exchange carried out in an aqueous solution or aqueous phase environment, the OPAE SPE was performed in the organic phase environments, and the time-consuming and challenging extraction of the nine UV absorbers from vegetable oil with aqueous solution could be readily omitted. The method was proved to have good linearity (r≥0.99992), precision (intra-day RSD≤3.3%), and accuracy(91.0%≤recoveries≤107%); furthermore, the lower limit of quantifications (0.05-0.2mg/kg) in five types of food simulants(10% ethanol, 3% acetic acid, 20% ethanol, 50% ethanol and olive oil) was observed. The method was found to be well suited for quantitative determination of the total specific migration of the nine UV absorbers both in aqueous and vegetable oil simulant according to Commission Regulation (EU) No. 10/2011. Migration levels of the nine UV absorbers were determined in 31 plastic samples, and UV-24, UV-531, HHBP and UV-326 were frequently detected, especially in olive oil simulant for UV-326 in PE samples. In addition, the OPAE SPE procedure was also been applied to efficiently enrich or purify seven antioxidants in olive oil simulant. Results indicate that this procedure will have more extensive applications in the enriching or purification of the extremely weak acidic compounds with phenol hydroxyl group that are relatively stable in TMG n-hexane solution and that can be barely extracted from vegetable oil. Copyright © 2016 Elsevier B.V. All rights reserved.

Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

PubMed

Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode

2012-01-01

Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis

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

Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br; Iscaife, Alexandre, E-mail: iscaifeboni@yahoo.com.br; Yoshinaga, Eduardo M., E-mail: dumuracca@ig.com.br

PurposeTo compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia.MethodsWe prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL).ResultsAll groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q{sub max}), both of which were significantly better in the TURP group,more » and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q{sub max}. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q{sub max} and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria.ConclusionsTURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.« less

Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

PubMed

Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

2015-01-01

This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

PubMed Central

Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

2015-01-01

This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3–4–5 months of age) and booster vaccination (17–19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children. PMID:25830489

Impact of temporal, spatial and cascaded effects on the pulse formation in ultra-broadband parametric amplifiers.

PubMed

Lang, T; Harth, A; Matyschok, J; Binhammer, T; Schultze, M; Morgner, U

2013-01-14

A 2 + 1 dimensional nonlinear pulse propagation model is presented, illustrating the weighting of different effects for the parametric amplification of ultra-broadband spectra in different regimes of energy scaling. Typical features in the distribution of intensity and phase of state-of-the-art OPA-systems can be understood by cascaded spatial and temporal effects.

Development of a simple fluorescence-based microplate method for the high-throughput analysis of proline in wine samples.

PubMed

Robert-Peillard, Fabien; Boudenne, Jean-Luc; Coulomb, Bruno

2014-05-01

This paper presents a simple, accurate and multi-sample method for the determination of proline in wines thanks to a 96-well microplate technique. Proline is the most abundant amino acid in wine and is an important parameter related to wine characteristics or maturation processes of grape. In the current study, an improved application of the general method based on sodium hypochlorite oxidation and o-phthaldialdehyde (OPA)-thiol spectrofluorometric detection is described. The main interfering compounds for specific proline detection in wines are strongly reduced by selective reaction with OPA in a preliminary step under well-defined pH conditions. Application of the protocol after a 500-fold dilution of wine samples provides a working range between 0.02 and 2.90gL(-1), with a limit of detection of 7.50mgL(-1). Comparison and validation on real wine samples by ion-exchange chromatography prove that this procedure yields accurate results. Simplicity of the protocol used, with no need for centrifugation or filtration, organic solvents or high temperature enables its full implementation in plastic microplates and efficient application for routine analysis of proline in wines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ozone-initiated terpene reaction products in five European offices: replacement of a floor cleaning agent.

PubMed

Nørgaard, A W; Kofoed-Sørensen, V; Mandin, C; Ventura, G; Mabilia, R; Perreca, E; Cattaneo, A; Spinazzè, A; Mihucz, V G; Szigeti, T; de Kluizenaar, Y; Cornelissen, H J M; Trantallidi, M; Carrer, P; Sakellaris, I; Bartzis, J; Wolkoff, P

2014-11-18

Cleaning agents often emit terpenes that react rapidly with ozone. These ozone-initiated reactions, which occur in the gas-phase and on surfaces, produce a host of gaseous and particulate oxygenated compounds with possible adverse health effects in the eyes and airways. Within the European Union (EU) project OFFICAIR, common ozone-initiated reaction products were measured before and after the replacement of the regular floor cleaning agent with a preselected low emitting floor cleaning agent in four offices located in four EU countries. One reference office in a fifth country did not use any floor cleaning agent. Limonene, α-pinene, 3-carene, dihydromyrcenol, geraniol, linalool, and α-terpineol were targeted for measurement together with the common terpene oxidation products formaldehyde, 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), 6-methyl-5-heptene-2-one, (6-MHO), 4-oxopentanal (4-OPA), and dihydrocarvone (DHC). Two-hour air samples on Tenax TA and DNPH cartridges were taken in the morning, noon, and in the afternoon and analyzed by thermal desorption combined with gas chromatography/mass spectrometry and HPLC/UV analysis, respectively. Ozone was measured in all sites. All the regular cleaning agents emitted terpenes, mainly limonene and linalool. After the replacement of the cleaning agent, substantially lower concentrations of limonene and formaldehyde were observed. Some of the oxidation product concentrations, in particular that of 4-OPA, were also reduced in line with limonene. Maximum 2 h averaged concentrations of formaldehyde, 4-AMCH, 6-MHO, and IPOH would not give rise to acute eye irritation-related symptoms in office workers; similarly, 6-AMCH, DHC and 4-OPA would not result in airflow limitation to the airways.

Genetic analysis of Bacillus stearothermophilus by protoplast fusion

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

Chen, Z.; Wojcik, S.F.; Welker, N.E.

1986-03-01

Efficient and reliable protoplasting, regeneration, and fusion techniques were established for the prototrophic strain Bacillus stearothermophilus NUB36. Auxotrophic mutants were isolated, and protoplast fusion was used to construct isogenic mutant strains and for chromosomal mapping. Markers were mapped using two-, three-, and four-factor crosses. The order of the markers was hom-1-thr-1-his-1-(gly-1 or gly-2)-pur-1-pur-2. These markers may be analogous to hom, thrA, hisA, glyC, and purA markers on the Bacillus subtilis chromosome. No analogous pur-1 marker has been reported in B. subtilis. The relative order of three of the markers (hom-1-thr-1-gly-1) was independently confirmed by transduction.

Surgical and Functional Outcomes After Multilevel Cervical Fusion for Degenerative Disc Disease Compared With Fusion for Radiculopathy: A Study of Workers' Compensation Population.

PubMed

Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

2017-05-01

Retrospective cohort comparative study. To evaluate presurgical and surgical factors that affect return to work (RTW) status after multilevel cervical fusion, and to compare outcomes after multilevel cervical fusion for degenerative disc disease (DDD) versus radiculopathy. Cervical fusion provides more than 90% of symptomatic relief for radiculopathy and myelopathy. However, cervical fusion for DDD without radiculopathy is considered controversial. In addition, multilevel fusion is associated with poorer surgical outcomes with increased levels fused. Data of cervical comorbidities was collected from Ohio Bureau of Workers' Compensation for subjects with work-related injuries. The study population included subjects who underwent multilevel cervical fusion. Patients with radiculopathy or DDD were identified. Multivariate logistic regression was performed to identify factors that affect RTW status. Surgical and functional outcomes were compared between groups. Stable RTW status within 3 years after multilevel cervical fusion was negatively affected by: fusion for DDD, age > 55 years, preoperative opioid use, initial psychological evaluation before surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P= 0.0003) compared with radiculopathy group. DDD patients were less likely to have a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P= 0.001), and higher rate of disability after surgery (P= 0.002). Multiple detriments affect stable RTW status after multilevel cervical fusion including DDD. DDD without radiculopathy was associated with lower RTW rates, less likelihood to return to work, higher disability, and higher opioid use after surgery. Multilevel cervical fusion for DDD may be counterproductive. Future studies should investigate further treatment options of DDD, and optimize patient selection criteria for surgical intervention. 3.

What are the Risk Factors for Cerebrovascular Accidents After Elective Orthopaedic Surgery?

PubMed

Minhas, Shobhit V; Goyal, Preeya; Patel, Alpesh A

2016-03-01

Perioperative cerebrovascular accidents (CVAs) are one of the leading causes of patient morbidity, mortality, and medical costs. However, little is known regarding the rates of these events and risk factors for CVA after elective orthopaedic surgery. Our goals were to (1) establish the national, baseline proportion of patients experiencing a 30-day CVA and the timing of CVA; and (2) determine independent risk factors for 30-day CVA rates after common elective orthopaedic procedures. Patients undergoing elective TKA, THA, posterior or posterolateral lumbar fusion, anterior cervical discectomy and fusion, and total shoulder arthroplasty, from 2006 to 2012, were identified from the American College of Surgeons National Surgical Quality Improvement Program(®) database. A total of 42,150 patients met inclusion criteria. Thirty-day CVA rates were recorded for each procedure, and patients were assessed for characteristics associated with CVA through univariate analysis. Multivariate regression models were created to identify independent risk factors for CVA. A total of 55 (0.13%) patients experienced a CVA within 30 days of the procedure, occurring a median of 2 days after surgery (range, 1-30 days) with 0.08% of patients experiencing a CVA after TKA, 0.15% after THA, 0.00% after single-level anterior cervical discectomy and fusion, 0.38% after multilevel anterior cervical discectomy and fusions, 0.20% after single-level posterior or posterolateral lumbar fusion, 0.70% after multilevel posterior or posterolateral lumbar fusion, and 0.22% after total shoulder arthroplasty. Independent risk factors for CVA included age of 75 years or older (odds ratio [OR], 2.50; 95% CI, 1.44-4.35; p = 0.001), insulin-dependent diabetes mellitus (OR, 3.08; CI, 1.47-6.45; p = 0.003), hypertension (OR, 2.71; CI, 1.19-6.13; p = 0.017), history of transient ischemic attack (OR, 2.83; CI, 1.24-6.45; p = 0.013), dyspnea (OR, 2.51; CI, 1.30-4.86; p = 0.006), chronic obstructive pulmonary disease (OR, 2.33; CI, 1.06-5.13; p = 0.036), and operative time of 180 minutes or greater (OR, 3.25; CI 1.60-6.60; p = 0.001). Numerous nonmodifiable patient comorbidities and increased operative time were associated with CVA after elective orthopaedic procedures. However, the American College of Surgeons National Surgical Quality Improvement Program(®) database does not code for cardiac arrhythmia or atrial fibrillation, which other studies have suggested may be important predictor variables; those may be important risk factors, although we were unable to evaluate them in our study. Surgeons should counsel patients with these risk factors and limit their operative time to reduce the risk of these adverse events, and future studies should examine other patient characteristics such as arrhythmia and noncoronary heart disease and assess the role of pharmacologic prophylaxis in patients with these risk factors. Level III, prognostic study.

3D Neutronic Analysis in MHD Calculations at ARIES-ST Fusion Reactors Systems

NASA Astrophysics Data System (ADS)

Hançerliogulları, Aybaba; Cini, Mesut

2013-10-01

In this study, we developed new models for liquid wall (FW) state at ARIES-ST fusion reactor systems. ARIES-ST is a 1,000 MWe fusion reactor system based on a low aspect ratio ST plasma. In this article, we analyzed the characteristic properties of magnetohydrodynamics (MHD) and heat transfer conditions by using Monte-Carlo simulation methods (ARIES Team et al. in Fusion Eng Des 49-50:689-695, 2000; Tillack et al. in Fusion Eng Des 65:215-261, 2003) . In fusion applications, liquid metals are traditionally considered to be the best working fluids. The working liquid must be a lithium-containing medium in order to provide adequate tritium that the plasma is self-sustained and that the fusion is a renewable energy source. As for Flibe free surface flows, the MHD effects caused by interaction with the mean flow is negligible, while a fairly uniform flow of thick can be maintained throughout the reactor based on 3-D MHD calculations. In this study, neutronic parameters, that is to say, energy multiplication factor radiation, heat flux and fissile fuel breeding were researched for fusion reactor with various thorium and uranium molten salts. Sufficient tritium amount is needed for the reactor to work itself. In the tritium breeding ratio (TBR) >1.05 ARIES-ST fusion model TBR is >1.1 so that tritium self-sufficiency is maintained for DT fusion systems (Starke et al. in Fusion Energ Des 84:1794-1798, 2009; Najmabadi et al. in Fusion Energ Des 80:3-23, 2006).

ALS-associated mutation SOD1G93A leads to abnormal mitochondrial dynamics in osteocytes.

PubMed

Wang, Huan; Yi, Jianxun; Li, Xuejun; Xiao, Yajuan; Dhakal, Kamal; Zhou, Jingsong

2018-01-01

While the death of motor neuron is a pathological hallmark of amyotrophic lateral sclerosis (ALS), defects in other cell types or organs may also actively contribute to ALS disease progression. ALS patients experience progressive skeletal muscle wasting that may not only exacerbate neuronal degeneration, but likely has a significant impact on bone function. In our previous published study, we have discovered severe bone loss in an ALS mouse model with overexpression of ALS-associated mutation SOD1 G93A (G93A). Here we further provide a mechanistic understanding of the bone loss in ALS animal and cellular models. Combining mitochondrial fluorescent indicators and confocal live cell imaging, we discovered abnormalities in mitochondrial network and dynamics in primary osteocytes derived from the same ALS mouse model G93A. Those mitochondrial defects occur in ALS mice after the onset of neuromuscular symptoms, indicating that mitochondria in bone cells respond to muscle atrophy during ALS disease progression. To examine whether ALS mutation has a direct contribution to mitochondrial dysfunction independent of muscle atrophy, we evaluated mitochondrial morphology and motility in cultured osteocytes (MLO-Y4) with overexpression of mitochondrial targeted SOD1 G93A . Compared with osteocytes overexpressing the wild type SOD1 as a control, the SOD1 G93A osteocytes showed similar defects in mitochondrial network and dynamic as that of the primary osteocytes derived from the ALS mouse model. In addition, we further discovered that overexpression of SOD1 G93A enhanced the expression level of dynamin-related protein 1 (Drp1), a key protein promoting mitochondrial fission activity, and reduced the expression level of optic atrophy protein 1 (OPA1), a key protein related to mitochondrial fusion. A specific mitochondrial fission inhibitor (Mdivi-1) partially reversed the effect of SOD1 G93A on mitochondrial network and dynamics, indicating that SOD1 G93A likely promotes mitochondrial fission, but suppresses the fusion activity. Our data provide the first evidence that mitochondria show abnormality in osteocytes derived from an ALS mouse model. The accumulation of mutant SOD1 G93A protein inside mitochondria directly causes dysfunction in mitochondrial dynamics in cultured MLO-Y4 osteocytes. In addition, the ALS mutation SOD1 G93A -mediated dysfunction in mitochondrial dynamics is associated with an enhanced apoptosis in osteocytes, which could be a potential mechanism underlying the bone loss during ALS progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of Glycemic Control on Morbidity and Mortality in Adult Idiopathic Scoliosis Patients Undergoing Spinal Fusion.

PubMed

Shin, John I; Phan, Kevin; Kothari, Parth; Kim, Jun S; Guzman, Javier Z; Cho, Samuel K

2017-08-01

This is a retrospective analysis of administrative database. To elucidate the effect of glycemic control on surgical outcomes of middle-aged and elderly idiopathic scoliosis patients undergoing spinal fusion surgery. Diabetes mellitus (DM) is a condition thought to adversely affect outcomes of spine surgery. However, no study has stratified glycemic control levels and their impact on outcome for idiopathic scoliosis patients receiving a spinal fusion surgery. Previous studies may have reported higher than true rates of complications for controlled diabetic patients, who are the majority of diabetic patients. The Nationwide Inpatient Sample was queried from years 2002 to 2011. We extracted idiopathic scoliosis patients older than 45 years of age that received spinal fusion and analyzed complications and outcomes variables among 3 cohorts: nondiabetic patients, controlled diabetics, and uncontrolled diabetics. Multivariate analyses were used to assess whether glycemic control was a risk factor for adverse postoperative outcomes. Controlled diabetics had significantly increased rates of acute renal failure (ARF), while uncontrolled diabetics had significantly increased rates of acute postoperative hemorrhage. In multivariate analyses controlling for patient factors and comorbidities, controlled DM was found to be an independent predictor of ARF [odds ratio (OR), 1.863; 95% confidence interval (CI), 1.346-2.579; P=0.0002), and uncontrolled DM was found to be a significant risk factor for acute postoperative hemorrhage (OR, 2.182; 95% CI, 1.192-3.997; P=0.0115), ARF (OR, 4.839; 95% CI, 1.748-13.392; P=0.0024), deep vein thrombosis (OR, 5.825; 95% CI, 1.329-25.522, P=0.0194) and in-patient mortality (OR, 8.889; 95% CI, 1.001-78.945; P=0.0499). Controlled DM was found to be a risk factor for ARF in adult idiopathic scoliosis patients undergoing spinal fusion surgery, while uncontrolled DM was shown to be a risk factor for postoperative hemorrhage, ARF, deep vein thrombosis, and mortality. The present study provides valuable data for better informed consent for patients with diabetes considering surgery for idiopathic scoliosis. Level III.

Hybrid testing of lumbar CHARITE discs versus fusions.

PubMed

Panjabi, Manohar; Malcolmson, George; Teng, Edward; Tominaga, Yasuhiro; Henderson, Gweneth; Serhan, Hassan

2007-04-20

An in vitro human cadaveric biomechanical study. To quantify effects on operated and other levels, including adjacent levels, due to CHARITE disc implantations versus simulated fusions, using follower load and the new hybrid test method in flexion-extension and bilateral torsion. Spinal fusion has been associated with long-term accelerated degeneration at adjacent levels. As opposed to the fusion, artificial discs are designed to preserve motion and diminish the adjacent-level effects. Five fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension and bilateral torsion with 400 N follower load. Intact specimen total ranges of motion were determined with +/-10 Nm unconstrained pure moments. The intact range of motion was used as input for the hybrid tests of 5 constructs: 1) CHARITE disc at L5-S1; 2) fusion at L5-S1; 3) CHARITE discs at L4-L5 and L5-S1; 4) CHARITE disc at L4-L5 and fusion at L5-S1; and 5) 2-level fusion at L4-L5-S1. Using repeated-measures single factor analysis of variance and Bonferroni statistical tests (P < 0.05), intervertebral motion redistribution of each construct was compared with the intact. In flexion-extension, 1-level CHARITE disc preserved motion at the operated and other levels, while 2-level CHARITE showed some amount of other-level effects. In contrast, 1- and 2-level fusions increased other-level motions (average, 21.0% and 61.9%, respectively). In torsion, both 1- and 2-level discs preserved motions at all levels. The 2-level simulated fusion increased motions at proximal levels (22.9%), while the 1-level fusion produced no significant changes. In general, CHARITE discs preserved operated- and other-level motions. Fusion simulations affected motion redistribution at other levels, including adjacent levels.

Risk of revision surgery for adult idiopathic scoliosis: a survival analysis of 517 cases over 25 years.

PubMed

Riouallon, Guillaume; Bouyer, Benjamin; Wolff, Stéphane

2016-08-01

Little is known about the long-term status of patients operated for spine deformities. The aim of this study was to determine the survival of primary fusion in adult idiopathic scoliosis and identify the risk factors of revision surgery. Adult patients who underwent primary fusion for idiopathic scoliosis between 1983 and 2011 were included in a continuous monocentric retrospective series. Any additional surgery was registered for survival analysis. Survival and follow-up were estimated by the Kaplan-Meier method and an analysis was performed to identify the risk factors of revision surgery. This series included 447 women (86.5 %) and 70 men (13.5 %) reviewed after a mean follow-up of 7 years (range 0-26.4). Mean age was 44.4 years. Fusion was performed on a median 11 levels (range 3-15); revision rate was 13 % (CI 10-17), 18 % (CI 14-23) and 20 % (CI 16-26) at 5, 10 and 15 years, respectively. Revision surgery was associated with age, anterior release, length of fusion, the inferior limit of fusion, post-operative sagittal balance and junctional kyphosis. The length of fusion (HR 1.13 per vertebrae fused, p = 0.007) and the lower limit of fusion (HR 5.9, p < 0.001) remained independent predictors of revision surgery on multivariate analysis. This series evaluated the risk of revision surgery following spinal fusion for idiopathic scoliosis. Our results show that the risk seemed to increase linearly with a rate of nearly 20 % after 10 years. The length and lower limit of fusion are the main risk factors for revision surgery. Level IV (e.g. case series).

A rapid and efficient newly established method to detect COL1A1-PDGFB gene fusion in dermatofibrosarcoma protuberans

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

Yokoyama, Yoko; Shimizu, Akira; Okada, Etsuko

Highlights: Black-Right-Pointing-Pointer We developed new method to rapidly identify COL1A1-PDGFB fusion in DFSP. Black-Right-Pointing-Pointer New PCR method using a single primer pair detected COL1A1-PDGFB fusion in DFSP. Black-Right-Pointing-Pointer This is the first report of DFSP with a novel COL1A1 breakpoint in exon 5. -- Abstract: The detection of fusion transcripts of the collagen type 1{alpha}1 (COL1A1) and platelet-derived growth factor-BB (PDGFB) genes by genetic analysis has recognized as a reliable and valuable molecular tool for the diagnosis of dermatofibrosarcoma protuberans (DFSP). To detect the COL1A1-PDGFB fusion, almost previous reports performed reverse transcription polymerase chain reaction (RT-PCR) using multiplex forward primersmore » from COL1A1. However, it has possible technical difficulties with respect to the handling of multiple primers and reagents in the procedure. The objective of this study is to establish a rapid, easy, and efficient one-step method of PCR using only a single primer pair to detect the fusion transcripts of the COL1A1 and PDGFB in DFSP. To validate new method, we compared the results of RT-PCR in five patients of DFSP between the previous method using multiplex primers and our established one-step RT-PCR using a single primer pair. In all cases of DFSP, the COL1A1-PDGFB fusion was detected by both previous method and newly established one-step PCR. Importantly, we detected a novel COL1A1 breakpoint in exon 5. The newly developed method is valuable to rapidly identify COL1A1-PDGFB fusion transcripts in DFSP.« less

The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged?

PubMed

Rizo, Josep; Südhof, Thomas C

2012-01-01

Neurotransmitter release is governed by proteins that have homo-logs in most types of intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes together. SNARE maintenance in a functional state depends on two chaperone systems (Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration. Munc18-1 binds to an autoinhibitory closed conformation of syntaxin-1, gating formation of SNARE complexes, and also binds to SNARE complexes, which likely underlies the crucial function of Munc18-1 in membrane fusion by an as-yet unclear mechanism. Syntaxin-1 opening is mediated by Munc13s through their MUN domain, which is homologous to diverse tethering factors and may also have a general role in fusion. MUN domain activity is likely modulated in diverse presynaptic plasticity processes that depend on Ca(2+) and RIM proteins, among others.

Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

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

Wünsche, Martin; Fuchs, Silvio; Aull, Stefan

A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

DOE PAGES

Wünsche, Martin; Fuchs, Silvio; Aull, Stefan; ...

2017-03-16

A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

Pioneer Venus Data Analysis

NASA Technical Reports Server (NTRS)

Jones, Douglas E.

1996-01-01

Analysis and interpretation of data from the Orbiter Retarding Potential Analyzer (ORPA) onboard the Pioneer Venus Orbiter is reported. By comparing ORPA data to proton data from the Orbiter Plasma Analyzer (OPA), it was found that the ORPA suprathermal electron densities taken outside the Venusian ionopause represent solar wind electron densities, thus allowing the high resolution study of Venus bow shocks using both magnetic field and solar wind electron data. A preliminary analysis of 366 bow shock penetrations was completed using the solar wind electron data as determined from ORPA suprathermal electron densities and temperatures, resulting in an estimate of the extent to which mass loading pickup of O+ (UV ionized O atoms flowing out of the Venus atmosphere) upstream of the Venus obstacle occurred. The pickup of O+ averaged 9.95%, ranging from 0.78% to 23.63%. Detailed results are reported in two attached theses: (1) Comparison of ORPA Suprathermal Electron and OPA Solar Wind Proton Data from the Pioneer Venus Orbiter and (2) Pioneer Venus Orbiter Retarding Potential Analyzer Observations of the Electron Component of the Solar Wind, and of the Venus Bow Shock and Magnetosheath.

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

ESWR1-CREM Fusion in an Intracranial Myxoid Angiomatoid Fibrous Histiocytoma-Like Tumor: A Case Report and Literature Review.

PubMed

Gareton, Albane; Pierron, Gaëlle; Mokhtari, Karima; Tran, Suzanne; Tauziède-Espariat, Arnault; Pallud, Johan; Louvel, Guillaume; Meary, Eric; Capelle, Laurent; Chrétien, Fabrice; Varlet, Pascale

2018-05-19

Gene fusions of EWSR1 with members of the CREB family of transcription factors (CREB1, ATF1, and CREM) have recently been described in exceptional intracranial myxoid mesenchymal tumors. Although this is a known gene fusion found in various mesenchymal tumors, EWSR1 fusion with CREM has only been observed in 3 intracranial myxoid tumors. In this paper, we present 1 such tumor with in-depth histopathological description and long-term follow-up. There is controversy regarding whether these tumors represent a novel entity or simply an intracranial localization of the myxoid variant of angiomatoid fibrous histiocytoma, a rare soft tissue tumor of the extremities. Out of 11 cases mentioned in the literature, the 3 isolated case reports by Dunham et al, Ochalski et al, and Alshareef et al are designated as angiomatoid fibrous histiocytoma, whereas the others are defined as a novel tumoral entity called intracranial myxoid mesenchymal tumor with EWSR1-CREB fusion. We believe the vast morphological and immunohistochemical spectrum of angiomatoid fibrous histiocytoma makes it difficult to dismiss this diagnosis.

Mitochondrial shaping cuts.

PubMed

Escobar-Henriques, Mafalda; Langer, Thomas

2006-01-01

A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.

Tbx1 is necessary for palatal elongation and elevation.

PubMed

Goudy, Steven; Law, Amy; Sanchez, Gabriela; Baldwin, H Scott; Brown, Christopher

2010-01-01

The transcription factor TBX1 is a key mediator of developmental abnormalities associated with DiGeorge/Velocardiofacial Syndrome. Studies in mice have demonstrated that decreased dosage of Tbx1 results in defects in pharyngeal arch, cardiovascular, and craniofacial development. The role of Tbx1 in cardiac development has been intensely studied; however, its role in palatal development is poorly understood. By studying the Tbx1-/- mice we found defects during the critical points of palate elongation and elevation. The intrinsic palate defects in the Tbx1-/- mice were determined by measuring changes in palate shelf length, proliferation, apoptosis, expression of relevant growth factors, and in palate fusion assays. Tbx1-/- embryos exhibit cleft palate with failed palate elevation in 100% and abnormal palatal-oral fusions in 50%. In the Tbx1-/- mice the palate shelf length was reduced and tongue height was greater, demonstrating a physical impediment to palate elevation and apposition. In vitro palate fusion assays demonstrate that Tbx1-/- palate shelves are capable of fusion but a roller culture assay showed that the null palatal shelves were unable to elongate. Diminished hyaluronic acid production in the Tbx1-/- palate shelves may explain failed palate shelf elevation. In addition, cell proliferation and apoptosis were perturbed in Tbx1-/- palates. A sharp decrease of Fgf8 expression was detected in the Tbx1-/- palate shelves, suggesting that Fgf8 is dependent on Tbx1 in the palate. Fgf10 is also up-regulated in the Tbx1-/- palate shelves and tongue. These data demonstrate that Tbx1 is a critical transcription factor that guides palatal elongation and elevation and that Fgf8 expression in the palate is Tbx1-dependent.

Tbx1 is Necessary for Palatal Elongation and Elevation

PubMed Central

Goudy, Steven; Law, Amy; Sanchez, Gabriela; Baldwin, H. Scott; Brown, Christopher

2010-01-01

The transcription factor TBX1 is a key mediator of developmental abnormalities associated with DiGeorge/Velocardiofacial Syndrome. Studies in mice have demonstrated that decreased dosage of Tbx1 results in defects in pharyngeal arch, cardiovascular, and craniofacial development. The role of Tbx1 in cardiac development has been intensely studied; however, its role in palatal development is poorly understood. By studying the Tbx1-/- mice we found defects during the critical points of palate elongation and elevation. The intrinsic palate defects in the Tbx1-/- mice were determined by measuring changes in palate shelf length, proliferation, apoptosis, expression of relevant growth factors, and in palate fusion assays. Tbx1-/- embryos exhibit cleft palate with failed palate elevation in 100% and abnormal palatal-oral fusions in 50%. In the Tbx1-/- mice the palate shelf length was reduced and tongue height was greater, demonstrating a physical impediment to palate elevation and apposition. In vitro palate fusion assays demonstrate that Tbx1-/- palate shelves are capable of fusion but a roller culture assay showed that the null palatal shelves were unable to elongate. Diminished hyaluronic acid production in the Tbx1-/- palate shelves may explain failed palate shelf elevation. In addition, cell proliferation and apoptosis were perturbed in Tbx1-/- palates. A sharp decrease of Fgf8 expression was detected in the Tbx1-/- palate shelves, suggesting that Fgf8 is dependent on Tbx1 in the palate. Fgf10 is also up-regulated in the Tbx1-/- palate shelves and tongue. These data demonstrate that Tbx1 is a critical transcription factor that guides palatal elongation and elevation and that Fgf8 expression in the palate is Tbx1-dependent. PMID:20214979

Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing's sarcoma in vitro.

PubMed

Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan

2012-11-12

Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251-343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing's sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing's Sarcoma.

The effect of 10% carbamide peroxide bleaching material on microhardness of sound and demineralized enamel and dentin in situ.

PubMed

Basting, R T; Rodrigues Júnior, A L; Serra, M C

2001-01-01

This in situ study evaluated the microhardness of sound and demineralized enamel and dentin submitted to treatment with 10% carbamide peroxide for three weeks. A 10% carbamide peroxide bleaching agent--Opalescence/Ultradent (OPA)--was evaluated against a placebo agent (PLA). Two hundred and forty dental fragments--60 sound enamel fragments (SE), 60 demineralized enamel fragments (DE), 60 sound dentin fragments (SD) and 60 demineralized dentin fragments (DD)--were randomly fixed on the vestibular surface of the first superior molars and second superior premolars of 30 volunteers. The volunteers were divided into two groups that received bleaching or the placebo agent at different sequences and periods at a double blind 2 x 2 crossover study with a wash-out period of two weeks. Microhardness tests were performed on the enamel and dentin surface. The SE and DE submitted to treatment with OPA showed lower microhardness values than the SE and DE submitted to treatment with PLA. There were no statistical differences in microhardness values for SD and DD submitted to the treatment with OPA and PLA. The results suggest that treatment with 10% carbamide peroxide bleaching material for three weeks alters the enamel microhardness, although it does not seem to alter the dentin microhardness.

2016 Service Academy Gender Relations Survey: Overview Report

DTIC Science & Technology

2017-02-01

environment within the Academies. This Executive Summary will provide a summary of the methodology used and the top line results from the survey.1 Summary...discussion of the measurement constructs, a description of the survey methodology , and detailed presentation of the results. Each report section...are determined statistically significant at an alpha (α) level of .05.6 Survey Methodology Statistical Design OPA conducts cross-Service surveys that

Epidural Abscess: A Propensity Analysis of Surgical Treatment Strategies.

PubMed

Chaker, Anisse N; Bhimani, Abhiraj D; Esfahani, Darian R; Rosinski, Clayton L; Geever, Brett W; Patel, Akash S; Hobbs, Jonathan G; Burch, Taylor G; Patel, Saavan; Mehta, Ankit I

2018-06-18

Observational analysis of retrospectively collected data. A retrospective study was performed in order to compare the surgical profile of risk factors and perioperative complications for laminectomy and laminectomy with fusion procedures in the treatment of SEA. Spinal epidural abscess (SEA) is a highly morbid condition typically presenting with back pain, fever, and neurologic deficits. Posterior fusion has been used to supplement traditional laminectomy of SEA to improve spinal stability. At present, the ideal surgical strategy - laminectomy with or without fusion - remains elusive. 30-day outcomes such as reoperation and readmission following laminectomy and laminectomy with fusion in patients with SEA were investigated utilizing the American College of Surgeons National Quality Improvement Program database. Demographics and clinical risk factors were collected, and propensity matching was performed to account for differences in risk profiles between the groups. 738 patients were studied (608 laminectomy alone, 130 fusion). The fusion population was in worse health. The fusion population experienced significantly greater rate of return to the operating room (odds ratio (OR) 1.892), with the difference primarily accounted for by cervical spine operations. Additionally, fusion patients had significantly greater rates of blood transfusion. Infection was the most common reason for reoperation in both populations. Both laminectomy and laminectomy with fusion effectively treat SEA, but addition of fusion is associated with significantly higher rates of transfusion and perioperative return to the operating room. In operative situations where either procedure is reasonable, surgeons should consider that fusion nearly doubles the odds of reoperation in the short-term, and weigh this risk against the benefit of added stability. 3.

Functional Genomic Screening Reveals Splicing of the EWS-FLI1 Fusion Transcript as a Vulnerability in Ewing Sarcoma.

PubMed

Grohar, Patrick J; Kim, Suntae; Rangel Rivera, Guillermo O; Sen, Nirmalya; Haddock, Sara; Harlow, Matt L; Maloney, Nichole K; Zhu, Jack; O'Neill, Maura; Jones, Tamara L; Huppi, Konrad; Grandin, Magdalena; Gehlhaus, Kristen; Klumpp-Thomas, Carleen A; Buehler, Eugen; Helman, Lee J; Martin, Scott E; Caplen, Natasha J

2016-01-26

Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1 pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1 fusion transcripts to the loss of function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1 transcript alters EWS-FLI1 protein expression and EWS-FLI1-driven expression. Our results show that the processing of the EWS-FLI1 fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate.

PubMed

Zou, Ying S; Hoppman, Nicole L; Singh, Zeba N; Sawhney, Sameer; Kotiah, Sandy D; Baer, Maria R

2017-04-01

We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of Occupational and Leisure-Time Physical Activity with Aerobic Capacity in a Working Population.

PubMed

Mundwiler, Jonas; Schüpbach, Ulla; Dieterle, Thomas; Leuppi, Jörg Daniel; Schmidt-Trucksäss, Arno; Wolfer, David Paul; Miedinger, David; Brighenti-Zogg, Stefanie

2017-01-01

Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (β = 0.212) and sufficient moderate-to-vigorous physical activity (β = 0.100) on workdays. Female gender (β = -0.622), age (β = -0.264), BMI (β = -0.220), the ratio of maximum to resting heart rate (β = 0.192), occupational group (low vs. high OPA, β = -0.141), and smoking (β = -0.133) were also identified as independent predictors of VO2max. The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits.

Association of Occupational and Leisure-Time Physical Activity with Aerobic Capacity in a Working Population

PubMed Central

Mundwiler, Jonas; Schüpbach, Ulla; Dieterle, Thomas; Leuppi, Jörg Daniel; Schmidt-Trucksäss, Arno; Wolfer, David Paul; Miedinger, David; Brighenti-Zogg, Stefanie

2017-01-01

Introduction Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. Methods In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. Results Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (β = 0.212) and sufficient moderate-to-vigorous physical activity (β = 0.100) on workdays. Female gender (β = -0.622), age (β = -0.264), BMI (β = -0.220), the ratio of maximum to resting heart rate (β = 0.192), occupational group (low vs. high OPA, β = -0.141), and smoking (β = -0.133) were also identified as independent predictors of VO2max. Conclusions The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits. PMID:28045939

Strategies for enhancing bioluminescent bacterial sensor performance by promoter region manipulation

PubMed Central

Bilic, Benny; Belkin, Shimshon

2010-01-01

Genetically engineered microbial reporter strains are based upon the fusion of an inducible sensing element upstream of a reporting element, so that the construct emits a dose-dependent signal when exposed to the inducing compound(s) or stress factor(s). In this communication1 we described several general approaches undertaken in order to enhance the sensing performance of such promoter::reporter fusions. Significant improvements in detection sensitivity, response kinetics and signal intensity were achieved by modi fication of the length of the promoter-containing DNA fragment, by random or site-directed mutagenesis and by promoter duplication. The general nature of these genetics manipulations makes them applicable to other types of promoter::reporter fusions. PMID:21326942

Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step.

PubMed

Harmon, Brooke; Campbell, Nancy; Ratner, Lee

2010-06-17

Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Galphaq-mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients.

Renewability and sustainability aspects of nuclear energy

NASA Astrophysics Data System (ADS)

Şahin, Sümer

2014-09-01

Renewability and sustainability aspects of nuclear energy have been presented on the basis of two different technologies: (1) Conventional nuclear technology; CANDU reactors. (2) Emerging nuclear technology; fusion/fission (hybrid) reactors. Reactor grade (RG) plutonium, 233U fuels and heavy water moderator have given a good combination with respect to neutron economy so that mixed fuel made of (ThO2/RG-PuO2) or (ThC/RG-PuC) has lead to very high burn up grades. Five different mixed fuel have been selected for CANDU reactors composed of 4 % RG-PuO2 + 96 % ThO2; 6 % RG-PuO2 + 94 % ThO2; 10 % RG-PuO2 + 90 % ThO2; 20 % RG-PuO2 + 80 % ThO2; 30 % RG-PuO2 + 70 % ThO2, uniformly taken in each fuel rod in a fuel channel. Corresponding operation lifetimes have been found as ˜ 0.65, 1.1, 1.9, 3.5, and 4.8 years and with burn ups of ˜ 30 000, 60 000, 100 000, 200 000 and 290 000 MW.d/ton, respectively. Increase of RG-PuO2 fraction in radial direction for the purpose of power flattening in the CANDU fuel bundle has driven the burn up grade to 580 000 MW.d/ton level. A laser fusion driver power of 500 MWth has been investigated to burn the minor actinides (MA) out of the nuclear waste of LWRs. MA have been homogenously dispersed as carbide fuel in form of TRISO particles with volume fractions of 0, 2, 3, 4 and 5 % in the Flibe coolant zone in the blanket surrounding the fusion chamber. Tritium breeding for a continuous operation of the fusion reactor is calculated as TBR = 1.134, 1.286, 1.387, 1.52 and 1.67, respectively. Fission reactions in the MA fuel under high energetic fusion neutrons have lead to the multiplication of the fusion energy by a factor of M = 3.3, 4.6, 6.15 and 8.1 with 2, 3, 4 and 5 % TRISO volume fraction at start up, respectively. Alternatively with thorium, the same fusion driver would produce ˜160 kg 233U per year in addition to fission energy production in situ, multiplying the fusion energy by a factor of ˜1.3.

The European FP7 ULTimateCO2 project: A comprehensive approach to study the long term fate of CO2 geological storage sites

NASA Astrophysics Data System (ADS)

Audigane, P.; Brown, S.; Dimier, A.; Pearce, J.; Frykman, P.; Maurand, N.; Le Gallo, Y.; Spiers, C. J.; Cremer, H.; Rutters, H.; Yalamas, T.

2013-12-01

The European FP7 ULTimateCO2 project aims at significantly advance our knowledge of specific processes that could influence the long-term fate of geologically stored CO2: i) trapping mechanisms, ii) fluid-rock interactions and effects on mechanical integrity of fractured caprock and faulted systems and iii) leakage due to mechanical and chemical damage in the well vicinity, iv) brine displacement and fluid mixing at regional scale. A realistic framework is ensured through collaboration with two demonstration sites in deep saline sandstone formations: the onshore former NER300 West Lorraine candidate in France (ArcelorMittal GeoLorraine) and the offshore EEPR Don Valley (former Hatfield) site in UK operated by National Grid. Static earth models have been generated at reservoir and basin scale to evaluate both trapping mechanisms and fluid displacement at short (injection) and long (post injection) time scales. Geochemical trapping and reservoir behaviour is addressed through experimental approaches using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions and through geochemical simulations. Collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland) (OPA), an analogue for caprock well investigated in the past for nuclear waste disposal purpose: - Characterization of elastic parameters in intact samples by measuring strain during an axial experiment, - A recording of hydraulic fracture flow properties by loading and shearing samples in order to create a 'realistic' fracture, followed by a gas injection in the fracture plan, - An assessment of temperature influences on carbonate and water content which affect carbonate bearing fault gouge using shear experiments at 20C and 120C on simulated fault gouges prepared by crushed OPA samples. To evaluate the interactions between CO2 (and formation fluids) and the well environment (formation, cement, casing) and to assess the consequences of these interactions on the transport properties of well materials, a 1:1 scale experiment has been set in the OPA to reproduce classical well objects (cemented annulus, casing and cement plug) perforating caprock formations (OPA). Innovative probabilistic modelling tools are also under development in order to build robust calibration methods for uncertainty management of the simulated long term scenarios.

Optimization of a Precolumn OPA Derivatization HPLC Assay for Monitoring of l-Asparagine Depletion in Serum during l-Asparaginase Therapy.

PubMed

Zhang, Mei; Zhang, Yong; Ren, Siqi; Zhang, Zunjian; Wang, Yongren; Song, Rui

2018-06-06

A method for monitoring l-asparagine (ASN) depletion in patients' serum using reversed-phase high-performance liquid chromatography with precolumn o-phthalaldehyde and ethanethiol (ET) derivatization is described. In order to improve the signal and stability of analytes, several important factors including precipitant reagent, derivatization conditions and detection wavelengths were optimized. The recovery of the analytes in biological matrix was the highest when 4% sulfosalicylic acid (1:1, v/v) was used as a precipitant reagent. Optimal fluorescence detection parameters were determined as λex = 340 nm and λem = 444 nm for maximal signal. The signal of analytes was the highest when the reagent ET and borate buffer of pH 9.9 were used in the derivatization solution. And the corresponding derivative products were stable up to 19 h. The validated method had been successfully applied to monitor ASN depletion and l-aspartic acid, l-glutamine, l-glutamic acid levels in pediatric patients during l-asparaginase therapy.

Transcriptomic analysis of neuregulin-1 regulated genes following ischemic stroke by computational identification of promoter binding sites: A role for the ETS-1 transcription factor.

PubMed

Surles-Zeigler, Monique C; Li, Yonggang; Distel, Timothy J; Omotayo, Hakeem; Ge, Shaokui; Ford, Byron D

2018-01-01

Ischemic stroke is a major cause of mortality in the United States. We previously showed that neuregulin-1 (NRG1) was neuroprotective in rat models of ischemic stroke. We used gene expression profiling to understand the early cellular and molecular mechanisms of NRG1's effects after the induction of ischemia. Ischemic stroke was induced by middle cerebral artery occlusion (MCAO). Rats were allocated to 3 groups: (1) control, (2) MCAO and (3) MCAO + NRG1. Cortical brain tissues were collected three hours following MCAO and NRG1 treatment and subjected to microarray analysis. Data and statistical analyses were performed using R/Bioconductor platform alongside Genesis, Ingenuity Pathway Analysis and Enrichr software packages. There were 2693 genes differentially regulated following ischemia and NRG1 treatment. These genes were organized by expression patterns into clusters using a K-means clustering algorithm. We further analyzed genes in clusters where ischemia altered gene expression, which was reversed by NRG1 (clusters 4 and 10). NRG1, IRS1, OPA3, and POU6F1 were central linking (node) genes in cluster 4. Conserved Transcription Factor Binding Site Finder (CONFAC) identified ETS-1 as a potential transcriptional regulator of NRG1 suppressed genes following ischemia. A transcription factor activity array showed that ETS-1 activity was increased 2-fold, 3 hours following ischemia and this activity was attenuated by NRG1. These findings reveal key early transcriptional mechanisms associated with neuroprotection by NRG1 in the ischemic penumbra.

Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH.

PubMed

Cliteur, Vincent Pm; Szuhai, Károly; Baelde, Hans J; van Dam, Jurriaan; Gelderblom, Hans; Hogendoorn, Pancras Cw

2012-01-25

Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma.Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences.

Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH

PubMed Central

2012-01-01

Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma. Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences. PMID:22587803

Asymmetric Mbc, active Rac1 and F-actin foci in the fusion-competent myoblasts during myoblast fusion in Drosophila

PubMed Central

Haralalka, Shruti; Shelton, Claude; Cartwright, Heather N.; Katzfey, Erin; Janzen, Evan; Abmayr, Susan M.

2011-01-01

Myoblast fusion is an intricate process that is initiated by cell recognition and adhesion, and culminates in cell membrane breakdown and formation of multinucleate syncytia. In the Drosophila embryo, this process occurs asymmetrically between founder cells that pattern the musculature and fusion-competent myoblasts (FCMs) that account for the bulk of the myoblasts. The present studies clarify and amplify current models of myoblast fusion in several important ways. We demonstrate that the non-conventional guanine nucleotide exchange factor (GEF) Mbc plays a fundamental role in the FCMs, where it functions to activate Rac1, but is not required in the founder cells for fusion. Mbc, active Rac1 and F-actin foci are highly enriched in the FCMs, where they localize to the Sns:Kirre junction. Furthermore, Mbc is crucial for the integrity of the F-actin foci and the FCM cytoskeleton, presumably via its activation of Rac1 in these cells. Finally, the local asymmetric distribution of these proteins at adhesion sites is reminiscent of invasive podosomes and, consistent with this model, they are enriched at sites of membrane deformation, where the FCM protrudes into the founder cell/myotube. These data are consistent with models promoting actin polymerization as the driving force for myoblast fusion. PMID:21389053

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.

PubMed

Ma, Cui; Beyer, Andreas M; Durand, Matthew; Clough, Anne V; Zhu, Daling; Norwood Toro, Laura; Terashvili, Maia; Ebben, Johnathan D; Hill, R Blake; Audi, Said H; Medhora, Meetha; Jacobs, Elizabeth R

2018-03-01

We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter-binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction. © 2018 American Heart Association, Inc.

Multidirectional testing of one- and two-level ProDisc-L versus simulated fusions.

PubMed

Panjabi, Manohar; Henderson, Gweneth; Abjornson, Celeste; Yue, James

2007-05-20

An in vitro human cadaveric biomechanical study. To evaluate intervertebral rotation changes due to lumbar ProDisc-L compared with simulated fusion, using follower load and multidirectional testing. Artificial discs, as opposed to the fusions, are thought to decrease the long-term accelerated degeneration at adjacent levels. A biomechanical assessment can be helpful, as the long-term clinical evaluation is impractical. Six fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension, bilateral lateral bending, and bilateral torsion using the Hybrid test method. First, intact specimen total range of rotation (T12-S1) was determined. Second, using pure moments again, this range of rotation was achieved in each of the 5 constructs: A) ProDisc-L at L5-S1; B) fusion at L5-S1; C) ProDisc-L at L4-L5 and fusion at L5-S1; D) ProDisc-L at L4-L5 and L5-S1; and E) 2-level fusion at L4-L5 to L5-S1. Significant changes in the intervertebral rotations due to each construct were determined at the operated and nonoperated levels using repeated measures single factor ANOVA and Bonferroni statistical tests (P < 0.05). Adjacent-level effects (ALEs) were defined as the percentage changes in intervertebral rotations at the nonoperated levels due to the constructs. One- and 2-level ProDisc-L constructs showed only small ALE in any of the 3 rotations. In contrast, 1- and 2-level fusions showed increased ALE in all 3 directions (average, 7.8% and 35.3%, respectively, for 1 and 2 levels). In the disc plus fusion combination (construct C), the ALEs were similar to the 1-level fusion alone. In general, ProDisc-L preserved physiologic motions at all spinal levels, while the fusion simulations resulted in significant ALE.

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis.

PubMed

Elder, Benjamin D; Ishida, Wataru; Goodwin, C Rory; Bydon, Ali; Gokaslan, Ziya L; Sciubba, Daniel M; Wolinsky, Jean-Paul; Witham, Timothy F

2017-01-01

OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I 2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I 2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants.

PubMed

Patel, Nimesh R; Salim, Alaa A; Sayeed, Hadi; Sarabia, Stephen F; Hollingsworth, Faith; Warren, Mikako; Jakacky, Jared; Tanas, Munir; Oliveira, Andre M; Rubin, Brian P; Lazar, Alexander J; López-Terrada, Dolores; Wang, Wei-Lien

2015-11-01

Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE. Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC. This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity. © 2015 John Wiley & Sons Ltd.

Role of lipid phase separations and membrane hydration in phospholipid vesicle fusion.

PubMed

Hoekstra, D

1982-06-08

The relationship between lipid phase separation and fusion of small unilamellar phosphatidylserine-containing vesicles was investigated. The kinetics of phase separation were monitored by following the increase of self-quenching of the fluorescent phospholipid analogue N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine, which occurs when the local concentration of the probe increases upon Ca2+-induced phase separation in phosphatidylserine (PS) bilayers [Hoekstra, D. (1982) Biochemistry 21, 1055-1061]. Fusion was determined by using the resonance energy transfer fusion assay [Struck, D. K., Hoekstra, D., & Pagano, R. E. (1981) Biochemistry 20, 4093-4099], which monitors the mixing of fluorescent lipid donor and acceptor molecules, resulting in an increase in energy transfer efficiency. The results show that in the presence of Ca2+, fusion proceeds much more rapidly (t 1/2 less than 5 s) than the process of phase separation (T 1/2 congruent to 1 min). Mg2+ also induced fusion, albeit at higher concentrations than Ca2+. Mg2+-induced phase separation were not detected, however. Subthreshold concentrations of Ca2+ (0.5 mM) or Mg2+ (2 mM) induced extensive fusion of PS-containing vesicles in poly(ethylene glycol) containing media. This effect did not appear to be a poly(ethylene glycol)-facilitated enhancement of cation binding to the bilayer, and consequently Ca2+-induced phase separation was not observed. The results suggest that macroscopic phase separation may facilitate but does not induced the fusion process and is therefore, not directly involved in the actual fusion mechanism. The fusion experiments performed in the presence of poly(ethylene glycol) suggest that the degree of bilayer dehydration and the creation of "point defects" in the bilayer without rigorous structural rearrangements in the membrane are dominant factors in the initial fusion events.

Investigation of fusion gene expression in HCT116 cells.

PubMed

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-12-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2) , EIF3E(e1)-RSPO2(e3) , PTPRK(e1)-RSPO3(e2) , PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E , RSPO2 , PTPRK , RSPO3 , TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma.

Investigation of fusion gene expression in HCT116 cells

PubMed Central

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-01-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma. PMID:29181107

Symposium I: Nanoscale Magnetic Materials and Applications. Held in Boston, Massachusetts on November 25-30, 2007

DTIC Science & Technology

2008-06-01

preparation of the exposed edge MTJ were performed. In- plane magnetization and cooling to 77 K further decreased the MMJ current to 1-1OpA level (1OOmV...temperature magnetic anneals due to dissimilar CoFeB/MgO interfaces. The effect is reduced by half for a bias of 1.88V, and the largest output voltage of...field induced interactions between the FM and AFM layers. Most of the studies dealt with in- plane angular dependence of magnetization hysteresis for FM

The PL/OPA Multichannel Transmissometer Control and Data Acquisition System

DTIC Science & Technology

1990-12-12

System Calibration and Data Reduction Voltages vi output from the transmissometer measuring beam attenuation over an 7 atmospheric path must be...supporting measurements of extinction and particle counts from visibility meters (0.89 pm) and Particle Measurement Systems aerosol distrometers respectively...The Multichannel Transmissometer is shown schematically in Figures 2.0-1 and 2.0-2. Measurements are made over the two-way path from transmitter

Examination of Neisseria Gonorrhoeae Opacity Protein Expression During Experimental Murine Genital Tract Infection

DTIC Science & Technology

2005-01-01

These alterations abolished Opa-dependent invasion. Also, cells deficient in proteoglycan synthesis were resistant to gonococcal invasion...volunteers. Gonococcal mutants deficient in production of pilin (40), RecA (40), or IgA1 protease (106) were not attenuated in this model. Interestingly...proliferative or high estrogen phase of the menstrual cycle. Endocervical cultures from these same patients taken during the luteal or high progesterone

Registration of a Dynamic Multimodal Target Image Test Set for the Evaluation of Image Fusion Techniques

DTIC Science & Technology

2013-10-17

imagery. 2. Report describing the registration algorithms and parameters . 3.2 Deliverables from Phase 2 (current phase, ongoing) 1. Selected and...representation. To be submitted to Information Fusion [Impact factor 2.262 ] . 2. De Jong, M., Toet, A., Hogervorst, M.A., Hooge , I., Pinkus, A. R. (in...Impact factor 3.376] . 3. Koenderink, J.J., van Doorn, A., De Jong, M., Toet, A., Hogervorst, M.A., Hooge , I., Pinkus, A. R. (in preparation

Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.

PubMed

Chen, Z; Chen, J; Gu, Y; Hu, C; Li, J-L; Lin, S; Shen, H; Cao, C; Gao, R; Li, J; Ha, P K; Kaye, F J; Griffin, J D; Wu, L

2014-07-17

Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 fusion oncogene, encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a frequent genetic alteration found in >50% of mucoepidermoid carcinomas (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth and survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and in vivo. The CRTC1-MAML2 oncoprotein induced the upregulation of the epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co-activating the transcription factor CREB, and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with advanced, unresectable CRTC1-MAML2-positive MEC.

High-level expression of human stem cell factor fused with erythropoietin mimetic peptide in Escherichia coli.

PubMed

Su, Lin; Chen, Song-Sen; Yang, Ke-Gong; Liu, Chang-Zheng; Zhang, Yan-Li; Liang, Zhi-Quan

2006-06-01

Stem cell factor (SCF) and erythropoietin are essential for normal erythropoiesis and induce proliferation and differentiation synergistically for erythroid progenitor cells. Here, we report our work on construction of SCF/erythropoietin mimetic peptide (EMP) fusion protein gene, in which human SCF cDNA (1-165aa) and EMP sequence (20aa) were connected using a short (GGGGS) or long (GGGGSGGGGGS) linker sequence. The SCF/EMP gene was cloned into the pBV220 vector and expressed in the Escherichia coli DH5alpha strain. The expression level of the fusion protein was about 30% of total cell protein. The resulting inclusion bodies were solubilized with 8 M urea, followed by dilution refolding. The renatured protein was subsequently purified by Q-Sepharose FF column. The final product was >95% pure by SDS-PAGE and the yield of fusion protein was about 40 mg/L of culture. UT-7 cell proliferation and human cord blood cell colony-forming assays showed that the fusion proteins exhibited more potent activity than recombinant human SCF, suggesting a new strategy to enhance biological activities of growth factors.

Development of the 1.6μm OPG/OPA system wavelength-controlled precisely for CO2 DIAL

NASA Astrophysics Data System (ADS)

Abo, M.; Shibata, Y.; Nagasawa, C.

2010-12-01

We developed an optical parametric oscillator (OPO) laser system for 1.6μm CO2 DIAL1). In order to improve the measurement accuracy of CO2 profiles, development of high power and wavelength stabilized laser system has been conducted. We report a new high-power 1.6μm laser transmitter based on a parametric master oscillator-power amplifier (MOPA) system pumped by a LD-pumped Q-switched Nd:YAG laser which has the injection seed laser locked to the iodine absorption line. The master oscillator is an optical parametric generator (OPG), based on an MgO-doped periodically poled LiTaO3 (PPMgLT) crystal. The OPOs require either active control of the cavity length or slight misalignment of the cavity. On the other hand, the OPGs do not require a cavity and instead rely on sufficient conversion efficiency to be obtained with a single pass through the crystal. The single-frequency oscillation of the OPG was achieved by injection seeding. The 1.6μm emission of the OPG is amplified by two-stage optical parametric amplifiers (OPAs). The each PPMgLT crystal was mounted on the copper holder, and the temperature control of the each holder was carried out within 0.01 K. The wavelength feedback system of the Nd:YAG seed laser is performed with the side locking of the iodine absorption spectrum (line No.1107) and the frequency stability is realized within 10 MHz rms. Stabilization of the 1.6μm DFB seed laser is estimated to within 4 MHz rms at the CO2 absorption line center and within 1.8 MHz rms at the CO2 absorption line slope using the wavelength control unit. We demonstrated single-longitudinal-mode emission with the OPG and two OPAs. The beam quality was TEM00 mode, the pulse energy was 12 mJ at 500 Hz repetition rate and the frequency stability was less than 10MHz rms. The unique performances of this optical parametric system make a relevant transmitter for CO2 DIAL. This work was financially supported by the System Development Program for Advanced Measurement and Analysis of the Japan Science and Technology Agency. Reference (1) D. Sakaisawa, C. Nagasawa, T. Nagai, M. Abo, Y. Shibata, H. Nagai, M. Nakazato, and T. Sakai, Development of a 1.6μm differential absorption lidar with a quasi-phase-matching optical parametric oscillator and photon-counting detector for the vertical CO2 profile, Applied Optics, Vol.48, No.4, pp.748-757, 2009.

Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.

PubMed

Viringipurampeer, Ishaq A; Ferreira, Todd; DeMaria, Shannon; Yoon, Jookyung J; Shan, Xianghong; Moosajee, Mariya; Gregory-Evans, Kevin; Ngai, John; Gregory-Evans, Cheryl Y

2012-05-15

Tissue fusion is an essential morphogenetic mechanism in development, playing a fundamental role in developing neural tube, palate and the optic fissure. Disruption of genes associated with the tissue fusion can lead to congenital malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For instance, the Pax2 transcription factor is required for optic fissure closure, although the mechanism of Pax2 action leading to tissue fusion remains elusive. This lack of information defining how transcription factors drive tissue morphogenesis at the cellular level is hampering new treatments options. Through loss- and gain-of-function analysis, we now establish that pax2 in combination with vax2 directly regulate the fas-associated death domain (fadd) gene. In the presence of fadd, cell proliferation is restricted in the developing eye through a caspase-dependent pathway. However, the loss of fadd results in a proliferation defect and concomitant activation of the necroptosis pathway through RIP1/RIP3 activity, leading to an abnormal open fissure. Inhibition of RIP1 with the small molecule drug necrostatin-1 rescues the pax2 eye fusion defect, thereby overcoming the underlying genetic defect. Thus, fadd has an essential physiological function in protecting the developing optic fissure neuroepithelium from RIP3-dependent necroptosis. This study demonstrates the molecular hierarchies that regulate a cellular switch between proliferation and the apoptotic and necroptotic cell death pathways, which in combination drive tissue morphogenesis. Furthermore, our data suggest that future therapeutic strategies may be based on small molecule drugs that can bypass the gene defects causing common congenital tissue fusion defects.

RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

PubMed

Wang, Zhixiong; Cheng, Yulan; Abraham, John M; Yan, Rong; Liu, Xi; Chen, Wei; Ibrahim, Sariat; Schroth, Gary P; Ke, Xiquan; He, Yulong; Meltzer, Stephen J

2017-10-15

Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor.

PubMed

Cook, Jonathan D; Soto-Montoya, Hazel; Korpela, Markus K; Lee, Jeffrey E

2015-07-24

Segment 5, ORF 1 of the infectious salmon anemia virus (ISAV) genome, encodes for the ISAV F protein, which is responsible for viral-host endosomal membrane fusion during a productive ISAV infection. The entry machinery of ISAV is composed of a complex of the ISAV F and ISAV hemagglutinin esterase (HE) proteins in an unknown stoichiometry prior to receptor engagement by ISAV HE. Following binding of the receptor to ISAV HE, dissociation of the ISAV F protein from HE, and subsequent endocytosis, the ISAV F protein resolves into a fusion-competent oligomeric state. Here, we present a 2.1 Å crystal structure of the fusion core of the ISAV F protein determined at low pH. This structure has allowed us to unambiguously demonstrate that the ISAV entry machinery exhibits typical class I viral fusion protein architecture. Furthermore, we have determined stabilizing factors that accommodate the pH-dependent mode of ISAV transmission, and our structure has allowed the identification of a central coil that is conserved across numerous and varied post-fusion viral glycoprotein structures. We then discuss a mechanistic model of ISAV fusion that parallels the paramyxoviral class I fusion strategy wherein attachment and fusion are relegated to separate proteins in a similar fashion to ISAV fusion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Oil Pollution Act (OPA) and Federal Facilities

EPA Pesticide Factsheets

The Oil Pollution Prevention regulation sets forth requirements for prevention of, preparedness for, and response to oil discharges at specific non-transportation-related facilities, including federal facilities.

Surgical Wound Infection Rates and Risk Factors in Spinal Fusion in a University Teaching Hospital in Madrid, Spain.

PubMed

Hijas-Gómez, Ana I; Egea-Gámez, Rosa M; Martínez-Martín, Javier; González-Díaz, Rafael; Losada-Viñas, José I; Rodríguez-Caravaca, Gil

2017-05-15

Prospective cohort study. To study risk factors linked to spinal fusion surgical wound infection (SWI) incidence and compare the incidence with rates in Madrid Region, Spain and United States as a whole. SWI is one of the complications posed by spinal surgery. Indeed, spinal surgery has a higher infection rate than do other orthopedic surgeries such as total hip or knee arthroplasty. The study of risk factors that are susceptible to be modified will enable both the incidence of SWI and, by extension, related morbidity, mortality, and costs to be reduced. All patients undergoing spinal fusion at a tertiary hospital from June 2011 to June 2014 were included. Infection rate was calculated, and the association between risk factors and SWI incidence was assessed by reference to odds ratio (OR) with univariate and multivariate analysis. The study population (n = 892) had a SWI rate of 3.9%. The standardized infection ratio of our hospital was 0.58 with respect to the Madrid Region, 0.76 with respect to Spain's national rate and 2.05 with respect to the US NHSN/CDC. The multivariate analysis showed that predictive factors of SWI were diabetes mellitus (OR 2.81, 95% confidence interval, CI: 1.18-6.72, P < 0.05), chronic obstructive pulmonary disease (COPD) (OR 5.16, 95% CI: 2.04-13.08, P < 0.05), duration of surgery higher than the 75th percentile (OR 5.39, 95% CI: 1.77-110.84, P < 0.05) and dirty surgery (OR 14.01, 95% CI: 1.01-28.88, P < 0.05). Independent risk factors for SWI in spinal fusion are existence of diabetes mellitus, COPD, duration of surgery higher than the 75th percentile and dirty surgery. Knowing these risk factors enables action to be taken to reduce the SWI rate. 3.

Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

PubMed Central

Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-01-01

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901

Influence of collective nonideal shielding on fusion reaction in partially ionized classical nonideal plasmas

NASA Astrophysics Data System (ADS)

Lee, Myoung-Jae; Jung, Young-Dae

2017-04-01

The collective nonideal effects on the nuclear fusion reaction process are investigated in partially ionized classical nonideal hydrogen plasmas. The effective pseudopotential model taking into account the collective and plasma shielding effects is applied to describe the interaction potential in nonideal plasmas. The analytic expressions of the Sommerfeld parameter, the fusion penetration factor, and the cross section for the nuclear fusion reaction in nonideal plasmas are obtained as functions of the nonideality parameter, Debye length, and relative kinetic energy. It is found that the Sommerfeld parameter is suppressed due to the influence of collective nonideal shielding. However, the collective nonideal shielding is found to enhance the fusion penetration factor in partially ionized classical nonideal plasmas. It is also found that the fusion penetration factors in nonideal plasmas represented by the pseudopotential model are always greater than those in ideal plasmas represented by the Debye-Hückel model. In addition, it is shown that the collective nonideal shielding effect on the fusion penetration factor decreases with an increase of the kinetic energy.

Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.

PubMed

Ko, Su Hyuk; Jeon, Jong Ik; Myung, Hyun Soo; Kim, Young-Jeon; Kim, Jung Mogg

2017-10-01

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy. Copyright © 2017 American Society for Microbiology.

The Transcription Factor Ste12 Mediates the Regulatory Role of the Tmk1 MAP Kinase in Mycoparasitism and Vegetative Hyphal Fusion in the Filamentous Fungus Trichoderma atroviride

PubMed Central

Gruber, Sabine; Zeilinger, Susanne

2014-01-01

Mycoparasitic species of the fungal genus Trichoderma are potent antagonists able to combat plant pathogenic fungi by direct parasitism. An essential step in this mycoparasitic fungus-fungus interaction is the detection of the fungal host followed by activation of molecular weapons in the mycoparasite by host-derived signals. The Trichoderma atroviride MAP kinase Tmk1, a homolog of yeast Fus3/Kss1, plays an essential role in regulating the mycoparasitic host attack, aerial hyphae formation and conidiation. However, the transcription factors acting downstream of Tmk1 are hitherto unknown. Here we analyzed the functions of the T. atroviride Ste12 transcription factor whose orthologue in yeast is targeted by the Fus3 and Kss1 MAP kinases. Deletion of the ste12 gene in T. atroviride not only resulted in reduced mycoparasitic overgrowth and lysis of host fungi but also led to loss of hyphal avoidance in the colony periphery and a severe reduction in conidial anastomosis tube formation and vegetative hyphal fusion events. The transcription of several orthologues of Neurospora crassa hyphal fusion genes was reduced upon ste12 deletion; however, the Δste12 mutant showed enhanced expression of mycoparasitism-relevant chitinolytic and proteolytic enzymes and of the cell wall integrity MAP kinase Tmk2. Based on the comparative analyses of Δste12 and Δtmk1 mutants, an essential role of the Ste12 transcriptional regulator in mediating outcomes of the Tmk1 MAPK pathway such as regulation of the mycoparasitic activity, hyphal fusion and carbon source-dependent vegetative growth is suggested. Aerial hyphae formation and conidiation, in contrast, were found to be independent of Ste12. PMID:25356841

The transcription factor Ste12 mediates the regulatory role of the Tmk1 MAP kinase in mycoparasitism and vegetative hyphal fusion in the filamentous fungus Trichoderma atroviride.

PubMed

Gruber, Sabine; Zeilinger, Susanne

2014-01-01

Mycoparasitic species of the fungal genus Trichoderma are potent antagonists able to combat plant pathogenic fungi by direct parasitism. An essential step in this mycoparasitic fungus-fungus interaction is the detection of the fungal host followed by activation of molecular weapons in the mycoparasite by host-derived signals. The Trichoderma atroviride MAP kinase Tmk1, a homolog of yeast Fus3/Kss1, plays an essential role in regulating the mycoparasitic host attack, aerial hyphae formation and conidiation. However, the transcription factors acting downstream of Tmk1 are hitherto unknown. Here we analyzed the functions of the T. atroviride Ste12 transcription factor whose orthologue in yeast is targeted by the Fus3 and Kss1 MAP kinases. Deletion of the ste12 gene in T. atroviride not only resulted in reduced mycoparasitic overgrowth and lysis of host fungi but also led to loss of hyphal avoidance in the colony periphery and a severe reduction in conidial anastomosis tube formation and vegetative hyphal fusion events. The transcription of several orthologues of Neurospora crassa hyphal fusion genes was reduced upon ste12 deletion; however, the Δste12 mutant showed enhanced expression of mycoparasitism-relevant chitinolytic and proteolytic enzymes and of the cell wall integrity MAP kinase Tmk2. Based on the comparative analyses of Δste12 and Δtmk1 mutants, an essential role of the Ste12 transcriptional regulator in mediating outcomes of the Tmk1 MAPK pathway such as regulation of the mycoparasitic activity, hyphal fusion and carbon source-dependent vegetative growth is suggested. Aerial hyphae formation and conidiation, in contrast, were found to be independent of Ste12.

Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.

PubMed

Malli, Theodora; Buxhofer-Ausch, Veronika; Rammer, Melanie; Erdel, Martin; Kranewitter, Wolfgang; Rumpold, Holger; Marschon, Renate; Deutschbauer, Sabine; Simonitsch-Klupp, Ingrid; Valent, Peter; Muellner-Ammer, Kirsten; Sebesta, Christian; Birkner, Thomas; Webersinke, Gerald

2016-01-01

Myeloid and lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) abnormalities, also known as 8p11 myeloproliferative syndrome (EMS), represent rare and aggressive disorders, associated with chromosomal aberrations that lead to the fusion of FGFR1 to different partner genes. We report on a third patient with a fusion of the translocated promoter region (TPR) gene, a component of the nuclear pore complex, to FGFR1 due to a novel ins(1;8)(q25;p11p23). The fact that this fusion is a rare but recurrent event in EMS prompted us to examine the localization and transforming potential of the chimeric protein. TPR-FGFR1 localizes in the cytoplasm, although the nuclear pore localization signal of TPR is retained in the fusion protein. Furthermore, TPR-FGFR1 enables cytokine-independent survival, proliferation, and granulocytic differentiation of the interleukin-3 dependent myeloid progenitor cell line 32Dcl3, reflecting the chronic phase of EMS characterized by myeloid hyperplasia. 32Dcl3 cells transformed with the TPR-FGFR1 fusion and treated with increasing concentrations of the tyrosine kinase inhibitors ponatinib (AP24534) and infigratinib (NVP-BGJ398) displayed reduced survival and proliferation with IC50 values of 49.8 and 7.7 nM, respectively. Ponatinib, a multitargeted tyrosine kinase inhibitor, is already shown to be effective against several FGFR1-fusion kinases. Infigratinib, tested only against FGFR1OP2-FGFR1 to date, is also efficient against TPR-FGFR1. Taking its high specificity for FGFRs into account, infigratinib could be beneficial for EMS patients and should be further investigated for the treatment of myeloproliferative neoplasms with FGFR1 abnormalities. © 2015 Wiley Periodicals, Inc.

Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

PubMed

Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

2013-12-09

Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour.

PubMed

Lee, Jen-Chieh; Jeng, Yung-Ming; Su, Sheng-Yao; Wu, Chen-Tu; Tsai, Keh-Sung; Lee, Cheng-Han; Lin, Chung-Yen; Carter, Jodi M; Huang, Jenq-Wen; Chen, Shu-Hwa; Shih, Shyang-Rong; Mariño-Enríquez, Adrián; Chen, Chih-Chi; Folpe, Andrew L; Chang, Yih-Leong; Liang, Cher-Wei

2015-03-01

Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour-induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1-FGFR1 fusion gene in three out of four PMTs by next-generation RNA sequencing. The fusion transcripts and proteins were subsequently confirmed with RT-PCR and western blotting. Fluorescence in situ hybridization analysis showed six cases with FN1-FGFR1 fusion out of an additional 11 PMTs. Overall, nine out of 15 PMTs (60%) harboured this fusion. The FN1 gene possibly provides its constitutively active promoter and the encoded protein's oligomerization domains to overexpress and facilitate the activation of the FGFR1 kinase domain. Interestingly, unlike the prototypical leukaemia-inducing FGFR1 fusion genes, which are ligand-independent, the FN1-FGFR1 chimeric protein was predicted to preserve its ligand-binding domains, suggesting an advantage of the presence of its ligands (such as FGF23 secreted at high levels by the tumour) in the activation of the chimeric receptor tyrosine kinase, thus effecting an autocrine or a paracrine mechanism of tumourigenesis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Experimental realization of a feedback optical parametric amplifier with four-wave mixing

NASA Astrophysics Data System (ADS)

Pan, Xiaozhou; Chen, Hui; Wei, Tianxiang; Zhang, Jun; Marino, Alberto M.; Treps, Nicolas; Glasser, Ryan T.; Jing, Jietai

2018-04-01

Optical parametric amplifiers (OPAs) play a fundamental role in the generation of quantum correlation for quantum information processing and quantum metrology. In order to increase the communication fidelity of the quantum information protocol and the measurement precision of quantum metrology, it requires a high degree of quantum correlation. In this Rapid Communication we report a feedback optical parametric amplifier that employs a four-wave mixing (FWM) process as the underlying OPA and a beam splitter as the feedback controller. We first construct a theoretical model for this feedback-based FWM process and experimentally study the effect of the feedback control on the quantum properties of the system. Specifically, we find that the quantum correlation between the output fields can be enhanced by tuning the strength of the feedback.

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

PubMed

Katz, Bradley J; Zhao, Yu; Warner, Judith E A; Tong, Zongzhong; Yang, Zhenglin; Zhang, Kang

2006-10-15

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such as glaucoma and ischemic optic neuropathy. (c) 2006 Wiley-Liss, Inc.

Renewability and sustainability aspects of nuclear energy

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

Şahin, Sümer, E-mail: ssahin@atilim.edit.tr

Renewability and sustainability aspects of nuclear energy have been presented on the basis of two different technologies: (1) Conventional nuclear technology; CANDU reactors. (2) Emerging nuclear technology; fusion/fission (hybrid) reactors. Reactor grade (RG) plutonium, {sup 233}U fuels and heavy water moderator have given a good combination with respect to neutron economy so that mixed fuel made of (ThO{sub 2}/RG‐PuO{sub 2}) or (ThC/RG-PuC) has lead to very high burn up grades. Five different mixed fuel have been selected for CANDU reactors composed of 4 % RG‐PuO{sub 2} + 96 % ThO{sub 2}; 6 % RG‐PuO{sub 2} + 94 % ThO{sub 2};more » 10 % RG‐PuO{sub 2} + 90 % ThO{sub 2}; 20 % RG‐PuO{sub 2} + 80 % ThO{sub 2}; 30 % RG‐PuO{sub 2} + 70 % ThO{sub 2}, uniformly taken in each fuel rod in a fuel channel. Corresponding operation lifetimes have been found as ∼ 0.65, 1.1, 1.9, 3.5, and 4.8 years and with burn ups of ∼ 30 000, 60 000, 100 000, 200 000 and 290 000 MW.d/ton, respectively. Increase of RG‐PuO{sub 2} fraction in radial direction for the purpose of power flattening in the CANDU fuel bundle has driven the burn up grade to 580 000 MW.d/ton level. A laser fusion driver power of 500 MW{sub th} has been investigated to burn the minor actinides (MA) out of the nuclear waste of LWRs. MA have been homogenously dispersed as carbide fuel in form of TRISO particles with volume fractions of 0, 2, 3, 4 and 5 % in the Flibe coolant zone in the blanket surrounding the fusion chamber. Tritium breeding for a continuous operation of the fusion reactor is calculated as TBR = 1.134, 1.286, 1.387, 1.52 and 1.67, respectively. Fission reactions in the MA fuel under high energetic fusion neutrons have lead to the multiplication of the fusion energy by a factor of M = 3.3, 4.6, 6.15 and 8.1 with 2, 3, 4 and 5 % TRISO volume fraction at start up, respectively. Alternatively with thorium, the same fusion driver would produce ∼160 kg {sup 233}U per year in addition to fission energy production in situ, multiplying the fusion energy by a factor of ∼1.3.« less

State of Washington, Aquatic Plant Management Program: Design Memorandum.

DTIC Science & Technology

1979-10-01

3 days after appit- cation, fed ior 90 da- fo11-nIng haorst1ing equipment catIon. Swimming shouldt oe aplication . oring narventing opa- restricted...labor, maintenance, profit, capitalization of equipment costs, and mobilization -demobilization. 2/Local administrative costs are $2,000 for 100 acres...rental of two boats at a cost of $64/day each, mobilization - demobilization of equipment, and a capability of treating 100 acres/day. 2/The treatment boat

A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans.

PubMed

Knowlton, Wendy M; Hubert, Thomas; Wu, Zilu; Chisholm, Andrew D; Jin, Yishi

2017-01-01

The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo , we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1 . Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7 , and isp-1 , and the putative oxidoreductase rad-8 . In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1 . Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury.

A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans

PubMed Central

Knowlton, Wendy M.; Hubert, Thomas; Wu, Zilu; Chisholm, Andrew D.; Jin, Yishi

2017-01-01

The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo, we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1. Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7, and isp-1, and the putative oxidoreductase rad-8. In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1. Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury. PMID:28539870

Integrated on-chip derivatization and electrophoresis for the rapid analysis of biogenic amines.

PubMed

Beard, Nigel P; Edel, Joshua B; deMello, Andrew J

2004-07-01

We demonstrate the monolithic integration of a chemical reactor with a capillary electrophoresis device for the rapid and sensitive analysis of biogenic amines. Fluorescein isothiocyanate (FITC) is widely employed for the analysis of amino-group containing analytes. However, the slow reaction kinetics hinders the use of this dye for on-chip labeling applications. Other alternatives are available such as o-phthaldehyde (OPA), however, the inferior photophysical properties and the UV lambdamax present difficulties when using common excitation sources leading to a disparity in sensitivity. Consequently, we present for the first time the use of dichlorotriazine fluorescein (DTAF) as a superior in situ derivatizing agent for biogenic amines in microfluidic devices. The developed microdevice employs both hydrodynamic and electroosmotic flow, facilitating the creation of a polymeric microchip to perform both precolumn derivatization and electrophoretic analysis. The favorable photophysical properties of the DTAF and its fast reaction kinetics provide detection limits down to 1 nM and total analysis times (including on-chip mixing and reaction) of <60 s. The detection limits are two orders of magnitude lower than current limits obtained with both FITC and OPA. The optimized microdevice is also employed to probe biogenic amines in real samples.

Determination of ammonium on an integrated microchip with LED-induced fluorescence detection.

PubMed

Xue, Shuhua; Uchiyama, Katsumi; Li, Hai-Fang

2012-01-01

A simply fabricated microfluidic device integrated with a fluorescence detection system has been developed for on-line determination of ammonium in aqueous samples. A 365-nm light-emitting diode (LED) as an excitation source and a minor band pass filter were mounted into a polydimethylsiloxane (PDMS)-based microchip for the purpose of miniaturization of the entire analytical system. The ammonium sample reacted with o-phthaldialdehyde (OPA) on-chip with sodium sulfite as reducing reagent to produce a fluorescent isoindole derivative, which can emit fluorescence signal at about 425 nm when excited at 365 nm. Effects of pH, flow rate of solutions, concentrations of OPA-reagent, phosphate and sulfite salt were investigated. The calibration curve of ammonium in the range of 0.018-1.8 microg/mL showed a good linear relationship with R2 = 0.9985, and the detection limit was (S/N = 3) 3.6 x 10(-4) microg/mL. The relative standard deviation was 2.8% (n = 11) by calculating at 0.18 microg/mL ammonium for repeated detection. The system was applied to determine the ammonium concentration in rain and river waters, even extent to other analytes fluorescence detection by the presented device.

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

PubMed Central

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul

2015-01-01

ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. PMID:26136569

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

PubMed

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

2015-09-01

HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

Igor V. Litvinyuk, and Itzik Ben-Itzhak

Our principal goal was the experimental demonstration of Laser-Induced Electron Diffraction (LIED). Key steps along the development of this experimental technique have been accomplished and reported in the publications listed in this brief report. We started with measuring 3D electron momenta spectra in aligned nitrogen and oxygen molecules. Chakra Maharjan (Ph.D. student of Lew Cocke) was a lead researcher on this project. Although Chakra succeeded in obtaining those spectra, we were scooped by the publication of identical results in Science by the NRC Ottawa group. Our results were never published as a refereed article, but became a part of Chakra'smore » Ph.D. dissertation. That Science paper was the first experimental demonstration of Laser-Induced Electron Diffraction (LIED). Chakra also worked on wavelength dependence of 3D ATI spectra of atoms and molecules using tunable OPA pulses. Another Ph.D. student, Maia Magrakvelidze (her GRA was funded by the grant), started working on COLTRIMS experiments using OPA pulses (1800 nm wavelength). After some initial experiments it became apparent that COLTRIMS did not yield sufficient count rates of electrons in the high-energy part of the spectrum to see diffraction signatures with acceptable statistics (unfavorable scaling of the electron yield with laser wavelength was partly to blame). Nevertheless, Maia managed to use COLTRIMS and OPA to measure the angular dependence of the tunneling ionization rate in D{sub 2} molecules. Following the initial trial experiments, the decision was made to switch from COLTRIMS to VMI in order to increase the count rates by a factor of {approx}100, which may have given us a chance to see LIED. Research Associate Dr. Sankar De (his salary was funded by the grant), in collaboration with Matthias Kling's group (then at MPQ Garching), proceeded to design a special multi-electrode VMI spectrometer for capturing high-energy ATI electrons and to install it in place of COLTRIMS inside our experimental chamber. That apparatus was later used for the first demonstration of field-free orientation in CO using two-color laser pulses as well as for a series of other experiments, such as pump-probe studies of molecular dynamics with few-cycle laser pulses, control of electron localization in dissociating hydrogen molecules using two-color laser pulses, and ATI spectra of Xe ionized by two-color laser pulses. In parallel, Dipanwita Ray (Ph.D. student of Lew Cocke) worked on measuring angle-resolved ATI spectra of noble gases using a stereo-ATI phasemeter as a TOF electron spectrometer. She observed the angular diffraction structures in 3D ATI spectra of Ar, Kr and Xe, which were interpreted in terms of the Quantitative Rescattering theory newly developed by C.D. Lin. We also attempted to use a much more powerful OPA (five times more energy per pulse than the one we had at JRML) available at the Advanced Laser Light Source (ALLS) in Montreal to observe LIED. Two visits to ALLS by the PI, Igor Litvinyuk, and one visit by the PI's Ph.D. student (Irina Bocharova) were funded by the grant. Though we failed to observe LIED (the repetition rate of the ALLS OPA was too low at only 100 Hz), this international collaboration resulted in several publications on other related subjects, such as the wavelength dependence of laser Coulomb explosion of hydrogen, the wavelength dependence of non-sequential double ionization of neon and argon, the demonstration of charge-resonance enhanced ionization in CO{sub 2}, and the study of non-elastic scattering processes in H{sub 2}. Theoretical efforts to account for the hydrogen Coulomb explosion experiment resulted in another paper by Maia Magrakvelidze as lead author. Although for various reasons we failed to achieve our main goal of observing LIED, we salute the recent success in this endeavor by Lou DiMauro's group (with theoretical support from our KSU colleague C.D. Lin) published in Nature, which validates our approach.« less

Development of DEMO-FNS tokamak for fusion and hybrid technologies

NASA Astrophysics Data System (ADS)

Kuteev, B. V.; Azizov, E. A.; Alexeev, P. N.; Ignatiev, V. V.; Subbotin, S. A.; Tsibulskiy, V. F.

2015-07-01

The history of fusion-fission hybrid systems based on a tokamak device as an extremely efficient DT-fusion neutron source has passed through several periods of ample research activity in the world since the very beginning of fusion research in the 1950s. Recently, a new roadmap of the hybrid program has been proposed with the goal to build a pilot hybrid plant (PHP) in Russia by 2030. Development of the DEMO-FNS tokamak for fusion and hybrid technologies, which is planned to be built by 2023, is the key milestone on the path to the PHP. This facility is in the phase of conceptual design aimed at providing feasibility studies for a full set of steady state tokamak technologies at a fusion energy gain factor Q ˜ 1, fusion power of ˜40 MW and opportunities for testing a wide range of hybrid technologies with the emphasis on continuous nuclide processing in molten salts. This paper describes the project motivations, its current status and the key issues of the design.

A phorbol ester-binding protein is required downstream of Rab5 in endosome fusion.

PubMed

Aballay, A; Barbieri, M A; Colombo, M I; Arenas, G N; Stahl, P D; Mayorga, L S

1998-12-28

Previous observations indicate that a zinc and phorbol ester binding factor is necessary for endosome fusion. To further characterize the role of this factor in the process, we used an in vitro endosome fusion assay supplemented with recombinant Rab5 proteins. Both zinc depletion and addition of calphostin C, an inhibitor of protein kinase C, inhibited endosome fusion in the presence of active Rab5. Addition of the phorbol ester PMA (phorbol 12-myristate 13-acetate) reversed the inhibition of endosome fusion caused by a Rab5 negative mutant. Moreover, PMA stimulated fusion in the presence of Rab5 immunodepleted cytosol. These results suggest that the phorbol ester binding protein is acting downstream of Rab5 in endosome fusion.

Fugacity ratio estimations for high-melting rigid aromatic compounds.

PubMed

Van Noort, Paul C M

2004-07-01

Prediction of the environmental fate of organic compounds requires knowledge of their tendency to stay in the gas and water phase. Vapor pressure and aqueous solubility are commonly used descriptors for these processes. Depending on the type of distribution process, values for either the pure solid state or the (subcooled) liquid state have to be used. Values for the (subcooled) liquid state can be calculated from those for the solid state, and vice versa, using the fugacity ratio. Fugacity ratios are usually calculated from the entropy of fusion and the melting point. For polycyclic aromatic hydrocarbons, chlorobenzenes, chlorodibenzofuranes, and chlorodibenzo(p)dioxins, fugacity ratios calculated using experimental entropies of fusion were systematically less than those obtained from a thermodynamically more rigorous approach using heat capacity data. The deviation was more than 1 order of magnitude at the highest melting point. The use of a universal value for the entropy of fusion of 56 J/molK resulted in either over or underestimation by up to more than 1 order of magnitude. A simple correction factor, based on the melting point only, was derived. This correction factor allowed the fugacity ratios to be estimated from experimental entropies of fusion and melting point with an accuracy better than 0.1-0.2 log units. Copyright 2004 Elsevier Ltd.

15 CFR 990.11 - Scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Introduction § 990.11 Scope. The Oil Pollution Act of 1990 (OPA), 33 U.S.C. 2701 et seq., provides...

Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes

PubMed Central

Dhanasekaran, Saravana M.; Balbin, O. Alejandro; Chen, Guoan; Nadal, Ernest; Kalyana-Sundaram, Shanker; Pan, Jincheng; Veeneman, Brendan; Cao, Xuhong; Malik, Rohit; Vats, Pankaj; Wang, Rui; Huang, Stephanie; Zhong, Jinjie; Jing, Xiaojun; Iyer, Matthew; Wu, Yi-Mi; Harms, Paul W.; Lin, Jules; Reddy, Rishindra; Brennan, Christine; Palanisamy, Nallasivam; Chang, Andrew C.; Truini, Anna; Truini, Mauro; Robinson, Dan R.; Beer, David G.; Chinnaiyan, Arul M.

2014-01-01

Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here, we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyze 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations. In addition, we observe exon skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations. PMID:25531467

Origin of a maximum of the astrophysical S factor in heavy-ion fusion reactions at deep subbarrier energies

NASA Astrophysics Data System (ADS)

Hagino, K.; Balantekin, A. B.; Lwin, N. W.; Thein, Ei Shwe Zin

2018-03-01

The hindrance phenomenon of heavy-ion fusion cross sections at deep subbarrier energies often accompanies a maximum of an astrophysical S factor at a threshold energy for fusion hindrance. We argue that this phenomenon can naturally be explained when the fusion excitation function is fitted with two potentials, with a larger (smaller) logarithmic slope at energies lower (higher) than the threshold energy. This analysis clearly suggests that the astrophysical S factor provides a convenient tool to analyze the deep subbarrier hindrance phenomenon, even though the S factor may have a strong energy dependence for heavy-ion systems unlike that for astrophysical reactions.

A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice

PubMed Central

Illendula, Anuradha; Pulikkan, John A.; Zong, Hongliang; Grembecka, Jolanta; Xue, Liting; Sen, Siddhartha; Zhou, Yunpeng; Boulton, Adam; Kuntimaddi, Aravinda; Gao, Yan; Rajewski, Roger A.; Guzman, Monica L.; Castilla, Lucio H.; Bushweller, John H.

2015-01-01

Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. PMID:25678665

Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation.

PubMed

Mima, Junko; Koshino, Aya; Oka, Kyoko; Uchida, Hitoshi; Hieda, Yohki; Nohara, Kanji; Kogo, Mikihiko; Chai, Yang; Sakai, Takayoshi

2013-01-01

Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1(-/-)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1(-/-) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(-/-)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.

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

Henderson, Ian M.; Collins, Aaron M.; Quintana, Hope A.

In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS.more » The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

Adjacent segment disease after instrumented fusion for adult lumbar spondylolisthesis: Incidence and risk factors.

PubMed

Zhong, Zhao-Ming; Deviren, Vedat; Tay, Bobby; Burch, Shane; Berven, Sigurd H

2017-05-01

A potential long-term complication of lumbar fusion is the development of adjacent segment disease (ASD), which may necessitate second surgery and adversely affect outcomes. The objective of this is to determine the incidence of ASD following instrumented fusion in adult patients with lumbar spondylolisthesis and to identify the risk factors for this complication. We retrospectively assessed adult patients who had undergone decompression and instrumented fusion for lumbar spondylolisthesis between January 2006 and December 2012. The incidence of ASD was analyzed. Potential risk factors included the patient-related factors, surgery-related factors, and radiographic variables such as sagittal alignment, preexisting disc degeneration and spinal stenosis at the adjacent segment. A total of 154 patients (mean age, 58.4 years) were included. Mean duration of follow-up was 28.6 months. Eighteen patients (11.7%) underwent a reoperation for ASD; 15 patients had reoperation at cranial ASD and 3 at caudal ASD. The simultaneous decompression at adjacent segment (p=0.002) and preexisting spinal stenosis at cranial adjacent segment (p=0.01) were identified as risk factors for ASD. The occurrence of ASD was not affected by patient-related factors, the types, grades and levels of spondylolisthesis, surgical approach, fusion procedures, levels of fusion, number of levels fused, types of bone graft, use of bone morphogenetic proteins, sagittal alignment, preexisting adjacent disc degeneration and preexisting spinal stenosis at caudal adjacent segments. Our findings suggest the overall incidence of ASD is 11.7% in adult patients with lumbar spondylolisthesis after decompression and instrumented fusion at a mean follow-up of 28.6 months, the simultaneous decompression at the adjacent segment and preexisting spinal stenosis at cranial adjacent segment are risk factors for ASD. Copyright © 2017. Published by Elsevier B.V.

Bone bridge formation across the neuroforamen 14 years after instrumented fusion for isthmic spondylolisthesis—a case report

PubMed Central

Lim, Joel Louis; Tan, Kimberly-Anne

2017-01-01

This case report describes the first case of a bone bridge formation across the left L5/S1 neuroforamen after instrumented posterolateral fusion for L5/S1 isthmic spondylolisthesis. Our patient was a 70-year-old lady who had grade 2, L5/S1 isthmic spondylolisthesis and bilateral S1 nerve root compression. She suffered from mechanical low back pain and neurogenic claudication, with radicular pain over both S1 dermatomes. She underwent in-situ, instrumented, posterolateral fusion and was asymptomatic for more than 13 years before developing progressive onset of left radicular pain over the L5 dermatome. Imaging revealed a bisected left L5/S1 neuroforamen secondary to a bone bridge formation resulting in stenosis. The pars defect in this case may have had sufficient osteogenic and osteoinductive factors to heal following spinal stabilization. Although in-situ posterolateral fusion is an accepted surgical treatment for isthmic spondylolisthesis, surgeons should consider reduction of the spondylolisthesis and excision of the pars defects to avoid this possible long-term complication. PMID:28435923

Bone bridge formation across the neuroforamen 14 years after instrumented fusion for isthmic spondylolisthesis-a case report.

PubMed

Lim, Joel Louis; Tan, Kimberly-Anne; Hey, Hwee Weng Dennis

2017-03-01

This case report describes the first case of a bone bridge formation across the left L5/S1 neuroforamen after instrumented posterolateral fusion for L5/S1 isthmic spondylolisthesis. Our patient was a 70-year-old lady who had grade 2, L5/S1 isthmic spondylolisthesis and bilateral S1 nerve root compression. She suffered from mechanical low back pain and neurogenic claudication, with radicular pain over both S1 dermatomes. She underwent in-situ, instrumented, posterolateral fusion and was asymptomatic for more than 13 years before developing progressive onset of left radicular pain over the L5 dermatome. Imaging revealed a bisected left L5/S1 neuroforamen secondary to a bone bridge formation resulting in stenosis. The pars defect in this case may have had sufficient osteogenic and osteoinductive factors to heal following spinal stabilization. Although in-situ posterolateral fusion is an accepted surgical treatment for isthmic spondylolisthesis, surgeons should consider reduction of the spondylolisthesis and excision of the pars defects to avoid this possible long-term complication.

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

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

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

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

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE PAGES

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.; ...

2017-08-16

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

Fluorescent protein-tagged Vpr dissociates from HIV-1 core after viral fusion and rapidly enters the cell nucleus.

PubMed

Desai, Tanay M; Marin, Mariana; Sood, Chetan; Shi, Jiong; Nawaz, Fatima; Aiken, Christopher; Melikyan, Gregory B

2015-10-29

HIV-1 Vpr is recruited into virions during assembly and appears to remain associated with the viral core after the reverse transcription and uncoating steps of entry. This feature has prompted the use of fluorescently labeled Vpr to visualize viral particles and to follow trafficking of post-fusion HIV-1 cores in the cytoplasm. Here, we tracked single pseudovirus entry and fusion and observed that fluorescently tagged Vpr gradually dissociates from post-fusion viral cores over the course of several minutes and accumulates in the nucleus. Kinetics measurements showed that fluorescent Vpr released from the cores very rapidly entered the cell nucleus. More than 10,000 Vpr molecules can be delivered into the cell nucleus within 45 min of infection by HIV-1 particles pseudotyped with the avian sarcoma and leukosis virus envelope glycoprotein. The fraction of Vpr from cell-bound viruses that accumulated in the nucleus was proportional to the extent of virus-cell fusion and was fully blocked by viral fusion inhibitors. Entry of virus-derived Vpr into the nucleus occurred independently of envelope glycoproteins or target cells. Fluorescence correlation spectroscopy revealed two forms of nuclear Vpr-monomers and very large complexes, likely involving host factors. The kinetics of viral Vpr entering the nucleus after fusion was not affected by point mutations in the capsid protein that alter the stability of the viral core. The independence of Vpr shedding of capsid stability and its relatively rapid dissociation from post-fusion cores suggest that this process may precede capsid uncoating, which appears to occur on a slower time scale. Our results thus demonstrate that a bulk of fluorescently labeled Vpr incorporated into HIV-1 particles is released shortly after fusion. Future studies will address the question whether the quick and efficient nuclear delivery of Vpr derived from incoming viruses can regulate subsequent steps of HIV-1 infection.

Structure and Biophysics of CBFβ/RUNX and Its Translocation Products.

PubMed

Tahirov, Tahir H; Bushweller, John

2017-01-01

The core binding factor (CBF) transcription factor is somewhat unique in that it is composed of a DNA binding RUNX subunit (RUNX1, 2, or 3) and a non-DNA binding CBFβ subunit, which modulates RUNX protein activity by modulating the auto-inhibition of the RUNX subunits. Since the discovery of this fascinating transcription factor more than 20 years ago, there has been a robust effort to characterize the structure as well as the biochemical properties of CBF. More recently, these efforts have also extended to the fusion proteins that arise from the subunits of CBF in leukemia. This chapter highlights the work of numerous labs which has provided a detailed understanding of the structure and function of this transcription factor and its fusion proteins.

Guidance: Use of Contract Inspectors for EPA's Federal Facility Compliance Inspections/Evaluations

EPA Pesticide Factsheets

This guidance clarifies that properly trained authorized and federally credentialed EPA contract inspectors can perform compliance inspections at federal facilities under the CWA, RCRA, TSCA, OPA and the SDWA.

Phase-matching properties of BaGa₄Se₇ for SHG and SFG in the 0.901-10.5910  μm range.

PubMed

Kato, Kiyoshi; Miyata, Kentaro; Petrov, Valentin

2017-04-10

We report new experimental results on the phase-matching properties of a BaGa₄Se₇ crystal for harmonic generation of a Nd:YAG laser-pumped AgGaS₂ optical parametric oscillator (OPO) and a CO₂ laser in the 0.901-10.5910 μm range. In addition, we present new Sellmeier equations that provide a good reproduction of the present experimental results as well as the published data points for a Nd:YAG laser-pumped OPO and an optical parametric amplifier (OPA) in the 3.10-15.22 μm range and a Ho:YAG laser-pumped OPA in the 3.49-5.18 μm range.

Precision resection of lung cancer in a sheep model using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Beck, Rainer J.; Mohanan, Syam Mohan P. C.; Góra, Wojciech S.; Cousens, Chris; Finlayson, Jeanie; Dagleish, Mark P.; Griffiths, David J.; Shephard, Jonathan D.

2017-02-01

Recent developments and progress in the delivery of high average power ultrafast laser pulses enable a range of novel minimally invasive surgical procedures. Lung cancer is the leading cause of cancer deaths worldwide and here the resection of lung tumours by means of picosecond laser pulses is presented. This represents a potential alternative to mitigate limitations of existing surgical treatments in terms of precision and collateral thermal damage to the healthy tissue. Robust process parameters for the laser resection are demonstrated using ovine pulmonary adenocarcinoma (OPA). OPA is a naturally occurring lung cancer of sheep caused by retrovirus infection that has several features in common with some forms of human pulmonary adenocarcinoma, including a similar histological appearance, which makes it ideally suited for this study. The picosecond laser was operated at a wavelength of 515 nm to resect square cavities from fresh ex-vivo OPA samples using a range of scanning strategies. Process parameters are presented for efficient ablation of the tumour with clear margins and only minimal collateral damage to the surrounding tissue. The resection depth can be controlled precisely by means of the pulse energy. By adjusting the overlap between successive laser pulses, deliberate heat transfer to the tissue and thermal damage can be achieved. This can be beneficial for on demand haemostasis and laser coagulation. Overall, the application of ultrafast lasers for the resection of lung tumours has potential to enable significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

A Low Cost Rokkaku Kite Setup for Aerial Photogrammetric System

NASA Astrophysics Data System (ADS)

Khan, A. F.; Khurshid, K.; Saleh, N.; Yousuf, A. A.

2015-03-01

Orthogonally Projected Area (OPA) of a geographical feature has primarily been studied utilizing rather time consuming field based sampling techniques. Remote sensing on the contrary provides the ability to acquire large scale data at a snapshot of time and lets the OPA to be calculated conveniently and with reasonable accuracy. Unfortunately satellite based remote sensing provides data at high cost and limited spatial resolution for scientific studies focused at small areas such as micro lakes micro ecosystems, etc. More importantly, recent satellite data may not be readily available for a particular location. This paper describes a low cost photogrammetric system to measure the OPA of a small scale geographic feature such as a plot of land, micro lake or an archaeological site, etc. Fitted with a consumer grade digital imaging system, a Rokkaku kite aerial platform with stable flight characteristics is designed and fabricated for image acquisition. The data processing procedure involves automatic Ground Control Point (GCP) detection, intelligent target area shape determination with minimal human input. A Graphical User Interface (GUI) is built from scratch in MATLAB to allow the user to conveniently process the acquired data, archive and retrieve the results. Extensive on-field experimentation consists of multiple geographic features including flat land surfaces, buildings, undulating rural areas, and an irregular shaped micro lake, etc. Our results show that the proposed system is not only low cost, but provides a framework that is easy and fast to setup while maintaining the required constraints on the accuracy.

MIXTA-Like Transcription Factors and WAX INDUCER1/SHINE1 Coordinately Regulate Cuticle Development in Arabidopsis and Torenia fournieri[C][W

PubMed Central

Oshima, Yoshimi; Shikata, Masahito; Koyama, Tomotsugu; Ohtsubo, Norihiro; Mitsuda, Nobutaka; Ohme-Takagi, Masaru

2013-01-01

The waxy plant cuticle protects cells from dehydration, repels pathogen attack, and prevents organ fusion during development. The transcription factor WAX INDUCER1/SHINE1 (WIN1/SHN1) regulates the biosynthesis of waxy substances in Arabidopsis thaliana. Here, we show that the MIXTA-like MYB transcription factors MYB106 and MYB16, which regulate epidermal cell morphology, also regulate cuticle development coordinately with WIN1/SHN1 in Arabidopsis and Torenia fournieri. Expression of a MYB106 chimeric repressor fusion (35S:MYB106-SRDX) and knockout/down of MYB106 and MYB16 induced cuticle deficiencies characterized by organ adhesion and reduction of epicuticular wax crystals and cutin nanoridges. A similar organ fusion phenotype was produced by expression of a WIN1/SHN1 chimeric repressor. Conversely, the dominant active form of MYB106 (35S:MYB106-VP16) induced ectopic production of cutin nanoridges and increased expression of WIN1/SHN1 and wax biosynthetic genes. Microarray experiments revealed that MYB106 and WIN1/SHN1 regulate similar sets of genes, predominantly those involved in wax and cutin biosynthesis. Furthermore, WIN1/SHN1 expression was induced by MYB106-VP16 and repressed by MYB106-SRDX. These results indicate that the regulatory cascade of MIXTA-like proteins and WIN1/SHN1 coordinately regulate cutin biosynthesis and wax accumulation. This study reveals an additional key aspect of MIXTA-like protein function and suggests a unique relationship between cuticle development and epidermal cell differentiation. PMID:23709630

Generic Stellarator-like Magnetic Fusion Reactor

NASA Astrophysics Data System (ADS)

Sheffield, John; Spong, Donald

2015-11-01

The Generic Magnetic Fusion Reactor paper, published in 1985, has been updated, reflecting the improved science and technology base in the magnetic fusion program. Key changes beyond inflation are driven by important benchmark numbers for technologies and costs from ITER construction, and the use of a more conservative neutron wall flux and fluence in modern fusion reactor designs. In this paper the generic approach is applied to a catalyzed D-D stellarator-like reactor. It is shown that an interesting power plant might be possible if the following parameters could be achieved for a reference reactor: R/ < a > ~ 4 , confinement factor, fren = 0.9-1.15, < β > ~ 8 . 0 -11.5 %, Zeff ~ 1.45 plus a relativistic temperature correction, fraction of fast ions lost ~ 0.07, Bm ~ 14-16 T, and R ~ 18-24 m. J. Sheffield was supported under ORNL subcontract 4000088999 with the University of Tennessee.

Detection of osteoclastic cell-cell fusion through retroviral vector packaging.

PubMed

Kondo, Takako; Ikeda, Kyoji; Matsuo, Koichi

2004-11-01

Cell-cell fusion generates multinucleated cells such as osteoclasts in bone, myotubes in muscle, and trophoblasts in placenta. Molecular details governing these fusion processes are still largely unknown. As a step toward identification of fusogenic genes, we tested the concept that retroviral vectors can be packaged as a result of cell-cell fusion. First, we introduced replication-deficient retroviral vectors expressing mCAT-1, which mediates fusogenic interaction with the retroviral envelope protein Env, into Chinese hamster ovary (CHO) cells to generate vector cells. Plasmids expressing virion proteins Gag, Pol, and Env were introduced into a separate culture of CHO cells to generate packaging cells. Co-culturing vector and packaging cells resulted in production of infectious retroviruses carrying the mCAT-1 gene as a consequence of cell-cell fusion. Second, we introduced a retroviral vector into primary osteoclast precursors and co-cultured them with established osteoclast precursor RAW264.7 cells, which turned out to harbor packaging activity. Packaged retroviral vector was detected in culture supernatants only where the osteoclast differentiation factor receptor activator for NF-kappaB ligand (RANKL) induced fusion between these two cell types. These data suggest that retrovirus production can occur as a result of cell-cell fusion. This provides a novel approach for isolating and characterizing fusogenic genes using retroviral expression vectors.

The effect of multispectral image fusion enhancement on human efficiency.

PubMed

Bittner, Jennifer L; Schill, M Trent; Mohd-Zaid, Fairul; Blaha, Leslie M

2017-01-01

The visual system can be highly influenced by changes to visual presentation. Thus, numerous techniques have been developed to augment imagery in an attempt to improve human perception. The current paper examines the potential impact of one such enhancement, multispectral image fusion, where imagery captured in varying spectral bands (e.g., visible, thermal, night vision) is algorithmically combined to produce an output to strengthen visual perception. We employ ideal observer analysis over a series of experimental conditions to (1) establish a framework for testing the impact of image fusion over the varying aspects surrounding its implementation (e.g., stimulus content, task) and (2) examine the effectiveness of fusion on human information processing efficiency in a basic application. We used a set of rotated Landolt C images captured with a number of individual sensor cameras and combined across seven traditional fusion algorithms (e.g., Laplacian pyramid, principal component analysis, averaging) in a 1-of-8 orientation task. We found that, contrary to the idea of fused imagery always producing a greater impact on perception, single-band imagery can be just as influential. Additionally, efficiency data were shown to fluctuate based on sensor combination instead of fusion algorithm, suggesting the need for examining multiple factors to determine the success of image fusion. Our use of ideal observer analysis, a popular technique from the vision sciences, provides not only a standard for testing fusion in direct relation to the visual system but also allows for comparable examination of fusion across its associated problem space of application.

The Human Factors of Sensor Fusion

DTIC Science & Technology

2008-05-01

tool in future military operations. 23 7. References Abdi, H. Neural Networks. In M. Lewis-Beck, A . Bryman , T. Futing (Eds), Encyclopedia for... a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...This report discusses select, cognitively based principles associated with the sensor fusion process. A review is made of the standard

Multiple kernel SVR based on the MRE for remote sensing water depth fusion detection

NASA Astrophysics Data System (ADS)

Wang, Jinjin; Ma, Yi; Zhang, Jingyu

2018-03-01

Remote sensing has an important means of water depth detection in coastal shallow waters and reefs. Support vector regression (SVR) is a machine learning method which is widely used in data regression. In this paper, SVR is used to remote sensing multispectral bathymetry. Aiming at the problem that the single-kernel SVR method has a large error in shallow water depth inversion, the mean relative error (MRE) of different water depth is retrieved as a decision fusion factor with single kernel SVR method, a multi kernel SVR fusion method based on the MRE is put forward. And taking the North Island of the Xisha Islands in China as an experimentation area, the comparison experiments with the single kernel SVR method and the traditional multi-bands bathymetric method are carried out. The results show that: 1) In range of 0 to 25 meters, the mean absolute error(MAE)of the multi kernel SVR fusion method is 1.5m,the MRE is 13.2%; 2) Compared to the 4 single kernel SVR method, the MRE of the fusion method reduced 1.2% (1.9%) 3.4% (1.8%), and compared to traditional multi-bands method, the MRE reduced 1.9%; 3) In 0-5m depth section, compared to the single kernel method and the multi-bands method, the MRE of fusion method reduced 13.5% to 44.4%, and the distribution of points is more concentrated relative to y=x.

A toddler PCV booster dose following 3 infancy priming doses increases circulating serotype-specific IGG levels but does not increase protection against carriage.

PubMed

Dagan, Ron; Ben-Shimol, Shalom; Simell, Birgit; Greenberg, David; Porat, Nurith; Käyhty, Helena; Givon-Lavi, Noga

2018-05-11

We compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1). A prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844. Overall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7-30 months and for 0+2 group at 19-30 months. PCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

PubMed

Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

2016-08-04

Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors associated with spinal fusion after posterior fossa decompression in pediatric patients with Chiari I malformation and scoliosis.

PubMed

Mackel, Charles E; Cahill, Patrick J; Roguski, Marie; Samdani, Amer F; Sugrue, Patrick A; Kawakami, Noriaki; Sturm, Peter F; Pahys, Joshua M; Betz, Randal R; El-Hawary, Ron; Hwang, Steven W

2016-12-01

OBJECTIVE The authors performed a study to identify clinical characteristics of pediatric patients diagnosed with Chiari I malformation and scoliosis associated with a need for spinal fusion after posterior fossa decompression when managing the scoliotic curve. METHODS The authors conducted a multicenter retrospective review of 44 patients, aged 18 years or younger, diagnosed with Chiari I malformation and scoliosis who underwent posterior fossa decompression from 2000 to 2010. The outcome of interest was the need for spinal fusion after decompression. RESULTS Overall, 18 patients (40%) underwent posterior fossa decompression alone, and 26 patients (60%) required a spinal fusion after the decompression. The mean Cobb angle at presentation and the proportion of patients with curves > 35° differed between the decompression-only and fusion cohorts (30.7° ± 11.8° vs 52.1° ± 26.3°, p = 0.002; 5 of 18 vs 17 of 26, p = 0.031). An odds ratio of 1.0625 favoring a need for fusion was established for each 1° of increase in Cobb angle (p = 0.012, OR 1.0625, 95% CI 1.0135-1.1138). Among the 14 patients older than 10 years of age with a primary Cobb angle exceeding 35°, 13 (93%) ultimately required fusion. Patients with at least 1 year of follow-up whose curves progressed more 10° after decompression were younger than those without curve progression (6.1 ± 3.0 years vs 13.7 ± 3.2 years, p = 0.001, Mann-Whitney U-test). Left apical thoracic curves constituted a higher proportion of curves in the decompression-only group (8 of 16 vs 1 of 21, p = 0.002). CONCLUSIONS The need for fusion after posterior fossa decompression reflected the curve severity at clinical presentation. Patients presenting with curves measuring > 35°, as well as those greater than 10 years of age, may be at greater risk for requiring fusion after posterior fossa decompression, while patients less than 10 years of age may require routine monitoring for curve progression. Left apical thoracic curves may have a better response to Chiari malformation decompression.

Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2).

PubMed

Ross, T S; Bernard, O A; Berger, R; Gilliland, D G

1998-06-15

We report the fusion of the Huntingtin interactin protein 1 (HIP1) gene to the platelet-derived growth factor betareceptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFbetaR gene probe demonstrated rearrangement of the PDGFbetaR gene. Anchored polymerase chain reaction using PDGFbetaR primers identified a chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFbetaR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFbetaR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFbetaR. The reciprocal PDGFbetaR/HIP1 transcript is not expressed. HIP1/PDGFbetaR is a 180-kD protein when expressed in the murine hematopoietic cell line, Ba/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFbetaR transforms the Ba/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFbetaR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

Failure analysis of knee arthrodesis with the WichitaFusion Nail.

PubMed

Parcel, Ted W; Levering, Melissa; Polikandriotis, John A; Gustke, Kenneth A; Bernasek, Thomas L

2013-11-01

Arthrodesis is a salvage procedure for failed total knee arthroplasty with the intent to create a stable, pain-free limb on which to ambulate or transfer. For many patients, the alternative to arthrodesis may be an above-knee amputation. Available techniques for knee arthrodesis include compression plating, external fixators, and intramedullary fixation. The purpose of this study was to report the knee fusion rate of consecutive patients at 1 institution using an intramedullary fusion nail and to identify patient risk factors for fusion failure. Between November 1998 and November 2008, twenty-eight patients undergoing knee arthrodesis with an average follow-up of 18 months (range, 3-64 months) were retrospectively studied. Demographic information, presence of fusion, clinical function, pain level, and bone defect data were collected and analyzed. Eighty-two percent (23/28) of patients had radiographic evidence of successful fusion with an average time to fusion of 21 weeks (range, 10-58 weeks). When examining patient variables that could correlate with fusion rates, patients with an Anderson Orthopaedic Research Institute type 3 femoral or type 3 tibial defect had a statistically significant lower fusion rate. The intramedullary fusion nail is an effective device for knee arthrodesis that offers ease of insertion through the knee wound with the advantages of initial bone compression and rigid fixation. Although the use of intramedullary fusion nails leads to a high fusion rate, significant bone deficiency limits successful fusion. Copyright 2013, SLACK Incorporated.

Protect Yourself Against HPV | NIH MedlinePlus the Magazine

MedlinePlus

... gov/opa/reproductive-health/stis/hpv/ Human Papillomavirus Block this cervical-cancer causing virus More than half ... against all these forms of cancer. Gardasil also blocks two HPV strains that cause 90 percent of ...

Oil Pollution Research and Technology Plan

DOT National Transportation Integrated Search

1997-04-01

Title VII of the Oil Pollution Act of 1990 (OPA 90) established the thirteen member Interagency Coordinating Committee on Oil Pollution Research (Committee). The Committee is charged with coordinating a comprehensive program of research, technology d...

Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis

PubMed Central

Schaub, Christoph; Frasch, Manfred

2013-01-01

The T-Box family of transcription factors plays fundamental roles in the generation of appropriate spatial and temporal gene expression profiles during cellular differentiation and organogenesis in animals. In this study we report that the Drosophila Tbx1 orthologue optomotor-blind-related-gene-1 (org-1) exerts a pivotal function in the diversification of circular visceral muscle founder cell identities in Drosophila. In embryos mutant for org-1, the specification of the midgut musculature per se is not affected, but the differentiating midgut fails to form the anterior and central midgut constrictions and lacks the gastric caeca. We demonstrate that this phenotype results from the nearly complete loss of the founder cell specific expression domains of several genes known to regulate midgut morphogenesis, including odd-paired (opa), teashirt (tsh), Ultrabithorax (Ubx), decapentaplegic (dpp) and wingless (wg). To address the mechanisms that mediate the regulatory inputs from org-1 towards Ubx, dpp, and wg in these founder cells we genetically dissected known visceral mesoderm specific cis-regulatory-modules (CRMs) of these genes. The analyses revealed that the activities of the dpp and wg CRMs depend on org-1, the CRMs are bound by Org-1 in vivo and their T-Box binding sites are essential for their activation in the visceral muscle founder cells. We conclude that Org-1 acts within a well-defined signaling and transcriptional network of the trunk visceral mesoderm as a crucial founder cell-specific competence factor, in concert with the general visceral mesodermal factor Biniou. As such, it directly regulates several key genes involved in the establishment of morphogenetic centers along the anteroposterior axis of the visceral mesoderm, which subsequently organize the formation of midgut constrictions and gastric caeca and thereby determine the morphology of the midgut. PMID:23380635

Synaptotagmin C2B Domain Regulates Ca2+-triggered Fusion in Vitro

PubMed Central

Gaffaney, Jon D.; Dunning, F. Mark; Wang, Zhao; Hui, Enfu; Chapman, Edwin R.

2008-01-01

Synaptotagmin (syt) 1 is localized to synaptic vesicles, binds Ca2+, and regulates neuronal exocytosis. Syt 1 harbors two Ca2+-binding motifs referred to as C2A and C2B. In this study we examine the function of the isolated C2 domains of Syt 1 using a reconstituted, SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor)-mediated, fusion assay. We report that inclusion of phosphatidylethanolamine into reconstituted SNARE vesicles enabled isolated C2B, but not C2A, to regulate Ca2+-triggered fusion. The isolated C2B domain had a 6-fold lower EC for Ca2+ 50-activated fusion than the intact cytosolic domain of Syt 1 (C2AB). Phosphatidylethanolamine increased both the rate and efficiency of C2AB- and C2B-regulated fusion without affecting their abilities to bind membrane-embedded syntaxin-SNAP-25 (t-SNARE) complexes. At equimolar concentrations, the isolated C2A domain was an effective inhibitor of C2B-, but not C2AB-regulated fusion; hence, C2A has markedly different effects in the fusion assay depending on whether it is tethered to C2B. Finally, scanning alanine mutagenesis of C2AB revealed four distinct groups of mutations within the C2B domain that play roles in the regulation of SNARE-mediated fusion. Surprisingly, substitution of Arg-398 with alanine, which lies on the opposite end of C2B from the Ca2+/membrane-binding loops, decreases C2AB t-SNARE binding and Ca2+-triggered fusion in vitro without affecting Ca2+-triggered interactions with phosphatidylserine or vesicle aggregation. In addition, some mutations uncouple the clamping and stimulatory functions of syt 1, suggesting that these two activities are mediated by distinct structural determinants in C2B. PMID:18784080

Analysis of linear and cyclic oligomers in polyamide-6 without sample preparation by liquid chromatography using the sandwich injection method. II. Methods of detection and quantification and overall long-term performance.

PubMed

Mengerink, Y; Peters, R; Kerkhoff, M; Hellenbrand, J; Omloo, H; Andrien, J; Vestjens, M; van der Wal, S

2000-05-05

By separating the first six linear and cyclic oligomers of polyamide-6 on a reversed-phase high-performance liquid chromatographic system after sandwich injection, quantitative determination of these oligomers becomes feasible. Low-wavelength UV detection of the different oligomers and selective post-column reaction detection of the linear oligomers with o-phthalic dicarboxaldehyde (OPA) and 3-mercaptopropionic acid (3-MPA) are discussed. A general methodology for quantification of oligomers in polymers was developed. It is demonstrated that the empirically determined group-equivalent absorption coefficients and quench factors are a convenient way of quantifying linear and cyclic oligomers of nylon-6. The overall long-term performance of the method was studied by monitoring a reference sample and the calibration factors of the linear and cyclic oligomers.

49 CFR 192.113 - Longitudinal joint factor (E) for steel pipe.

Code of Federal Regulations, 2010 CFR

2010-10-01

... class Longitudinal joint factor (E) ASTM A 53/A53M Seamless 1.00 Electric resistance welded 1.00 Furnace butt welded .60 ASTM A 106 Seamless 1.00 ASTM A 333/A 333M Seamless 1.00 Electric resistance welded 1.00 ASTM A 381 Double submerged arc welded 1.00 ASTM A 671 Electric-fusion-welded 1.00 ASTM A 672...

Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma

PubMed Central

Vasir, Baldev; Uhl, Lynne; Blotta, Simona; MacNamara, Claire; Somaiya, Poorvi; Wu, Zekui; Joyce, Robin; Levine, James D.; Dombagoda, Dilani; Yuan, Yan Emily; Francoeur, Karen; Fitzgerald, Donna; Richardson, Paul; Weller, Edie; Anderson, Kenneth; Kufe, Donald; Munshi, Nikhil; Avigan, David

2011-01-01

We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocyte-macrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α and fused with myeloma cells obtained from marrow aspirates. Vaccine generation was successful in 17 of 18 patients. Successive cohorts were treated with 1 × 106, 2 × 106, and 4 × 106 fusion cells, respectively, with 10 patients treated at the highest dose level. Vaccination was well tolerated, without evidence of dose-limiting toxicity. Vaccination resulted in the expansion of circulating CD4 and CD8 lymphocytes reactive with autologous myeloma cells in 11 of 15 evaluable patients. Humoral responses were documented by SEREX (Serologic Analysis of Recombinant cDNA Expression Libraries) analysis. A majority of patients with advanced disease demonstrated disease stabilization, with 3 patients showing ongoing stable disease at 12, 25, and 41 months, respectively. Vaccination with DC/multiple myeloma fusions was feasible and well tolerated and resulted in antitumor immune responses and disease stabilization in a majority of patients. PMID:21030562

Matrix factorization-based data fusion for gene function prediction in baker's yeast and slime mold.

PubMed

Zitnik, Marinka; Zupan, Blaž

2014-01-01

The development of effective methods for the characterization of gene functions that are able to combine diverse data sources in a sound and easily-extendible way is an important goal in computational biology. We have previously developed a general matrix factorization-based data fusion approach for gene function prediction. In this manuscript, we show that this data fusion approach can be applied to gene function prediction and that it can fuse various heterogeneous data sources, such as gene expression profiles, known protein annotations, interaction and literature data. The fusion is achieved by simultaneous matrix tri-factorization that shares matrix factors between sources. We demonstrate the effectiveness of the approach by evaluating its performance on predicting ontological annotations in slime mold D. discoideum and on recognizing proteins of baker's yeast S. cerevisiae that participate in the ribosome or are located in the cell membrane. Our approach achieves predictive performance comparable to that of the state-of-the-art kernel-based data fusion, but requires fewer data preprocessing steps.

Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.

PubMed

Bhalla, Akhil; Chicka, Michael C; Chapman, Edwin R

2008-08-01

Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells is regulated by the Ca(2+)-binding protein synaptotagmin (syt) I. Sixteen additional isoforms of syt have been identified, but little is known concerning their biochemical or functional properties. Here, we assessed the abilities of fourteen syt isoforms to directly regulate SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor)-catalyzed membrane fusion. One group of isoforms stimulated neuronal SNARE-mediated fusion in response to Ca(2+), while another set inhibited SNARE catalyzed fusion in both the absence and presence of Ca(2+). Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion, further establishing PS and SNAREs as critical effectors for syt action. The ability of syt I to efficiently stimulate fusion was specific for certain SNARE pairs, suggesting that syts might contribute to the specificity of intracellular membrane fusion reactions. Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other.

FGFR1 is essential for N-acetyl-seryl-aspartyl-lysyl-proline regulation of mitochondrial dynamics by upregulating microRNA let-7b-5p.

PubMed

Hu, Qiongying; Li, Jinpeng; Nitta, Kyoko; Kitada, Munehiro; Nagai, Takako; Kanasaki, Keizo; Koya, Daisuke

2018-01-15

Fibroblast growth factor receptor (FGFR) 1 plays a key role in endothelial homeostasis by inducing microRNA (miR) let-7. Our previous paper showed that anti-fibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) were associated with restoring diabetes-suppressed expression of FGFR1 and miR let-7, the key contributor of mitochondrial biogenesis, which is regulated by mitochondrial membrane GTPase proteins (MFN2 and OPA1). Here, we found that the FGFR1 signaling pathway was critical for AcSDKP in maintaining endothelial mitochondrial biogenesis through induction of miR let-7b-5p. In endothelial cells, AcSDKP restored the triple cytokines (TGF-β2, interleukin-1β, tumor necrosis factor-α)-suppressed miR let-7b-5p and protein levels of the mitochondrial membrane GTPase. This effect of AcSDKP was lost with either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1-treated cells. Similarly, AcSDKP had no effect on the miR let-7b-5p inhibitor-suppressed GTPase levels in endothelial cells. In addition, a miR let-7b-5p mimic restored the levels of FRS2 siRNA-reduced GTPases in endothelial cells. These findings were also confirmed using MitoTracker Green and an immunofluorescence assay. Our results demonstrated that the AcSDKP-FGFR1 signaling pathway is critical for maintaining mitochondrial dynamics by control of miR let-7b-5p in endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of Tgfß3.

PubMed

Serrano, Maria J; Liu, Jingpeng; Svoboda, Kathy K H; Nawshad, Ali; Benson, M Douglas

2015-12-01

The mammalian secondary palate forms from shelves of epithelia-covered mesenchyme that meet at midline and fuse. The midline epithelial seam (MES) is thought to degrade by apoptosis, epithelial-to-mesenchymal transition (EMT), or both. Failure to degrade the MES blocks fusion and causes cleft palate. It was previously thought that transforming growth factor ß3 (Tgfß3) is required to initiate fusion. Members of the Eph tyrosine kinase receptor family and their membrane-bound ephrin ligands are expressed on the MES. We demonstrated that treatment of mouse palates with recombinant EphB2/Fc to activate ephrin reverse signaling (where the ephrin acts as a receptor and transduces signals from its cytodomain) was sufficient to cause mouse palatal fusion when Tgfß3 signaling was blocked by an antibody against Tgfß3 or by an inhibitor of the TgfßrI serine/threonine receptor kinase. Cultured palatal epithelial cells traded their expression of epithelial cell markers for that of mesenchymal cells and became motile after treatment with EphB2/Fc. They concurrently increased their expression of the EMT-associated transcription factors Snail, Sip1, and Twist1. EphB2/Fc did not cause apoptosis in these cells. These data reveal that ephrin reverse signaling directs palatal fusion in mammals through a mechanism that involves EMT but not apoptosis and activates a gene expression program not previously associated with ephrin reverse signaling. © 2015 Wiley Periodicals, Inc.

Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

PubMed

Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

2018-04-01

MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India.

PubMed

Lalwani, Sanjay; Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-09-01

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Tat-APE1/ref-1 protein inhibits TNF-{alpha}-induced endothelial cell activation

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

Song, Yun Jeong; Lee, Ji Young; Joo, Hee Kyoung

2008-03-28

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/ref-1) is a multifunctional protein involved both in DNA base excision repair and redox regulation. In this study we evaluated the protective role of Tat-mediated APE1/ref-1 transduction on the tumor necrosis factor (TNF)-{alpha}-activated endothelial activation in cultured human umbilical vein endothelial cells. To construct Tat-APE1/ref-1 fusion protein, human full length of APE1/ref-1 was fused with Tat-protein transduction domain. Purified Tat-APE1/ref-1 fusion protein efficiently transduced cultured endothelial cells in a dose-dependent manner and reached maximum expression at 1 h after incubation. Transduced Tat-APE1/ref-1 showed inhibitory activity on the TNF-{alpha}-induced monocyte adhesion and vascular cell adhesion molecule-1 expressionmore » in cultured endothelial cells. These results suggest Tat-APE1/ref-1 might be useful to reduce vascular endothelial activation or vascular inflammatory disorders.« less

Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles

DOE PAGES

Henderson, Ian M.; Collins, Aaron M.; Quintana, Hope A.; ...

2015-12-13

In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS.more » The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

33 CFR 138.40 - Forms.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.30 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.130 - Fees.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.40 - Forms.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.30 - General.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.130 - Fees.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.10 - Scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.10 - Scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.40 - Forms.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.40 - Forms.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.30 - General.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.10 - Scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.130 - Fees.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.130 - Fees.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.30 - General.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.30 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.40 - Forms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

33 CFR 138.130 - Fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels...

Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms

PubMed Central

Ernst, Thomas; Chase, Andrew; Zoi, Katerina; Waghorn, Katherine; Hidalgo-Curtis, Claire; Score, Joannah; Jones, Amy; Grand, Francis; Reiter, Andreas; Hochhaus, Andreas; Cross, Nicholas C.P.

2010-01-01

Background Aberrant activation of tyrosine kinases, caused by either mutation or gene fusion, is of major importance for the development of many hematologic malignancies, particularly myeloproliferative neoplasms. We hypothesized that hitherto unrecognized, cytogenetically cryptic tyrosine kinase fusions may be common in non-classical or atypical myeloproliferative neoplasms and related myelodysplastic/myeloproliferative neoplasms. Design and Methods To detect genomic copy number changes associated with such fusions, we performed a systematic search in 68 patients using custom designed, targeted, high-resolution array comparative genomic hybridization. Arrays contained 44,000 oligonucleotide probes that targeted 500 genes including all 90 tyrosine kinases plus downstream tyrosine kinase signaling components, other translocation targets, transcription factors, and other factors known to be important for myelopoiesis. Results No abnormalities involving tyrosine kinases were detected; however, nine cytogenetically cryptic copy number imbalances were detected in seven patients, including hemizygous deletions of RUNX1 or CEBPA in two cases with atypical chronic myeloid leukemia. Mutation analysis of the remaining alleles revealed non-mutated RUNX1 and a frameshift insertion within CEBPA. A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients. Analysis of other transcription factors known to be frequently mutated in acute myeloid leukemia revealed NPM1 mutations in six (3%) and WT1 mutations in two (1%) patients with myelodysplastic/myeloproliferative neoplasms. Univariate analysis indicated that patients with mutations had a shorter overall survival (28 versus 44 months, P=0.019) compared with patients without mutations, with the prognosis for cases with CEBPA, NPM1 or WT1 mutations being particularly poor. Conclusions We conclude that mutations of transcription and other nuclear factors are frequent in myelodysplastic/myeloproliferative neoplasms and are generally mutually exclusive. CEBPA, NPM1 or WT1 mutations may be associated with a poor prognosis, an observation that will need to be confirmed by detailed prospective studies. PMID:20421268

Efficient expression of stable recombinant human insulin-like growth factor-1 fusion with human serum albumin in Chinese hamster ovary cells.

PubMed

Wan, Aini; Xu, Dongsheng; Liu, Kedong; Peng, Lin; Cai, Yanfei; Chen, Yun; He, Yang; Yang, Jianfeng; Jin, Jian; Li, Huazhong

2017-08-09

Insulin-like growth factor-1 (IGF-1) plays a crucial role in cell development, differentiation, and metabolism, and has been a potential therapeutic agent for many diseases. Chinese hamster ovary (CHO) cells are widely used for production of recombinant therapeutic proteins, but the expression level of IGF-1 in CHO cells is very low (1,500 µg/L) and the half-life of IGF-1 in blood circulation is only 4.5 min according to previous studies. Therefore, IGF-1 was fused to long-circulating serum protein human serum albumin (HSA) and expressed in CHO cells. After 8-day fed-batch culture, the expression level of HSA-IGF-1 reached 100 mg/L. The fusion protein HSA-IGF-1 was purified with a recovery of 35% using a two-step chromatographic procedure. According to bioactivity assay, the purified HSA-IGF-1 could stimulate the proliferation of NIH3T3 cells in a dose-dependent fashion and promote the cell-cycle progression. Besides this, HSA-IGF-1 could bind to IGF-1 receptor on cell membrane and activate the intracellular PI3K/AKT signaling pathway. Our study suggested that HSA fusion technology carried out in CHO cells not only provided bioactivity in HSA-IGF-1 for further research but also offered a beneficial strategy to produce other similar cytokines in CHO cells.

Interaction of cord factor (alpha, alpha'-trehalose-6,6'-dimycolate) with phospholipids.

PubMed

Crowe, L M; Spargo, B J; Ioneda, T; Beaman, B L; Crowe, J H

1994-08-24

We previously reported that cord factor (alpha,alpha'-trehalose-6,6'-dimycolate) isolated from Nocardia asteroides strain GUH-2 strongly inhibits fusion between unilamellar vesicles containing acidic phospholipid. We chose to study the effects of this molecule on liposome fusion since the presence of N. asteroides GUH-2 in the phagosomes of mouse macrophages had been shown to prevent phagosomal acidification and inhibit phagosome-lysosome fusion. A virtually non-virulent strain, N. asteroides 10905, does not prevent acidification or phagosome-lysosome fusion and, further, contains only trace amounts of cord factor. In the present paper, we have investigated the effects of cord factor on phospholipid bilayers that could be responsible for the inhibition of fusion. We show that cord factor increases molecular area, measured by isothermal compression of a monolayer film, in a mixed monolayer more than would be expected based in its individual contribution to molecular area. Cord factor, as well as other glycolipids investigated, increased the overall hydration of bilayers of dipalmitoylphosphatidylcholine by 50%, as estimated from the unfrozen water fraction measured by differential scanning calorimetry. The effect of calcium on this increased molecular area and headgroup hydration was measured by fluorescence anisotropy and FTIR spectroscopy of phosphatidylserine liposomes. Both techniques showed that cord factor, incorporated at 10 mol%, increased acyl chain disorder over controls in the presence of Ca2+. However, FTIR showed that cord factor did not prevent headgroup dehydration by the Ca2+. The other glycolipids tested did not prevent either the Ca(2+)-induced chain crystallization or headgroup dehydration of phosphatidylserine bilayers. These data point to a possible role of the bulky mycolic acids of cord factor in preventing Ca(2+)-induced fusion of liposomes containing acidic phospholipids.

Coronal imbalance in Lenke 5C adolescent idiopathic scoliosis regarding selecting the lowest instrumented vertebra: Lower-end vertebra versus lower-end vertebra +1 in posterior fusion.

PubMed

Hu, Bowen; Yang, Xi; Yang, Huiliang; Liu, Limin; Chen, Peiran; Wang, Linnan; Zhu, Ce; Zhou, Chunguang; Song, Yueming

2018-06-18

Choosing the fusion level for posterior fusion in Lenke 5C adolescent idiopathic scoliosis patients is highly associated with coronal balance. Previous studies indicated that in patients with lowest end vertebra tilt > 25°, surgeons could extend distal fusion to avoid coronal imbalance. This study aimed to assess the risk factors for coronal imbalance in Lenke 5C scoliosis, and to discuss how to select fusion level. We reviewed 59 Lenke 5C AIS patients in one institution with at least 2-years' follow-up from 2010 through 2015. Preoperative, and 3-month and 2-year postoperative follow-up radiographs were measured using a number of specific measurements related to coronal balance. Patients were categorized into an LEV group and an LEV+1 group. Coronal imbalance was found in 6/31 patients in the LEV+1 group at final follow-up , and not in the LEV-group at the first or final follow-up. The C7 plumb line shifted to the convex side of the central sacral vertical line in 47/59 patients, including all of the 19 CIB patients after surgery. Patients who underwent fusion at LEV+1 with > 25° LEV tilt also showed poor results regarding coronal imbalance. Statistically, coronal balance at the final follow-up was correlated with preoperative bending lumbosacral hemi-curve (p=0.002) and all of the 6 patients with CIB had bending lumbosacral hemi-curve exceeds 15°. No significant difference were found in SRS-22 scores between the two groups at 2-year-follow-up. Distal fusion extension at LEV+1 is more likely to result in coronal imbalance at the first and final follow-up, especially when bending lumbosacral hemi-curve exceeds 15°. Fusion at LEV+1 should not be chosen when LEV is at L4. Copyright © 2018. Published by Elsevier Inc.

Results of instrumented posterolateral fusion in treatment of lumbar spondylolisthesis with and without segmental kyphosis: A retrospective investigation.

PubMed

Chen, Szu-Yuan; Lu, Meng-Ling; Niu, Chi-Chien; Tsai, Tsung-Ting; Liao, Jen-Chung; Chen, Lih-Huei; Chen, Wen-Jer

2015-01-01

Treatment by posterolateral fusion (PLF) with pedicle-screw instrumentation can be unsuccessful in one-segment and low-grade lumbar spondylolisthesis. Segmental kyphosis, either rigid or dynamic, was hypothesized to be one of the factors interfering with the fusion results. From 2004 to 2005, 239 patients with single-segment and low-grade spondylolisthesis were recruited and divided into two groups: Group 1 consisting of 129 patients without segmental kyphosis and group 2 consisting of 110 patients with segmental kyphosis. All patients underwent instrumented PLF at the same medical institute, and the average follow-up period was 31 ± 19 months. We obtained plain radiographs of the lumbosacral spine with the anteroposterior view, the lateral view, and the dynamic flexion-extension views before the operation and during the follow-ups. The results of PLF in the two groups were then compared. There was no significant difference in the demographic data of the two groups, except for gender distribution. The osseous fusion rates were 90.7% in group 1 and 68.2% in group 2 (p < 0.001). Instrumented PLF resulted in significantly higher osseous fusion rate in patients without segmental kyphosis than in the patients with segmental kyphosis. For the patients with sagittal imbalance, such as rigid or dynamic kyphosis, pedicle-screw fixation cannot ensure successful PLF. Interbody fusion by the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion technique might help overcome this problem.

Developing the Pulsed Fission-Fusion (PuFF) Engine

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Cassibry, Jason; Bradley, David; Fabisinski, Leo; Statham, Geoffrey

2014-01-01

In September 2013 the NASA Innovative Advanced Concept (NIAC) organization awarded a phase I contract to the PuFF team. Our phase 1 proposal researched a pulsed fission-fusion propulsion system that compressed a target of deuterium (D) and tritium (T) as a mixture in a column, surrounded concentrically by Uranium. The target is surrounded by liquid lithium. A high power current would flow down the liquid lithium and the resulting Lorentz force would compress the column by roughly a factor of 10. The compressed column would reach criticality and a combination of fission and fusion reactions would occur. Our Phase I results, summarized herein, review our estimates of engine and vehicle performance, our work to date to model the fission-fusion reaction, and our initial efforts in experimental analysis.

Novel Chromosomal Rearrangements and breakpoints at the t(6;9) in Salivary Adenoid Cystic Carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome

PubMed Central

Mitani, Yoshitsugu; Rao, Pulivarthi H.; Futreal, P. Andrew; Roberts, Dianna B.; Stephens, Philip J.; Zhao, Yi-Jue; Zhang, Li; Mitani, Mutsumi; Weber, Randal S.; Lippman, Scott M.; Caulin, Carlos; El-Naggar, Adel K.

2011-01-01

Objective To investigate the molecular-genetic heterogeneity associated with the t(6:9) in adenoid cystic carcinoma (ACC) and correlate the findings with patient clinical outcome. Experimental Design Multi-molecular and genetic techniques complemented with massive pair-ended sequencing and SNP array analyses were used on tumor specimens from 30 new and 52 previously RT-PCR analyzed fusion transcript negative ACCs. MYB mRNA expression level was determined by quantitative RT-PCR. The results of 102 tumors (30 new and 72 previously reported cases) were correlated with the clinicopathologic factors and patients’ survival. Results The FISH analysis showed 34/82 (41.5%) fusion positive tumors and molecular techniques identified fusion transcripts in 21 of the 82 (25.6%) tumors. Detailed FISH analysis of 11 out the 15 tumors with gene fusion without transcript formation showed translocation of NFIB sequences to proximal or distal sites of the MYB gene. Massive pair-end sequencing of a subset of tumors confirmed the proximal translocation to an NFIB sequence and led to the identification of a new fusion gene (NFIB-AIG1) in one of the tumors. Overall, MYB-NFIB gene fusion rate by FISH was in 52.9% while fusion transcript forming incidence was 38.2%. Significant statistical association between the 5′ MYB transcript expression and patient survival was found. Conclusions We conclude that: 1) t(6;9) results in a complex genetic and molecular alterations in ACC, 2) MYB-NFIB gene fusion may not always be associated with chimeric transcript formation, 3) non-canonical MYB, NFIB gene fusions occur in a subset of tumors, 4) high MYB expression correlates with worse patient survival. PMID:21976542

In vivo characterization of fusion protein comprising of A1 subunit of Shiga toxin and human GM-CSF: Assessment of its immunogenicity and toxicity.

PubMed

Oloomi, Mana; Bouzari, Saeid; Shariati, Elaheh

2010-10-01

Most cancer cells become resistant to anti-cancer agents. In the last few years, a new approach for targeted therapy of human cancer has been developed using immunotoxins which comprise both the cell targeting and the cell killing moieties. In the present study, the recombinant Shiga toxin A1 subunit fused to human granulocyte-macrophage colony stimulating factor (A1-GM-CSF), previously produced in E. coli, was further characterized. The recombinant protein could cause 50% cytotoxicity and induced apoptosis in cells bearing GM-CSF receptors. The non-specific toxicity of the fusion protein was assessed in C57BL/6 and BALB/c mice. No mortality was observed in either group of mice, with different concentration of fusion protein. The lymphocyte proliferation assay, induction of specific IgG response and a mixed (Th1/Th2) response were observed only in BALB/c mice. The mixed response in BALB/c mice (Th1/Th2) could be explained on the basis of the two components of the fusion protein i.e. A1 and GM-CSF.

Fusion gene addiction: can tumours be forced to give up the habit?

PubMed

Selfe, Joanna L; Shipley, Janet

2017-07-01

Fusion of genes in tumours can have oncogenic roles in reprogramming cells through overexpression of oncogenes or the production of novel fusion proteins. A fundamental question in cancer biology is what genetic events are critical for initiation and whether these are also required for cancer progression. In recent work published in The Journal of Pathology, dependency on a fusion protein was addressed using a model of alveolar rhabdomyosarcomas - a sarcoma subtype with frequent fusion of PAX3 and FOXO1 genes that is associated with poor outcome. PAX3-FOXO1 encodes a potent transcription factor that together with MYCN alters the transcriptional landscape of cells. Building on previous work, an inducible model in human myoblast cells was used to show that PAX3-FOXO1 and MYCN can initiate rhabdomyosarcoma development but, contrary to current thinking, tumour recurrences occasionally arose independent of the fusion protein. Further work needs to identify the molecular nature of this independence and assess any relevance in human tumours. Such functional approaches are required together with computational modeling of molecular data to unravel spatial and temporal dependencies on specific genetic events. This may support molecular prognostic markers and therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Measurement and modelling of reactive transport in geological barriers for nuclear waste containment

DOE PAGES

Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; ...

2015-10-26

Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. Here, this balancesmore » the insufficient characterisation information and provides the means for future mechanical–physical–chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(VI) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(VI) diffusion the method is extended to account for sorption and convection. Finally, rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic.« less

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

PubMed

Madhi, Shabir A; Violari, Avy; Klugman, Keith P; Lin, Gina; McIntyre, James A; von Gottberg, Anne; Jean-Philippe, Patrick; Cotton, Mark F; Adrian, Peter

2011-09-16

Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy. We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses. Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥ 8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥ 8 than the effect of colonization on the lower proportion with antibody ≥ 0.35 μg/ml. Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype. Copyright © 2011 Elsevier Ltd. All rights reserved.

Measurement and modelling of reactive transport in geological barriers for nuclear waste containment.

PubMed

Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; Jivkov, Andrey P

2015-11-11

Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. This balances the insufficient characterisation information and provides the means for future mechanical-physical-chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(vi) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(vi) diffusion the method is extended to account for sorption and convection. Rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic.

Increases thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase by fusion of cellulose binding domain derived from Trichoderma reesei

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

Thongekkaew, Jantaporn, E-mail: jantaporn_25@yahoo.com; Ikeda, Hiroko; Iefuji, Haruyuki

Highlights: Black-Right-Pointing-Pointer The CSLP and fusion enzyme were successfully expressed in the Pichia pastoris. Black-Right-Pointing-Pointer The fusion enzyme was stable at 80 Degree-Sign C for 120-min. Black-Right-Pointing-Pointer The fusion enzyme was responsible for cellulose-binding capacity. Black-Right-Pointing-Pointer The fusion enzyme has an attractive applicant for enzyme immobilization. -- Abstract: To improve the thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase (CSLP), the cellulose-binding domain originates from Trichoderma reesei cellobiohydrolase I was engineered into C-terminal region of the CSLP (CSLP-CBD). The CSLP and CSLP-CBD were successfully expressed in the Pichia pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1)more » promoter and the secretion signal sequence from Saccharomyces cerevisiae ({alpha} factor). The recombinant CSLP and CSLP-CBD were secreted into culture medium and estimated by SDS-PAGE to be 22 and 27 kDa, respectively. The fusion enzyme was stable at 80 Degree-Sign C and retained more than 80% of its activity after 120-min incubation at this temperature. Our results also found that the fusion of fungal exoglucanase cellulose-binding domain to CSLP is responsible for cellulose-binding capacity. This attribute should make it an attractive applicant for enzyme immobilization.« less

Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1.

PubMed

Varodayan, F P; Pignataro, L; Harrison, N L

2011-10-13

Many synapses within the central nervous system are sensitive to ethanol. Although alcohol is known to affect the probability of neurotransmitter release in specific brain regions, the effects of alcohol on the underlying synaptic vesicle fusion machinery have been little studied. To identify a potential pathway by which ethanol can regulate neurotransmitter release, we investigated the effects of acute alcohol exposure (1-24 h) on the expression of the gene encoding synaptotagmin 1 (Syt1), a synaptic protein that binds calcium to directly trigger vesicle fusion. Syt1 was identified in a microarray screen as a gene that may be sensitive to alcohol and heat shock. We found that Syt1 mRNA and protein expression are rapidly and robustly up-regulated by ethanol in mouse cortical neurons, and that the distribution of Syt1 protein along neuronal processes is also altered. Syt1 mRNA up-regulation is dependent on the activation of the transcription factor heat shock factor 1 (HSF1). The transfection of a constitutively active Hsf1 construct into neurons stimulates Syt1 transcription, while transfection of Hsf1 small interfering RNA (siRNA) or a constitutively inactive Hsf1 construct into neurons attenuates the induction of Syt1 by ethanol. This suggests that the activation of HSF1 can induce Syt1 expression and that this may be a mechanism by which alcohol regulates neurotransmitter release during brief exposures. Further analysis revealed that a subset of the genes encoding the core synaptic vesicle fusion (soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor; SNARE) proteins share this property of induction by ethanol, suggesting that alcohol may trigger a specific coordinated adaptation in synaptic function. This molecular mechanism could explain some of the changes in synaptic function that occur following alcohol administration and may be an important step in the process of neuronal adaptation to alcohol. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: dermatofibrosarcoma protuberans

MedlinePlus

... part of a large molecule called type I collagen, which strengthens and supports many tissues in the ... the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor ...

Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle.

PubMed

Fealy, Ciaran E; Mulya, Anny; Lai, Nicola; Kirwan, John P

2014-08-01

Defects in mitochondrial dynamics, the processes of fission, fusion, and mitochondrial autophagy, may contribute to metabolic disease including type 2 diabetes. Dynamin-related protein-1 (Drp1) is a GTPase protein that plays a central role in mitochondrial fission. We hypothesized that aerobic exercise training would decrease Drp1 Ser(616) phosphorylation and increase fat oxidation and insulin sensitivity in obese (body mass index: 34.6 ± 0.8 kg/m(2)) insulin-resistant adults. Seventeen subjects performed supervised exercise for 60 min/day, 5 days/wk at 80-85% of maximal heart rate for 12 wk. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and fat oxidation was determined by indirect calorimetry. Skeletal muscle biopsies were obtained from the vastus lateralis muscle before and after the 12-wk program. The exercise intervention increased insulin sensitivity 2.1 ± 0.2-fold (P < 0.01) and fat oxidation 1.3 ± 0.3-fold (P < 0.01). Phosphorylation of Drp1 at Ser(616) was decreased (pre vs. post: 0.81 ± 0.15 vs. 0.58 ± 0.14 arbitrary units; P < 0.05) following the intervention. Furthermore, reductions in Drp1 Ser(616) phosphorylation were negatively correlated with increases in fat oxidation (r = -0.58; P < 0.05) and insulin sensitivity (rho = -0.52; P < 0.05). We also examined expression of genes related to mitochondrial dynamics. Dynamin1-like protein (DNM1L; P < 0.01), the gene that codes for Drp1, and Optic atrophy 1 (OPA1; P = 0.05) were significantly upregulated following the intervention, while there was a trend towards an increase in expression of both mitofusin protein MFN1 (P = 0.08) and MFN2 (P = 0.07). These are the first data to suggest that lifestyle-mediated improvements in substrate metabolism and insulin sensitivity in obese insulin-resistant adults may be regulated through decreased activation of the mitochondrial fission protein Drp1. Copyright © 2014 the American Physiological Society.

Enhanced Mitogenic Activity of Recombinant Human Vascular Endothelial Growth Factor VEGF121 Expressed in E. coli Origami B (DE3) with Molecular Chaperones.

PubMed

Kaplan, Ondřej; Zárubová, Jana; Mikulová, Barbora; Filová, Elena; Bártová, Jiřina; Bačáková, Lucie; Brynda, Eduard

2016-01-01

We describe the production of a highly-active mutant VEGF variant, α2-PI1-8-VEGF121, which contains a substrate sequence for factor XIIIa at the aminoterminus designed for incorporation into a fibrin gel. The α2-PI1-8-VEGF121 gene was synthesized, cloned into a pET-32a(+) vector and expressed in Escherichia coli Origami B (DE3) host cells. To increase the protein folding and the solubility, the resulting thioredoxin-α2-PI1-8-VEGF121 fusion protein was co-expressed with recombinant molecular chaperones GroES/EL encoded by independent plasmid pGro7. The fusion protein was purified from the soluble fraction of cytoplasmic proteins using affinity chromatography. After cleavage of the thioredoxin fusion part with thrombin, the target protein was purified by a second round of affinity chromatography. The yield of purified α2-PI1-8-VEGF121 was 1.4 mg per liter of the cell culture. The α2-PI1-8-VEGF121 expressed in this work increased the proliferation of endothelial cells 3.9-8.7 times in comparison with commercially-available recombinant VEGF121. This very high mitogenic activity may be caused by co-expression of the growth factor with molecular chaperones not previously used in VEGF production. At the same time, α2-PI1-8-VEGF121 did not elicit considerable inflammatory activation of human endothelial HUVEC cells and human monocyte-like THP-1 cells.

A system for activity recognition using multi-sensor fusion.

PubMed

Gao, Lei; Bourke, Alan K; Nelson, John

2011-01-01

This paper proposes a system for activity recognition using multi-sensor fusion. In this system, four sensors are attached to the waist, chest, thigh, and side of the body. In the study we present two solutions for factors that affect the activity recognition accuracy: the calibration drift and the sensor orientation changing. The datasets used to evaluate this system were collected from 8 subjects who were asked to perform 8 scripted normal activities of daily living (ADL), three times each. The Naïve Bayes classifier using multi-sensor fusion is adopted and achieves 70.88%-97.66% recognition accuracies for 1-4 sensors.

33 CFR 138.15 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-07-01

... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

33 CFR 138.15 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

33 CFR 138.15 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

33 CFR 138.15 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

33 CFR 138.15 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION FINANCIAL RESPONSIBILITY FOR WATER POLLUTION (VESSELS) AND OPA 90 LIMITS OF LIABILITY (VESSELS AND DEEPWATER PORTS) Financial Responsibility for Water Pollution (Vessels) § 138.15 Applicability. (a) This subpart applies to the operator as defined herein of...

Supervisory Control of the Right Arm of the Beam Assembly Teleoperator.

DTIC Science & Technology

1985-05-10

22332 L pQ5)1OLLA, Fg & E AND ADDRESS 12. REPORT DATE ATTN: DAPC-OPA-E 10 May 85 200 Stovall Street 13 NUMBEROF PAGES tf1 Alexandria. V4rqi nia 22332 171...MODUOE MOO FIGURE~ I. RgTArSuste -ll7- DC MOTOR END EFFECTOR FOR ROLLER SMALL POWER MODULE SOLENOID VALVE BOX MAIN POWER FIGURE A.6 Left Arm Subsystem...closed pneumatically. It is controlled by the ICS through the solenoid valve box and the RRT. At the base of the end effector is a roller. This roller

Analysis of the financial factors governing the profitability of lunar helium-3

NASA Technical Reports Server (NTRS)

Kulcinski, G. L.; Thompson, H.; Ott, S.

1989-01-01

Financial factors influencing the profitability of the mining and utilization of lunar helium-3 are examined. The analysis addressed the following questions: (1) which financial factors have the greatest leverage on the profitability of He-3; (2) over what range can these factors be varied to keep the He-3 option profitable; and (3) what ultimate effect could this energy source have on the price of electricity for U.S. consumers. Two complementary methods of analysis were used in the assessment: rate of return on incremental investment required and reduction revenue requirements (total cost to customers) achieved. Some of the factors addressed include energy demand, power generation costs with and without fusion, profitability for D-He(3) fusion, annual capital and operating costs, launch mass and costs, He-3 price, and government funding. Specific conclusions are made with respect to each of the companies considered: utilities, lunar mining company, and integrated energy company.